Acquired Immunity to Malaria

Queensland Institute of Medical Research, The Bancroft Centre, Post Office Royal Brisbane Hospital, Brisbane, Queensland 4029, Australia.
Clinical microbiology reviews (Impact Factor: 17.41). 02/2009; 22(1):13-36, Table of Contents. DOI: 10.1128/CMR.00025-08
Source: PubMed


Naturally acquired immunity to falciparum malaria protects millions of people routinely exposed to Plasmodium falciparum infection from severe disease and death. There is no clear concept about how this protection works. There is no general agreement about the rate of onset of acquired immunity or what constitutes the key determinants of protection; much less is there a consensus regarding the mechanism(s) of protection. This review summarizes what is understood about naturally acquired and experimentally induced immunity against malaria with the help of evolving insights provided by biotechnology and places these insights in the context of historical, clinical, and epidemiological observations. We advocate that naturally acquired immunity should be appreciated as being virtually 100% effective against severe disease and death among heavily exposed adults. Even the immunity that occurs in exposed infants may exceed 90% effectiveness. The induction of an adult-like immune status among high-risk infants in sub-Saharan Africa would greatly diminish disease and death caused by P. falciparum. The mechanism of naturally acquired immunity that occurs among adults living in areas of hyper- to holoendemicity should be understood with a view toward duplicating such protection in infants and young children in areas of endemicity.

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Available from: Carlota Dobaño Lázaro
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    • "Infection with P. falciparum can result in a simply asymptomatic carriage, uncomplicated or severe malaria. In fact, there is an exposurerelated immunity in malaria that could explain these different expressions[2]. In high transmission settings, symptomatic malaria is often concerning children below five years as they havenot been for long time exposed to the parasite and asymptomatic infections generally concern adults that acquired an antidisease and/or an antiparasite immunity during their exposure time3456. Asymptomatic malaria cases are known to be prevalent in endemic areas789and are generally untreated, resulting in a significant source of gametocytes that may serve as reservoir of disease transmission[10]. "
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    ABSTRACT: Malaria remains a major public health problem in the Democratic Republic of Congo (DRC) with 14 million cases reported by the WHOMalaria Report in 2014. Asymptomaticmalaria cases are known to be prevalent in endemic areas and are generally untreated, resulting in a significant source of gametocytes that may serve as reservoir of disease transmission. Considering that microscopy certainly underestimates the prevalence of Plasmodium infections within asymptomatic carriers and that PCR assays are currently recognized as the most sensitive methods for Plasmodium identification, this study was conducted to weigh the asymptomatic carriage in DRC by a molecular method. Six provinces were randomly selected for blood collection in which 80 to 100 individuals were included in the study. Five hundred and eighty blood sampleswere collected andmolecular diagnosiswas performed. Globally, almost half of the samples collected from asymptomatic individuals (280/580; 48.2%) had Plasmodium infections and the most species identified was P. falciparum alone in combination with P. malariae. The high prevalence reported here should interpellate the bodies involved in malaria control in DR Congo to take into account asymptomatic carriers in actions taken and consider asymptomatic malaria as a major hurdle for malaria elimination.
    Full-text · Article · Jan 2016 · Journal of Malaria Research
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    • "As shown in Fig. 4, infected naïve samples showed Pvs25 expression earlier than those from semi-immune individuals who had experienced multiple previous malaria episodes and were known to have specific anti-Plasmodium vivax antibodies before experimental infection[14]. A better understanding of the role asymptomatic infections play in transmission is essential for implementation of improved malaria elimination programmes[24,303132. Currently, the fact that asymptomatic carriers with low parasitaemias are not detected with the operative diagnosis methods (thick smears and RDTs) represents a great hurdle for malaria elimination. "
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    ABSTRACT: Background The use of molecular techniques has put in the spotlight the existence of a large mass of malaria sub-microscopic infections among apparently healthy populations. These sub-microscopic infections are considered an important pool for maintained malaria transmission. Methods In order to assess the appearance of Plasmodium vivax gametocytes in circulation, gametocyte density and the parasite infectivity to Anopheles mosquitoes, a study was designed to compare three groups of volunteers either experimentally infected with P. vivax sporozoites (early infections; n = 16) or naturally infected patients (acute malaria, n = 16 and asymptomatic, n = 14). In order to determine gametocyte stage, a quantitative reverse transcriptase PCR (RT-qPCR) assay targeting two sexual stage-specific molecular markers was used. Parasite infectivity was assessed by membrane feeding assays (MFA). Results In early infections P. vivax gametocytes could be detected starting at day 7 without giving rise to infected mosquitoes during 13 days of follow-up. Asymptomatic carriers, with presumably long-lasting infections, presented the highest proportion of mature gametocytes and were as infective as acute patients. Conclusions This study shows the potential role of P. vivax asymptomatic carriers in malaria transmission should be considered when new policies are envisioned to redirect malaria control strategies towards targeting asymptomatic infections as a tool for malaria elimination. Electronic supplementary material The online version of this article (doi:10.1186/s12936-016-1104-1) contains supplementary material, which is available to authorized users.
    Full-text · Article · Jan 2016 · Malaria Journal
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    • "However, many factors influence the infectivity of gametocytes, and their transmission potential (Bousema and Drakeley, 2011; Stone et al. 2015). Gametocyte prevalence and density are highest in infants and young children (Shute and Maryon, 1951), decreasing with age in parallel with cumulative exposure to malaria infection and acquired immunity to the parasite's asexual stages (Doolan et al. 2009; Ouedraogo et al. 2010). Though once thought to be rare, molecular detection methods have revealed that gametocytes are produced by the majority of infected individuals of all ages (Schneider et al. 2006; Shekalaghe et al. 2007; Bousema et al. 2010a; Bousema and Drakeley, 2011; Joice et al. 2013; Bousema et al. 2014) and that onward malaria transmission is not restricted to microscopically detectable gametocyte densities (Schneider et al. 2007; Ouedraogo et al. 2009; Beshir et al. 2013; Gaye et al. 2015). "
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    ABSTRACT: Gametocytes are the specialized form of Plasmodium parasites that are responsible for human-to-mosquito transmission of malaria. Transmission of gametocytes is highly effective, but represents a biomass bottleneck for the parasite that has stimulated interest in strategies targeting the transmission stages separately from those responsible for clinical disease. Studying targets of naturally acquired immunity against transmission-stage parasites may reveal opportunities for novel transmission reducing interventions, particularly the development of a transmission blocking vaccine (TBV). In this review, we summarize the current knowledge on immunity against the transmission stages of Plasmodium . This includes immune responses against epitopes on the gametocyte-infected erythrocyte surface during gametocyte development, as well as epitopes present upon gametocyte activation in the mosquito midgut. We present an analysis of historical data on transmission reducing immunity (TRI), as analysed in mosquito feeding assays, and its correlation with natural recognition of sexual stage specific proteins Pfs48/45 and Pfs230. Although high antibody titres towards either one of these proteins is associated with TRI, the presence of additional, novel targets is anticipated. In conclusion, the identification of novel gametocyte-specific targets of naturally acquired immunity against different gametocyte stages could aid in the development of potential TBV targets and ultimately an effective transmission blocking approach.
    Full-text · Article · Jan 2016 · Parasitology
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