Surface antigens of Plasmodium falciparum gametocytes--a new class of transmission-blocking vaccine targets?
ABSTRACT The re-establishment of elimination and eradication on the malaria control agenda has led to calls for renewed effort in the development of parasite transmission-blocking interventions. Vaccines are ideally suited to this task, but progress towards an anti-gamete transmission-blocking vaccine, designed to act on parasites in blood-fed mosquitoes, has been slow. Recent work has confirmed that the surface of the gametocyte-infected erythrocyte presents antigens to the host immune system, and elicits specific humoral immune responses to these antigens, termed gametocyte surface antigens (GSAs). Likely candidate molecules, including antigens encoded by sub-telomeric multi-gene families, are discussed, and a hypothetical group of parasite molecules involved in spatial and temporal signal transduction in the human host is proposed, the tropins and circadins. The next steps for development of anti-gametocyte transmission-blocking vaccines for P. falciparum and the other human malaria species are considered.
Article: Mosquito feeding assays to determine the infectiousness of naturally infected Plasmodium falciparum gametocyte carriers.[show abstract] [hide abstract]
ABSTRACT: In the era of malaria elimination and eradication, drug-based and vaccine-based approaches to reduce malaria transmission are receiving greater attention. Such interventions require assays that reliably measure the transmission of Plasmodium from humans to Anopheles mosquitoes. WE COMPARED TWO COMMONLY USED MOSQUITO FEEDING ASSAY PROCEDURES: direct skin feeding assays and membrane feeding assays. Three conditions under which membrane feeding assays are performed were examined: assays with i) whole blood, ii) blood pellets resuspended with autologous plasma of the gametocyte carrier, and iii) blood pellets resuspended with heterologous control serum. 930 transmission experiments from Cameroon, The Gambia, Mali and Senegal were included in the analyses. Direct skin feeding assays resulted in higher mosquito infection rates compared to membrane feeding assays (odds ratio 2.39, 95% confidence interval 1.94-2.95) with evident heterogeneity between studies. Mosquito infection rates in membrane feeding assays and direct skin feeding assays were strongly correlated (p<0.0001). Replacing the plasma of the gametocyte donor with malaria naïve control serum resulted in higher mosquito infection rates compared to own plasma (OR 1.92, 95% CI 1.68-2.19) while the infectiousness of gametocytes may be reduced during the replacement procedure (OR 0.60, 95% CI 0.52-0.70). Despite a higher efficiency of direct skin feeding assays, membrane feeding assays appear suitable tools to compare the infectiousness between individuals and to evaluate transmission-reducing interventions. Several aspects of membrane feeding procedures currently lack standardization; this variability makes comparisons between laboratories challenging and should be addressed to facilitate future testing of transmission-reducing interventions.PLoS ONE 01/2012; 7(8):e42821. · 4.09 Impact Factor
Article: Epidemiology and infectivity of Plasmodium falciparum and Plasmodium vivax gametocytes in relation to malaria control and elimination.[show abstract] [hide abstract]
ABSTRACT: Malaria remains a major cause of morbidity and mortality in the tropics, with Plasmodium falciparum responsible for the majority of the disease burden and P. vivax being the geographically most widely distributed cause of malaria. Gametocytes are the sexual-stage parasites that infect Anopheles mosquitoes and mediate the onward transmission of the disease. Gametocytes are poorly studied despite this crucial role, but with a recent resurgence of interest in malaria elimination, the study of gametocytes is in vogue. This review highlights the current state of knowledge with regard to the development and longevity of P. falciparum and P. vivax gametocytes in the human host and the factors influencing their distribution within endemic populations. The evidence for immune responses, antimalarial drugs, and drug resistance influencing infectiousness to mosquitoes is reviewed. We discuss how the application of molecular techniques has led to the identification of submicroscopic gametocyte carriage and to a reassessment of the human infectious reservoir. These components are drawn together to show how control measures that aim to reduce malaria transmission, such as mass drug administration and a transmission-blocking vaccine, might better be deployed.Clinical microbiology reviews 04/2011; 24(2):377-410. · 14.69 Impact Factor
Article: Naturally acquired immune responses to Plasmodium falciparum sexual stage antigens Pfs48/45 and Pfs230 in an area of seasonal transmission.[show abstract] [hide abstract]
ABSTRACT: Acquisition of immunity to Plasmodium falciparum sexual stages is a key determinant for reducing human-mosquito transmission by preventing the fertilization and the development of the parasite in the mosquito midgut. Naturally acquired immunity against sexual stages may therefore form the basis for the development of transmission-blocking vaccines, but studies conducted to date offer little in the way of consistent findings. Here, we describe the acquisition of antigametocyte immune responses in malaria-exposed individuals in Burkina Faso. A total of 719 blood samples were collected in a series of three cross-sectional surveys at the start, peak, and end of the wet season. The seroprevalence of antibodies with specificity for the sexual stage antigens Pfs48/45 and Pfs230 was 2-fold lower (22 to 28%) than that for an asexual blood stage antigen glutamate-rich protein (GLURP) (65%) or for the preerythrocytic stage antigen circumsporozoite protein (CSP) (54%). The youngest children responded at frequencies similar to those for all four antigens but, in contrast with the immune responses to GLURP and CSP that increased with age independently of season and area of residence, there was no evidence for a clear age dependence of responses to Pfs48/45 and Pfs230. Anti-Pfs230 antibodies were most prevalent at the peak of the wet season (P < 0.001). Our findings suggest that naturally acquired immunity against Pfs48/45 and Pfs230 is a function of recent exposure rather than of cumulative exposure to gametocytes.Infection and immunity 12/2011; 79(12):4957-64. · 4.21 Impact Factor