Immunoglobulin G Antibodies to Merozoite Surface Antigens Are Associated with Recovery from Chloroquine-Resistant<i>Plasmodium falciparum</i>in Gambian Children

Pinder, Margaret; Sutherland, Colin J.; Sisay-Joof, Fatoumatta; Ismaïli, Jamila; McCall, Matthew; Ord, Rosalyn; Hallett, Rachel; Holder, Anthony A.; Milligan, Paul

doi:10.1128/iai.74.5.2887-2893.2006

Cited by 14 publications

(22 citation statements)

References 38 publications

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“…This finding is in contrast to previous studies that found anti-MSP-1 19 levels at the time of treatment to be protective against treatment failure [32], [33]. While our finding may represent a spurious result, given the marginal significance when taking into account multiple testing, there are some biologically plausible mechanisms for this seemingly paradoxical association.…”

Section: Discussioncontrasting

confidence: 99%

“…These studies have found associations between positive or high IgG responses to a number of antigens (NANP repeat of CSP [39], K1 and MAD20 block 2 variants of MSP-1 [34], MSP-1 19 [32], [33], and GLURP-R0 and R2 [36]) and protection from treatment failure. Three of these studies included assessment of AMA-1 antibodies in their analyses, but these did not show strong associations between anti-AMA-1 levels and clearance of parasitemia [33], [36], [37]. Differences between our results and prior studies may be attributable to the antimalarial therapy used, due to varying efficacy and pharmacokinetics; differences in the epidemiological setting and patient characteristics; different means of assessing treatment outcome; and the use of different laboratory and analytical methods.…”

Section: Discussionmentioning

confidence: 99%

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Associations between Antibodies to a Panel of Plasmodium falciparum Specific Antigens and Response to Sub-Optimal Antimalarial Therapy in Kampala, Uganda

Keh

Jha²,

Nzarubara

et al. 2012

PLoS ONE

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BackgroundAntibodies are important in the control of blood stage Plasmodium falciparum infection. It is unclear which antibody responses are responsible for, or even associated with protection, partly due to confounding by heterogeneous exposure. Assessment of response to partially effective antimalarial therapy, which requires the host to assist in clearing parasites, offers an opportunity to measure protection independent of exposure.MethodsA cohort of children aged 1–10 years in Kampala, Uganda were treated with amodiaquine+sulfadoxine-pyrimethamine for uncomplicated malaria. Serum samples from the time of malaria diagnosis and 14 days later were analyzed for total IgG to 8 P. falciparum antigens using a quantitative indirect ELISA. Associations between antibody levels and risk of treatment failure were estimated using Cox proportional hazard regression.ResultsHigher levels of antibodies to apical membrane antigen 1 (AMA-1), but to none of the other 7 antigens were significantly associated with protection against treatment failure (HR 0.57 per 10-fold increase in antibody level, CI 0.41–0.79, p = 0.001). Protection increased consistently across the entire range of antibody levels.ConclusionsMeasurement of antibody levels to AMA-1 at the time of malaria may offer a quantitative biomarker of blood stage immunity to P. falciparum, a tool which is currently lacking.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Associations between Antibodies to a Panel of Plasmodium falciparum Specific Antigens and Response to Sub-Optimal Antimalarial Therapy in Kampala, Uganda

Keh

Jha²,

Nzarubara

et al. 2012

PLoS ONE

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“…Low-level exposure related to subtherapeutic drug concentrations of antimalarials due to moderate resistance also has been shown to have important effects on immune responses (25). Higher titers of IgG responses to MSP-1 19 enhanced the likelihood of parasitological clearance in individuals treated with a suboptimal drug regimen, and it was suggested that recovery from uncomplicated malaria in patients carrying drug-resistant P. falciparum is a phenotypic marker of acquired functional immunity (12,13,31).…”

Section: Discussionmentioning

confidence: 99%

Impact of Intermittent Preventive Treatment with Sulfadoxine-Pyrimethamine on Antibody Responses to Erythrocytic-StagePlasmodium falciparumAntigens in Infants in Mozambique

Quelhas

Puyol

Quintó

et al. 2008

Clin Vaccine Immunol

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We evaluated the impact of intermittent preventive treatment in infants (IPTi) with sulfadoxine-pyrimethamine (SP), which was given at ages 3, 4, and 9 months through the Expanded Program on Immunization (EPI), on the development of antibody responses to Plasmodium falciparum in Mozambique. Immunoglobulin M (IgM) and IgG subclass antibodies specific to whole asexual parasites and to recombinant MSP-1 19 , AMA-1, and EBA-175 were measured at ages 5, 9, 12, and 24 months for 302 children by immunofluorescence antibody tests and by enzyme-linked immunosorbent assays. Antibody responses did not significantly differ between children receiving IPTi with SP and those receiving a placebo at any time point measured, with the exception of the responses of IgG and IgG1 to AMA-1 and/or MSP-1 19 , which were significantly higher in the SP-treated group than in the placebo group at ages 5, 9, and/or 24 months. IPTi with SP given through the EPI reduces the frequency of malarial illness while allowing the development of naturally acquired antibody responses to P. falciparum antigens.Malaria remains one of the major infectious diseases globally, causing up to 3 million deaths and close to 5 billion episodes of clinical illness per year (7). In areas characterized by hyperendemic transmission, the greatest burden of malaria occurs in children less than 12 months of age (38); consequently, infants in sub-Saharan Africa are the main target population for any malaria control tool.Intermittent preventive treatment in infants (IPTi) that consists of the administration of a full dose of an antimalarial within the Expanded Program on Immunization (EPI) has proven to reduce the risk of malaria in this vulnerable group (37). This strategy has gained increasing interest, and several intervention trials evaluating the efficacy of IPTi in the reduction of malaria morbidity have been and are still being carried out in several sub-Saharan countries (Tanzania, Ghana, Senegal, Mozambique, Gabon, and Kenya) as part of an international consortium (www.ipti-malaria.org). However, before setting any policy recommendation for the large-scale implementation of IPTi for malaria control, it is necessary to fully evaluate the consequences that this early preventive intervention may have later in life.An important issue that needs to be considered is the impact that IPTi may have on the development of naturally acquired immunity to malaria. Early studies of continuous malaria chemoprophylaxis raised concerns regarding the loss of or delay in the acquisition of protective immunity (16,23,34). Weekly chemoprophylaxis between 2 and 11 months of age in infants in Tanzania significantly reduced the incidence of malaria and anemia during the first year of life, but the risk increased in the second year after stopping the intervention (26), suggesting that protection against Plasmodium falciparum infection during infancy had delayed the development of immunity to malaria. However, subsequent studies of IPTi in Tanzania (37) and Mozambique (24) showed that, as ...

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“…However, this relationship is not seen to hold, as people in higher transmission areas have more acquired immunity, and this appears to be a more important determinant of treatment success for a population than the prevalence of drug resistance alleles (80). Within local populations, individual treatment success with chloroquine is strongly age dependent in a manner that appears to clearly reflect acquired immunity (55) and correlates with acquired antibodies to merozoite antigens (148). There are effective antimalarial drugs that have not yet been widely used in populations in areas of endemicity, generally because they are too expensive.…”

Section: Surveillance and Preventionmentioning

confidence: 99%

Molecular Epidemiology of Malaria

Conway

2007

Clin Microbiol Rev

103

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SUMMARY Malaria persists as an undiminished global problem, but the resources available to address it have increased. Many tools for understanding its biology and epidemiology are well developed, with a particular richness of comparative genome sequences. Targeted genetic manipulation is now effectively combined with in vitro culture assays on the most important human parasite, Plasmodium falciparum, and with in vivo analysis of rodent and monkey malaria parasites in their laboratory hosts. Studies of the epidemiology, prevention, and treatment of human malaria have already been influenced by the availability of molecular methods, and analyses of parasite polymorphisms have long had useful and highly informative applications. However, the molecular epidemiology of malaria is currently undergoing its most substantial revolution as a result of the genomic information and technologies that are available in well-resourced centers. It is a challenge for research agendas to face the real needs presented by a disease that largely exists in extremely resource-poor settings, but it is one that there appears to be an increased willingness to undertake. To this end, developments in the molecular epidemiology of malaria are reviewed here, emphasizing aspects that may be current and future priorities.

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Immunoglobulin G Antibodies to Merozoite Surface Antigens Are Associated with Recovery from Chloroquine-ResistantPlasmodium falciparumin Gambian Children

Cited by 14 publications

References 38 publications

Associations between Antibodies to a Panel of Plasmodium falciparum Specific Antigens and Response to Sub-Optimal Antimalarial Therapy in Kampala, Uganda

Associations between Antibodies to a Panel of Plasmodium falciparum Specific Antigens and Response to Sub-Optimal Antimalarial Therapy in Kampala, Uganda

Impact of Intermittent Preventive Treatment with Sulfadoxine-Pyrimethamine on Antibody Responses to Erythrocytic-StagePlasmodium falciparumAntigens in Infants in Mozambique

Molecular Epidemiology of Malaria

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