The incubation period varies, being:
• 10-14 days in P. vivax, P. ovale and P. falciparum
• 18 days to 6 weeks in P. malariae infection Although individual variations in clinical presentation are noted, febrile paroxysms, anaemia, splenomegaly and · epatomegaly are usually present. Malarial febrile paroxms typically have three stages:
1 The ‘cold stage’ is characterized by marked vasoconstriction and lasts from 30 min to 1 hour. The patient feels intensely cold and uncomfortable. There is marked shivering. The temperature rises rapidly, often to as high as 41°C.
2 The ‘hot stage’ abruptly follows and lasts for 2-6 hours. The patient feels intensely hot and uncomfortable. Delirium may be present.
3 The ‘sweating stage’ then occurs, during which the bedclothes are drenched. The patient feels fatigued and exhausted but otherwise well and often sleeps. The fever is due to schizont rupture and the release of pyrogens. Herpes labialis frequently occurs in established malaria. Anaemia is usually present and is largely a result of haemolysis. P. vivax and P. ovale The fever occurs every other day when established. These species of Plasmodium give rise to a clinically mild infection. The presence of an exoerythrocytic stage is responible for relapses and makes eradication of the organisms difficult. P. malariae This is usually a mild disease with a fever, but tends to run a more chronic course. The nephrotic syndrome can complicate this type of malaria and may be fatal between the ages of 4 and 5 years. Because of its chronicity, the patient develops a sallow complexion, marked muscle wasting, mild icterus and massive splenomegaly. Growth retardation may occur in children.
This is the most severe form of malaria (pernicious malaria), with high levels of parasitaemia. Infected RBCs develop peculiar knob-like surface projections that facili-tate adhesion of these RBCs to the endothelium of bloodvessels via I CAM-l. The consequent vascular occlusion causes severe organ damage, chiefly in the kidneys, liver, brain and gastrointestinal tract. The prodrome tends to be severe. The fever follows no particular pattern. Splenomegaly tends to occur late and the characteristic cold, hot and sweating stages are not prominent. The following clinical forms of falciparum malaria are recognized and are likely to occur when more than 2% of RBCs are parasitized (Information box 1.4).
CEREBRAL MALARIA is characterized by a marked elevation in body temperature, a rapid deterioration in consciousness, convulsions, coma and death.
BLACKWATER FEVER, so called because of the production of dark brown-black urine owing to intravascular haemolysis, is seen only in falciparum malaria. It can be precipitated by very small amounts of quinine in quinine-sensitive cases. This is a rapidly progressive illness characterized by the abrupt onset of fever, marked haemolysis, haemoglobinuria, hyperbilirubinaemia, vomiting, circulatory collapse and acute renal failure. Malarial parasites cannot usually be detected in peripheral blood smears after the onset of intravascular haemolysis.
Tropical splenomegaly syndrome
Tropical splenomegaly syndrome is seen in areas where malaria is hyperendemic. It is uncommon before 10 years of age. Characteristic features are massive splenomegaly, marked elevation in serum IgM levels, and IgM aggregates (detected by immunofluorescence) in Kupffer cells in the liver. The splenomegaly responds to antimalarial therapy. However, malarial parasites are not detected in the spleen or peripheral blood smears.
The following indices are used to measure the prevalence of malaria:
SPLEEN RATE, defined as the percentage of children between 2 and 10 years of age with splenomegaly, is used as a measure of the endemicity of malaria in a community.
INFANT PARASITE RATE, defined as the percentage of infants below 1 year of age in whom malarial parasites are demonstrable in peripheral blood smears, is regarded as the most sensitive index of transmission of malaria to a locality.
The parasite can be demonstrated in either thin or thick peripheral blood smears stained with Giemsa, Wright or Leishman stains. Two to three blood smears taken each day for 3 or 4 days and found to be negative are necessary before a patient is declared malaria-free. Serological methods are not widely used but include indirect immunofluorescence, indirect haem agglutination and gel diffusion techniques. ELISA for antigen detection and probes for parasite DNA are currently being evaluated.
Analgesics and antipyretics such as aspirin and paracetamol are given as necessary. Intravenous fluids may be required to combat dehydration and shock. Treatment of an acute attack The 4-aminoquinolines are the drugs of choice. Chloroquine- sensitive malaria is treated with chloroquine 600 mg of the base followed by 300 mg in 6 hours and then 150 mg twice daily for 3 days, or amodiaquine hydrochloride 600 mg of the base followed by 400-600 mg daily for 2 days up to a total maximum dose of 2400 mg. Chloroquine-resistant malaria is treated with quinine sulphate 650 mg three times daily for 5 days given in combination with pyrimethamine 25 mg twice daily for 3 days and sulphadiazine 500 mg twice daily for 5 days. Mefloquine is a synthesized quinolone which is useful in chloroquine- and some quinine-resistant cases; again resistance to this is developing. Halofantrine, an amino alcohol, is another drug for resistant cases. Both these last two drugs are too expensive for widespread use.
DRUG SIDE-EFFECTS. These drugs are potentially toxic. With quinine, tinnitus, haemolytic anaemia and drug fever may occur. Chloroquine may cause vomiting, abdominal pain, agranulocytosis or convulsions.
1 P. [alciparum. Chloroquine alone or in combination with either pyrimethamine 25 mg or primaquine 45 mg as a single dose effects a radical cure because there is no exoerythrocytic stage in falciparum malaria.
2 P. vivax, P. malariae and P. ovale. Primaquine, an 8- aminoquinoline, is essential for eliminating the exoer-ythrocytic cycle and effecting a radical cure. A course of one of the 4-aminoquinolines should be followed by primaquine 7.5 mg daily for 14 days. Alternatively, 300 mg chloroquine combined with 45 mg primaquine once a week for 8 weeks is also effective.
Treatment of severe malaria
Severe malaria (more than 1% of RBCs infected) or any of the pernicious forms of falciparum malaria constitutes a medical emergency. Quinine, given by a slow intravenous infusion, is the drug of choice: Quinine dihydrochloride 20 mg kg” intravenously over 4 hours followed by 100 mg kg-t infused over 4 hours at 8-hourly intervals until the patient is able to tolerate oral therapy.
PREVENTION AND CONTROL
Owing to changing patterns of resistance, advice about chemoprophylaxis should be sought prior to leaving for a malaria-endemic area. Chemoprophylaxis is essential for those visiting endemic areas-generally chloroquine 300 mg once a week in areas where there is no chloroquine resistance, but where there is resistance it should be combined with proguanil 200 mg daily or in South East Asia or Papua New Guinea dapsone/pyrimethamine (Maloprim) one tablet (100 mg and 125 mg respectively) each week as above. Mefloquine 250 mg weekly (adults) can be used where falciparum malaria is highly resistant to chloroquine (East and Central Africa) for periods up to 6 months. Doxycycline has also been used apparently successfully in South East Asia. Prophylaxis should be continued for 6 weeks after leaving a high-risk area. On the basis of the 1979 WHO Expert Committee report on malaria, the following preventive measures have been suggested. Measures to be applied to the community include prevention of man-vector contact, destruction of adult mosquitoes and mosquito larvae, and active elimination of human infection by presumptive treatment (i.e. treatment of all fevers in endemic areas with antimalarials) and radical treatment. Measures to be applied to individuals include use of mosquito repellents, impregnated bed nets, protective clothing, chemoprophylaxis and chemotherapy where indicated.