Malaria is a febrile illness characterised by fever and related
symptoms. However it is very important to remember that malaria is not a simple disease of
fever, chills and rigors. In fact, in a malarious area, it can present with such varied
and dramatic manifestations that malaria may have to be considered as a differential
diagnosis for almost all the clinical problems! Malaria is a great imitator and trickster,
particularly in areas where it is endemic.
All the clinical features of malaria are caused by the erythrocytic schizogony in
the blood. The growing parasite progressively consumes and degrades intracellular
proteins, principally hemoglobin, resulting in formation of the 'malarial pigment' and hemolysis of the infected red cell. This also alters the transport properties of the red
cell membrane, and the red cell becomes more spherical and less deformable. The rupture of
red blood cells by merozoites releases certain factors and toxins (such as red cell
membrane lipid, glycosyl phosphatidyl inositol anchor of a parasite membrane protein),
which could directly induce the release of cytokines such as TNF and interleukin-1 from
macrophages, resulting in chills and high grade fever. This occurs once in 48 hours,
corresponding to the erythrocytic cycle. In the initial stages of the illness, this
classical pattern may not be seen because there could be multiple groups (broods) of the
parasite developing at different times, and as the disease progresses, these broods
synchronise and the classical pattern of alternate day fever is established. It has been
observed that in primary attack of malaria, the symptoms may appear with lesser degree of
parasitemia or even with submicroscopic parasitemia. However, in subsequent attacks and
relapses, a much higher degree of parasitemia is needed for onset of symptoms. Further,
there may be great individual variations with regard to the degree of parasitemia required
to induce the symptoms.
The first symptoms of malaria after the
pre-patent period (period between inoculation and symptoms, the time when the sporozoites
undergo schizogony in the liver) are called the primary attack. It is
usually atypical and may resemble any febrile illness. As the disease gets established,
the patient starts getting relapse of symptoms at regular intervals of 48-72 hours. The
primary attack may spontaneously abort in some patients and the patient may suffer from
relapses of the clinical illness periodically after 8-10 days owing to the persisting
blood forms of the parasite. These are called as short term relapses
(recrudescences). Some patients will get long term relapses after a
gap of 20-60 days or more and these are due to the reactivation of the hypnozoites in the
liver in case of vivax and ovale malaria. In falciparum and malariae infections,
recrudescences can occur due to persistent infection in the blood.
Manifestations of acute malarial
While most of
the the clinical manifestations of malaria are caused by the malarial infection per se,
high grade fever as well as the side effects of anti malarial therapy can also contribute
to the clinical manifestations. All these may act in unison, further confusing the
picture. In some cases, secondary infections like pneumonia or urinary tract infection can
add to the woes. All these facts should always be kept in mind.
The characteristic, text-book picture of malarial illness is not commonly seen. It
includes three stages viz. Cold stage, Hot stage and Sweating stage. The febrile episode
starts with shaking chills, usually at mid-day between 11 a.m. to 12 noon, and this lasts
from 15 minutes to 1 hour (the cold stage), followed by high grade fever, even reaching
above 1060 F, which lasts 2 to 6 hours (the hot stage). This is followed by
profuse sweating and the fever gradually subsides over 2-4 hours. These typical features
are seen after the infection gets established for about a week. The febrile paroxysms are
usually accompanied by head aches, vomiting, delirium, anxiety and restlessness. These are
as a rule transient and disappear with normalization of the temperature.
In vivax malaria, this typical pattern of
fever recurs once every 48 hours and this is called as Benign Tertian malaria.
Similar pattern may be seen in ovale malaria too (Ovale tertian malaria). In
falciparum infection (Malignant tertian malaria), this pattern may not be
seen often and the paroxysms tend to be more frequent (Sub-tertian). In P.
malariae infection, the relapses occur once every 72 hours and it is called Quartan
an endemic area, malaria often presents with atypical manifestations
Atypical features are more
common in the following situations:
Patients at extremes of age
Patients who are immune-compromised
(extremes of age, malnourished, AIDS, tuberculosis, cancers, on immunosuppressive therapy
Patients on chemoprophylaxis for malaria
Patients who have had recurrent attacks of
Patients with end stage organ failure
Last but not the least, pregnancy.
In an endemic area, it is rather unusual to find cases with typical fever pattern. Some
patients may not have fever at all and may present with other symptoms listed below. Many
present with fever of various patterns - low grade to high grade, with or without chills,
intermittent to continuous, or even as cases of prolonged fever. In the initial stages of
the illness, fever may be quotidian, with more than one spike per day and this is due to
the development of multiple broods of the parasite. As the disease progresses, these
broods get synchronised and the fever tends to be more uniform. However in cases of P.
falciparum malaria and mixed infections, this pattern of multiple spikes may
Headache: Headache may be a
presenting feature of malaria, with or without fever. It can be unilateral or bilateral.
Some times the headache could be so intense that it may mimic intra-cranial infections or
intra-cranial space occupying lesions. It may also mimic migraine, sinusitis etc. Presence
of projectile vomiting, papilloedema, neck stiffness and focal neurological signs would
suggest other possibilities.
Body ache, back ache and joint pains:
These symptoms are fairly common in malaria. These can occur even during the prodromal
period and at that stage these are generally ignored and diagnosis of malaria is
impossible owing to lack of peripheral parasitemia. They are also common accompaniments of
the malaria paroxysm. Sometimes, malaria may present only with these symptoms,
particularly in cases of recurrent malaria.
Dizziness, vertigo: Some patients
may present with dizziness or vertigo, with or without fever. They may also have
associated vomiting and/or diarrhoea. This may mimic labyrinthitis, Menniere's disease,
vertebro-basilar insufficiency etc. Rarely patients may present with swaying and
cerebellar signs. Drugs like chloroquine, quinine, mefloquine and halofantrine can also
cause dizziness, vertigo, and tinnitus.
Altered behaviour, acute psychosis:
Patients may present with altered behaviour, mood changes, hallucinosis or even acute
psychosis, with or without fever. Malaria may be detected accidentally in such cases and
they improve completely with anti malarial therapy. Altered behaviour may also be due to
high grade fever or drugs. Antimalarial drugs like chloroquine, quinine, mefloquine and
halofantrine can cause restlessness, hallucinations, confusion, delirium or even frank
In a study of 118 cases of malaria in
Mangalore, Nagesh Pai, Satish Rao and B.S. Kakkilaya found varied psychiatric
manifestations. Most of these patients were already on antimalarial treatment at the time
of referral to the psychiatric service (unpublished data).
vague complaints > 7days
Patients with P. falciparum malaria may present with altered sensorium due to
severe infection, hypoglycemia, electrolyte imbalance due to vomiting or diarrhoea
(particularly the elderly), hyperpyrexia, subclinical convulsions etc. Differential
diagnosis will include acute encephalitis, meningitis, metabolic encephalopathy etc. As a
rule of the thumb, malaria should be considered a possibility in all cases of acute
neuropsychiatric syndromes and in cases of proven malaria, other possibilities should be
considered in the presence of papilloedema, increasesd ICT, neck stiffness and focal
Convulsions, coma: Patients with
cerebral malaria present with generalised seizures and deep unarousable coma. Sometimes
one single fit can precipitate deep, unarousable coma. These could also be due to
hypoglycemia and all patients presenting with these manifestations should be administered
25-50% dextrose immediately. Drugs like chloroquine, quinine, mefloquine and halofantrine
may also trigger convulsions.
Cough: Cough may be a presenting
feature of malaria, particularly P. falciparum infection. Patient may have pharyngeal
congestion and features of mild bronchitis. Patients who have persistent cough and/or
fever even after clearance of parasitemia should be evaluated for secondary bacterial
pneumonias/ bronchopneumonia and bronchitis.
Breathlessness: In severe
falciparum malaria, patients may present with history of breathlessness, due to either
severe anemia or non-cardiogenic pulmonary oedema. Secondary respiratory tract infections
and lactic acidosis are other rarer causes for tachypnoea and/or breathlessness in these
patients. Patients with pre-existing cardio-vascular or pulmonary compromise may
deteriorate or even die if they suffer from severe malaria.
Chest pain: Acute retrosternal or
precordial pain may be presenting feature of malaria. It may radiate to the left or right
shoulder tips or arms. It is due to rapid increase in the splenic size and perisplenitis.
This pain may mimic acute myocardial infarction, pleurisy, neuralgia etc. Coupled with
breathlessness, sweating and hypotension (algid malaria), the picture will very closely
resemble that of acute MI.
Acute abdomen: Patients can
present with acute abdominal pain, guarding and rigidity, mimicking bowel perforation,
acute appendicitis, acute cholecystitis, ureteric colic etc.
One such patient
presented with pain abdomen and vomiting with low grade fever, and on examination had
tenderness in the right lower abdomen. He was posted for appendicectomy. Pre operative
blood test revealed P. falciparum malaria and he recovered completely with anti malarials!
Weakness: Sometimes patients may
present with history of weakness, malaise and prostration. On examination they may have
significant pallor, hypotension, dehydration etc. Algid malaria may present like this and
the patient may not have fever at all. Chloroquine is also known to cause profound
muscular weakness and a new disease called macrophagic
myofaciitis has been described in patients receiving chloroquine.
Vomiting and diarrhoea: Malaria
can present as a case of acute gastroenteritis with profuse vomiting and watery diarrhoea
(Choleraic form). Vomiting is very common in malaria and is due to high grade fever, the
disease itself or even drugs. Vomiting may pose problems in administering antimalarial
treatment. These could also be due to drugs like chloroquine and due to secondary
bacterial or amebic colitis.
Jaundice: Patients may present with
history of yellowish discoloration of eyes and urine. Mild jaundice is fairly common in
malaria and may be seen in 20-40% of the cases. Deeper jaundice with serum bilirubin of
more than 3 mg/dL is seen in severe P. falciparum malaria and is associated with
anemia, hyperparasitemia and malarial hepatitis with elevated serum enzymes. Malaria must
be considered as a differential diagnosis for all cases of jaundice in a malarious area.
Pallor: Severe anemia can be a
presenting feature of malaria. It is usually normocytic normochromic. It may pose special
problems in pregnancy and in children. Pre-existing nutritional anemia may be aggravated
Puffiness of lids: Occasionally
patients may present with puffiness of lids, with or without renal dysfunction.
Secondary infections: Malaria
produces significant immune suppression and this can result in secondary infections.
Common among them are pneumonia, aspiration bronchopneumonia (in the elderly), urinary
tract infection, colitis etc. Meningitis and enteric fever have also been reported. In
falciparum malaria, severe infection can lead to septicaemic shock (algid malaria).
Persistence of fever, neutrophilic leucocytosis and focal signs of infection should always
alert the clinician to this possibility of secondary infections.
Hepatosplenomegaly: Patients can
present with enlargement of liver and/or spleen, tender or non-tender, with or without
fever. Rapid enlargement of spleen or liver in malaria can cause acute pain in the abdomen
or chest. Generally, organomegaly is noticed in the second week of malarial illness.
However, in cases of relapse or recrudescence, it may be present earlier. Also, in immune
compromised patients splenomegaly may be absent. In pregnancy, particularly second half,
splenomegaly may be smaller or an enlarged spleen may regress in size due to immune
suppression. Although splenomegaly is a cardinal sign of malaria, absence of splenomegaly
does not rule out the possibility of malaria.
Combinations of the above:
Patients can frequently present with various combinations of the above mentioned symptoms
and signs, further confusing the picture.
This list is not exhaustive and
malaria may present in many other ways. In all the above listed situations, patients may
not have associated fever, thus confusing the picture. In some, fever may follow these
symptoms. Therefore, one should not wait for the typical symptoms of malaria to get a
blood test done; it is always better to do a smear whenever reasonable doubt exists.
Clinical features suggesting P.
Presence of any of the complications of P. falciparum malaria viz. altered
sensorium; convulsions; coma; jaundice; severe anemia; hypotension; prostration;
hyperpyrexia; renal failure etc.
responding to chloroquine therapy within 48 hours.
within 2 weeks.
Don't miss malaria -
Malaria can be offered as a differential
diagnosis for a big list of diseases.
General: All other causes of
fever, migraine, sinusitis, tension headache etc.
Respiratory system: Pharyngitis,
bronchitis, pneumonia, bronchopneumonia, pleurisy.
Cardiovascular: Acute myocardial
infarction, cardiogenic shock, left ventricular failure, pericarditis
Abdominal: Hepatitis, liver
abscess, splenitis, splenic abscess, other causes of splenomegaly, subdiaphragmatic
abscess, acute abdomen, cholecystitis, cholangitis, gastroenteritis, amebiasis,
Central nervous system: Acute
encephalitis, meningitis, intra-cranial space occupying lesions, stroke, metabolic
Psychiatry: Acute confusional
states, acute psychosis, mood disorders
Renal: Acute nephritis, nephrotic
syndrome, acute renal failure
Haematological: All other causes
of anemia; blood dyscrasias, hemoglobinopathies, hemolytic anemias, intra vascular
hemolysis, bleeding diathesis, DIC etc.
Now you know!
Malaria can mimic
anything and everything!