Antibody profiles to plasmodium merozoite surface protein-1 in Cambodian adults during an active surveillance cohort with nested treatment study.

Michele D Spring,Sathit Pichyangkul,Montida Auayapon,Sheetij Dutta,David L Saunders,Kosol Yongvanichit,Sabaithip Sriwichai,Chanthap Lon,Utaiwan Srichairatanakul,Chaiyaporn Chaisatit,Char Meng Chour,Panita Gosi,Soklyda Chann,Douglas S Walsh,Amporn Limsalakpeth,Suwanna Chaorattanakawee,Satharath Prom,Evelina Angov

doi:10.1186/s12936-015-1058-8

Abstract

BackgroundIn addition to evidence for a protective role of antibodies to the malaria blood stage antigen merozoite surface protein 1 (MSP1), MSP1 antibodies are also considered as a marker of past malaria exposure in sero-epidemiological studies.MethodsIn order to better assess the potential use of MSP1 serology in malaria chemoprophylaxis trials in endemic areas, an analysis for the prevalence of antibodies to both Plasmodium falciparum and Plasmodium vivax MSP142 in healthy Cambodian adults was conducted at two sites as part of an active, observational cohort evaluating the efficacy of dihydroartemisinin-piperaquine (DP) for uncomplicated malaria (ClinicalTrials.gov identifier NCT01280162).ResultsRates of baseline sero-positivity were high (59 and 73 % for PfMSP142 and PvMSP142, respectively), and titers higher in those who lived in a higher transmission area, although there was little correlation in titers between the two species. Those volunteers who subsequently went on to develop malaria had higher baseline MSP142 titers than those who did not for both species. Titers to both antigens remained largely stable over the course of the 4–6 month study, except in those infected with P. falciparum who had multiple recurrences.ConclusionThese findings illuminate the difficulties in using MSP142 serology as either a screening criterion and/or biomarker of exposure in chemoprophylaxis studies. Further work remains to identify useful markers of malarial infection and/or immunity.

Highlights

In addition to evidence for a protective role of antibodies to the malaria blood stage antigen merozoite surface protein 1 (MSP1), MSP1 antibodies are considered as a marker of past malaria exposure in sero-epidemiological studies
Titers and sero‐positivity to Plasmodium falciparum and Plasmodium vivax MSP142 in adults in northern Cambodia A total of 256 adults were screened for the study with serum samples obtained from all but one
All nine patients with P. falciparum or mixed P. falciparum/P. vivax malaria were seropositive for PfMSP142 with a geomean titer of 12,300 units, nearly 15× higher than those who did not have P. falciparum (822 units, unpaired t test, p < 0.0001)

Summary

Introduction

In addition to evidence for a protective role of antibodies to the malaria blood stage antigen merozoite surface protein 1 (MSP1), MSP1 antibodies are considered as a marker of past malaria exposure in sero-epidemiological studies. Non-inferiority studies between active comparator drugs is an alternative approach hampered by the logistical challenges and costs associated with very large sample sizes needed to compare products with 95 % or better efficacy This was underscored in a trial comparing weekly mefloquine with tafenoquine in Australian soldiers deployed to East Timor. While there were no cases of Plasmodium falciparum malaria in either treatment arm, true efficacy could not be determined due to lack of a surrogate endpoint for malaria exposure [6], and required an estimate based on attack rates in nearby indigenous personnel [7] Another key challenge is extrapolation of chemoprophylactic efficacy results from semi-immune populations living in endemic areas to non-immune travelers, a population who may be at great risk for more severe illness

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