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.
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|
|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
(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:
- 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.
- The risk of acquiring chloroquine resistant P. falciparum malaria (CRPF) is another consideration.
- 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.
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
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.
- 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
- Drugs for the treatment and prevention of malaria Available at http://www.phac-aspc.gc.ca/publicat/ccdr-rmtc/04vol30/30s1/table8_e.html
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