Asymptomatic Multiclonal<i>Plasmodium falciparum</i>Infections Carried Through the Dry Season Predict Protection Against Subsequent Clinical Malaria

Sondén, Klara; Doumbo, Safiatou; Hammar, Ulf; Homann, Manijeh Vafa; Ongoïba, Aïssata; Traoré, Boubacar; Bottai, Matteo; Crompton, Peter D.; Färnert, Anna

doi:10.1093/infdis/jiv088

Cited by 52 publications

(57 citation statements)

References 37 publications

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“…Consistent with prior studies [18][19][20][21][22], asymptomatic P. falciparum infection at the end of the dry season was associated with lower risk of febrile malaria during the ensuing malaria season (p<0.0001; Figure 1C), an association that remained significant after adjusting for age, gender and hemoglobin (Hb) type (P<0.0001; Figure 1D). The risk of febrile malaria was not significantly different between PCR + smear + subjects and PCR + smear -subjects (p=0.51; Figure 1C), indicating that the difference in baseline parasitemia between these groups did not affect subsequent malaria risk.…”

Section: Asymptomatic P Falciparum Infection During the Dry Season Isupporting

confidence: 88%

“…We sought to confirm prior studies that associated asymptomatic P. falciparum infection with lower risk of clinical malaria [18,19,21,22]. During a two-week period in May 2011 we enrolled 695 asymptomatic subjects just prior to the 6-month malaria season ( Figure 1A).…”

Section: Asymptomatic P Falciparum Infection During the Dry Season Imentioning

confidence: 88%

“…Consistent with this hypothesis, studies in areas of seasonal malaria have shown that asymptomatic P. falciparum infection at the end of the dry season predicts decreased risk of febrile malaria during the ensuing malaria season [18][19][20][21][22]. This raises the question of whether treatment of asymptomatic infections during the dry season might increase the risk of symptomatic malaria in the event of P. falciparum reinfection.…”

Section: Introductionmentioning

confidence: 98%

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Treatment of Chronic Asymptomatic Plasmodium falciparum Infection Does Not Increase the Risk of Clinical Malaria Upon Reinfection

Portugal

Tran

Ongoïba

et al. 2016

Clinical Infectious Diseases

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Section: Asymptomatic P Falciparum Infection During the Dry Season Isupporting

confidence: 88%

Section: Asymptomatic P Falciparum Infection During the Dry Season Imentioning

confidence: 88%

Section: Introductionmentioning

confidence: 98%

See 1 more Smart Citation

Treatment of Chronic Asymptomatic Plasmodium falciparum Infection Does Not Increase the Risk of Clinical Malaria Upon Reinfection

Portugal

Tran

Ongoïba

et al. 2016

Clinical Infectious Diseases

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“…However, such an interpretation contradicts epidemiological evidence from areas of seasonal transmission where asymptomatic infections persisting during the dry season mostly comprise wild-type parasites [3]. Another study found that the proportion of mixed-genotype infections and the number of genotypes per person was higher among asymptomatic than symptomatic infections and that this diversity of infecting strains might enhance protection against clinical malaria [30]. Additional evidence has further suggested that multiplicity of genotypes could also favor the parasite by extending the duration of infections through the selection of genotypes that ensure parasite survival and transmissibility [31].…”

Section: Multiplicity Of Infection and Drug Resistancementioning

confidence: 95%

Malaria Parasites in the Asymptomatic: Looking for the Hay in the Haystack

Galatas

Bassat

Mayor

2016

Trends in Parasitology

120

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With malaria elimination back on the international agenda, programs face the challenge of targeting all Plasmodium infections, not only symptomatic cases. As asymptomatic individuals are unlikely to seek treatment, they are missed by passive surveillance while remaining infectious to mosquitoes, thus acting as silent reservoirs of transmission. To estimate the risk of asymptomatic infections in various phases of malaria elimination, we need a deeper understanding of the underlying mechanisms favoring carriage over disease, which may involve both pathogen and host factors. Here we review our current knowledge on the determinants leading to Plasmodium falciparum symptomless infections. Understanding the host-pathogen interactions that are most likely to affect transitions between malaria disease states could guide the development of tools to tackle asymptomatic carriers in elimination settings. Being AsymptomaticPeaceful coexistence with the infected host, rarely causing clinical symptoms, is a common but poorly understood phenomenon that occurs for many human pathogens [1]. Because such asymptomatic cases of infection occur without eventual overt symptoms, they do not come to clinical attention, thus representing a large hidden reservoir of active infection that permits their persistence and eventual spread to other human hosts. This is the case for many malaria infections in semi-immune individuals from endemic areas, which commonly cause a mild febrile illness or no apparent symptoms at all, while keeping parasite numbers at low densities [2] (Box 1).Carriage of asymptomatic malaria (see Glossary) infections, being at the same time difficult to detect and to manage, has considerable implications for the design and use of malaria elimination strategies. Symptomless infections that persist during the dry season in areas of seasonal transmission have been suggested to seed the malaria outbreaks after annual rains when mosquitoes reappear [3]. Similarly, asymptomatic parasitemia may potentially contribute to persistence of transmission in low-transmission settings [4]. However, the precise contribution of asymptomatic malaria to transmission in areas that have achieved substantial reductions in the malaria burden remains a matter of debate [5], as is the assumption that detecting and targeting these individuals for radical treatment, as opposed to using mass drug administration approaches, would be an efficient and effective tactic. Moreover, eradication in Europe, North America, and other parts of the world using no better diagnostics than microscopy [6] suggest that key determinants of success might not be finding the last parasite. From a practical point of view, the proportion of asymptomatic infections in certain situations and phases of malaria elimination may impose the need for modifications of detection methods (active versus passive case detection) [7] if, for example, symptom-based surveillance at health facilities is insufficient and mass blood surveys are necessary to inform the design of elimination i...

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“…Asymptomatic carriage of parasites has been shown to be associated with reduced risk of symptomatic malaria [26, 27]. Much of the evidence seem to support the idea that the outcome of a malaria infection is associated with carriage of unique/variant parasite alleles.…”

Section: Introductionmentioning

confidence: 99%

Dynamics in multiplicity of Plasmodium falciparum infection among children with asymptomatic malaria in central Ghana

et al. 2017

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BackgroundThe determinants of malaria parasite virulence is not entirely known, but the outcome of malaria infection (asymptomatic or symptomatic) has been associated with carriage of distinct parasite genotypes. Alleles considered important for erythrocyte invasion and selected as candidate targets for malaria vaccine development are increasingly being shown to have distinct characteristics in infection outcomes. Any unique/distinct patterns or alleles linked to infection outcome should be reproducible for a given malaria-cohort regardless of location, time or intervention. This study compared merozoite surface protein 2 (MSP2) genotypes from children with asymptomatic malaria at same geographical location, from two time periods.ResultsAs the prevalence and incidence of malaria (measured for other studies) significantly reduced between 2004 (time point one) and 2009 (time point two), MSP2 multiplicity of infections (MOI) also reduced significantly from 2.3 at time point (TP) one to 1.9 at TP two. IC/3D7 genotypes out-numbered FC27 genotypes at both time points. At TP2 however, FC27 allele diversity was more than the IC/3D7 allele diversity. A decrease in the IC/3D7:FC27 genotype proportions from 2:1 at TP1 to 1:1 at TP2, seemed to be driven mainly by a decrease in carriage of IC/3D7 alleles. MOI was higher in the dry season than in the subsequent wet season, but the decrease was not significant at TP2.ConclusionMSP2 MOI was higher in the dry season than in the subsequent wet season, while the carriage of IC/3D7 alleles decreased over this time period. It may be that decreases in transmission are related specifically to the IC/3D7 allelic family. The influence of transmission on MSP2 allele diversity needs to be clearly deciphered in studies which should include the use of sensitive methods for the detection of polymorphic parasite markers for both symptomatic and asymptomatic malaria. Such studies will enable better understanding of associations between allelic variants, MOI, transmission, malaria infection and disease.

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Asymptomatic MulticlonalPlasmodium falciparumInfections Carried Through the Dry Season Predict Protection Against Subsequent Clinical Malaria

Abstract: The results suggest that persistent multiclonal infections carried through the dry season contribute to protection against subsequent febrile malaria, possibly by maintaining protective immune responses that depend on ongoing parasite infection.

Cited by 52 publications

References 37 publications

Treatment of Chronic Asymptomatic Plasmodium falciparum Infection Does Not Increase the Risk of Clinical Malaria Upon Reinfection

Treatment of Chronic Asymptomatic Plasmodium falciparum Infection Does Not Increase the Risk of Clinical Malaria Upon Reinfection

Malaria Parasites in the Asymptomatic: Looking for the Hay in the Haystack

Dynamics in multiplicity of Plasmodium falciparum infection among children with asymptomatic malaria in central Ghana

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