Measurement of Plasmodium falciparum Growth Rates in Vivo: A Test of Malaria Vaccines

Cheng, Qin; Lawrence, Gregory J.; Reed, Christie; Stowers, Anthony W.; Ranford-Cartwright, Lisa; Creasey, Alison M.; Carter, Richard; Saul, Allan

doi:10.4269/ajtmh.1997.57.495

Cited by 156 publications

(168 citation statements)

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“…3 This supports the view that low parasitemia detectable only by the PCR is not an artifact caused by residues of a past infection and confirms the findings showing that only viable parasites can be recognized by the PCR. 28,29 It has been suggested that antibodies against crude schizont antigens are not protective since high titers were not correlated with low parasite densities. 30,31 In other studies, titers of antibodies against erythrocytic stages were found to be associated with the extent and duration of parasitaemia.…”

Section: Discussionmentioning

confidence: 99%

High rate of mixed and subpatent malarial infections in southwest Nigeria.

May¹,

Mockenhaupt²,

Ademowo³

et al. 1999

The American Journal of Tropical Medicine and Hygiene

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Abstract. The rate of malarial parasitemia in children and adults was assessed by microscopy and the polymerase chain reaction in a holoendemic area in Nigeria. A high rate of subpatent Plasmodium falciparum parasitemia (19.6%) was found. Plasmodium malariae and P. ovale infections were common in a rural area (26.1% and 14.8%) but were observed sporadically in individuals from an urban area. Simultaneous infections with P. falciparum, P. malariae, and P. ovale were frequent in the rural area (11.7% triple infections). The rate of triple infections was higher than expected from the prevalences of each species (P Ͻ 0.00001). Spleen enlargement was associated with mixed infections of P. falciparum and P. malariae (odds ratio [OR] ϭ 5.9, 95% confidence interval [CI] 3.0-11.7) and less frequently observed in individuals without detectable parasitemia (OR ϭ 0.06, 95% CI ϭ 0.01-0.3). Spleen enlargement and titers of antibodies to schizonts were positively correlated with parasite densities. The results also suggest that in some individuals a long-lasting subpatent parasitemia might occur.In areas holoendemic for Plasmodium falciparum infection, clinical malaria affects mostly young children. Adults have acquired a partial immunity after years of successive exposure to a variety of different parasite strains. An antidisease immunity evolves in early childhood, while an antiparasite immunity develops at the age of 15-20 years. 1 It is yet unclear to what extent subpatent parasitemia contributes to acquired immunity and whether clinically asymptomatic infections reflect effective parasite control or may eventually convert to manifest disease.The polymerase chain reaction (PCR) allows the detection of parasitemia below the threshold of conventional microscopy. 2 Re-evaluations of the epidemiology of unstable malaria have now shown that the prevalence of submicroscopic P. falciparum infections is far higher than has previously been expected. 3 Until the PCR came into use it had been difficult to assess correlations of submicroscopic parasitemia with particular features of malarial infections such as spleen size or antibody titers.Although simultaneous infections with different Plasmodium species have been described in humans, 4 detailed reports of prevalences in holoendemic areas were rare before species-specific PCR assays became available. 5 The extent of interspecies interactions in mixed infections is currently the subject of discussion. In a recent study, it has been suggested that cross-immunity between P. falciparum and P. vivax antigens might occur. 6 However, there is a controversy whether anti-disease-and anti-parasite immunity are in fact species-specific. 7 In a cross-sectional study in an urban and a rural setting of southwest Nigeria, we determined the rates of simultaneous P. falciparum, P. malariae, and P. ovale infections, including submicroscopic parasitemia. Furthermore, we looked at associations of different plasmodial infections with spleen size and with antibody titers against crude schizont antigen. P...

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Section: Discussionmentioning

confidence: 99%

High rate of mixed and subpatent malarial infections in southwest Nigeria.

May¹,

Mockenhaupt²,

Ademowo³

et al. 1999

The American Journal of Tropical Medicine and Hygiene

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“…Follow-up visits were scheduled daily (days 5-21), every other day (days [22][23][24][25][26][27][28][29][30][31][32][33][34][35], then weekly until 12 weeks after challenge. Volunteers returned one year after challenge for final evaluation and to have the bracelets removed.…”

Section: Methodsmentioning

confidence: 99%

“…The DNA in 20-l aliquots was amplified in nested PCRs using primers and conditions described previously. 29 All samples were assayed at least twice. In our hands this method detects two parasites/ml of blood, consistent with previous reports 29 and roughly equivalent to the sensitivity of in vitro culture.…”

Section: Methodsmentioning

confidence: 99%

“…29 All samples were assayed at least twice. In our hands this method detects two parasites/ml of blood, consistent with previous reports 29 and roughly equivalent to the sensitivity of in vitro culture. 30 If just one parasite injected by a mosquito generates 30,000 in the liver, 31,32 then the initial parasitemia should be ϳ6/ml, a level readily detectable by our PCR and culture methods.…”

Section: Methodsmentioning

confidence: 99%

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Prophylactic activity of atovaquone against Plasmodium falciparum in humans.

Shapiro

Ranasinha²,

Kumar

et al. 1999

The American Journal of Tropical Medicine and Hygiene

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Abstract. The prophylactic antimalarial activity of atovaquone was determined in a randomized, double-blind, placebocontrolled study of healthy volunteers who were challenged by the bite of Plasmodium falciparum-infected Anopheles stephensi. Subjects were randomly assigned to one of three groups: six received seven daily doses of 750 mg of atovaquone, starting the day before challenge; six received a single dose of 250 mg of atovaquone the day before challenge; and four received placebo. Polymerase chain reaction-and culture-confirmed parasitemia developed in all four placebo recipients, but in none of the drug recipients, indicating that either of the atovaquone regimens provides effective prophylaxis (P ϭ 0.005). However, in low-dose recipients, the drug levels by day 6.5 were profoundly subtherapeutic, indicating that parasites were eliminated prior to the establishment of erythrocytic infection. Atovaquone thus protects non-immune subjects against mosquito-transmitted falciparum malaria, and has causal prophylactic activity.

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“…3 An alternative model, involving inoculation of donor blood-stage parasites 4 (BSP), is used less frequently. Both methods were historically employed in malaria therapy for neurosyphilis with comparable clinical and parasitologic outcomes.…”

Section: Introductionmentioning

confidence: 99%

Controlled Human Blood Stage Malaria Infection: Current Status and Potential Applications

Duncan¹,

Draper²

2012

The American Journal of Tropical Medicine and Hygiene

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Abstract. Controlled human malaria infection by blood stage parasite (BSP) inoculation is an alternative to the wellestablished model of infection with Plasmodium falciparum sporozoites delivered by mosquito bites. The BSP model has been utilized less frequently, but its use is increasing. Advantages of BSP challenge include greater ease of administration, better standardization of the infecting dose per volunteer, and good inter-study reproducibility of in vivo parasite dynamics. Recently, a surprising reduction in clinical symptoms at microscopic patency in the BSP model has been identified, which has an undefined and intriguing pathophysiologic basis, but may make this approach more acceptable to volunteers. We summarize clinical, parasitologic, and immunologic data from all BSP challenges to date, explore differences between the BSP and sporozoite models, and propose future applications for BSP challenge.

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Measurement of Plasmodium falciparum Growth Rates in Vivo: A Test of Malaria Vaccines

Cited by 156 publications

References 0 publications

High rate of mixed and subpatent malarial infections in southwest Nigeria.

High rate of mixed and subpatent malarial infections in southwest Nigeria.

Prophylactic activity of atovaquone against Plasmodium falciparum in humans.

Controlled Human Blood Stage Malaria Infection: Current Status and Potential Applications

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