Press Statement of Dr BS Kakkilaya

That two young siblings of a very poor family from the remote village of Shishila, Belthangady had to succumb to severe malaria in 2014 is highly shocking. There appear to be several lapses at multiple levels leading to these tragic deaths. There also appears to be a clear attempt to hush up at least 35 deaths due to malaria in the last 2 years.

According to the reports in the media and the information that we have collected, the older girl was initially taken to the Primary Health Centre at Hatyadka for fever and other related symptoms. She was diagnosed as a case of jaundice (hepatitis) and no test was done for malaria. The relatives chose to treat her jaundice with herbal remedies from a local healer. Two days later, she was taken to the same PHC again; malaria test was not done and she was referred to the district hospital with suspicions of infective hepatitis or leptospirosis. The relatives brought her to the district hospital after a delay of 2 more days and by then she had deteriorated irreversibly. Her younger brother was also brought to the district hospital under similar conditions. At the time of admission to the district hospital, both the kids had cerebral malaria, severe anemia, severe acidosis and respiratory distress and despite prompt treatment, both could not be saved.

The failure to diagnose malaria at PHC, Hatyadka, combined with the attempted herbal remedies, resulted in the delay and aggravation of the infection before reaching the district hospital. This clearly indicates the failure to adhere to the guidelines of the NVBDCP that every case of fever must be immediately tested for malaria either with a blood smear or with Rapid Diagnostic Test. This failure could have been due to non-availability of a trained microscopist or of the RDT at the PHC. Therefore, immediate measures must be taken to sensitise all the medical officers regarding early diagnosis and prompt treatment of malaria, as envisaged in the NVBDCP guidelines and measures must also be taken to strengthen laboratory/RDT supplies at all the PHCs. Strict and immediate action must be taken against the district NVBDCP officials for these lapses at PHC Hatyadka.

The claims of the two-doctor team from Directorate of Health and Family Welfare, Bangalore, as reported in the media, that the children were anaemic and could not resist the malarial attack and hence their deaths, are laughable. Anemia in these two children was the result of severe malaria, rather than being the cause of malaria. Therefore, such a statement is not only false but also a blatant attempt to divert the attention from the lapses of the health authorities.

The claims of the district NVBDCP and Epidemic Surveillance officials that there have been no reports of deaths due to malaria over the last 3 years are also totally baseless. The data that we have collected from six major hospitals of Mangalore reveal that not less than 35 cases of deaths due to malaria have been duly reported to the local health authorities in 2012 and 2013. If data from all other hospitals are collected, this number will be much more. The reasons for hushing up these reports, confirmed by relevant investigations in tertiary care hospitals and medical college hospitals, are only known to the concerned authorities. Hushing up the actual number of cases and the deaths due to malaria would adversely impact on the malaria control efforts in the district. Therefore, strict action must be initiated against all the officials responsible for this.

It is indeed worrisome that two young lives have been lost to malaria in 2014, when all the facilities are available for early diagnosis and prompt treatment. It is also worrisome that this has happened in the month of January when the transmission of malaria is expected to be the lowest. It is evident therefore that malaria transmission is high even during the lean season and the NVBDCP authorities have failed to record and contain it. Urgent investigations are needed to find out why and how the two children from a remote village could contract malaria, instead of brushing it aside as a freak incident.

I urge the Hon’ble minister of Health and Family Welfare to take immediate action against the concerned officials and to initiate an independent enquiry into the lapses that led to the delay in the diagnosis and treatment of these two children, as well as into the hushing up of reports of malarial transmission and deaths.

  ©malariasite.com ©BS Kakkilaya | Last Updated: Mar 11, 2015

 

Malaria Vaccines

One of the greatest challenges of medicine has been the development of an effective and safe vaccine against malaria. Despite the persistent efforts for more than a century, spending hundreds of millions of dollars and lifelong sacrifice from dedicated physicians and scientists, the malaria vaccine has remained elusive. Although many promising experimental vaccines have been developed, the confident promise of researchers in the mid-1980s that an effective vaccine against P. falciparum would be available within a decade has not been realized yet.[1-3] A Malaria Vaccine Technology Roadmap, developed by more than 230 experts representing 100 organizations from 35 countries, has set out a strategic goal to develop a malaria vaccine by 2025 that would have a protective efficacy of more than 80% against clinical disease and would provide protection for more than 4 years. In the interim, it seeks to develop and license a first generation malaria vaccine by 2015 that has a protective efficacy of more than 50% against severe disease and death, and lasts for at least 1 year.[4]

Development of a vaccine for malaria has turned out to be a highly complex exercise owing to a multitude of difficulties.[3] A natural malaria infection does not induce much immune protection: after repeated and prolonged exposure to malaria parasite over several years, only partially effective immunity is acquired, which is short-lived and is highly stage- and strain-specific.[2,3] This immunity is unable to eradicate all parasites nor does it provide complete protection against future challenge.[2] Instead, it only results in a mild, sometimes asymptomatic infection with the persistence of parasites.[3]

This kind of a partial immune response is due to the complex biology of the Plasmodium parasite, its extensive antigenic diversity, and its immune evasion strategies, and all these factors make vaccine development against malaria challenging.[5] Several vaccine candidates have been tested over the years, but without much success. As many as 80 malaria vaccine candidates are at the preclinical development stage, out of which more than 30 have entered clinical testing and at least 3 have gone as far as Phase IIb trials or beyond.[6-7] Updated information on malaria vaccine candidates is available on the WHO,[6,7] MVI, and Clinical Trials websites. These candidates have been chosen on the basis of their ability to elicit some form of inhibitory immune response against the parasite, and all these candidates have predated the publication of the complete genome sequence of Plasmodium.[2] Following the sequencing of the entire genome complement of 5300–5500 genes of P. falciparum, 579 of annotatedfalciparum genes have been predicted to encode proteins containing signal peptides. Only 197 of these proteins that are expressed in the life-cycle stages are targeted for vaccine development: 43 in gametocytes, 57 in sporozoites, and 94 in either the young or late schizont or merozoite stages.[2] Additional post-genome analyses have helped to pinpoint potential candidate proteins that are associated with surface/rhoptry transport structures called Maurer’s clefts in the parasite-infected erythrocytes or with schizont/merozoite lipid rafts enriched with GPI anchored proteins.[2] These studies have also helped in validating the existing vaccine candidates such as the apical membrane antigen 1 (AMA-1) and in identifying certain multistage vaccine candidates like the erythrocyte binding ligand MAEBL.[2]

Malaria Vaccine Candidates

Malaria Vaccine Candidates [Source]

Vaccine Types

The candidate malaria vaccines target the different phases of the parasite’s life cycle.

The preerythrocytic vaccines target sporozoites or schizont infected liver cells and are aimed at preventing infection by stopping the progression of hepatic stage. These vaccines are intended to induce antibody responses against sporozoites and thus prevent the entry of sporozoites into hepatocytes or to induce T cells against the antigens expressed by infected hepatocytes, so as to prevent merozoite release by killing the infected hepatocytes or by interfering with parasite development.[2,3,5,8] Such a vaccine must be 99% effective in interrupting the pre-erythrocytic stages if it has to provide sterile immunity in nonimmune individuals. Even a single sporozoite escaping vaccine-induced immunity may cause a fully pathogenic blood stage infection, as was found during the clinical trials of the latest antisporozoite RTS,S vaccine.[2,3,9]

The erythrocytic stage vaccines are aimed at reducing parasite multiplication and growth in order to protect against clinical disease, particularly severe disease.[2,5,8] These vaccines are designed to induce antibody responses against the targets on the asexual blood stage of the parasite such as merozoite surface proteins (such as MSP-1) or those contained in specialized organelles associated with invasion (such as AMA-1).[2,5,8] But the very short duration during which merozoites stay outside the red cells (about 2 minutes), the high degree of polymorphic variability, and the use of alternative invasion pathways by P. falciparum make such vaccines a difficult proposition.[2,8]

Transmission-blocking vaccines are aimed at reducing malaria transmission by interrupting the parasite life-cycle in the mosquito by inducing antibodies that prevent either fertilization of the gametes in the mosquito gut or the further development of the zygote into sporozoites. These vaccines do not protect the immunized individual but rather provide herd benefit.[2,5]

Antidisease vaccination, by preventing the parasite surface protein parasite-derived erythrocyte membrane protein (PfEMP1) from interacting with various vascular endothelial cell–surface receptors, may block the sequestration of parasite-infected erythrocytes and prevent the serious complications such as cerebral malaria or placental malaria.[2,8]

Technology Formats

Different technology formats have been developed to produce the candidate antigens and to deliver them into the recipient. Attenuated whole parasites can deliver a vast array of antigens, much like a multiepitope vaccine, inducing effective immunity.[10] However, it is practically not possible to produce malaria parasites on a scale required for a live or attenuated vaccine.630 Safety is also a major concern, as current technology requires that parasites are cultured in human erythrocytes, which is accompanied by the risk of serious blood-borne infections.[10] Ensuring consistent quality and precise irradiation are the other issues.[10] In vitro culture of P. vivax is difficult to sustain and large-scale production is not currently feasible.[10]

Considering these difficulties, almost all efforts in malaria vaccine development today are focused on the design and delivery of subunit vaccines.[3] Such subunit vaccines may comprise a single parasite antigen or a mix of many antigens, as in a polyvalent, multicomponent vaccine, targeting different proteins in different stages of the parasite life cycle.[2,3] Recombinant antigens or long synthetic peptides can be produced in larger scale and then delivered with appropriate adjuvants for better immunogenicity.[3,5,8] Use of DNA expression vectors such as viruses, bacteria, and plasmid DNA for delivering the parasite antigens is emerging as a promising strategy to generate the desired antibody and cell-mediated immunity by the vaccines.[2,3,5,8,10]

Priming of the immune response to chosen antigens using DNA expression vectors (plasmid or attenuated viral vectors, AVV) followed by boosting using AVV expressing the same antigens – the heterologous primeboost approach – is being employed in many of the recent vaccine candidates; different viral vectors and a range of different formulations such as liposomes, virosomes, microspheres, and nanoparticles are being tested, with the advantage of carrying multiple antigens.[2,10]

Whole Cell Sporozoite Vaccine

The possibility of using inactivated sporozoites for immunization was first demonstrated in 1910 in avian malaria.[11,12] In 1941, immunization of fowls with irradiated sporozoites was found to prevent infection[13] and in 1967, immunizing mice with radiation-attenuated P.  berghei sporozoites was reported to protect them against challenge with fully infectious sporozoites.[14] This was followed by human studies and during the 1970s, it was established that immunizing human volunteers with the bites of irradiated mosquitoes carrying P. falciparum sporozoites in their salivary glands could protect them against challenge with fully infectious P. falciparum sporozoites.[1] In these studies, sporozoites were collected from the mosquitoes made to feed on human volunteers with P. falciparum malaria (who were treated with chloroquine that clears only asexual forms) and the vaccine was delivered through bites of infected mosquitoes or intravenous injections (in mice). Later, mosquitoes fed on gametocytes grown in vitro cultures were used.[1] Although many studies demonstrated the efficacy of attenuated whole parasite vaccines in generating effective and (in some cases) long-lasting protection against both sporozoites and asexual blood stages, many technical difficulties hampered the progress of this model.[1,2]

The need for precise irradiation (too little irradiation will make the sporozoite remain infectious and generate a full-blown malaria infection in “vaccinated” subjects and too much irradiation will kill the parasite, not generating effective immunity), difficulties in producing enough numbers of such attenuated sporozoites to meet global demand, and many other technical difficulties were considered as major drawbacks for further development of this vaccine.[1,2]

The postgenome era has opened up the possibility of developing genetically attenuated parasites that are not capable of causing a full-blown infection, yet immunogenic. Early studies in P. berghei with deletion of UIS3, UIS4 [15], and P36p [16] genes were reported to be successful, with both forms of the mutant parasite providing full protection against subsequent challenge with wild-type parasites.[15,16] Creation of genetically attenuated P. falciparum parasite by deletions of the sporozoite-expressed genes P52 and P36, causing parasite developmental arrest during hepatocyte infection, has now been reported.[17] This double knockout, genetically attenuated, parasite may be an exciting candidate for whole-organism vaccine in humans.[17] With these reported successes in the development of genetically attenuated sporozoites of P. berghei as well as P. falciparum and with other issues such as sterility, cryopreservation, and mode of administration also being on the verge of getting solved, the possibilities of an engineered sporozoite vaccine appear encouraging.[2,5]

Meanwhile, a proof-of-concept study involving inoculation to intact sporozoites to human volunteers receiving a prophylactic regimen of chloroquine has been reported to offer protection against malaria infection.[18] Fifteen healthy volunteers – with 10 assigned to a vaccine group and 5 assigned to a control group – were exposed to the bites of mosquitoes once a month for 3 months while they were receiving a prophylactic regimen of chloroquine. The vaccine group was exposed to mosquitoes that were infected with P. falciparum, and the control group was exposed to mosquitoes that were not infected with the malaria parasite. One month after the discontinuation of chloroquine, protection was assessed by homologous challenge with five mosquitoes infected with P. falciparum. All 10 subjects in the vaccine group were protected against a malaria challenge with the infected mosquitoes while patent parasitemia developed in all five control subjects. Adverse events were mainly reported by vaccinees after the first immunization and by control subjects after the challenge; no serious adverse events occurred. Induction of parasite-specific pluripotent effector memory T cells producing interferon-γ, tumor necrosis factor-α, and interleukin-2 was observed.[18]

Pre-erythrocytic Vaccines

Pre-erythocytic stage vaccines are based on the circum sporozoite protein (CSP) and liver-stage antigens (LSAs). These vaccines are aimed at induction of antibodies that alter the sporozoite surface or block the mobility or inhibit their invasion into hepatocytes and/or aimed at induction of cells cytolytic to the infected hepatocyte or induction of cytokines (IFN-γ) or free radicals that inhibit intrahepatic parasite development.[5]

Circumsporozoite protein

The CSP has been the subject of numerous trials based on a variety of peptides, recombinant proteins, modified virus vectors, plasmids, and a large diversity of adjuvants and immunization regimens.[5]

RTS,S/AS: At present, the RTS,S/AS02 vaccine is undoubtedly the most advanced and promising vaccine candidate.[5] The designation “RT” refers to approximately 190 amino acids from the C-terminus of the P. falciparum CSP and “S” refers to the hepatitis-B surface antigen. RTS,S virus-like particles form when the RTS malaria–hepatitis B fusion protein is coexpressed with S antigen alone in yeast cells (Saccharomyces cerevisiae). The adjuvant AS01 consists of liposomes plus MPL plus QS21. An earlier version of the RTS,S vaccine was adjuvanted with AS02 (an oil–water emulsion plus MPL plus QS21).[19] In Phase IIa trials, RTS,S/AS02 protected 40–86% of malaria-naive individuals after artificial challenge and two proof-of-concept Phase IIb trials demonstrated a partial delay of infection, a 30% reduction in clinical episodes of malaria,[5] and reduction in severe malaria by 58%.[5] A phase III trial of RTS,S has been conducted in 11 countries of sub-Saharan Africa from March 2009 through January 2011, in 15460 children in two age categories (6–12 weeks of age and 5–17 months of age), with a dose of 25 µg in a three-dose schedule delivered intramuscularly at the ages of 0, 1, and 2 months.[19] The first results have shown a reduction in the total number of episodes of clinical malaria by 55.1% and reduction in severe malaria by 47%, both in the older group.[19] However, recalculating the trial data has shown that RTS,S protected just 35–36% after 12 months and combining the results of both age groups cut the reduction in severe malaria to 34.8%.[19,20] Serious adverse events, such as convulsions and meningitis, was significantly higher in the vaccinated group, although the data are too preliminary to draw firm conclusions.[19,20] The mortality was similar in vaccinated and control groups.[19] Nevertheless, these initial reports have been considered as encouraging, raising the hopes of an effective malaria vaccine in the near future. [Also see]

Long Synthetic Peptide (LSP) PfCS102: Although the LSPs coding for the C-terminal 282–383 region of the CSP showed promising results in Phase Ia trials, the Phase IIa trial performed with PfCS102 showed no protection and no delay in patent parasitemia after artificial challenge and therefore the development of this candidate was stopped.[5]

Multiple Epitope, Thrombospondin-Related Adhesion Protein-, CS-, and LSA1-Expressing Fowlpox 9 and Modified Vaccine Ankara: A heterologous prime-boost vaccine, comprising a multiepitope string containing B-cell, CD4, and CD8 T-cell epitopes derived from six sporozoite and/or LSAs, including CS, LSA-1, and LSA-3 fused to the thrombospondin-related adhesion protein (T9/96 strain) was developed at the University of Oxford. These antigens are delivered as a DNA plasmid or expressed by recombinant attenuated viruses – fowl pox strain (FP9) or modified vaccine Ankara (MVA). The prime-boost approach – DNA or FP9 then MVA – has been shown to induce high T-cell responses, but two Phase IIb studies failed to show protection against malaria.

Other FP9 and MVA polyprotein constructs including combination vaccines with CS and LSA1 antigens are being developed at the University of Oxford with the European Malaria Vaccine Initiative and Wellcome Trust support.[8]

Adenovirus-35-CS: Priming with a vaccine candidate consisting a replication-deficient recombinant adenovirus serotype 35 expressing P. falciparum CS followed by RTS,S/AS01B boosting demonstrated high humoral and T-cell immunogenicity. This vaccine is undergoing Phase I trial.[8,21,22]

Plasmid DNA Vaccines: Several DNA-based vaccines, encoding one or several antigens, have been tested in clinical trials and have shown to actively induce T-, but not B-cell, immunity. Priming with one CS-encoding candidate, P. falciparum CS protein DNA, followed by RTS,S/AS02, demonstrated activation of both cellular and antibody responses in malaria-naive Americans.[8]

Liver-stage antigen-1

Liver-stage antigen (LSA)-1 is a pre-erythrocytic antigen expressed during the liver stage of P. falciparum infection. In adults living in malaria-endemic areas, levels of anti-LSA-1 IgG have been found to correlate with protection against malaria. An LSA-1-based vaccine candidate is being developed as a recombinant protein antigen expressed in E. coli. In Phase I/IIa trials, the vaccine showed a good safety profile and was immunogenic, but it did not protect against infection nor delay the parasitemia following P. falciparum experimental challenge.[8]

Liver-stage antigen-3

Liver-stage antigen-3 is expressed by sporozoites, liver schizonts, and maturing hepatic merozoites and has been found to induce partial protection against sporozoite challenge in mice and monkeys. This candidate vaccine is being developed as long synthetic peptides, a lipopeptide formulation and a recombinant protein in a Lactococcus lactis expression system. A Phase I/IIa trial of the recombinant LSA-3 candidate vaccine is ongoing.[8]

Asexual Blood-Stage Vaccines

Vaccines against the asexual blood stage of the parasite are aimed at preventing the disease and its complications by inducing antibodies against the merozoites. The merozoite exposes at its surface several functional proteins involved in erythrocyte invasion and most blood stage vaccines are based on the use of MSP-1–3, AMA-1, and glutamate-rich protein (GLURP).[5,8]

Merozoite surface protein-1

Merozoite surface protein (MSP)-1 is expressed at the surface of blood- and liver-stage merozoites and plays an important role in initial binding and invasion of the erythrocyte. More than 20 different MSP-1 constructs are in preclinical or clinical development. The most advanced is the MSP-142 of the 3D7 clone of P. falciparum. E. coli expressed recombinant protein MSP-1 42-kd 3D7 [falciparum malaria protein-1 (FMP-1)], E. coli expressed recombinant protein MSP-1 42-kd FVO, etc., are undergoing trials.[6] Although Phase Ia/Ib trials confirmed the safety and immunogenicity of the FMP1/AS02A formulation, Phase IIb trial in Kenyan children showed no efficacy to reduce malaria morbidity.[5,8]

Other merozoite surface proteins

An MSP-2 vaccine candidate including equal amounts of 3D7 and FC27, the two allelic variants of MSP-2, is being developed.[5] The MSP-3 has been developed as an LSP and the Phase I trial showed good immunogenicity with high antibody responses. Phase Ib trials of MSP-3 LSP vaccine among children in Burkina Faso and Tanzania have shown promising results.[23,24] MSP-4 and -5 are also being developed as subunit vaccines against malaria.[5]

Apical membrane antigen-1

The apical membrane antigen (AMA)-1 is another leading asexual blood-stage vaccine candidate and several variants have been tested. FMP2.1/AS02A (Phase I/IIb trial), AMA1-C1/alhydrogel (Phase Ia/Ib/IIb), and recombinant Pichia pastoris AMA-1 (25-545FVO) (Phase Ia trial) are some examples.[5,8]

Serine-repeat antigen

The serine-repeat antigen, also known as P126 antigen, is the largest protein that accumulates in the parasitophorous vacuole of trophozoites and schizonts. A recombinant vaccine candidate including the N-terminal part of the serine repeat antigen-5 is under development and Phase I trial has been conducted.[5,8]

Glutamate-rich protein

The Glutamate-rich protein (GLURP) is a P. falciparum protein expressed in both the pre-erythrocytic and erythrocytic stages. Antibodies to the GLURP 85-213 sequence (LR67) mediate the strongest biological effect in vitro and a Phase Ia trial showed the candidate vaccine to be safe and immunogenic, with a high level of antibodies.[5,8]

Erythrocyte-binding antigen-175

Erythrocyte-binding antigen (EBA)-175 mediates erythrocyte invasion. A Phase I trial with a recombinant PfEBA-175 region II-nonglycosylated (EBA-175 RII-NG) is ongoing and other candidates, including the N-terminal, conserved, cysteine-rich region of EBA-175 or the Duffybinding antigen, are currently being developed as recombinant vaccine candidates or as DNA vaccines in prime-boost regimens.[5,8]

PfEMP1

PfEMP1 mediates the binding of P. falciparum–infected erythrocytes to the vascular endothelium and to uninfected erythrocytes. Its extreme variability is proving to be a major challenge for the development of an anticytoadhesion vaccine; immunization studies with a recombinant conserved CD36-binding portion of PfEMP1 failed to confer protection in Aotus monkeys.[5]

A single PfEMP1 variant, termed VAR2CSA, which is structurally distinct from all other PfEMP1 family members, has been identified to play a key role in sequestration to the placenta by binding to chondroitin sulfate A.[5] The increased ability of multigravidae women to control pregnancy-associated malaria has been attributed to the acquisition of anti-PfEMP1 immunity during successive pregnancies.[8] Work is on to develop a candidate vaccine based on PfEMP1 antigens aimed at the prevention of pregnancy-associated malaria.[8]

Multiantigen Blood-Stage Vaccines

The belief that a single malaria antigen is unlikely to induce the desired level of protection has led to the development of multicomponent vaccines that combine more than one antigen in a formulation, but it is unclear whether this approach will speed up the vaccine development process or not.[5]

RTS,S-based combination vaccines

Several options for improvement of RTS,S-based vaccines are under investigation; sequential immunization schedules with RTS,S/AS02 combined to prior PfCSP DNA vaccination or CS-expressing adenovirus 35 or followed by CS-expressing live MVA have been investigated and a multistage, multiantigen recombinant vaccine based on RTS,S, and MSP-1 from the 3D7 strain is also under evaluation.[8]

Recombinant hybrid GLURP plus MSP-3 (GMZ-2)

GMZ-2 is a recombinant hybrid of GLURP and MSP-3 expressed in L. lactis. A Phase Ia trial in malaria-naive volunteers has been completed and a Phase Ib trial is ongoing.[5,8]

Chimeric fusion protein MSP-1 plus AMA-1 (PfCP-2.9)

An MSP-1/AMA-1 fusion antigen vaccine, consisting of the C-terminal region of AMA-1 and the 19-kDa fragment of MSP-1 using the yeast P. pastoris is undergoing Phase Ia trials and found to be safe and immunogenic.[5,8]

PEV 301, PEV 302

A new antigen-delivery system, based on synthetic peptides displayed on the surface of reconstituted influenza virosomes, is under development. It comprises phospholipid-anchored antigenic peptides mixed with nonbounded phospholipids and nfluenza surface glycoproteins, creating virus-like particles supposed to be strong inducers of B- and T-cell immunity. This allows the inclusion of several antigenic peptides in a multiantigen, multistage vaccine. Presently, two virosome formulations using synthetic peptide mimicking a CS-like sequence (PEV 301) and an AMA-1 like sequence (PEV 302), are undergoing Phase I/Phase Ib/Phase IIa trials.[5,8]

Multivalent NMRC-M3V-Ad-PfCA

NMRC-M3V-Ad-PfCA vaccine candidate is a mixture of two recombinant adenovectors comprising codon optimized sequences of the transgenes from the 3D7 strain of P. falciparum expressing CS or AMA1 and the replication deficient adenovector derived from adenovirus serotype 5. Phase I/IIa trials are ongoing.[5,8]

Combination B: MSP-1, MSP-2, and ring-stage infected erythrocyte surface antigen combination

Another vaccine candidate combining MSP-1, MSP-2, and the ring-stage infected erythrocyte surface antigen did not show a reduction or delay in parasitemia in a small Phase IIa challenge study, but in a subsequent Phase I/IIb trial in children, it showed a reduction in parasite density in some vaccinees compared with controls, thus becoming the first successful blood-stage vaccine to show some vaccine efficacy. Future vaccine candidates will include the opposite dimorphic form of MSP-2, FC27.[8]

Synthetic peptide vaccine SpF66

SPf66, developed in 1987 by Dr. M.E. Patarroyo in Columbia, was the first synthetic polymeric vaccine to be tested in humans.[25] It was based on polymeric synthetic peptides consisting of a number of epitope sequences from the blood as well as sporozoite stage proteins. Although the initial studies indicated a significant reduction in malaria morbidity, further trials of the same vaccine failed to reduce clinical disease in different locations in Latin America and Africa, resulting in the termination of its further development.[3] SPf66 paved the way for future design and field trials of subunit malaria vaccines and highlighted the complex nature and variability in field trials of malaria vaccines.[3]

Transmission-Blocking Vaccines

Transmission-blocking vaccines aim at induction of neutralizing antibody responses against gametocyte and ookinete surface proteins that can block the parasite cycle in the mosquito so as to interrupt malaria transmission. The main antigens assessed as vaccine candidates are the surface antigens Pfs25, Pfs28, Pfs48/45, and Pfs230. The surface antigens of ookinetes, Pvs25 of P. vivax and its P. falciparum analog, Pfs25, expressed as a recombinant protein in S. cerevisiae, have demonstrated moderate immunogenicity but suboptimal levels of transmission blocking activity in Phase Ia trials. Further improvements are being developed.[5,8]

Malaria Vaccine: Indian Research

In India, the Malaria Group at the International Center for Genetic Engineering and Biotechnology (ICGEB), New Delhi, has undertaken efforts to develop vaccines for both P. vivax and P. falciparum malaria.[3] The N-terminal conserved cysteine-rich region II (PvRII) has been identified as the receptor-binding domains of P. vivax Duffy-binding protein and antibodies against PvRII are expected to block the parasite invasion of erythrocytes. Methods to produce recombinant PvRII have been developed and attempts are on for the production of clinical grade recombinant PvRII for use in human clinical trials to test the safety, immunogenicity, and efficacy of a vaccine based on PvRII.[3] The vaccine for P. falciparum malaria, being developed at ICGEB, contains a physical mixture of recombinant PfMSP-119 and PfF2, expressed in E. coli. Immunogenicity studies in small animals have demonstrated that immunization with the recombinant PfMSP-119 and PfF2 mixture elicits high titers of invasion inhibitory antibodies against both antigens and plans are afoot to study the safety, immunogenicity, and efficacy of the vaccine in a series of Phase I and II trials.[3]

It is hoped that the vigorous pursuit of an effective and safe malaria vaccine may yield results in the near future. An ideal malaria vaccine should be safe, highly effective, and provide long-term immunity, besides being stable, easy to administer, inexpensive to manufacture, and affordable in poor malaria-endemic countries.[3]

However, from the existing knowledge and experience, it is more likely that the first-generation malaria vaccine will be partially protective, although safe but not entirely free of small side effects and provide protective immunity for a limited period. These vaccines will be expensive to manufacture and not easily affordable by those who will need them the most, without the help of donor funds.[3]

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  20. Butler D. Malaria vaccine results face scrutiny: Experts question early release of incomplete trial data. Nature. October 2011;478:439-440. doi: 10.1038/478439a
  21. Ann Stewart V, McGrath SM, Dubois PM, et al. Priming with an adenovirus 35-circumsporozoite protein (CS) vaccine followed by RTS,S/AS01B boosting significantly improves immunogenicity to Plasmodium falciparum CS compared to that with either malaria vaccine alone. Infect Immunity. 2007;75(5):2283–2290.
  22. Crucell. Malaria Vaccine. Available at http://www.crucell.com/R_and_D-Clinical_Development-Malaria_Vaccine.
  23. Lusingu JPA, Gesase S, Msham S, et al. Satisfactory safety and immunogenicity of MSP3 malaria vaccine candidate in Tanzanian children aged 12–24 months. Malaria J. 2009;8:163.
  24. Sirima SB, Tiono AB, Ouédraogo A, et al. Safety and immunogenicity of the malaria vaccine candidate MSP3 long synthetic peptide in 12–24 months-old Burkinabe children. PLoS One. 2009;4(10):e7549.
  25. Moreno A, Patarroyo ME, Development of an asexual blood stage malaria vaccine. Blood. 1989;74:537–546.

 ©malariasite.com ©BS Kakkilaya | Last Updated: Mar 23, 2015

Paul Muller

Paul Hermann Müller was born at Olten, Solothurn, Switzerland, on January 12th, 1899. He started working in 1916 as a laboratory assistant and later worked as an assistant chemist gaining a wealth of practical knowledge. He matriculated in 1918 and earned his Doctorate in 1925. He began his career with J. R. Geigy A.G., Basle, in May, 1925, to become Deputy Director of Scientific Research on Substances for Plant Protection in 1946. Müller worked on vegetable dyes and natural tanning agents, synthetic tanning agents, and on pesticides. Four years of intensive work led to the synthesis of dichlorodiphenyltrichloroethane (DDT) in 1939 and the basic Swiss patent was granted in 1940.

mullerpAlthough DDT was first synthesized in 1874 by a Viennese pharmacist, Othmar Zeidler, he did not investigate the properties of the new substance but simply published his synthesis. Field trials of the compound resynthesised by Muller showed it to be effective against a wide variety of pests including the common housefly, the louse, Colorado beetle, and mosquito. The Geigy Company began to market the substance in 1940-41 as a 5% dust called Gesarol spray insecticide and a 3% dust called Neocid dust insecticide. The now universally used name, DDT, was first applied by the British Ministry of Supply in 1943. DDT was first added to U.S. Army supply lists in May 1943. Gahan and colleagues, in August 1943, made the first practical tests of DDT as a residual insecticide against adult vector mosquitoes. The first field test in which residual DDT was applied to the interior surfaces of all habitations and outbuildings of a community to test its effect on Anopheles vectors and malaria incidence was begun in Italy in the spring of 1944. During World War II, when supplies of pyrethrum were not adequate to meet the demand, DDT proved to be of enormous value in combating typhus and malaria. In malaria-endemic areas, spraying DDT twice a year on the inside walls of houses could prevent mosquitoes from transmitting malaria. Indoor residual insecticide spraying contributed to the eradication of malaria from many countries (including the United States) during the 1950s – 1970s. These compounds have also had great value in agricultural entomology and they have provided a great stimulus in the search for other insecticides.

Paul Muller was awarded the Nobel Prize in Physiology and Medicine in 1948 “for his discovery of the high efficiency of DDT as a contact poison against several arthropods”.

Muller married Friedel Rüegsegger in 1927 and has two sons, Heinrich (b. 1929) and Niklaus (b. 1933), and one daughter, Margaretha (b. 1934), all married. Paul Müller died on October 12, 1965.

Sources:

  1. http://stevenlehrer.com/explorers/images/explor1.pdf
  2. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=188345
  3. http://www.libertyindia.org/pdfs/malaria_climatechange2002.pdf
  4. http://www.cdc.gov/malaria/history/panama_canal.htm
  5. http://www.cdc.gov/malaria/history/history_cdc.htm
  6. http://www.litsios.com/socrates/page5.php
  7. http://history.amedd.army.mil/booksdocs/wwii/Malaria/chapterI.htm
  8. From Nobel Lectures, Physiology or Medicine 1942-1962, Elsevier Publishing Company, Amsterdam, 1964. http://nobelprize.org/medicine/laureates/1948/muller-lecture.pdf

 ©malariasite.com ©BS Kakkilaya | Last Updated: Mar 11, 2015

Malaria Prophylaxis for Indian States

Prophylaxis for the states of Jammu and Kashmir, Himachal Pradesh and Sikkim

Malaria transmission is nil or very low in these states at a higher altitude. Routine chemoprophylaxis is therefore not essential for travelers to these states of the Indian Union. However it may be prudent to inquire about the ground situations by talking to the local medical professionals whenever possible.

Prophylaxis for all states other than Jammu and Kashmir, Himachal Pradesh and Sikkim and the North Eastern States of Assam, Manipur, Nagaland, Mizoram, Tripura and Arunachal Pradesh

The National Vector Borne Disease Control Programme (NVBDCP) recommends chemoprophylaxis for selective groups in high P. falciparum endemic areas. Use of personal protection measures including Insecticide Treated bed Nets (ITN) / Long Lasting Insecticidal Nets (LLIN) [See Personal protection measures] is encouraged for pregnant women and other vulnerable population including travellers for longer stay. However, for longer stay of Military and Para-military forces in high P. falciparum endemic areas, the practice of chemoprophylaxis should be followed wherever appropriate, e.g. troops on night patrol duty, and decisions of their Medical Administrative Authority should be followed.

For Short Term Prophylaxis (less than 6 weeks): Doxycycline, 100 mg daily in adults and 1.5 mg/kg for children more than 8 years old; it should be started 2 days before travel and continued for 4 weeks after leaving the malarious area. Doxycycline is contraindicated in pregnant women and children less than 8 years.

For long-term chemoprophylaxis (more than 6 weeks): Mefloquine 5 mg/kg bw (up to 250 mg) weekly; it should be administered two weeks before, during and four weeks after leaving the area. Mefloquine is contraindicated in cases with history of convulsions, neuropsychiatric problems and cardiac conditions.

Prophylaxis for States of Assam, Manipur, Nagaland, Mizoram, Tripura, Arunachal Pradesh

The north eastern states of India have higher incidence of chloroquine resistant P. falciparum malaria.

The National Vector Borne Disease Control Programme (NVBDCP) recommends chemoprophylaxis for selective groups in high P. falciparum endemic areas. Use of personal protection measures including Insecticide Treated bed Nets (ITN) / Long Lasting Insecticidal Nets (LLIN) [See Personal protection measures] is encouraged for pregnant women and other vulnerable population including travellers for longer stay. However, for longer stay of Military and Para-military forces in high P. falciparum endemic areas, the practice of chemoprophylaxis should be followed wherever appropriate, e.g. troops on night patrol duty, and decisions of their Medical Administrative Authority should be followed.

For Short Term Prophylaxis (less than 6 weeks): Doxycycline, 100 mg daily in adults and 1.5 mg/kg for children more than 8 years old; it should be started 2 days before travel and continued for 4 weeks after leaving the malarious area. Doxycycline is contraindicated in pregnant women and children less than 8 years.

For long-term chemoprophylaxis (more than 6 weeks): Mefloquine 5 mg/kg bw (up to 250 mg) weekly; it should be administered two weeks before, during and four weeks after leaving the area. Mefloquine is contraindicated in cases with history of convulsions, neuropsychiatric problems and cardiac conditions.

©malariasite.com ©BS Kakkilaya | Last Updated: Mar 11, 2015

Malaria Prophylaxis

Every year, more than 125 million people visit over 100 countries endemic for malaria. Each year up to 30 000 travelers are estimated to contract malaria and late or wrong malaria diagnosis in their home country may make things worse for them. Fever occurring in a traveler within three months of leaving a malaria-endemic area is considered a medical emergency and should be investigated urgently.

As there is no vaccine available for protection against malaria despite decades of research, there is a need for an alternative method that offers a fairly reliable protection against malaria. And as malaria can be severe in the non-immune, all visitors from non-malarious area to a malarious area should be protected. Anti malarial drugs offer protection against clinical attacks of malaria.

The risk of contracting malaria depends on the region visited, the length of stay, time of visit, type of activity, protection against mosquito bites, compliance with chemoprophylaxis etc. Pregnant women, infants and young children and people who have undergone splenectomy should avoid travel to a malarious area as these people are at higher risk of severe malaria. If travel is unavoidable, these people should take strict precautions to avoid mosquito bites and also take adequate chemoprophylaxis without fail.

Chemoprophylaxis:

Use of anti-malarial drugs to prevent the development of malaria is known as chemoprophylaxis.

The choice of chemoprophylaxis varies depending on the species and drug resistance prevalent in a country.

It must be remembered that no chemoprophylaxis regime provides 100% protection. Therefore it is essential to prevent mosquito bites as well as to comply with chemoprophylaxis. A possibility of malaria should be considered if a febrile illness develops after a week of entering a malarious area as well as up to over a year after visiting such an area, although it is more likely within the first 3 months of return.

Other residents of a malarious area are not advised chemoprophylaxis. It should not be prescribed as a remedy to prevent re-infections in an endemic area.

Primary Prophylaxis: Use of antimalaria drugs at recommended dosage, started 2-20 days before departure to a malarious area and continued for the duration of stay and for 1-4 weeks after return.

  • Causal prophylaxis: This prevents the establishment of infection in the liver by inhibiting the pre-erythrocytic schizogony. Primaquine and proguanil are effective as causal prophylactic drugs. Potential adverse effects on long term use and non-availability of primaquine make it a difficult drug for this purpose. In one study in the Papua- New Guinea, it was found to be effective as a prophylactic agent. It is however not yet recommended for general use. Daily doses of proguanil provide causal prophylaxis in areas where resistance to this drug is not present.
  • Suppressive prophylaxis: Use of blood schizonticides suppresses the blood forms of the malaria parasite and thus protects against clinical illness. However, P. vivax and P. ovale may cause relapses from the hypnozoites and to prevent this, terminal prophylaxis may be needed. [See below]

Terminal Prophylaxis: Terminal prophylaxis is the administration of primaquine for two weeks after returning from travel to tackle the hypnozoites of P. vivax and P. ovale that can cause relapses of malaria. It is indicated only for persons who have had prolonged exposure in malaria-endemic regions, such as expatriates and long-term travelers like missionaries and Peace Corps volunteers. Primaquine is administered after the traveler leaves an endemic area and usually in conjunction with chloroquine during the last 2 weeks of the 4-week period of prophylaxis after exposure in an endemic area has ended.

Drugs and Dosage for Chemoprophylaxis
Drugs Dosage Pros and Cons Adverse Effects
Adults Children
Atovaquone plus Proguanil (Malarone®) Adult tablet of 250 mg atovaquone and 100 mg proguanil – 1 tab. daily Pediatric tablet of 62.5 mg atovaquone and 25 mg proguanil:
5-8 kg: 1/2 tablet daily >8-10 kg: 3/4 tablet daily
>10-20 kg: 1 tablet daily
>20-30 kg: 2 tablets daily
>30-40 kg: 3 tablets daily
>40 kg: 1 adult tablet daily
Daily dosing; only have to continue for 7 days after exposure; not in pregnancy and lactation Nausea, vomiting, abdominal pain, diarrhea, increased liver enzyme levels; rarely seizures, rash, mouth
ulcers
Chloroquine
(Tablet with 150mg base)
300 mg base once weekly 5mg/kg base weekly;
maximum 300 mg
Long-term safety known; chloroquine resistance reported from most parts of the world; not for persons with epilepsy, psoriasis Pruritis, nausea, headache, skin eruptions, nail and mucous membrane discoloration, partial hair loss, photophobia, nerve deafness, myopathy, blood dyscrasias, psychosis and seizures
Proguanil 200 mg daily < 2 yrs: 50 mg/day;
2-6 yrs: 100 mg/day;
7-9 yrs: 150 mg/day;
>9 yrs: 200 mg/day
Used in combination
Doxycycline (100mg) 100mg once daily 1.5mg base/kg once daily
(max. 100 mg)
<25kg or <8 yr: Not given
25-35kg or 8-10 yr: 50mg
36-50kg or 11-13 yr: 75mg
>50kg or >14 yr: 100mg
Daily dosing required; not in pregnancy and lactation Abdominal discomfort, vaginal candidiasis, photosensitivity, worsening of renal function tests in renal diseases, allergic reactions, blood dyscrasias, esophageal ulceration
Mefloquine (Tablet with 250mg base, 274mg salt) 250 mg base once weekly <15 kgs: 5mg of salt/kg;
15-19 kg: ¼ tab/wk;
20-30 kg: ½ tab/wk;
31-45 kg: ¾ tab/wk;
>45 kg: 1 tab/wk
Weekly dosing; occasional reports of severe intolerance; not in first trimester of pregnancy, breast feeding, high altitudes or deep sea diving, patients with epilepsy, psychosis, heart blocks, receiving β blockers Dizziness, headache, sleep disorders, nightmares, nausea, vomiting, diarrhea, seizures, abnormal coordination, confusion, hallucinations, forgetfulness, emotional problems including anxiety, aggression, agitation, depression, mood changes, panic attacks, psychotic or paranoid reactions, restlessness, ?suicidal ideation and suicide

Chemoprophylaxis Regimen: Preferably, it should be started 1-2 weeks prior to travel to a malarious area. In addition to assuring adequate blood levels of the drug, this regimen allows for evaluation of any potential side effects. Chemoprophylaxis should continue during the stay in malarious area and for 1-4 weeks after departure from the area.

The following factors should be considered while chosing an appropriate chemoprophylactic regimen:

  1. The travel itinerary should be reviewed in detail and compared with the information on areas of risk within a given country to determine whether the traveler will actually be at risk of acquiring malaria.
  2. The risk of acquiring chloroquine resistant P. falciparum malaria (CRPF) is another consideration.
  3. Any previous allergic or other reaction to the antimalarial drug of choice and the accessibility of medical care during travel must also be determined.

Areas with Chloroquine Sensitive P. falciparum: Chloroquine, to be started one week before exposure, continued during exposure and for 4 weeks thereafter

Areas with chloroquine resistant P. falciparum (low degree, not wide spread): Chloroquine, to be started one week before, continued during exposure and for 4 weeks thereafter Plus Proguanil, to be started 1-2 days before, continued during exposure and for 4 weeks thereafter

Areas with chloroquine resistant P. falciparum (High degree, widespread): Chloroquine Plus Proguanil as above OR Mefloquine, to be started 2-3 weeks before, continued during exposure and for 4 weeks thereafter OR Doxycycline, to be started 2 days before, continued during exposure and for 4 weeks thereafter, OR Atovaquone Plus Proguanil, to be started 2 days before, continued during exposure and for 7 days thereafter

Recommendations for travelers to malaria endemic areas:

All travelers to malaria-endemic areas are at risk of contracting malaria and being non-immune, P. falciparum infection in these individuals can become severe. Therefore, all travelers to malaria endemic areas are advised to use an appropriate chemoprophylaxis and personal protection measures to prevent malaria. However, it should be remembered that, regardless of methods employed, malaria can still be contracted. Symptoms can develop as early as 8 days after initial exposure in a malarious area and as late as several months after departure from a malarious area. Malaria is easily treatable early in the course of the disease but delay in treatment can lead to serious or even fatal consequences. Therefore, individuals who develop symptoms of malaria should seek prompt medical help, including blood smear (or QBC test) for malaria.

Personal Protection Measures:

Anopheles mosquitoes bite at nights, with peak biting between 10pm and 4am and malaria transmission occurs at these hours. Travelers must take personal protective measures against mosquito bites at nights. Remaining in well-screened areas, using mosquito nets, and wearing clothes that cover most of the body are some simple but effective measures. In addition, mosquito repellents like N,N diethylmetatoluamide (DEET) can be used. It is better to have a pyrethrum-containing space spray to use in living and sleeping areas during evening and night hours.

See Malaria Control

Prophylaxis During Pregnancy:

Malaria infection in pregnant women may be more severe than in non-pregnant women. In addition, the risk of adverse pregnancy outcomes, including prematurity, abortion, and stillbirth, may be increased. For these reasons, and because chloroquine has not been found to have any harmful effects on the fetus when used in the recommended doses for malaria prophylaxis, pregnancy is not a contraindication to malaria prophylaxis with chloroquine or hydroxychloroquine. However, because no chemoprophylactic regimen is completely effective in areas with CRPF, women who are pregnant or likely to become so should avoid travel to such areas.

Chloroquine and Proguanil are the preferred chemoprophylactic drugs against malaria in the first 3 months of pregnancy. Mefloquine can be given during the second and third trimesters if the situation demands.

Mefloquine and doxycycline can be used in non-pregnant women with child bearing potential, but pregnancy should be avoided for 3 months after mefloquine use and for one week after doxycycline use. However, in case of unplanned pregnancy, malaria chemoprophylaxis is not considered an indication for termination of pregnancy.

Doxycycline, a tetracycline, is generally contraindicated for malaria prophylaxis during pregnancy. Adverse effects of tetracyclines on the fetus include discoloration and severe dysplasia of the teeth and inhibition of bone growth. In pregnancy, therefore, tetracyclines would be indicated only if required to treat life-threatening infections due to multi-drug resistant P. falciparum.

Primaquine should not be used during pregnancy because the drug may be passed transplacentally to a G6PD-deficient fetus and cause life-threatening hemolytic anemia in utero. Whenever radical cure or terminal prophylaxis with primaquine is indicated, chloroquine should be given once a week until delivery, at which time the decision to give primaquine may be made.

Prophylaxis while breast feeding:

Very small amounts of antimalarial drugs are secreted in the breast milk of lactating women. The amount of drug transferred is not thought to be harmful to the nursing infant; however, more information is needed. Because the quantity of antimalarials transferred in breast milk is insufficient to provide adequate protection against malaria, infants who require chemoprophylaxis should receive the recommended dosages of antimalarials.

Chemoprophylaxis for Children:

Children of any age can contract malaria. WHO advises against taking babies and young children to malarious areas, in particular where there is transmission of chloroquine-resistant P. falciparum. Malaria can rapidly cause complications in children and therefore any child suffering from fever after returning from a malarious area should be considered to have malaria until proved otherwise. Since it may be difficult to administer drugs to children and since paediatric formulations and accurate dosage may not be available, it is best to protect babies and children against mosquito bites.

The indications for prophylaxis are identical to those described for adults. Doxycycline is contraindicated for children less than 8 years of age.

Chloroquine phosphate, which is manufactured in the United States in tablet form only, tastes quite bitter. Pediatric doses should be calculated carefully according to body weight. Pharmacists can pulverize tablets and prepare gelatin capsules with calculated pediatric doses. Mixing the powder in food or drink may facilitate the weekly administration of chloroquine to children. Alternatively, chloroquine in suspension is widely available overseas.

OVERDOSE OF ANTIMALARIAL DRUGS CAN BE FATAL. THE MEDICATION SHOULD BE STORED IN CHILDPROOF CONTAINERS OUT OF REACH OF CHILDREN.

Chemoprophylaxis for Long Term Travelers:

Long-term travelers intending to stay for more than 1-3 months should seek the advice of local health care professionals familiar with the management of malaria in non-immune foreigners. The risk of serious side effects associated with long term use of chloroquine and proguanil are low. However, twice yearly screening for the detection of early retinal changes should be performed in anyone who has taken 300 mg of chloroquine (as base) weekly for over five years and requires further prophylaxis. If changes are observed, an alternative regimen should be considered. Data indicate no increased risk of serious side effects with long term use of mefloquine. The risk of long term use of doxycycline are not known. These two latter drugs should be reserved for those with greatest risk of infection.

Chemoprophylaxis for Frequent Travelers:

Frequent travelers such as members of the aircraft crew may reserve chemoprophylaxis for high risk areas only. They should maintain rigorous self-protection against mosquito bites and be prepared for an attack of malaria and should carry a course of antimalarials as stand-by.

Multi-drug resistant malaria: In areas of Thailand near the borders with Cambodia and Myanmar and in Western Cambodia, P. falciparum infections do not respond to chloroquine or pyrimethamine-sulfadoxine, and sensitivity to quinine is reduced. Treatment failures of over 50% are also being reported.

In these areas, chemoprophylaxis with doxycycline is recommended along with rigorous personal protection measures. Doxycycline is contraindicated in pregnant women and children below the age of 8 years, and therefore they should avoid traveling to these areas.

Atovaquone plus Proguanil – Malarone: See http://www.cdc.gov/travel/diseases/malaria/malarone.htm

Chemoprophylaxis for travelers to India:

Most parts of India have a high transmission of P. vivax malaria and chloroquine resistant P. falciparum is now reported from many parts of India. The high altitude states of Jammu and Kashmir, Himachal Pradesh and Sikkim are free from malaria. Malaria transmission is low or very low in areas at an altitude >2000 metres. For visitors to P. falciparum endemic areas, doxycycline 100mg once a day is now recommended as the drug of choice for short term prophylaxis.

Also see: Malaria in India and Malaria in Mangaluru

Also See

  1. http://wwwn.cdc.gov/travel/yellowBookCh4-Malaria.aspx
  2. Juckett G. Malaria Prevention in Travelers. American Family Physician Vol. 59/No. 9 (May 1, 1999). Available at  http://www.aafp.org/afp/990501ap/2523.html
  3. Drugs for the treatment and prevention of malaria Available at http://www.phac-aspc.gc.ca/publicat/ccdr-rmtc/04vol30/30s1/table8_e.html
  4. http://www.traveldoctor.co.uk/tables.htm

 ©malariasite.com ©BS Kakkilaya | Last Updated: Mar 31, 2015

Malaria Control in Mangaluru

Mangaluru is a coastal city in southern Karnataka with a population of 4,99,000 (2011 Census). The city has witnessed resurgence of malaria since 1990-91. [See Malaria in Mangaluru] The surge in malaria has been largely attributed to increased urbanisation and vigorous construction activities that brought in migrant labour from malarious regions of the country.

Malaria Surveillance Campaign by MCAC

Malaria Surveillance Campaign by MCAC

First deaths from malaria in Mangalore were reported in 1995. Alarmed by this, a voluntary initiative for malaria control was started by private medical practitioners in association with the local medical college, Mangalore City Corporation (MCC) and District Administration; Malaria Control Action Committee (MCAC) was thus constituted. In June 2003, a Malaria Cell was started with financial aid from the city based Corporation Bank.

The MCAC had drawn up a comprehensive strategy for control of malaria in Mangalore. With relentless efforts, Passive Surveillance was strengthened; almost all the hospitals and private laboratories were made to report the incidence of malaria cases on a weekly basis. A Hot Line was also established at the Malaria Cell for reporting cases and complaints. Computerization of data helped in analysis and monitoring.

Malaria Campaign by MCAC

Malaria Campaign by MCAC

MCAC had also helped in improving inter-departmental co-ordination. Better understanding between health dept. and the town planning dept. in the city A bye-law was enacted in 1998 and provisions were made for a Malaria clause in the construction license. Corporation had ensured that data on construction sites were readily available, the malaria clause was added in all licenses for construction and it was possible to initiate co-ordinated action against the offenders. Improved co-ordination between the MCC and DHO resulted in clear demarcation of responsibilities and areas of operation, better co-ordination in supply of drugs and insecticides, and in deputing staff (ANMs, Lab technicians) etc. Various other departments had also been brought to use: Fisheries College for Guppy breeding; Horticulture Dept for Guppy breeding tanks; Education Dept., NSS, Scouts and Guides for survey and IEC activities etc.

IEC activities were conducted all over the district. A video film on malaria and its control was prepared with the help of Corporation Bank. Hoardings, banners, pamphlets, posters, messages on radio, cinema halls and local cable network and regular press briefings were all used for the purpose.

mcacsite3

Mobile Fever Treatment Unit

Workshops were conducted for medical professionals, lab technicians, school teachers, builders and hoteliers. Hundreds of lectures and audio-visual presentations were held at schools, colleges and public places.

As a result, there was a significant decline in the incidence of malaria and by 2000, the annual incidence has dropped to 1798. However, due to complacence, the control actvities were relaxed and by 2003-4, the cases started rising yet again.

The Malaria Cell was constituted in June 2003 with financial aid from Corporation Bank. It had a co-ordinator, a computer operator and more than 30 field staff, including supervisors, ANMs, spray workers and Guppy distributors divided into six teams. Logistical support was provided by the MCC and DHO. These teams carried out active surveillance with special emphasis on migrant workers, construction workers, hotel workers and inmates of orphanages. The teams also carried out door-to-door surveys, IEC activities, source reduction, anti larval and anti adult spray operations, fogging, distribution of Guppy fish besides administering treatment to positive cases.

mcacsite4

Corporation officials inspecting construction sites for mosquito breeding

Five Fever Treatment Depots (FTDs) cum labs were established in the city, with one lab open during the evening hours (3pm-8pm) to cater to labourers. A Mobile FTD consisting of a health visitor and ANM and partly funded by Builders’ Association, was also started. The team visited construction sites to collect peripheral smear and provide treatment for all fever cases on intimation by mobile phone.

Active and inactive major constructions were closely monitored by the teams of the malaria cell on a weekly basis. Builders who failed to take anti larval measures were fined and repeated offenders were fined up to Rs. 25000.

Biolarvicides were also introduced into the wells and permanent water collections. Eight dedicated tanks for Guppy breeding were provided. Guppy fish were made available to general public through malaria cell. More than 6000 wells were covered.

tank2

Corporation officials inspecting construction sites for mosquito breeding

However, with changes in the authorities at the City Corporation, the malaria control activities have taken a turn for the worse. The well placed malaria control programme was disbanded and the collection of data from private hospitals and labs was discontinued so as to show a sharp reduction in the number of cases. The Malaria Cell, funded by a Nationalised Bank, was shut and the field work was instead outsourced to a private security agency with an annual budget of Rs. 5500000. Malaria has continued to increase ever since and by 2015, almost 60% of cases from the state are occurring in Mangaluru alone.

The City Corporation claims to have developed a new strategy yet again to try and tackle the menace. A new software has been developed and is expected to go on field trials soon. However, not much is happening on the ground and people are continuing to get infected and die of malaria.

News Reports:

  1. New Software being Developed to Aid Malaria Control in Mangalore, Supported by Mangalore Medical Relief Society [See]
  2. Mangalore City Corporation to Revamp Malaria Control Programme: Mayor Presides Meeting on July 21, 2014 [See The Hindu | Times of India| Deccan Herald | Vijaya Karnataka | Udayavani | Varthabharathi] Mangalore City Corporation Criticised for Failure to Tackle Malaria | MCC in dark about personnel doing its anti-malaria drives | MCC to revive panel on malaria control
  3. Deputy Commissioner Orders Probe into Lapses that Led to the Deaths of Two Kids | More on Malaria in Mangalore [The Hindu Feb 1 | The Hindu Feb 3 | Vijaya Karnataka | The Hindu
  4. 35 deaths due to malaria in two years in Mangalore; probe and act against officials: Dr Kakkilaya [See Press Statement | Report | Report | Report Jan 17]
  5. Lackadaisical attitude of malaria control officials claims the life of two siblings from rural Shishila, 90kms from Mangalore [Report]

 ©malariasite.com ©BS Kakkilaya | Last Updated: Mar 11, 2015

Malaria Control in India

Long before the British colonised India, malaria was a serious problem for the country, imposing enormous economic costs and a great deal of human misery. Malaria epidemics occurred throughout India with varying intensity. In 1852, one malaria epidemic wiped out the entire village of Ula and then spread across the Bhagirathi River to Hooghly and continued to devastate populations for many years in Burdwan. The development of the Indian railways under the British administration contributed to the spread of malaria. While the construction of railway embankments provided a number of breeding sites for the malaria vectors, the labourers probably introduced different strains of the parasite to the areas in which they worked. The city of Bombay suffered greatly from malaria epidemics. The construction of railroads or bridges were often associated with increases in malaria, probably due to imported labour from malarious areas. There were significant outbreaks of malaria during the construction of the Colaba causeway between 1821 and 1841 and during the construction of Alexander Dock and Hughes Dry Dock. Malaria epidemics in the Punjab and Bengal both show a startlingly high morbidity and mortality. In the early 1920s, Bengal suffered a severe malaria epidemic which resulted in over 730 000 deaths in 1921 alone. Thereafter, the number of deaths from malaria slowly decreased to within 300 to 400 000 per annum. During the Second World War however malaria deaths rose again, particularly in 1943, when Bengal recorded over 680 000 deaths and in 1944 when there were an appalling 763 220 deaths from the disease. Although quinine was available at the time, its supply was probably inadequate and patients did not seek treatment on time.

On the other, some of the great successes in controlling the disease were also achieved in India. Formal malaria control programmes were started under British colonial rule and continued after Indian Independence in 1946. Early malaria control efforts invloved removal of breeding sites and later used chemicals such as the larvicides Paris green and kerosene. One of the first formal operations to control the disease was at at Mian Mir, near the city of Lahore (now in Pakistan). Mian Mir had an intricate system of irrigation canals which provided excellent breeding grounds for the vectors. The malariologists Drs. J.W.W. Stephens and S.R. Christophers, who had worked with Sir Ronald Ross in Freetown, Sierra Leone earlier, arrived at Mian Mir in 1901 with ambitious plans to remove all the breeding sites, evacuate the infected people and administer quinine as both a curative and preventative measure. Their programme developed into a massive effort, with between four and five hundred soldiers set to work full time at filling in the irrigation canals. The programme of constantly filling in ditches and removing puddles and any other potential breeding site continued until 1909. During 1909 there was a serious malaria epidemic, as there was in 1908 throughout the Punjab, and the courageous, but ultimately useless control programme was abandoned.

Indian Medical Service (IMS) and Malaria

ross

Ronald Ross

The diseases endemic to India provided a rich field for research and the work of some of the IMS officers led to landmark discoveries. The foundation was laid by Surgeon-Major Dempster in 1845 with his work on the spleen rate as a reliable guide to the incidence of malaria. Major general Ronald Ross carried forward this work with distinction. He identified the mosquito as carrier of the malarial parasite in 1897-99. He was awarded the Nobel Prize in 1902 and knighted in 1911 in recognition of his outstanding contribution. Sir Samuel Rickard Christophers, who directed the Central Malarial Bureau from 1919 to 1924, supplemented Ross’s work. Further work was done by John Alexander Sinton, when he was the Director of Malarial Survey of India from 1927-38. In 1948, Henry Edward Shortt demonstrated the tissue phases of P. vivax malarial parasite for the first time.

Sinton [Source]

JA Sinton [Source]

Larviciding operations were also conducted at Bombay, Jhansi, Poona, Meerut, Secunderabad and all other military posts. In 1917, the Bengal Nagpur Railway and the East India Railways formed a separate malaria control organisation, specifically to control the disease in and around stations. National Railways managed to dramatically reduce the incidence of malaria among its staff though a comprehensive larviciding programme. Similar larviciding and breeding pool removal programmes were undertaken during the 1920s in the tea plantations of Assam and in Mysore by the Rockefeller Foundation. In 1927 the Central Malaria Bureau was expanded and renamed as the Malaria Survey of India. The first reported aerial spraying of Paris Green was in 1937. In 1938, pyrethrum was first used in malaria control in Delhi. The Rockefeller Foundation began using pyrethrum sprays experimentally in India to great success. The use of pyrethrum was then expanded to Assam by Dr. D. K. Viswanathan in 1942. However, all these interventions were unable to sustain the control of the disease. Vast breeding , colossal numbers of malaria vectors, limited effectiveness of pyrethrum sprays in houses and cattle sheds against the An. culicifacies vector, but not against An. fluviatilis and An. minimus were some of the causes for this setback.

DDT was first used in India by the armed forces in 1944 for the control of malaria and other vector borne diseases. In 1945, DDT was made available for civilian use in Bombay to control malaria and produced some remarkable results within a very short period. On 1st July 1945, the first civilian home was sprayed in India with a 5% solution of DDT mixed in kerosene. In 1946, pilot schemes using DDT were set up in several areas, including Karnataka, Maharashtra, West Bengal and Assam. Between 1948 and 1952 the WHO set up DDT demonstration teams in Uttar Pradesh, Rayagada, Wynad and Malnad. Use of DDT not only helped in the control of mosquitoes and malaria, but also improved the life expectancy. After the spraying in the Kanara district, the population began to grow because of a decrease in the death rate. Prior to DDT being used, the district reported an average of 50,000 malaria cases every year, which was reduced by around 97% to only 1,500 cases after DDT was introduced. The project was also blessed by Mahatma Gandhi.

During 1949, it is estimated that over 6 million people in Bombay were protected from malaria through the use of DDT and that at least half a million cases of malaria were prevented. In the early 1950s India’s population was estimated to be around 360 million and every year around 75 million people suffered from malaria and approximately 800,000 died from the disease.

Usefulness of DDT prompted the launch of the National Malaria Control Programme (NMCP) in 1953. The control programme first set out to control the disease in the endemic and hyperendemic areas with 125 control units. Each of these control units consisted of between 130 and 275 men and was to protect approximately 1 million people each. By 1958, the malaria control programme had been increased to protect at least 165 million people from the disease with 160 control units. The programme saw tremendous impact and the annual number of cases came down to 49151 by 1961. With this success, the programme was renamed as National Malaria Eradication Program (NMEP) in 1958 with a belief that malaria could be eradicated in seven to nine years. On the contrary, malaria began to re-emerge in 1965 to reach well over 1 million in 1971. One of the major problems with the eradication programme was that the supervisors could not manage to inspect all of the buildings that had been sprayed. There was a decline in the morale of the spray men and inspectors. With the declining number of cases, complacency set in among spray workers as well as the general population, as people turned the sprayers away. With the incomplete spraying operations, by 1959, resistance to DDT began to develop in certain areas and added to the problem. Furthermore, malaria cases were not treated properly.

With increase in malaria cases in urban areas, The Urban Malaria Scheme (UMS) was launched in 1971 with the objective of controlling malaria by reducing the vector population in the urban areas through recurrent anti larval measures and detection and treatment of cases through the existing health care services. Passive surveillance (case detection and treatment) and anti-larval measures are the main components of UMS strategy.

The number of malaria cases rose gradually and consistently with a peak of 6.47 million cases in 1976. With this, the focus was again shifted to control of malaria and in 1977 the Modified Plan of Operation (MPO) was launched which also comprised the P. falciparum Containment Programme (PfPC). The objectives of the MPO were

  • Effective Control of Malaria to reduce Malaria Morbidity
  • Prevent deaths due to Malaria
  • Retention of the achievements gained.

Fever Treatment Deport and Drug Distribution Centers were established for distribution of chloroquine. Residual insecticide Spray was limited to areas with an API (Annual Parasite Index) above two. By 1985, the incidence rate stabilized at 2 million cases. However, many focal outbreaks, particularly of P. falciparum malaria and deaths from malaria have occurred throughout India since the 1990’s and large scale epidemics have been reported from eastern India and Western Rajasthan since 1994. Many of these are related to irrigation projects aided by global funding agencies.

The National Anti Malaria Programme (NAMP) was launched in 1995 as a Centrally Sponsored Scheme on 50:50 Cost Sharing Basis between the Centre and the State Govts. As the Central share, the Central Govt. provides drugs, insecticides and larvicides and also technical assistance/guidance as and when required by the State Govts. The State Govts. meet the operational cost including salary of the staff. However, considering the difficulties faced by the seven North-Eastern States namely Arunachal Pradesh, Assam, Manipur, Meghalaya, Mizoram, Nagaland and Tripura, 100% Central Assistance except salary of the staff, which is a Non-Plan activity, is being provided since December, 1994. The Union Territories without Legislatures are also covered under 100% Central Assistance. An Enhanced Malaria Control Project with World Bank support is being implemented since September, 1997 covering a population of around 62.2 million in 1045 PHCs in 100 predominantly P.falciparum malaria endemic and tribal dominated districts in the peninsular States namely Andhra Pradesh, Bihar/Jharkhand, Gujarat, Madhya Pradesh/Chattisgarh, Maharashtra, Orissa and Rajasthan. The project lays emphasis on Early diagnosis and prompt treatment; selective vector control, eco-friendly methods like introduction of medicated mosquito nets (MMNs), larvivorus fishes, bio-larvicides etc.; epidemic planning and rapid response including inter-sectoral coordination and institutional and human resources development through training/reorientation training; strengthening management Information System (MIS), Information, Education and Communication (IEC) and operational research. It also aims to cover the most problematic areas and also has the flexibility to divert resources to any needy areas in the country in case of any outbreak of malaria.

In 2004, the integrated National Vector Borne Disease Control Programme (NVBDCP) for the prevention and control of vector borne diseases i.e. Malaria, Dengue, Lymphatic Filariasis, Kala-azar and Japanese Encephalitis has been launched and it has been changed to Enhanced Vector Borne Disease Control Programme (EVBDCP) with the World Bank support. [See NVBDCP website; See World Bank Site]

Source:

http://www.libertyindia.org/pdfs/malaria_climatechange2002.pdf

 ©malariasite.com ©BS Kakkilaya | Last Updated: Mar 11, 2015

Personal Protection

Personal Protection

Protective measures adopted by individuals and families not only help in protecting the individuals against mosquito bites and hence malaria, but also help in reducing the mosquito population by denying the blood meal essential for nourishment of the mosquito eggs in the female anopheles mosquito. Use of mosquito repellents, protective clothing and mosquito nets are important measures of personal protection against malaria. These are easy to use, safe and not very expensive. However, these should be used regularly without fail and therefore, demand such commitment form the users.

deetsprayMosquito repellents: Female mosquitoes bite human beings every 3 to 4 days for the blood meal and use visual, thermal, and most importantly, olfactory stimuli to locate a host. Carbon dioxide, released mainly from breath but also from skin, serves as a long-range airborne attractant and can be detected by mosquitoes at distances of up to 36 meters. Lactic acid, skin temperature, moisture, other volatile compounds, derived from sebum, eccrine and apocrine sweat, or the cutaneous microflora bacterial action on these secretions, may all act as attractants. Factors such as diet, general health condition, or reproductive status can also influence the odour profile of an individual and may explain the observed variation in human attractiveness to mosquitoes. In addition, floral fragrances from perfumes, soaps, lotions, and hair-care products may also attract mosquitoes and consumption of alcoholic drinks such as beer can also increase the attractiveness to mosquitoes. These attractants stimulate the chemoreceptors on the antennae of the mosquitoes and inhibition of these receptors by certain chemicals can produce mosquito repellent effect.Several synthetic and natural substances are being used as mosquito repellents. DEET (N,N-diethyl-m-toluamide [or N,N-diethyl-3-methylbenzamide]), picaridin (1-methyl-propyl 2-[2-hydroxyethyl]-1-piperidinecarboxylate [also known as KBR 3023]), PMD (p-menthane 3,8-diole [or oil of lemon eucalyptus]), MGK-326(dipropyl isocinchomeronate), MGK-264 (N-octyl bicycloheptane dicarboximide), IR3535 (ethyl butylacetylaminopropionate), and oil of citronella have been registered as insect repellents by the US Environmental Protection Agency.

deetliqOf these, DEET is the most effective, and best studied, synthetic insect repellent currently on the market. It has a remarkable safety profile after 40 years of worldwide use, although toxic reactions are known to occur. Developed by scientists at the U.S. Department of Agriculture and patented by the U.S. Army in 1946, it was subsequently registered for use by the general public in 1957. According to the estimates of the U.S. Environmental Protection Agency, more than 38% of the U.S. population uses a DEET-based broad-spectrum insect repellent every year and its worldwide use exceeds 200000000 people annually.DEET is available in 5% to 100% concentrations in multiple formulations, including solutions, lotions, creams, gels, aerosol and pump sprays, and impregnated towelettes. Products with 10% to 35% DEET will provide adequate protection under most conditions. Products with concentrations around 10% are effective for about two hours, concentration of 24% protects for about 5 hours and the efficacy plateaus at a concentration of about 30%. Generally DEET should be applied once a day and the lowest concentration effective for the amount of time spent outdoors should be chosen, especially for children. Use of 20% DEET is considered to be safe in pregnancy. In children, 30% DEET or less are considered to be safe, but these are not recommended for use in infants younger than 2 months.

Application of repellents: The repellents must be applied to lightly cover all exposed areas of skin; unprotected skin even a few centimeters away from a treated area can attract mosquitoes. It should be applied carefully over the face, avoiding contact with eyes and mouth. It should not be applied to children’s hands and after applying, repellent from the surfaces of the palms should be wiped off to prevent inadvertent contact with eyes, mouth, and genitals. Repellents should never be used over cuts, wounds, inflamed, irritated, or eczematous skin. Repellents may also be applied to clothing, window screens, mesh insect nets, tents, or sleeping bags. If DEET-treated garments are stored in a plastic bag between wearings, the repellent effect can last for many weeks.

Repellents containing DEET must be carefully applied because they can damage plastics (such as watch crystals and eyeglasses frames), rayon, other synthetic fabrics, leather, and painted or varnished surfaces. DEET does not damage natural fibers, such as cotton or wool, and has no effect on nylon. Using a DEET based insect repellent and a sunscreen together may reduce the sunscreen’s effectiveness.

How to apply mosquito repellents?

  • Apply during the biting time of the mosquitoes; for anopheles, it is dusk to dawn.
  • Take care to avoid contact with mucous membranes (eyes, nostrils, mouth, lips); do not spray on the face.
  • Do not allow young children to apply this product; do not apply to hands or near the eyes and mouth of young children.
  • Do not apply to sensitive, sunburned or damaged skin or deep skin folds.
  • Use just enough repellent to cover exposed skin and/or clothing; do not use under the clothing.
  • Avoid over-application.
  • Wash the hands after applying the repellent.
  • After returning indoors, wash treated skin with soap and water; wash treated clothing before wearing it again.
  • In case of repellants formulated as sprays:
    • Do not spray in enclosed areas.
    • Do not spray directly onto face; spray on hands first and then rub on face.
  • Repeated applications (every 3–4 hours) may be needed, especially in hot and humid climates.
  • Strictly adhere to the manufacturers’ instructions and do not exceed the dosage, especially for young children.

Adverse effects of DEET: DEET is generally well tolerated, although there are some reports of unpleasant odor or greasy feel. After topical application, average dermal absorption of 100% DEET was about 5.6% and for 15% DEET in ethanol, an average of 8.4% of the dose was absorbed. Studies on DEET’s toxicity, mutagenicity and oncogenicity did not indicate any significant toxicities with normal use. Some cases of contact urticaria and irritant contact dermatitis (mostly in soldiers) have been reported; the ante-cubital fossa is particularly sensitive to developing bullous irritant contact dermatitis if DEET products are allowed to remain on this area overnight. There are stray reports of fatalities, altered mental state, rashes, skin or mucous membrane irritation, transient numb or burning lips, dizziness, disorientation, and difficulty concentrating, headache and nausea etc., following the use of DEET based repellents. The use of 20% DEET during the second and third trimesters of pregnancy did not increase any adverse neurologic, gastrointestinal tract, or dermatologic effects in infants through 1 year of age. A study by Malaria Research Centre, India revealed that of those using DEET-based cream, 11.4 per cent reported skin reaction and itching. If any adverse reaction to this product is suspected, its use should be discontinued and the treated skin should be washed.

Many plant derived insect repellents have also been tested: oils of citronella, cedar, verbena, pennyroyal, geranium, lavender, pine, cajeput, cinnamon, rosemary, basil, thyme, allspice, garlic, peppermint and neem have been reported to have repellent activity. But most of these studies are poor and most of these oils provided short-lasting protection, usually 20 minutes to less than 2 hours.

Other repellents: Many other types of repellents, such as mats, coils, lotions and vaporizers are also available, in the market. The current Indian market for these repellents is estimated to be more than Rs 500–600 crores (US$ 12–15 million) with annual growth of 7 to 10%. Allethrin, bioallethrin, d-allethrin, d-transallethrin, s-bioallethrin, prallethrin etc., are used in these mats, coils and vaporizers. These compounds vaporize without decomposition on heating at temperatures up to 400°C and produce varying repellent action on the mosquitoes, depending on the type of product and species of mosquito.

mosqrepel

Mosquito Repellent Coil, Sticks, Mat and Liquid Vaporizer

Concerns have been raised about the safety of these products. In animal studies, these products have been reported to cause adverse effects on neurological, pulmonary, endocrinal and reproductive systems and to cause developmental impairment and cancers. A questionnaire-based survey among users of these products revealed that 11.8% users comprising all age groups and both sexes complained of a variety of acute toxicity, either soon after or within a few hours of using these repellents. Breathing problems were the most common (4.2%) and were frequently accompanied with headache or eye irritation or both. Pain in the ear and throat, cough, cold, running nose, wheezing, skin irritation etc., were also reported. Some coils containing pyrethroid insecticides, particularly d-allethrin, may contain octachlorodipropyl ether (S-2, S-421) as a synergist or active ingredient and the slow smoldering of the mosquito coils (about 8 hours/coil) may release bis(chloromethyl)ether (BCME), an extremely potent lung carcinogen.

Electronic mosquito repellents, ultrasonic devices, outdoor bug “zappers,” and bat houses are not effective against mosquitoes. Repellent-impregnated wristbands also do not offer any protection.

Air-conditioning: Although it has been said that air-conditioned rooms confer protection against mosquitoes, no systematic reviews or RCTs are available on the effects of air conditioning or electric fans to prevent malaria in travelers and some studies have even suggested that air conditioning does not offer any protection against anophelines.

Further reading:

  1. Mark S. Fradin. Mosquitoes and Mosquito Repellents: A Clinician’s Guide. Ann Int Med June 1, 1998;128(11):931-940. Full text at http://www.annals.org/content/128/11/931.full.pdf+html
  2. Lefèvre T, Gouagna L-C, Dabiré KR, Elguero E, Fontenille D et al. Beer Consumption Increases Human Attractiveness to Malaria Mosquitoes. PLoS ONE 2010;5(3): e9546. doi:10.1371/journal.pone.0009546. Full text at http://www.plosone.org/article/info:doi/10.1371/journal.pone.0009546
  3. Chen LH, Wilson ME, Schlagenhauf P. Prevention of Malaria in Long-term Travelers. JAMA. 2006;296(18):2234-2244. Full text at http://jama.ama-assn.org/cgi/reprint/296/18/2234
  4. Health Effects in Humans: DEET (N,N-Diethyl-meta-toluamide) – Chemical Technical Summary for Public Health and Public Safety Professionals. Agency for Toxic Substances and Disease Registry, Atlanta, Georgia. December 6, 2004. Available at http://www.atsdr.cdc.gov/consultations/deet/health-effects.html
  5. Fradin MS, Day JF. Comparative efficacy of insect repellents against mosquito bites. N Engl J Med. 2002;347:13-18. Full text at http://content.nejm.org/cgi/reprint/347/1/13.pdf
  6. Anderson RR, Harrington LC. Mosquito Biology for the Homeowner Available at http://www.entomology.cornell.edu/MedEnt/MosquitoFS/MosquitoFS.html
  7. Malaria Research Centre. Bioenvironmental Strategy for Malaria Control: Plant Origin Repellents and Insecticides. Available at http://www.mrcindia.org/MRC_profile/alternate_strategy/plant_ins.pdf
  8. http://www.epa.gov/pesticides/factsheets/chemicals/deet.htm
  9. Schoepke A, Steflen R, Gvatx N. Effectiveness of personal protection measures against mosquito bites for malaria prophylaxis in travelers. Journal of Travel Medicine. 1998;5(4):188-192. Full Text at http://www3.interscience.wiley.com/cgi-bin/fulltext/119944385/PDFSTART
  10. Harmful mosquito repellent. The Hindu. New Delhi, 2001 May 24. Available at http://www.indegene.com/Ent/Home/indEnt_Ind_News_26-05-2001_1.asp
  11. Sharma VP. Health hazards of mosquito repellents and safe alternatives. Current Science. 2001;80(3):341-343. Full text at http://www.ias.ac.in/currsci/feb102001/341.pdf
  12. Adanan CR, Zairi J, Ng KH. Efficacy and sublethal effects of mosquito mats on Aedes eegypti and Culex quinquefasciatus (Diptera: Culicidae). Proceedings of the Fifth International Conference on Urban Pests. Chow-Yang Lee and William H. Robinson (editors., Malaysia.2005. pp265-269. Available at http://www.icup.org.uk/reportsICUP041.pdf
  13. Amalraj DD, Sivagnaname N, Boopathidoss PS, Das PK. Bioefficacy of mosquito mat, coil and dispenser formulations containing allethrin group of synthetic pyrethroids against mosquito vectors. J Commun Dis. 1996;28(2):85-93.
  14. Amalraj DD, Kalyanasundaram M, Das PK. Evaluation of EMD vaporizers and bioallethrin vaporizing mats against mosquito vectors. Southeast Asian J Trop Med Public Health. 1992;23(3):474-8.
  15. Krieger RI, Dinoff TM, Zhang X. Octachlorodipropyl Ether (S-2) Mosquito coils are inadequately studied for residential use in Asia and illegal in the United States. Environ Health Perspect 2003;111:1439–1442 doi:10.1289/ehp.6177. Full text at http://ehpnet1.niehs.nih.gov/members/2003/6177/6177.pdf
  16. Enayati A, Hemingway J, Garner P. Electronic mosquito repellents for preventing mosquito bites and malaria infection. Cochrane Database of Systematic Reviews 2007, Issue 2. Art. No.: CD005434. DOI: 10.1002/14651858.CD005434.pub2. http://www.mrw.interscience.wiley.com/cochrane/clsysrev/articles/CD005434/pdf_fs.html
  17. Soto J, Medina F, Dember N, Berman J. Efficacy of permethrin-impregnated uniforms in the prevention of malaria and leishmaniasis in Colombian soldiers. Clin Infect Dis. 1995;21(3):599-602.
  18. Kimani EW, Vulule JM, Kuria IW, Mugisha F. Use of insecticide-treated clothes for personal protection against malaria: a community trial. Malaria Journal 2006;5:63. doi:10.1186/1475-2875-5-63. Full text at http://www.malariajournal.com/content/5/1/63
  19. Macintyre K, Sosler S, Letipila F et al. A new tool for malaria prevention?: Results of a trial of permethrin-impregnated bedsheets (shukas) in an area of unstable transmission. International Journal of Epidemiology 2003;32(1):157-160. Full text at http://ije.oxfordjournals.org/cgi/reprint/32/1/157
  20. World Health Organization. International travel and health: Situation as on 1 January 2010. WHO. Geneva. 2010. http://www.who.int/ith/ITH2010.pdf
  21. Freedman DO. Malaria Prevention in Short-Term Travelers. NEJM. 2008;359(6):603-612. Full text http://content.nejm.org/cgi/content/full/359/6/603
  22. Gahlinger PM, Reeves WC, Milby MM. Air Conditioning and Television as Protective Factors in Arboviral Encephalitis Risk. Am. J. Trop. Med. Hyg. 1986;35(3):601-610. Full text at http://www.ajtmh.org/cgi/reprint/35/3/601
  23. Jaenson TG. Air conditioning does not stop malaria carrying mosquitoes. Lakartidningen. 1991;88(11):938.
  24. http://www.andaman.org/book/Sane/Newsletter_2003-10/news_2003-10.htm
  25. http://www.who.int/water_sanitation_health/resources/en/vector059to87.pdf
  26. Octachlorodipropyl Ether (S-2) Mosquito Coils Are Inadequately Studied for Residential Use in Asia and Illegal in the United States
  27. http://www.cdc.gov/malaria/control_prevention/vector_control.htm
  28. Environ Health Perspect 111:1439-1442 (2003). doi:10.1289/ehp.6177 available via http://dx.doi.org/
  29. Chen SC, Wong RH, Shiu LJ, Chiou MC, Lee H. Exposure to mosquito coil smoke may be a risk factor for lung cancer in Taiwan. J Epidemiol. 2008;18(1):19-25. http://www.jstage.jst.go.jp/article/jea/18/1/19/_pdf

©malariasite.com ©BS Kakkilaya | Last Updated: Mar 27, 2015

Mosquito Control

Water logging at construction site

Water logging at construction site

Mosquito control is an important component of malaria control strategy, although elimination of malaria in an area does not require the elimination of all Anopheles mosquitoes. In North America and Europe for example, although the vector Anopheles mosquitoes are still present, the parasite has been eliminated. Socio-economic improvements (e.g., houses with screened windows, air conditioning) combined with vector reduction efforts and effective treatment have led to the elimination of malaria without the complete elimination of the vectors. On the other, controlling these highly adapted, flying and hiding vectors is indeed a formidable task. Development of resistance to insecticides has compounded the problem. Ban on non-biodegradable and non-eco-friendly insecticides like DDT also may have contributed to the resurgence of malaria.

Mosquito Control Measures: Every step taken to control the mosquitoes has a cumulative effect and contributes immensely to control malaria. The eggs developing within the female mosquito need human blood for nourishment and so the female mosquito bites humans. By personal protection against mosquito bites, this blood meal can be denied, leading to reduction in mosquito eggs and hence mosquito population. Personal protection includes closure of windows and doors to prevent entry; protection of humans against mosquito bite by using bednets (insecticide treated) and mosquito repellent. Female mosquitoes lay the eggs on water collections where they develop further over a week into adult mosquitoes. By preventing water logging, destroying unwanted water collections and keeping the water containers closed, sources of egg laying (Source Reduction) can be denied and breeding of mosquitoes can be prevented. Further, different types of chemical (insecticides) or biological (Guppy or Gambusia fish or bacteria or fungii) larvicides can be used on such breeding grounds to kill the developing larvae and pupae. It is far easier to kill the non-flying forms of the mosquitoes than going after the adults that can fly a kilometer or more. The adult mosquitoes can live up to 4-10 weeks depending on the ambient temperature and humidity. Space sprays are used to instantly kill the adults and residual sprays, on their resting places such as walls, are used for residual mosquitocidal effect. But most of such insecticides have effects on the human beings as well as the environment and other life forms. The adult mosquitoes enter the human dwellings between 5 pm and 10 pm and early morning and hide in dark corners, to come out and bite human beings at night, mostly between 11pm-4am. The entry of the adult mosquitoes can be prevented by keeping the doors and windows closed between 5-10pm and early morning. Screening of all the windows and vents is a very easy and sure method of controlling the entry of adult mosquitoes. The hiding places of the mosquitoes, such as clothes hanging in the open, can be minimised. Personal protection by covering the body with clothes and use of mosquito nets and repellents will further help in preventing mosquito bites. All these in turn will deny the blood meal and development of eggs. 

bucketsSource reduction involves preventing development of mosquito larvae. The female mosquitoes need a blood meal from a vertebrate host to nourish their eggs. About 50-200 eggs are laid per oviposition on the surface of stagnant water and these eggs develop into adult mosquitoes in a span of about 5-14 days, passing through the stages of larvae and pupae. High humidity and ambient temperature between 20-30ºC provide ideal conditions for breeding of Anopheline mosquitoes. Common sites of breeding for Anopheles mosquitoes include rainwater pools and puddles, borrow pits, river bed pools, irrigation channels, seepages, rice fields, wells, pond margins, sluggish streams with sandy margins, hoof prints, tyre tracks etc. Water stagnation due to construction of dams, reforestation, shrimp farming, fish ponds etc., have also been identified as possible sites of Anopheles breeding. An. stephensi is a well adapted urban vector, being a container breeder, making use of man-made sites such as building-construction sites, wells, garden ponds, cisterns, overhead tanks, ground level cement tanks, water coolers, tyres, barrels and tins, intra-domestic containers etc. Anopheles breeding sites increase with rainfall and resultant water stagnation, ; however, some larvae and pupae may be washed away by heavy rainfall.

tyresThe best method of mosquito control is preventing the development of the eggs into adult mosquitoes, by reducing the sources of breeding. These anti larval measures are not only simple and cost effective, but also environment friendly.

a. Preventing egg laying: The easiest, cheapest and most environment-friendly method to control malaria is by preventing the mosquito from laying eggs. This is done by avoiding or eliminating the clean water collections. As mentioned, most such collections are artificial, temporary and man made.

It is a common habit to throw the unutilized utensils, buckets, bottles, tyres etc., into the open. During the rains, water gets collected in these containers and provides ample breeding locations for the female anopheles mosquito.

tankIn the cities, the other sites for mosquito breeding are the water tanks. Shortage of water supply in large cities makes it necessary to have these tanks in virtually every building. Overhead tanks, sump tanks, storage tanks, ornamental tanks etc. are often left uncovered and this provides scope for mosquito breeding. Also, it is common to find puddles of water everywhere during the rainy season. This is the reason why malarial transmission is at its peak during the monsoon.

There is abundant scope for water collection in and around the construction sites: water stored in tanks; the layer of water on the surface of the cement concrete (used for ‘curing’ the concrete and left as such for 3 weeks); puddles of water in and around the place of construction – all these provide scope for mosquito breeding. To add to the problem, construction workers tend to harbour the malarial parasite, due to frequent infections owing to their poor standards of living. Thus, construction sites not only provide for mosquito breeding but also supply the parasites. This is the reason why malaria tends to be more common in cities where construction activities are in full swing.

tiled

Tiled roof

The older houses have tiled roofs that are sloping. This helps easy drainage of water during rains, thus minimising water logging. In the recent years, most new constructions have concrete roofs and terraces that tend to be flat and non-sloping. These roofs/terraces may not have proper drains for water-flow. As a result, water tends to collect on these rooftops during the rains and this provides ample scope for mosquito breeding. In addition, there are the natural collections of water like the wells, lakes, ponds, paddy fields, marshlands etc. where mosquito breeding occurs in abundance.

Therefore, unless these breeding sites (most of which are man-made and temporary) are taken care of, it is impossible to control mosquito breeding and hence malaria. And it is impossible to achieve this without the participation of the general public. Education of the people is thus very important for any meaningful action. The following measures are called for to minimize mosquito breeding and these measures require only a trifle of human efforts:

terrace

Flat terrace

  • Do not throw utensils, vessels, buckets, tyres, bottles, tender coconut shells etc. in the open. They should be either destroyed or buried or at least kept inverted so that water cannot collect in them. All such things should be cleared during the rainy season.
  • All tanks should be kept tightly closed. A black plastic sheet can be used for the purpose. Also, all tanks should be emptied, cleaned and allowed to dry for at least half an hour, once every week.
  • Terraces and roofs should ideally have a slope, particularly in places where monsoon tends to be heavy. All such roofs/terraces should have adequate drainage for water. Any collection of water on these surfaces should be cleared at least once a week.
  • At construction sites, all the care should be taken to avoid collection of water at one place for more than a week. The layer of water on the surface of the concrete, used for concrete curing, should be cleared at least once a week and allowed to dry for half an hour. All other puddles should be cleared regularly. Collections of water in the toilets and closets under construction should also be cleared. All tanks should be kept snugly closed. All labourers should be frequently checked for parasitemia and adequately treated. They should also be provided with mosquito nets.
  • All unused wells and tanks should be closed or destroyed. Engine oil or kerosene has been used as a larvicidal on these collections. Another method to prevent egg laying on unused wells is by adding EPS polyesterene beads onto the surface of water. These beads are non-toxic, cheap and long lasting. They coat the water surface and prevent the mosquito from laying eggs.
  • Wells that are being used and ornamental tanks can be treated with biological larvicides that do not harm the quality of drinking water. Also, these wells should be covered with either mosquito-proof nets or with plastic sheets.

How engineers can help in malaria control?
Public Health Engineering has lot to do with malaria control, especially by means of Source Reduction.

  • Prevent water logging – Design the buildings with sloping roofs to aid easy drainage of rain water; provide drains in adequate numbers and sizes in buildings with flat roofs
  • Prevent entry of insects – Screening of all windows and vents should be made mandatory. It is observed that this simple, common sense measure followed in every construction in the U.S.A. has in a big way helped in control of all insects including mosquitoes and hence malaria.
  • Engineering skills are also called for in draining and flushing of water collections; deepening or filling of water logged areas; proper maintenance of water levels and intermittent irrigation in dams and canals and in changing salt content of water so as to make it unsuitable for mosquito breeding. Mosquitoes that breed in irrigation water can be controlled through careful water management.

b. Use of Larvicides: If the above mentioned measures are not adequate or difficult to achieve, then measures should be taken to destroy the larvae developing in the breeding sites. This can be done by either larvicidal chemicals or by biological larvicides like fish or bacteria.

i. Chemicals: Themiphos and Fenthion are the two commonly used larvicidal agents. Themiphos is used on potable water collections and Fenthion, being more toxic, is used on non-potable water collections. Oils may be applied to the water surface, suffocating the larvae and pupae. Most oils in use today are rapidly biodegraded. Insect growth regulators such as methroprene is specific to mosquitoes and can be applied in the same way as chemical insecticides.

fishii. Biological larvicides: One of the safest and interesting methods in mosquito control is the use of biological agents that eat or destroy the larvae.

Eco-friendly larvivorous fish such as the top water minnow or mosquito fish (Gambusia affinis) or the common guppy (Poecilia reticulate) can be effectively used to control the mosquito population. These fish can be introduced into all collections of potable water like wells, tanks, ponds and lakes, particularly in rural and peri-urban areas and in freshwater bodies in rural areas.

Bacteria such as Bacillus sphaericus and Bacillus thuringiensis var israelensis are also effective larvicides. However, they need to be re-introduced every 15 days and their culture may need expertise.

Mermitid Nematod (Romanomermis culicivorax), Notonectid (Bug), Ambylospora (Protozoa), Coelomomyces (Fungus), Nuclear Polyhedrosis (Virus), and Cyclopoid copepods (Crustacean) are the other biological larvicides found to be effective.

A ‘saline solution’ from Kochi:

The Kochi Corporation in Kerala tried out a novel and cost effective method of reducing the mosquito population at the larvae stage itself. It has conducted experiments suggested by the retired National Institute of Oceanography (NIO) scientist, Dr. U.K. Gopalan, where the salinity of water in canals and stagnant pools is increased by adding sea water. The experiment was successful and mosquito larvae were found morbid in the canal portions where salinity was increased. When the salinity level reaches 30 parts per thousand or PPT (the normal percentage of salt in the sea), mosquito larvae cannot survive beyond 3 hours. Even at lower concentrations of 15 PPT, they are dead in 12 hours. And when the concentration is upped to 60 PPT, the larvae perish within the hour.[http://www.cochingateway.com/mkingdom.htm]

Further reading:

  1. CDC. Malaria: Anopheles Mosquitoes. Available at http://www.cdc.gov/malaria/about/biology/mosquitoes/index.html
  2. White NJ. Malaria. In Cook GC, Zumla AI. (Ed). Manson’s Tropical Diseases. 22nd Edition. Saunders Elsevier. 2009. pp 1201-1300
  3. Dash AP, Adak T, Raghavendra K, Singh OP. The biology and control of malaria vectors in India. Current Science. 2007;92(11):1571-78. Full text at http://www.ias.ac.in/currsci/jun102007/1571.pdf
  4. Operational Manual for Implementation of Malaria Programme. Government of India, Directorate of National Vector Borne Disease Control Programme; Directorate General of Health Services, Ministry of Health and Family Welfare. 2009. Available at http://nvbdcp.gov.in/Doc/Malaria-Operational-Manual-2009.pdf
  5. Singh N, Mehra RK, Sharma VP. Malaria and the Narmada-river development in India: a case study of the Bargi dam. Annals of Tropical Medicine and Parasitology 1999;93:477-88.
  6. Lindsay S, Kirby M, Baris E, Bos R. Environmental management for malaria control in the east Asia and Pacific (EAP) region. The International Bank for Reconstruction and Development / The World Bank. Washington. 2004. Available at http://www.who.int/water_sanitation_health/publications/whowbmalariacontrol.pdf
  7. Maheu-Girouxa M, Casapía M, Soto-Calle VE et al. Risk of malaria transmission from fish ponds in the Peruvian Amazon. Acta Tropica. 2010;115(1-2):112-118
  8. Kumar A, Thavaselvam D. Breeding habitats and their contribution to Anopheles stephensi in Panaji. Indian Journal of Malariology. 1992;29:35-40
  9. CDC. Malaria: Larval Control and Other Vector Control Interventions. Available at http://www.cdc.gov/malaria/malaria_worldwide/reduction/vector_control.html
  10. Kolsky P. Engineers and urban malaria: part of the solution, or part of the problem? Environment and Urbanization. 1999;11(1):159-163. Full Text at http://eau.sagepub.com/cgi/reprint/11/1/159.pdf
  11. NVBDCP. Guidelines on the use of larvivorous fish for vector control. Available at http://nvbdcp.gov.in/Doc/Guidelines-larvivorous-fish.pdf

Control of Adult Mosquitoes

Control of adult mosquitoes is not an easy task, considering their varied habits, their ability to fly all over and to hide in nooks and corners. Whereas vectors such as An. gambiae and An. funestus are highly anthropophilic (prefer human blood meal), the Indian anopheline vectors such as An. culicifacies, An. fluviatilis, An. minimus, An. philippinensis, An. dirus, and An. stephensi are essentially zoophilic (preferring blood meal from animals such as cattle) and feed on human beings when high densities build up. During the day, these mosquitoes rest in human dwellings and cattle sheds and enter the human dwellings between 5pm-10pm. They start biting indoors soon after, with peak biting at midnight, between 11 pm and 4 am. Adult female anopheles mosquitoes survive for 1-2 weeks or more depending on the ambient conditions and have a flight range of 0.5-3 kms.

Control of adult mosquitoes involve the following measures:

  • Preventing entry of adult mosquitoes into human dwellings
  • Mosquito nets (regular and insecticide treated)
  • Personal protection measures
    • Protective clothing
    • Mosquito repellents
  • Adult insecticides
    • Space sprays – for instant results
    • Residual sprays – for sustained effects
    • Combined
    • Insecticide vaporizers

The Global Malaria Action Plan enlists insecticidal nets (LLINs), indoor residual spraying (IRS) with long-lasting chemical insecticides, and other vector (mosquito) controls such as larviciding and environmental management as the key tools of the global malaria control strategy.
Preventing entry of adult mosquitoes into human dwellings: Measures to make the human dwellings inaccessible to the vector mosquitoes so as to reduce man-mosquito contacts are important in controlling malaria transmission. Mosquitoes do not fly more than about 2-4km from their breeding habitats and therefore positioning houses 1.5 to 2 km from large breeding sites will reduce the risk of transmission substantially. Villages at higher elevations and exposed to the wind tend to have fewer mosquitoes compared to sites situated in the lowlands that are less windy and have many small water bodies. As most mosquitoes fly close to the ground, raising buildings off the ground or on silts can help in preventing mosquito entry. Sitting on raised platforms or keeping the feet off the ground also help in minimizing mosquito bites.

Keeping the windows and doors closed during evenings and early morning hours can prevent the mosquitoes from gaining entry into households (it is important to close the doors of the toilets, which always open to the exterior through windows or vents). Modifying the house structure and mosquito-proofing of the houses were used by Manson, Ross, Celli and others to protect people from malaria in Italy, Greece, Panama and the USA and there is ample evidence that house screening contributed to the elimination of malaria from many parts of the world. Homes with ceilings or closed eaves also protect from mosquitoes and malaria; a study using experimental huts in Gambia demonstrated that installing a ceiling made of netting reduced transmission by 80%. As Anopheles mosquitoes tend to hide in the dark corners and amidst the clothes and other linen left hanging in the rooms, such hiding places should be avoided by keeping all the clothes and linen inside wardrobes and cupboards.

Mosquito nets: Mosquito nets act as physical barriers by blocking the vector mosquitoes. Application of pyrethroid insecticides adds a chemical barrier to the physical one, further reducing human–vector contact and increasing the protective efficacy of the mosquito nets. Pyrethroid insecticides have a long residual action and low mammalian toxicity and provide prolonged protection by their excito-repellent effect. As mosquitoes are positively attracted by the odour of the sleeper inside the net, these insecticide treated nets (ITNs) acts like a baited trap and the mosquitoes that come into contact with the ITN are, most often, killed. As the ITNs shorten the mean mosquito life span, very few mosquitoes can survive long enough for the sporogonic cycle to be completed, thus reducing the transmission. As the ITNs also inhibit mosquito feeding, the reproductive potential of highly anthropophilic vectors is also reduced. Due to these multiple effects, the ITNs have been shown to avert around 50% of malaria cases and provide at least double the protection than that provided by untreated nets.

The community-wide use of ITNs has been reported top reduce the vector population significantly and when used by a majority of the target population (around 60%), to provide protection for all people in the community, including those who do not themselves sleep under nets. ITNs have been found to be the most cost-effective interventions against malaria, and long-lasting insecticidal nets LLINs were found to be significantly cheaper to use than conventionally treated nets. ITNs/LLINs are particularly useful for high-risk populations that cannot be reached by residual spraying, for people in forest-fringe areas who are at risk of infection from forest stay, and for pregnant women who are highly vulnerable to malaria. Under NVBDCP, ITNs/LLINs are provided free to the target population.

Currently, most mosquito nets are made of polyester and rarely last longer than 2–3 years under field situations. Conventional ITNs, treated with pyrethroids such as alpha-cypermethrin, cyfluthrin, deltamethrin, lambda-cyhalothrin or permethrin, need to be re-treated after three washes, or at least once a year to ensure continued insecticidal effect. Long-lasting insecticidal nets [LLINs] are factory-treated mosquito nets, made with netting material that has the insecticide incorporated within or bound around the fibres and the insecticide is progressively released so that the net retains the efficacy after repeated washings. The LLINs are expected to retain their effective biological activity without re-treatment for at least 20 standard washes and for three years of recommended use under field conditions. Permethrin (high density polyethylene monofilament yarn blended with 2% permethrin), Deltamethrin (multifilament polyester netting treated with deltamethrin 55mg/m2), and alpha cypermethrin (multifilament polyester netting treated with alpha cypermethrin 200mg/m2) are used in LLINs.

Zooprophylaxis intends to control vector-borne infections by diverting vectors from humans to domestic animals such as cattle that act as dead-end or decoy hosts. Although this method has been suggested by WHO as one of the measures to control anopheline vectors, some of which are indeed zoophilic, studies on its efficacy have yielded varying results.

Indoor Residual Spraying:

IRS is an integral component of the Global Malaria Action Plan and currently DDT, pyrethroids (Deltamethrin 2.5% WP, Cyfluthrin 10% WP, Alphacypermethrin 5% WP and Lambdacyhalothrin 10% WP) or Malathion 25% are used in different parts of the world for this purpose. All the interior walls and ceilings as well as the underside of furniture, back of the doors and porches of permanent human dwellings as well as Jhoom huts where people sleep during the plantation or harvesting season are sprayed. For protection during the entire transmission season, two rounds of DDT or synthetic pyrethroids or three rounds of Malathion are used.

DDT has once again staged a comeback after nearly thirty years of being phased out from the widespread use in indoor spraying to control malaria. A 1990 cost comparison by the WHO found DDT to be considerably less expensive than other insecticides, which cost 2 to 23 times more on the basis of cost per house per 6 months of control and this advantage remains even today. In September 2006, the WHO once again recommended the use of DDT for indoor residual spraying, not only in epidemic areas but also in areas with constant and high malaria transmission, including throughout Africa with an assurance that DDT presents no health risk when used properly. The tough campaign by public health officials and malaria experts who had argued for years that DDT was a necessary public-health weapon in poor tropical countries, signature campaign by hundreds of physicians from all over the world urging resumption of DDT spraying and arguments of Amir Attaran, of Harvard University’s Center for International Development, that unlike agricultural uses which inject tons of DDT into the outdoors, the indoor residual house-spraying with DDT at minimal (2g/m2) quantities was an inexpensive and highly effective practice against malaria, all helped in making this decision.

See

Space sprays: These insecticides instantly kill the mosquitoes, but lack any residual effects. They are therefore sprayed into the air. By killing adult mosquitoes, not only bites are prevented, but breeding is also prevented, resulting in net reduction in the mosquito population. Space sprays must be repeated often, at least once every week. Pyrethroids are commonly used for this purpose.

Space spraying involves the application of small droplets of insecticide into the air, but recent studies have demonstrated that the method has little effect on the mosquito population. Moreover, when space spraying is conducted in a community, it creates a false sense of security among residents, which has a detrimental effect on community-based source reduction programmes. (In fact, in Mangalore, the ward level committees formed in the year 1995-96, lost steam and became defunct after fogging operations were introduced in late 1996!) Although it is highly visible and conveys the message that the government is doing something about the disease, this can be only a poor justification for using space sprays. (Often, members of the City Corporation order fogging in their constituencies to ‘satisfy’ their voters!).

fog1Space spraying operations should be carried out at the right time, at the right place, and according to the prescribed instructions with maximum coverage, so that the fog penetration effect is complete enough to achieve the desired results. Fogging should be primarily reserved for emergency situations: halting epidemics or rapidly reducing adult mosquito populations. It must be timed to coincide with the peak adult activity, because resting mosquitoes are often found in areas that are difficult for the insecticide to reach (e.g., under leaves, in small crevices). Generally, there are two forms of space-sprays, namely thermal fogs and cold fogs and both can be dispensed by vehicle-mounted or hand-operated machines.

Thermal fogs: Thermal fogs are produced when an insecticide formulation condenses after being vaporized at a high temperature. These formulations can be oil-based or water-based; the oil (diesel)-based formulations produce dense clouds of white smoke, whereas water-based formulations produce a colorless fine mist.

Ultra-low volume (ULV), aerosols (cold fogs) and mists: ULV involves the application of a small quantity (<4.6 litres/ha) of concentrated liquid insecticides. Aerosols, mists and fogs may be applied by portable machines, vehicle-mounted generators or aircraft equipment.

House-to-house application using portable equipment: Portable spray units can be used when the area to be treated is not very large or in areas where vehicle-mounted equipment cannot be used effectively. This equipment is meant for restricted outdoor use and for enclosed spaces (buildings) of not less than 14m3. Congested low-income housing areas, multistoried buildings, godowns and warehouses, covered drains, sewer tanks and residential or commercial premises are some examples.

fog2Vehicle-mounted fogging

Vehicle-mounted fogging can be used in urban or suburban areas with a good road system. One machine can cover up to 1500-2000 houses (or approximately 80 ha) per day. An educational effort may be required to persuade the residents to cooperate by opening doors and windows. The best time for application is in the early morning (6am-8.30am) or evening (5pm-7.30pm).

Insecticide formulations for space sprays

Organophosphate insecticides

  • Malathion
    • Undiluted technical grade malathion (active ingredient 95%+) for ULV spraying (0.5 liters per hectare for vehicle-mounted operations)
    • One part technical grade diluted with 24 parts of diesel for thermal fogging respectively
  • Fenitrothion
  • Pirimiphos methyl

Pyrethroids

  • Permethrin
  • Deltamethrin
  • Lambda-cyhalothin

Low dosages of pyrethroid insecticides are usually more effective indoors than outdoors.

Novel Genetic Methods: Sterile male release has been successfully applied in several small-scale areas. However, the need for large numbers of mosquitoes for release makes this approach impractical for most areas. Genetic modification of malaria vectors aims to develop mosquitoes that are refractory to the parasite. This approach is still several years from application in field settings.

Wolbachia Fungus to Control Malaria Vector Mosquitoes



Evolution, Resisted: Article by Elie Dolgin

Fungus fights malaria Science February 25, 2011 Abstract | Podcast | Report]

Further Reading:

  1. The Global Malaria Action Plan For a malaria free world. Roll Back Malaria Partnership, WHO. Geneva. 2008. Available at http://www.rollbackmalaria.org/gmap/gmap.pdf
  2. Lindsay S, Kirby M, Baris E, Bos R. Environmental management for malaria control in the east Asia and Pacific (EAP) region. The International Bank for Reconstruction and Development / The World Bank. Washington. 2004. Available at http://www.who.int/water_sanitation_health/publications/whowbmalariacontrol.pdf
  3. Charlwood JD, Pinto J, Ferrara PR et al. Raised houses reduce mosquito bites. Malaria Journal 2003;2:45. doi:10.1186/1475-2875-2-45 Full text at http://www.malariajournal.com/content/2/1/45
  4. Lindsay SW, Emerson P, Charlwood JD. Reducing malaria by mosquito-proofing homes. Trends in Parasitology 2002;18:510-514.75.
  5. Lindsay SW, Jawara M, Paine K, Pinder M et al. Changes in house design reduce exposure to malaria mosquitoes. Tropical Medicine and International Health. 2003;8(6):512–517.
  6. Ogoma SB, Kannady K, Sikulu M et al. Window screening, ceilings and closed eaves as sustainable ways to control malaria in Dar es Salaam, Tanzania. Malaria Journal 2009;8:221. doi:10.1186/1475-2875-8-221. Full Text at http://www.malariajournal.com/content/8/1/221
  7. WHO. Malaria vector control and personal protection: report of a WHO study group. (WHO technical report series: no. 936) World Health Organization. Geneva. 2006 Available at http://malaria.who.int/docs/WHO-TRS-936s.pdf
  8. WHO. Insecticide-Treated Mosquito Nets: a WHO Position Statement. WHO. Geneva. 2007. Available at http://www.who.int/malaria/publications/atoz/itnspospaperfinal.pdf
  9. WHO. Long-lasting insecticidal nets for malaria prevention: A manual for malaria programme managers. World Health Organization. Geneva. 2007. Available at http://www.who.int/malaria/publications/LLINmanual.pdf
  10. Operational Manual for Implementation of Malaria Programme. Government of India, Directorate of National Vector Borne Disease Control Programme; Directorate General of Health Services, Ministry of Health and Family Welfare. 2009. Available at http://nvbdcp.gov.in/Doc/Malaria-Operational-Manual-2009.pdf
  11. Kaburiae JC, Githutob JN, Muthamic L. Effects of long-lasting insecticidal nets and zooprophylaxis on mosquito feeding behaviour and density in Mwea, central Kenya. J Vector Borne Dis. 2009;46:184–190.Full text at http://www.mrcindia.org/journal/issues/463184.pdf
  12. Saul A. Zooprophylaxis or zoopotentiation: the outcome of introducing animals on vector transmission is highly dependent on the mosquito mortality while searching. Malaria Journal. 2003;2:32. doi:10.1186/1475-2875-2-32. Full text at http://www.malariajournal.com/content/2/1/32
  13. Bøgh C, Clarke SE, Walraven GE, Lindsay SW. Zooprophylaxis, artefact or reality? A paired-cohort study of the effect of passive zooprophylaxis on malaria in The Gambia. Trans R Soc Trop Med Hyg. 2002;96(6):593-6.
  14. WHO gives indoor use of DDT a clean bill of health for controlling malaria. Available at http://www.who.int/mediacentre/news/releases/2006/pr50/en/index.html
  15. Walker K. Cost-comparison of DDT and alternative insecticides for malaria control. Medical and Veterinary Entomology.2000;14(4):345–354
  16. Attaran A, Maharaj R. Ethical debate: Doctoring malaria, badly: the global campaign to ban DDT. BMJ 2000;321:1403-1405. Full text at http://www.bmj.com/cgi/content/full/321/7273/1403
  17. http://www.cdc.gov/malaria/control_prevention/vector_control.htm
  18. http://w3.whosea.org/en/Section10/Section332/Section554_2569.htm

 ©malariasite.com ©BS Kakkilaya | Last Updated: Mar 27, 2015

Control of Malaria

Scandalously scarce resource (Nature, Oct 3, 2002;419:417) for malaria control!

Malaria is an acute infectious disease caused by the parasites called Plasmodia and spread by the the vector, the female anopheles mosquito. Control of this dreaded menace would therefore involve three living beings: Man (The host), Plasmodia (The agent), and Anopheles mosquito (The vector). And due to this reason alone, control of malaria is a formidable task. The international efforts on malaria control were highly successful in the late 50’s and early 60’s. However, due to various reasons, the malaria control programmes received setbacks all over the world and today it has come back with a vengeance. Control of malaria is possible only by concerted community efforts. Relying only on the government machinery for the control of this problem will only heighten the dangers.

Malaria control measures:

W.H.O. Ministerial Conference held in October, 1992 at Amsterdam evolved a Global Strategy for Malaria Control. The strategy broadly suggests de-emphasis on vector control and renewed emphasis on treatment. Early diagnosis and treatment; prevention of deaths; promotion of personal protection measures like use of ITMs; epidemic forecasting, early detection and control; monitoring, evaluation and operative research and integration of activity in Primary Health Centres are the salient aspects of this strategy.

controlThe control of malaria involves control of 3 living beings and their environment. Man, the host is a moving target and can take the disease with him to far and wide. Mosquitoes are moving, highly adaptable and have shown resistance to insecticides. It is therefore important to target non-flying eggs and larvae. The parasite also is highly adaptable, hides in humans and mosquitoes and has also developed resistance to drugs. Therefore, for effective malaria control, target man first, control mosquitoes next and keep trying to tackle the parasite with development of effective drugs and vaccines.

Control of malaria is a complex chain of measures that often complement one another. The diagram on the left depicts this control chain: For example, by taking personal protective measures, three things can be achieved – prevention of malaria in the given individual, thus reduced parasite load and reduction in spread, and by denying blood meal to the mosquito the egg laying is also hampered! In the recent years, more emphasis is being laid on early diagnosis and treatment, on personal protection especially with insecticide treated bednets and on biological vector control. By these means, it is intended to minimise use of potentially harmful chemical insecticides.

Man, the Host: Treat the affected, protect the unaffected. Problem are compliance, accessibility and availability of treatment and protective measures, mostly due to poverty and backwardness.

Parasite, the Agent: Ensure full treatment; kill the asexual forms and prevent the progression of disease, kill the sexual forms and prevent the spread to mosquitoes. Problem is Drug resistance

Mosquito, the Vector: Prevent breeding, prevent entry into houses, prevent bites to humans. Problems are resistance to insecticides and compliance by humans

Man’s Role in Malaria Control: Man is the most important link in the malaria control chain. He can be made to understand the problem and he can help in breaking the chain at multiple points. Therefore great emphasis should be laid on educating the people about malaria and its control, so that common people can effectively contribute in controlling this disease. This includes education of doctors about the need for early diagnosis and prompt treatment of malaria.

  1. Early diagnosis and treatment – treat early to reduce parasite load, hence spread; prevent deaths
  2. Treat completely to prevent spread and relapse
  3. Ensure compliance with complete treatment
  4. Personal Protection- prevent malaria by using bed nets, insecticide sprays etc., and by chemoprophylaxis.
  5. Seek his help in mosquito control

1. Early diagnosis and treatment: This is a very important aspect of malaria control. In fact, early detection and treatment of the disease itself is enough to control this epidemic in its early stages. By this, the parasite load in the community is reduced, thereby reducing the transmission of the disease.

Presumptive treatment of all cases of fever is very important. Tests for malarial parasite should be done in all cases of fever, and presumptive treatment with first full dose of chloroquine should be administered. Chloroquine is highly effective as schizonticidal against all species of malaria and is also gametocytocidal against all except P. falciparum. Thus, by administering chloroquine to all cases of fever, it is possible to sterilize the gametocytes and thus prevent the spread to mosquitoes.

Whenever resistance to chloroquine is known or suspected, second line anti malarials should be used to treat P. falciparum malaria.

2. Radical treatment: All confirmed cases of fever should be administered radical treatment with primaquine. A single dose of primaquine must be administered in P. falciparum malaria to sterilize the gametocytes. A 14 days course of primaquine should be administered in P. vivax infection to destroy the hypnozoites in the liver and thus to prevent relapse.

3. Ensure compliance: Complete treatment should be ensured. If the patient vomits the drugs within an hour of ingestion, the same should be repeated. Incomplete treatment fails to clear the parasitemia and thereby aids spread. Many patients fail to complete the treatment due to either negligence, lack of proper education or sometimes due to adverse effects.

4. Personal protection: Man should be encouraged to protect himself against malaria. Personal protection measures include protection against mosquito bites and chemoprophylaxis against malaria.

Protection against mosquito bites: People living in endemic areas as well as travelers to such areas should be educated and encouraged to use protective measures against mosquito bites. These include closing the doors and windows in the evenings to prevent entry of mosquitoes into human dwellings; using mosquito repellant lotions, creams, mats or coils and regular use of bednets. Using bednets is one of the safest methods of preventing and controlling malaria. Now Insecticide Treated Bednets are available and it has been found in various studies that use of these ITMs leads to a 19% reduction in child mortality and 40-60% reduction in infection.

As mentioned above, protection against mosquito bites, especially the use of mosquito nets, has a spiraling effect on malaria control. By this measure, blood meal is denied for the female mosquito and this prevents development of eggs and hence a reduction in mosquito population and transmission.

For more details See Mosquito Control

Chemoprophylaxis: Travelers to endemic areas and high risk individuals living in endemic areas (pregnant, elderly, patients with end organ failure) should be started on chemoprophylaxis against malaria. This involves taking antimalarial drugs every week (some drugs may have to be taken everyday) so as to suppress malaria.

For details See Chemoprophylaxis

New Papers:

  1. Richard W. Steketee. Good News in Malaria Control… Now What? Am. J. Trop. Med. Hyg., 80(6), 2009, pp. 879–880. Available athttp://www.ajtmh.org/cgi/reprint/80/6/879

 ©malariasite.com ©BS Kakkilaya | Last Updated: Mar 11, 2015