Contrasting Asymptomatic and Drug Resistance Gene Prevalence of Plasmodium falciparum in Ghana: Implications on Seasonal Malaria Chemoprevention

Abstract

Malaria is a significant public health problem in Ghana. Seasonal Malaria Chemoprevention (SMC) using a combination of sulfadoxine-pyrimethamine and amodiaquine has been implemented since 2015 in northern Ghana where malaria transmission is intense and seasonal. In this study, we estimated the prevalence of asymptomatic P. falciparum carriers in three ecological zones of Ghana, and compared the sensitivity and specificity of different molecular methods in identifying asymptomatic infections. Moreover, we examined the frequency of mutations in pfcrt, pfmdr1, pfdhfr, and pfdhps that relate to the ongoing SMC. A total of 535 asymptomatic schoolchildren were screened by microscopy and PCR (18s rRNA and TARE-2) methods. Among all samples, 28.6% were detected as positive by 18S nested PCR, whereas 19.6% were detected by microscopy. A high PCR-based asymptomatic prevalence was observed in the north (51%) compared to in the central (27.8%) and south (16.9%). The prevalence of pfdhfr-N51I/C59R/S108N/pfdhps-A437G quadruple mutant associated with sulfadoxine-pyrimethamine resistance was significantly higher in the north where SMC was implemented. Compared to 18S rRNA, TARE-2 serves as a more sensitive molecular marker for detecting submicroscopic asymptomatic infections in high and low transmission settings. These findings establish a baseline for monitoring P. falciparum prevalence and resistance in response to SMC over time.

Diagnostic performance of an ultrasensitive HRP2-based malaria rapid diagnostic test kit used in surveys of afebrile people living in Southern Ghana

“…The lower specificity of the UsmRDT could be attributed to the ability of the UsmRDT to detect lower concentration of the HRP2 antigens which persists for extended periods after parasites have been cleared from the blood [ 20 , 21 ]. The persistence of HRP2 antigen levels in people living in malaria endemic countries, including Ghana is likely due to a frequent and constant exposure to malaria parasites [ 43 ], which results in a buildup of HRP2 antigen concentrations that persists over long periods of time [ 44 ]. Although the HRP2 antigen has been found to persist for extended periods, the antigen is also known to degrade over time such that HRP2 concentrations maybe present at concentrations that are below the detection limit of standard malaria RDTs but detectable by the UsmRDT.…”

Characterization of putative drug resistant biomarkers in Plasmodium falciparum isolated from Ghanaian blood donors

“…Importantly, K76T mutation has been implicated in chloroquine resistance [ 29 , 30 ]. In Ghana, incidence of K76T has been reported in several studies [ 22 , 31 , 32 ], however, K76T mutation may not complicate TTM, since chloroquine is no longer the drug of choice for the treatment of malaria. In Ghana, the drug of choice for management of uncomplicated malaria is artemisinin-based combination therapy (ACT).…”

“…In previous studies in Ghana, high frequencies of mutation in Pfcrt, Pfmdr1, Pfdhfr and Pfdhps were identified in P. falciparum infected children aged 4-15 years [22,23]. However, such study is yet to done in Ghanaian adults and for that matter, blood donors.…”

Progress in Parasite Genomics and Its Application to Current Challenges in Malaria Control

“…The 18 s rRNA gene has a reported detection thresholds of 0.5-5 parasites μl [35], but parasite density of asymptomatic infections especially in low transmission settings could be well below this threshold. As a result, many of these infections remain undetected in the general populations of several malaria-endemic countries [10,36,37] and provide perfect reservoirs for transmission at any time. Therefore, it is crucial to identify new gene targets or novel tools that are convenient and affordable for detecting asymptomatic infections, particularly in countries approaching elimination phase.…”

“…TARE-2 has been previously shown to be useful for detecting ultra-low density P. falciparum infections in Papua New Guinea and Tanzania [62]. A recent study in Ghana showed a slightly higher sensitivity of TARE-2 compared to 18 s rRNA (81.2% vs. 80.9%) using microscopy as a gold standard, but with a lower specificity reduced by almost two-fold [37], making this gene less desirable for active case surveillance.…”