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

ABSTRACT 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, Sep 29, 2015
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    • "Despite an urgent need for an effective vaccine against malaria, progress on vaccine development has been slow and disappointing (Salvador et al. 2012). Though naturally acquired immunity against Plasmodium falciparum can be gradually attained after years of multiple repeated infectious episodes in adults, it has been seen that it neither persists over long periods of time nor is seen in pregnant women or young children meaning that it is incomplete, nonsterilizing, and short-lived (Doolan et al. 2009) which underlines that the major obstacle for vaccine development is an incomplete understanding of the host immune response crucial for eradication of the malaria parasites. "
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    ABSTRACT: Cytokines and immune effector cells play an important role in determining the outcome of infection with various intracellular pathogens, including protozoan parasites. However, their role during lethal and nonlethal malaria needs further validation. In the present study, we examined the role of cytokines and various immune effector cells during lethal and nonlethal malaria caused by Plasmodium vinckei in AKR mice. We show that lethal P. vinckei infection (PvAS) in AKR mice is characterized by increased parasite growth, decreased production of pro-inflammatory cytokines, and attenuated cell proliferation and nitric oxide (NO) synthesis resulting in increased parasitemia which ultimately leads to death of all animals by day 5 post infection. In contrast, AKR mice infected with lethal parasite (PvAR) showed elevated levels of pro-inflammatory cytokines, heightened cell proliferation, and NO synthesis leading to complete parasite clearance by day 22 post infection. Flow cytometric analysis performed on splenocytes from PvAS- and PvAR-infected mice shows that host immunity is severely compromised in PvAS-infected mice as was evident by decreased percentages of CD4(+) and CD8(+) T cells, B cells, plasma cells, dendritic cells (DCs), and macrophages (MΦs) which was in complete contrast to PvAR-infected animals which exhibited elevated numbers of all the cell types analyzed. Taken together, findings of the present study show that coordinated actions of pro-inflammatory cytokines and other immune effector cells are essential to control lethal malarial infection and their attenuation leads to increased parasite growth and, ultimately, death of animals.
    Parasitology Research 06/2015; 114(9). DOI:10.1007/s00436-015-4570-4 · 2.10 Impact Factor
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    • "The low incidence of severe malaria in older children and adults in hightransmission settings suggests that this immunity is life-long under conditions of repeated exposure. However, whether protective immunity to severe malaria is maintained in the absence of re-exposure is debated, with some suggesting that this protection wanes rapidly [2] and others that it persists [3]. Understanding the longevity of immunity against malaria is important for the development of efficacious vaccines and for predictions of populations at risk in areas of changing transmission. "
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    ABSTRACT: In malaria-endemic areas, adults very rarely succumb to severe malaria, suggesting that immunity to severe disease is life-long under conditions of repeated exposure. To what extent this protection persists in the absence of exposure remains to be established. The aim of this study was to assess whether duration of residency in a malaria-free country affects the risk for severe malaria in immigrants originating from sub-Saharan Africa. We conducted a retrospective chart review of 948 cases of malaria diagnosed in Stockholm, Sweden in 1995-2013. Among 501 adult patients with Plasmodium falciparum (315 of endemic origin and 186 of non-endemic origin, mainly Sweden), 41 (8.2%) had severe malaria according to WHO criteria (including 5% with parasitaemia), 22 (4.4%) had factors prognostic of poor outcome, and 35 (7.0%) were admitted to intensive care. Overall, patient origin did not affect the odds of severe malaria, according to any of these definitions. However, when the immigrants were stratified with regard to their duration of residency in Sweden, the risk of factors prognostic for poor outcome was associated with duration of prior residency in a malaria-free country among patients of endemic origin (p 0.02), and immigrants who had lived for ≥15 years in Sweden had a similar risk as non-immune travellers. The results of this explorative study suggest that, although immunity to severe malaria is maintained for several years in African adults, this protection might be lost with time without repeated re-exposure. A larger study, preferably including multiple centres, will be needed to confirm our findings. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
    Clinical Microbiology and Infection 12/2014; 22(5). DOI:10.1016/j.cmi.2014.12.011 · 5.77 Impact Factor
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    • "In malaria-endemic countries, this preponderance of malarial morbidity and mortality in children has been attributed to insufficient protective immunity [2]. Repeated exposure to malaria infection eventually leads to a state of semi-immunity, as a result of which older children and adults may be infected with malaria parasites, but have no or minimal symptoms [3]. However, in the context of changing epidemiology globally, recent research raises concern that the burden of malaria disease among adults may be underestimated, or may begin to increase, possibilities that have led to a renewed interest in the disease burden in this older population [4]. "
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    ABSTRACT: Background As control interventions are rolled out, the burden of malaria may shift from young children to older children and adults as acquisition of immunity is slowed and persistence of immunity is short-lived. Data for malaria disease in adults are difficult to obtain because of co-morbid conditions and because parasitaemia may be asymptomatic. Regular surveys of adult admissions to a hospital in Malawi were conducted to characterize the clinical spectrum of malaria and to establish a baseline to monitor changes that occur in future. Methods In 2011–2012, at Queen Elizabeth Hospital, Blantyre, four separated one-week surveys in the peak malaria transmission period (wet season) and three one-week surveys in the low transmission period (dry season) were conducted using rapid diagnostic tests (RDT) with confirmation of parasitaemia by microscopy. All adults (aged ≥15) being admitted to the adult medical wards regardless of the suspected diagnosis, were enrolled. Participants with a positive malaria test underwent a standardized physical examination and laboratory tests. Malaria syndromes were characterized by reviewing charts and laboratory results on discharge. Results 765 adult admissions were screened. 63 (8.2%) were RDT-positive with 61 (8.0%) positive by microscopy. Over the course of the seven study weeks, two patients were judged to have incidental parasitaemia, 31 (4.1%) had uncomplicated malaria and 28 (3.7%) had severe malaria. Both uncomplicated and severe malaria cases were more common in the rainy season than the dry season. Prostration (22/28 cases) and hyperparasitaemia (>250,000 parasites/μl) (9/28) were the most common features of severe malaria. Jaundice (4/28), severe anaemia (2/28), hyperlactataemia (2/28), shock (1/28) and haemoglobinuria (1/28) were less commonly seen, and no patient had severe metabolic derangement or organ failure. There were no deaths attributable to malaria. Conclusion In this study of adults admitted to hospital in southern Malawi, an area with year-round transmission of Plasmodium falciparum, classical metabolic and organ complications of malaria were not encountered. Prostration and hyperparasitaemia were more common indicators of severity in patients admitted with malaria, none of whom died. These data will provide a baseline for monitoring trends in the frequency and clinical patterns of severe malaria in adults.
    Malaria Journal 10/2014; 13(1):391. DOI:10.1186/1475-2875-13-391 · 3.11 Impact Factor
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