Article

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: 16). 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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    • "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; DOI:10.1007/s00436-015-4570-4 · 2.33 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 · 3.49 Impact Factor
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    • "A T helper 1 (Th1) response predominantly characterizes human malaria infection and the production of proinflammatory cytokines such as interferon gamma (IFN-í µí»¾), IL-6, tumor necrosis factor (TNF-í µí»¼), and other inflammatory cytokines [20] [21]. These inflammatory cytokines are considered critical for the resolution of parasitemia and control of malaria infection, especially during the early stages of P. falciparum infection [22] [23]. Conversely, if these robust inflammatory responses are not regulated during chronic malaria infection, they can lead to immunopathology and severe forms of the disease response [24] [25] [26]. "
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    ABSTRACT: In Brazil, malaria is prevalent in the Amazon region and these regions coincide with high prevalence of intestinal parasites but few studies explore the interaction between malaria and other parasites. Therefore, the present study evaluates changes in cytokine, chemokine, C-reactive protein, and nitric oxide (NO) concentrations in 264 individuals, comparing plasma from infected individuals with concurrent malaria and intestinal parasites to individuals with either malaria infection alone and uninfected. In the studied population 24% of the individuals were infected with Plasmodium and 18% coinfected with intestinal parasites. Protozoan parasites comprised the bulk of the intestinal parasites infections and subjects infected with intestinal parasites were more likely to have malaria. The use of principal component analysis and cluster analysis associated increased levels of IL-6, TNF-α, IL-10, and CRP and low levels of IL-17A predominantly with individuals with malaria alone and coinfected individuals. In contrast, low levels of almost all inflammatory mediators were associated predominantly with individuals uninfected while increased levels of IL-17A were associated predominantly with individuals with intestinal parasites only. In conclusion, our data suggest that, in our population, the infection with intestinal parasites (mainly protozoan) does not modify the pattern of cytokine production in individuals infected with P. falciparum and P. vivax.
    Mediators of Inflammation 09/2014; 2014. DOI:10.1155/2014/857245 · 3.24 Impact Factor
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