The prevalence and degree of resistance ofPlasmodium falciparumto first-line antimalarial drugs: an in vitro study from a malaria endemic region in Yemen

Abstract

BACKGROUNDUnpublished studies on antimalarial drug efficacy have found low levels of chloroquine resistance in Yemen. This study was carried out to determine the current prevalence of drug resistance in Plasmodium falciparum in Yemen to the main anti-malarial drugs and to determine the effective concentration (EC) values.METHODSThe WHO standard protocol was used for the selection of subjects, collection of blood samples, culture techniques, examination of post-culture blood slides and interpretation of results. The in vitro micro-test Mark III was used for assessing susceptibility of P. falciparum isolates.RESULTSThe criteria for blood parasite density was met by 219 P. falciparum malaria patients. Chloroquine resistance was found in 47% of isolated P. falciparum schizonts. Mefloquine resistance was found in 5.2%. In addition, the EC50 and EC95 values in blood that inhibited schizont maturation in resistant isolates were higher than the normal therapeutic level for mefloquine. No resistance occurred against quinine or artemisinin, with no growth at the cut-off level for quinine and inhibition at low concentrations of artemisinin.CONCLUSIONOur study confirmed the occurrence of chloroquine-resistant P. falciparum and a slow increase in the rate of this resistance; it is likely that resistance will increase further and spread over all the foci of malaria in Yemen. The low rate of mefloquine-resistant P. falciparum, was lower than that reported in Africa or Southeast Asia, but it is the first report of mefloquine resistance in Yemen. Finally, the isolates were sensitive to low concentrations of quinine and artemisinin.

High frequency of Plasmodium falciparum chloroquine resistance marker (pfcrt T76 mutation) in Yemen: An urgent need to re-examine malaria drug policy

“…The study showed high prevalence of pfcrt 76T mutation in Yemen with coastal areas/foothills having higher rate as compared to highland areas. This finding is consistent with previous in vivo and in vitro studies carried out in coastal areas/foothills [ 24 , 30 ]. In Hodeidah (coastland areas), in vivo study found CQR in 71% of P. falciparum -infected patients[ 25 ].…”

“…In Hodeidah (coastland areas), in vivo study found CQR in 71% of P. falciparum -infected patients[ 25 ]. In in vitro study, carried out in the same area using mark III technique, reported 47% of CQR [ 30 ]. CQR was also reported from Taiz (foothills areas) using a 7-day in vivo test [ 24 ].…”

“…The CQR problem is constantly growing since the detection of the first indigenous cases of P. falciparum CQR in 1989 [ 24 ]. Over the past two decades, few studies have been carried out to examine antimalarial drug efficacies in Yemen, both in vivo and in vitro [ 24 , 25 , 30 ]. However, no information about antimalarial drug resistance is available from highland areas which are endemic for malaria in Yemen.…”

In Vitro Chloroquine Resistance in Plasmodium falciparum Isolates from Tertiary Care Hospital

“…These results indicate high level of resistance of P. falciparum to chloroquine among the isolates tested, and this is confirmed by high EC values which are excessively higher than effective therapeutic concentration. These values are significantly higher than those reported from India and other countries [ 13 , 14 ]. This high-level resistance to chloroquine in our patients may be due to previous exposure to improper therapeutic regimes, over-the-counter availability of drug, and high drug pressure by improper prescribing habits of private practitioners.…”

Survey of chloroquine-resistant mutations in the Plasmodium falciparum pfcrt and pfmdr-1 genes in Hadhramout, Yemen

“…The first detection of the indigenous chloroquine resistance (CQR) cases in Yemen was reported in 1989 in Taiz (Mamser, 1989;Alkadi et al, 2006), and then in Hodeidah (Al-Shamahy et al, 2006). In addition, recent studies have shown high prevelance of CQR marker pfcrt 76T in Hodeidah, Dhammar, Rymah and Taiz (Al-Mekhlafi et al, 2011;Abdul-Ghani et al, 2013;Al-Hamidhi et al, 2013) tion of artesunate-sulphadoxine/pyrimethamine as the first-line therapy and artemether-lumefantrine as a second line treatment for uncomplicated malaria.…”