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

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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-017-1815-y) contains supplementary material, which is available to authorized users.

Evidence of interaction between humoral immunity and drug half-life in determining treatment outcome for artemisinin combination therapy in high transmission settings in western Kenya

“…Overall, signal intensities of younger participants were lower than those of older participants. Normalizing the mean signal intensities to P falciparum proteins from participants at varying ages against the mean intensities for the oldest subject group revealed that the magnitude of antibody responses to these antigens increased with age ( These findings suggest that antibody responses associated with nPC-ACPR are acquired over time through repeated exposures as children age into adults, thus corroborating previous studies (4,18,19).…”

Effects of lemon decoction on malaria parasite clearance and selected hematological parameters in Plasmodium berghei ANKA infected mice

“…The immune-modulating potential of the decoction was performed by comparing hematological results of the standard treated mice with the control. It has been reported in studies that for an effective cure of malaria, the immunity of a person is an important factor [7]. Assessment of total white blood cell counts has shown elevated levels to a group that used a combination (A/LU + CILI extract).…”

“…The treatment failure due to artemisinin-based combination therapies (ACTs) has been attributed to its uneven pharmacokinetics among individuals and its requirement to be taken with a fatty meal to improve absorption [5,6]. Moreover, the dosage, the compliance and the immune status of the patient are all implicated [7]. Failure may also happen in immune-compromised patients as they are likely to be taking other medications like efavirenz.…”

Practical example of multiple antibody screening for evaluation of malaria control strategies

“…Such immunity is related to the degree of adherence to control measures, and analysis of antibody responses to validated antigens could be an indirect way of tracking compliance to measures such as LLINs which is the largest contributor to sustained protection [2]. Importantly, immunity affects treatment outcome with a significant impact when using the current first-line artemisinin combined treatments [38]. Monitoring of parasite clearance times in symptomatic malaria, which is routinely done in Côte d'Ivoire, is [6].…”