Clinical Case Study 1: Fever 6 months after a visit to Pakistan

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This is the most probable diagnosis. The reported microscopic findings are compatible with P. vivax: some infected red cells are enlarged and deformed, and the "other forms with four nuclei" are compatible with the presence of schizonts. Plasmodium vivax does occur in Pakistan, where it is found in slightly more than 50% of malaria cases.

The history suggests a relapse of P. vivax malaria, following an earlier episode five weeks ago. The earlier treatment apparently did not include primaquine, thus allowing the persistence of hypnozoites which caused this relapse.

An alternate explanation would be that the earlier infection was caused by chloroquine-resistant P. vivax (which has been reported in Pakistan), with recrudescence of blood-stage parasites occurring after an unsuccessful earlier treatment (if indeed the earlier treatment included chloroquine). However, recrudescences usually occur within 28 days of the intial episode, rather than at five weeks as described here.

The other species are less likely:

• While P. falciparum does occur in Pakistan (slightly less than 50% of malaria cases), this patient reportedly did not develop symptoms until 10 months after departure from the exposure area: most cases of P. falciparum would have become symptomatic earlier.
• P. ovale occurs mainly in Africa and has been found only occasionally in Asia (in the western Pacific).
• P. malariae occurs worldwide, but its distribution is spotty, and its frequency in Pakistan is low to negligible.
• Babesia would not fit with the microscopic description; in addition, babesiosis has not been reported in Pakistan, although admittedly the disease might have escaped detection.

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A reasonable option, signifying that in the absence of definitive microscopic diagnosis, you prefer to play it safe and treat the patient for the most dangerous and rapidly progressing infection possible.

The safest course of action is to initially admit all cases of proven or suspected P. falciparum to the hospital until one can begin treatment and ensure that they are improving clinically and parasitologically.

However in this case, if the patient is only minimally symptomatic, one might elect against hospitalization and instead treat as an outpatient provided that close follow-up can be arranged. Once the definitive microscopic diagnosis is made the following day, you can always switch treatment.

That is correct.

A reasonable option, signifying that in the absence of definitive microscopic diagnosis, you prefer to play it safe and treat the patient for the most dangerous and rapidly progressing infection possible.

The safest course of action is to initially admit all cases of proven or suspected P. falciparum to the hospital until one can begin treatment and ensure that they are improving clinically and parasitologically.

However in this case, if the patient is only minimally symptomatic, one might elect against hospitalization and instead treat as an outpatient provided that close follow-up can be arranged. Once the definitive microscopic diagnosis is made the following day, you can always switch treatment.

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You should exclude G6PD deficiency first, then give the patient primaquine, 30 mg per day for 14 days.

In case of G6PD deficiency, consultation with an expert in infectious diseases or tropical medicine is advised to discuss options for relapse prevention. For some patients with partial G6PD deficiency, an alternative regimen of primaquine 45 mg weekly for 8 weeks can sometime be used. Alternatively, weekly chloroquine prophylaxis may also be considered. Treatment with primaquine is justified because this patient probably has already had a relapse, and is at risk for further relapses. No test exists to detect the presence of liver stage parasites.

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Even to visit friends and relatives, preventive measures must be taken. Chloroquine-resistant Plasmodium falciparum occurs in Pakistan, and thus the drugs recommended would be atovaquone-proguanil (Malarone®), doxycycline or mefloquine. Other preventive measures against mosquito bites also apply. Even though the patient was born in Pakistan, whatever acquired immunity he has developed would most likely have waned; negligence of preventive measures often occurs in individuals visiting friends and relatives, a situation that needs to be remedied.