Final Diagnosis -- Plasmodium vivax

FINAL DIAGNOSIS    Plasmodium vivax

An antigen detection test was used on-site and identified a non-falciparum malaria parasitemia. Hours later, microscopic evaluation of thick and thin blood smears confirmed this finding and was suggestive of Plasmodium vivax. A sample was sent to the Centers for Disease Control for molecular confirmation by a two-step nested PCR based technique with application of the DNA products to an agarose gel.


Malaria is a vector-borne infectious disease caused by the protozoan parasite Plasmodium and carried by the female Anopheles mosquito. It is a worldwide disease and an enormous public health burden. There are roughly 250 million cases and nearly one million deaths attributed to the disease annually (1). Malaria is essentially endemic in most tropical areas where environmental conditions permit the expansion of its mosquito vector. Of the greater than 100 named species of Plasmodium, four are known to infect humans: malariae, ovale, vivax, and falciparum. Of the four, falciparum is most predominant with a global distribution; ovale is seen mostly in sub-Saharan Africa, and vivax in Asia. P. malariae is also widely spread but less commonly associated with cases of infection (2). Of note, the simian parasite Plasmodium knowlesi has recently been recognized in the human population in Malaysian Borneo.

Plasmodium owes its resilience in part to a sophisticated life cycle. Infection for humans begins when an infected female Anopheles mosquito contaminates the human blood stream during feeding. Sporozoites make their way through the blood stream and infect hepatocytes where they mature into schizonts. P. vivax and P. ovale can stay dormant at this stage for months to years. The schizonts later rupture, and release merozoites into the blood stream. Within erythrocytes, merozoites multiply and mature into trophozoites (ring forms). Trophozoites then mature into schizonts which rupture and once again release merozoites. This cycle of rupture, erythrocyte infection, asexual multiplication and rupture has clinical manifestations which will be outlined below. Some species are able to differentiate into gametocytes capable of sexual reproduction. When, male and female gametocytes are later ingested at a subsequent human blood meal, they combine within the mosquito stomach creating a zygote. The zygotes become ookinetes, and then oocysts which rupture and release sporozoites; the latter make their way to the mosquito salivary glands. There, Plasmodium is able to infect another human host.

Clinical Features
The symptoms of an uncomplicated malaria infection can be relatively non-specific making diagnosis difficult. Infection should be considered in patients who have traveled or lived in endemic areas. The most common symptoms include fever and chills accompanied by headache, arthralgias, myalgias, vomiting, diarrhea, and weakness. Depending upon the infecting species and severity of infection splenomegaly, anemia, thrombocytopenia, hypoglycemia, and neurologic, pulmonary, or renal dysfunction can also be seen. Severe malarial infection, particularly with P. falciparum, is capable of involving the nervous system, causing renal failure, severe anemia, or adult respiratory distress syndrome (3,4).

Morphological speciation of the Plasmodium organism is crucially important for guiding management decisions including prompt and appropriate treatment. P. falciparum is capable of severe, rapidly progressive illness or death in untreated patients at a rate approaching 5% (5). It is also commonly resistant to chloroquine. P. vivax infection, though less severe, can result in splenic rupture. Proper differentiation is made on the basis of the morphological variation of the four forms. The differences between P. falciparum and P. vivax are outlined below. Rapid on site antigen detection tests and send-out molecular techniques can also be employed. The latter is used to identify P. knowlesi since the early and late blood stages of this species are morphologically identical to those of P. falciparum and P.malariae, respectively.

Figure 1: Excerpt from the CDC "Comparison of the Plasmodium Species that cause human Malaria"

Treatment varies depending on the species, the geographic area where the infection was acquired (local variations in antimicrobial resistance), and the clinical severity of the illness. Published treatment guidelines are available from the Centers for Disease Control. According to these recommendations (6), for an uncomplicated case of chloroquine sensitive P. vivax in the United States, the patient should receive 600 mg of oral Chloroquine phosphate followed by 300 mg at 6, 24, and 48 hours. Chloroquine, by preventing the biocrystallization of heme, is toxic to circulating Plasmodium organisms. To prevent relapse, this would be accompanied by Primaquine phosphate, 30 mg every day for 14 days. Primaquine helps eliminate the liver stage of the parasite. Of note, malaria is a reportable disease and must be reported to the health department. Finally, on the horizon are multiple vaccines in development that may help to reduce malaria's prevalence in the future.


  1. "WHO World Malaria Report 2008." Centers for Disease Control. 10 Dec. 2008. [].
  2. "Laboratory Identification of Parasites of Public Health Concern. CDC, 2008." Centers for Disease Control. 12 Dec. 2008. [ htm].
  3. Mohan A, Sharma SK, Bollineni S. Acute lung injury and acute respiratory distress syndrome in malaria. J Vector Borne Dis. 2008 Sep; 45(3):179-93.
  4. Trang TT et al. Acute renal failure in patients with severe falciparum malaria. Clin Infect Dis. 1992 Nov;15(5):874-80.
  5. Sudre P, Breman JG, McFarland D, Koplan JP (1992) Treatment of chloroquine-resistant malaria in African children: a cost effectiveness analysis. International Journal of Epidemiology 21, 146 154.
  6. Guidelines for treatment of Malaria in the United States. Centers for Disease Control. 16 Dec. 2008. 2008. []

Contributed by Chris Gilbert, MD and Nadia Habib-Bein, MD, PhD

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