Studies on parasitic crisis in malaria: I. Signs of impending crisis in Plasmodium berghei infections of the white rat.

White rats infected with Plasmodiam berghei were observed throughout the course of infection for indicators of impending crisis (penultimate stage). Two ratios, percentage young compact forms:percentage trophozoites and percentage reticulocytes:percentage parasitaemia, were reliable markers of the penultimate period and impending crisis. When the percentage young compact form:percentage trophozoite ratio exceeded 1.0 and was coincident with an increase of uninfected reticulocytes in the circulation (as given by a percentage reticulocyte:percentage parasitaemia ratio greater than 1.0) the parasitaemic decline of crisis consistently occurred 24-48 hours later.     

Resolution of acute malaria (Plasmodium berghei in the rat): reversibility and spleen dependence

Six-week-old rats infected with Plasmodium berghei developed a peak parasitemia of 55.2 +/- 3.1% by day 15 of infection, followed by spontaneous resolution of the infection during a process referred to as crisis. Crisis was accompanied by the appearance in circulation of infected erythrocytes in which the parasites appeared abnormal ("crisis forms"). Rats splenectomized at different times during the crisis period experienced a sudden increase in parasitemia, with a marked decrease in the number of circulating crisis forms. Splenectomy in parasitemia, with a marked decrease in the number of circulating crisis forms. Splenectomy resulted in a 100% mortality, whereas all control and sham-operated rats survived their infection. Although P. berghei is restricted to developing within young erythrocytes, our observations could not be explained by the effects of splenectomy on the number of circulating reticulocytes. Indeed, the reticulocytosis which accompanies crisis was unaffected by splenectomy. Our observations therefore suggest that crisis is a reversible process and, specifically, that the spleen is necessary for its maintenance.     

Role of macrophage-processed antigen in a Plasmodium berghei model

Summary The present study demonstrates that malarial parasite could be processed by macrophages in vitro to release 'super antigens'. These super antigens obtained from the peritoneal macrophages were more protective than those processed by the splenic adherent cells. BCG-stimulated macrophages were also able to process the antigens efficiently and these antigens were even superior to those obtained from the unstimulated macrophages. These modified antigens were potent inducers of DFPS to malarial antigens. It is thus concluded that parasite antigens, processed in vitro, carry specific immunogenic potential and are able to protect the recipients to parasite challenge.     

Aquaglyceroporin PbAQP during intraerythrocytic development of the malaria parasite Plasmodium berghei

The malaria parasite can use host plasma glycerol for lipid biosynthesis and membrane biogenesis during the asexual intraerythrocytic development. The molecular basis for glycerol uptake into the parasite is undefined. We hypothesize that the Plasmodium aquaglyceroporin provides the pathway for glycerol uptake into the malaria parasite. To test this hypothesis, we identified the orthologue of Plasmodium falciparum aquaglyceroporin (PfAQP) in the rodent malaria parasite, Plasmodium berghei (PbAQP), and examined the biological role of PbAQP by performing a targeted deletion of the PbAQP gene. PbAQP and PfAQP are 62% identical in sequence. In contrast to the canonical NPA (Asn-Pro-Ala) motifs in most aquaporins, the PbAQP has NLA (Asn-Leu-Ala) and NPS (Asn-Leu-Ser) in those positions. PbAQP expressed in Xenopus oocytes was permeable to water and glycerol, suggesting that PbAQP is an aquaglyceroporin. In P. berghei, PbAQP was localized to the parasite plasma membrane. The PbAQP-null parasites were viable; however, they were highly deficient in glycerol transport. In addition, they proliferated more slowly compared with the WT parasites, and mice infected with PbAQP-null parasites survived longer. Taken together, these findings suggest that PbAQP provides the pathway for the entry of glycerol into P. berghei and contributes to the growth of the parasite during the asexual intraerythrocytic stages of infection. In conclusion, we demonstrate here that PbAQP plays an important role in the blood-stage development of the rodent malaria parasite during infection in mice and could be added to the list of targets for the design of antimalarial drugs.     

Apparent relapse of imported Plasmodium ovale malaria in a pregnant woman

A 27 week pregnant woman who had lived in Bangkok, Thailand, for 18 months presented to her obstetrician with a 1-week history of intermittent fever and malaise. Medical history was significant for multiple episodes of malaria during her 10 years of employment in sub-Saharan Africa before her relocation to Thailand. The initial malaria smear was negative. She returned a week later with no resolution of her symptoms, at which time she was found to have Plasmodium ovale by microscopy and polymerase chain reaction. She had an excellent response to chloroquine, which she continued weekly until 36 weeks of gestation. She delivered a healthy term infant and received radical cure with primaquine after cessation of breastfeeding. This case shows challenging issues in detection and management of imported P. ovale malaria.     

Re-ingestion of Plasmodium berghei sporozoites after delivery into the host by mosquitoes

Malaria-infected mosquitoes feeding on a mammalian host inject sporozoites into the skin to induce a malaria infection. The numbers of sporozoites ultimately able to reach the liver may be important determinants of the characteristics of the ensuing blood infection. Because feeding mosquitoes not only inject sporozoites into the host but concomitantly ingest blood to obtain their bloodmeal, some sporozoites are re-ingested by the feeding mosquito. We studied transmission of fluorescent Plasmodium berghei sporozoites injected into mice by Anopheles stephensi mosquitoes and found that the numbers of sporozoites re-ingested by mosquitoes are comparable to numbers previously reported to be delivered directly into mice. Thus, re-ingestion of sporozoites likely plays a significant role in transmission dynamics of malaria by mosquitoes, and may account for the failure of some sporozoite-infected mosquitoes to induce a blood infection.