Immunity as a predictor of anti-malarial treatment failure: a systematic review

Katherine O’Flaherty,Julie A Simpson,Julia Maguire,Freya J I Fowkes

doi:10.1186/s12936-017-1815-y

Katherine O’Flaherty, Julie A Simpson + Show 2 more

Open Access

https://doi.org/10.1186/s12936-017-1815-y

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Abstract

BackgroundNaturally acquired immunity can reduce parasitaemia and potentially influence anti-malarial treatment outcomes; however, evidence for this in the current literature provides conflicted results. The available evidence was synthesized to determine and quantify the association between host immunity and anti-malarial treatment failure.MethodsFour databases were searched to identify studies investigating malaria antibody levels in patients receiving anti-malarial treatment for symptomatic malaria with treatment failure recorded according to the World Health Organization classification. Odds ratios or hazard ratios were extracted or calculated to quantify the association between malarial antibody levels and treatment failure, and findings from different studies were visualized using forest plots.ResultsEight studies, including patients with falciparum malaria treated with mono- and combination therapy of artemisinin derivatives, sulfadoxine, pyrimethamine and chloroquine, were identified. Reported and calculated effect estimates varied greatly between studies, even those assessing the same antigens and treatments. An association between blood-stage IgG responses and treatment efficacy was observed. The greatest magnitudes of effect were observed for artemisinin [OR/HR (95% CI) range 0.02 (0.00, 0.45)–1.08 (0.57, 2.06)] and chloroquine [0.24 (0.04, 1.37)–0.32 (0.05, 1.96)] treatments, and larger magnitudes of effect were observed for variant surface antigen responses [0.02 (0.00, 0.45)–1.92 (0.94, 3.91)] when compared with merozoite specific responses [0.24 (0.04, 1.37)–2.83 (1.13, 7.09)].ConclusionsNaturally acquired malarial immunity is associated with reduced anti-malarial treatment failure in malaria endemic populations. Anti-malarial IgG effects treatment outcome differently for different anti-malarial drugs and antigen targets, and had the greatest impact during treatment with the current first-line treatments, the artemisinins. This has implications for the assessment of the therapeutic efficacy of anti-malarials, particularly in the context of emerging artemisinin resistance.

Highlights

Acquired immunity can reduce parasitaemia and potentially influence anti-malarial treatment outcomes; evidence for this in the current literature provides conflicted results
Anti-malarial treatment outcome is determined, according to World Health Organization (WHO) criteria, as either adequate clinical and parasitological response (ACPR) or treatment failure, which can be further categorized as early treatment failure (ETF), late clinical failure (LCF), or late parasitological failure (LPF) [7, 8]
Two authors independently assessed each article against inclusion and quality criteria and extracted descriptive information, with discrepancies resolved by discussion with all authors

Summary

Introduction

Acquired immunity can reduce parasitaemia and potentially influence anti-malarial treatment outcomes; evidence for this in the current literature provides conflicted results. The available evidence was synthesized to determine and quantify the association between host immunity and anti-malarial treatment failure. The World Health Organization (WHO) currently recommends artemisinin-based combination therapy (ACT) as the first-line treatment for all falciparum malaria [2]. Anti-malarial treatment outcome is determined, according to WHO criteria, as either adequate clinical and parasitological response (ACPR) or treatment failure, which can be further categorized as early treatment failure (ETF), late clinical failure (LCF), or late parasitological failure (LPF) [7, 8]. The predominant cause of treatment failure is resistance to the active drug, or in the. O’Flaherty et al Malar J (2017) 16:158 case of combination therapy, resistance to one or more of the active components. Patients vary greatly in their drug concentration versus time profiles, the parasite burden and age distribution of the parasites at initial treatment, and the level of withinhost immunity to malaria [9]

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