The main protozoans that produce disease in humans are those causing malaria, amoebiasis, pneumocystis infection, trypanosomiasis and leishmaniasis.
Malaria, a mosquito-borne disease caused by various Plasmodium species, is a major killer in the developing world and sporadic cases occur elsewhere as a result of air travel. The female anopheline mosquito injects sporozoites during a blood meal. Fig. 32.1 shows the subsequent sequence of changes in the parasite and their relation to the bouts of fever.
The main malarial parasites are Plasmodium vivax and Plasmodium falciparum , both of which cause fever every third day (tertian malaria), P. vivax causing benign and P. falciparum causing malignant tertian malaria (malignant because it is a very severe form of the disease and can be fatal). P . vivax gives rise to hypnozoites in the liver; these lie dormant and can produce relapses months or years later. P. falciparum does not form hypnozoites and thus has no exo-erythrocytic stage. P. malariae , which is rare, has a 72-h cycle (quartan malaria) and also has no exo-erythrocytic stage.
|For the clinical attack||For chemoprophylaxis|
|All infections except chloroquine- resistant Plasmodium falciparum||Oral chloroquine; then primaquine to attack the hypnozoites and prevent relapse||Oral chloroquine or proguanil|
|Chloroquine-resistant P. falciparum||Quinine then doxycycline or proguanil + atovaquone||Doxycycline or proguanil + atovaquone|
Chloroquine reduces the necessary digestion of haemoglobin by the plasmodium and also inhibits the parasite’s haem polymerase (the enzyme that inactivates the toxic free haem generated by the organism, which is fatal for it). It is usually given orally (half-life 0.5 h) but can be given by injection. It is widely distributed in the body, but much is concentrated in the parasite-infected red cells. Unwanted effects include nausea, vomiting and dizziness. Large doses cause retinopathy and bolus injections can cause dysrhythmias. P. falciparum is resistant in most parts of the world and P. vivax is resistant in some places.
Halofantrine is given orally; the parent drug has a half-life of 1–2 days and the active metabolite 3–5 days. Unwanted effects include gastrointestinal (GI) tract disturbances and, occasionally, cardiac dysrhythmias.
Quinine is given orally (half-life 10 h) but can be given by intravenous (IV) infusion. It is usually followed by doxycycline (see below) and either dapsone (given orally, half-life 24–48 h) or sulfadoxine, a long-acting sulphonamide (half-life ∼ 8 days). Quinine causes GI upsets, tinnitus, headache, blurred vision and allergic reactions. Large doses affect the heart (dysrhythmias) and/or the central nervous system (CNS) (delirium). Blackwater fever may be associated with the use of this drug.
Mefloquine is given orally (half-life 30 days) and has a slow onset of action. Like chloroquine, it inhibits the plasmodial haem polymerase. It can cause GI tract disturbances and is known to produce neuropsychiatric symptoms.
Pyrimethamine is a folate antagonist inhibiting folate utilization having greater affinity for the plasmodial than for the mammalian system. It is only used with sulfadoxine. It is given orally and is slow acting (half-life 4 days). It has few unwanted effects.
Proguanil has a similar action to pyrimethamine. It is a slow-acting schizonticide (half-life 16 h) with some action on the pre-erythrocytic stage of P. vivax . It is given orally.
Primaquine is given orally (half-life 3–6 h) and usually with chloroquine. It can cause haemolysis in individuals with genetic deficiency of red cell glucose 6-phosphate dehydrogenase.
Doxycycline is a broad-spectrum tetracycline antibiotic that acts by inhibiting plasmodial protein synthesis.
Artemether is a semi-synthetic derivative of artemisinin – a compound extracted from a shrub used in traditional Chinese medicine. Given orally, rectally or intramuscularly (IM). Mechanism of action: It is concentrated in parasitized cells where it generates reactive oxygen species and may inhibit a calcium transporter. It inhibits haemoglobin degradation in the parasite. Only used in combination therapy. Unwanted effects are few, but neurotoxicity can occur with high doses.
Other Protozoal Infections
Amoebiasis is caused by the ingestion of the cysts of Entamoeba histolytica . The cysts develop in the GI tract into motile trophozoites which can invade the intestinal wall and, rarely, migrate to the liver. The presence of the organism in the GI tract usually causes dysentery; its presence in the liver causes amoebic abscesses. Some individuals remain symptom-free carriers, i.e. they excrete the cysts, which can infect others.
Acute severe dysentery: metronidazole (or tinidazole) followed by diloxanide.
Chronic amoebiasis: diloxanide.
Hepatic amoebiasis: metronidazole followed by diloxanide.
Treatment of carriers: diloxanide.