Longitudinal study assessing the return of chloroquine susceptibility of Plasmodium falciparum in isolates from travellers returning from West and Central Africa, 2000–2011

Abstract

BackgroundChloroquine (CQ) was the main malaria therapy worldwide from the 1940s until the 1990s. Following the emergence of CQ-resistant Plasmodium falciparum, most African countries discontinued the use of CQ, and now promote artemisinin-based combination therapy as the first-line treatment. This change was generally initiated during the last decade in West and Central Africa. The aim of this study is to describe the changes in CQ susceptibility in this African region, using travellers returning from this region as a sentinel system.MethodsThe study was conducted by the Malaria National Reference Centre, France. The database collated the pfcrtK76T molecular marker for CQ susceptibility and the in vitro response to CQ of parasites from travellers’ isolates returning from Senegal, Mali, Ivory Coast or Cameroon. As a proxy of drug pressure, data regarding CQ intake in febrile children were collated for the study period. Logistic regression models were used to detect trends in the proportions of CQ resistant isolates.ResultsA total of 2874 parasite isolates were genotyped between 2000–2011. The prevalence of the pfcrt76T mutant genotype significantly decreased for Senegal (from 78% to 47%), Ivory Coast (from 63% to 37%), Cameroon (from 90% to 59%) and remained stable for Mali. The geometric mean of the 50% inhibitory concentration (IC50) of CQ in vitro susceptibility and the proportion of resistant isolates (defining resistance as an IC50 value > 100 nM) significantly decreased for Senegal (from 86 nM (59%) to 39 nM (25%)), Mali (from 84 nM (50%) to 51 nM (31%)), Ivory Coast (from 75 nM (59%) to 29 nM (16%)) and Cameroon (from 181 nM (75%) to 51 nM (37%)). Both analyses (molecular and in vitro susceptibility) were performed for the 2004–2011 period, after the four countries had officially discontinued CQ and showed an accelerated decline of the resistant isolates for the four countries. Meanwhile, CQ use among children significantly deceased in this region (fixed effects slope = −0.3, p < 10-3).ConclusionsAn increase in CQ susceptibility following official withdrawal of the drug was observed in travellers returning from West and Central African countries. The same trends were observed for molecular and in vitro analysis between 2004-2011and they correlated to the decrease of the drug pressure.

A SYBR Green 1-based in vitro test of susceptibility of Ghanaian Plasmodium falciparum clinical isolates to a panel of anti-malarial drugs

“…These observations are consistent with reports from East African countries, Malawi and Kenya, indicating the return of chloroquine-sensitive isolates following a similar official withdrawal of the drug [30-32]. It also confirms an observation made in a study conducted in France using isolates collected from returning visitors from Senegal, Mali, Ivory Coast, and Cameroon [33]. The large improvement in the efficacy of chloroquine observed in the present study is important as it seems to reflect the real situation on the ground.…”

Drug sensitivity of Plasmodium falciparum field isolates to selected antimalarial drugs in Ghana using the in-vitro DAPI assay

“…Again, it is a drastic drop from the national average of resistance of 56% in 2004 [33] to the 9% we saw over the period (2015-2017). Our data supports findings from Ghana and other parts of Africa which have demonstrated the return of Chloroquinesensitive strains after the withdrawal of chloroquine as the first-line drug for the treatment of malaria [23,[34][35][36][37] with a continuous drop in the prevalence of CQ resistance markers since its withdrawal as the first-line drug for the treatment of uncomplicated malaria.…”

Characterising temporal trends in asymptomatic Plasmodium infections and transporter polymorphisms during transition from high to low transmission in Zanzibar, 2005–2013

“…High prevalence of sub-microscopic malaria has been reported in many other endemic areas (Ganguly et al, 2013;Golassa et al, 2013;Manjurano et al, 2011;Roper et al, 1996;Stresman et al, 2014). Okell et al estimated that in low-transmission settings, where PCR-determined prevalence is less than 10%, microscopy would only detect on average 12% of all PCR-detectable infections (Okell et al, 2009(Okell et al, , 2012.…”

“…Resistance-mediating polymorphisms, that are associated with substantial fitness costs, result in the selection of wild-type alleles both in vitro and in areas of diminishing drug pressure (Babiker et al, 2009;Froberg et al, 2013;Rosenthal, 2013). A typical example is the return of the chloroquine sensitive form (pfcrt K76) in areas where chloroquine use has been discontinued due to high levels of resistance (Gharbi et al, 2013;Kublin et al, 2003;Ndiaye et al, 2012;Nkhoma et al, 2007;Wurtz et al, 2012). Genetic dilution by imported parasites from the African main-land could be another contributing factor to the decline in frequency since Artemether-lumefantrine, which selects in the opposite direction of artesunate-amodiaquine (pfcrt K76, pfmdr1 N86, 184F, D1246) (Venkatesan et al, 2014), is the first-line treatment in main-land Tanzania and Kenya.…”