Plasmodium falciparum diagnostic tools in HIV-positive under-5-year-olds in two ART clinics in Ghana: are there missed infections?

Ewurama D A Owusu,Samson K Djonor,Petra F Mens,Martin P Grobusch,Charles A Brown

doi:10.1186/s12936-018-2231-7

Abstract

BackgroundPlasmodium falciparum, the most dominant species in sub-Saharan Africa, causes the most severe clinical malaria manifestations. In resource-limited Ghana, where malaria and HIV geographically overlap, histidine-rich protein 2 (HRP2)-based rapid diagnostic test (RDT) is a faster, easier and cheaper alternative to clinical gold standard light microscopy. However, mutations in parasite hrp2 gene may result in missed infections, which have severe implications for malaria control.MethodsThe performance of a common HRP2-based RDT and expert light microscopy in HIV-positive and HIV-negative children under 5 years old was compared with PCR as laboratory gold standard. Finger-prick capillary blood was tested with First Response® Malaria Ag P. falciparum (HRP2). Giemsa-stained thick and thin blood films were examined with ≥ 200 high power fields and parasites counted per 200 white blood cells. Nested PCR species identification of P. falciparum was performed and resolved on agarose gel. False negatives from RDT were further tested for deleted pfhrp2/3 and flanking genes, using PCR. The study was performed in two anti-retroviral therapy clinics in Accra and Atibie.ResultsOut of 401 participants enrolled, 150 were HIV positive and 251 HIV negative. Malaria was more prevalent in children without HIV. Microscopy had a higher sensitivity [100% (99–100)] than RDT [83% (53.5–100)]. Parasites with pfhrp2/3 deletions contributed to missed infections from RDT false negatives.ConclusionCirculation of malaria parasites with pfrhp2/3 deletions in this population played a role in missed infections with RDT. This ought to be addressed if further strides in malaria control are to be made.

Highlights

Plasmodium falciparum, the most dominant species in sub-Saharan Africa, causes the most severe clinical malaria manifestations
Improved rapid diagnostic tests (RDT), which are faster, cheaper and easier compared to the gold standard expert microscopy, are complementing malaria control efforts in resource-limited sub-Saharan African countries such as Ghana [8]
When RDT was used to test for malaria among both groups, 5/150 (3.3%) of HIV positive patients had malaria whilst 44/251 (17.5%) of those without HIV had malaria

Summary

Introduction

Plasmodium falciparum, the most dominant species in sub-Saharan Africa, causes the most severe clinical malaria manifestations. In resource-limited Ghana, where malaria and HIV geographically overlap, histidine-rich protein 2 (HRP2)-based rapid diagnostic test (RDT) is a faster, easier and cheaper alternative to clinical gold standard light microscopy. Out of the 9248 AIDS deaths reported in Ghana in 2014, 1295 (14%) were children; and 31.6% of the children who died from AIDS were under 5 years old This age group is considered a malaria-vulnerable group [6]. Improved rapid diagnostic tests (RDT), which are faster, cheaper and easier compared to the gold standard expert microscopy, are complementing malaria control efforts in resource-limited sub-Saharan African countries such as Ghana [8]. Recent reports have shown that hrp-2 deletions in parasite genes (pfhrp2), which previously prevailed only in the South Americas, have been detected in African countries like Ghana, Democratic Republic of Congo, Eritrea, Uganda and Rwanda, regardless of level of transmission [8]. The lack of pfhrp expression can prevent the detection of parasites by HRP2-based RDTs and give false negative results [8]

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