Asymptomatic malaria infections and Pfmdr1 mutations in an endemic area of Nigeria

Abstract

Background Malaria eradication globally is yet to be achieved and transmission is sustained in many endemic countries. Plasmodium falciparum continues to develop resistance to currently available anti-malarial drugs, posing great problems for malaria elimination. This study evaluates the frequencies of asymptomatic infection and multidrug resistance-1 ( mdr-1 ) gene mutations in parasite isolates, which form the basis for understanding persistently high incidence in South West, Nigeria. Methods A total of 535 individuals aged from 6 months were screened during the epidemiological survey evaluating asymptomatic transmission. Parasite prevalence was determined by histidine-rich protein II rapid detection kit (RDT) in healthy individuals. Plasmodium falciparum mdr-1 gene mutations were detected by polymerase chain reaction (PCR) followed by restriction enzyme digest and electrophoresis to determine polymorphism in parasite isolates. Sequencing was done to confirm polymorphism. Proportions were compared using Chi-square test at p value < 0.05. Results Malaria parasites were detected by RDT in 204 (38.1%) individuals. Asymptomatic infection was detected in 117 (57.3%) and symptomatic malaria confirmed in 87 individuals (42.6%). Overall, individuals with detectable malaria by RDT was significantly higher in individuals with symptoms, 87 of 197 (44.2%), than asymptomatic persons; 117 of 338 (34.6%), p = 0.02. In a sub-set of 75 isolates, 18(24%) and 14 (18.6%) individuals had Pfmdr1 86Y and 1246Y mutations. Conclusions There is still high malaria transmission rate in Nigeria with higher incidence of asymptomatic infections. These parasites harbour mutations on Pfmdr1 which contribute to artemisinin partner drug resistance; surveillance strategies to reduce the spread of drug resistance in endemic areas are needed to eliminate the reservoir of malaria parasites that can mitigate the eradication of malaria in Nigeria.

Zoonotic and vector-borne parasites and epilepsy in low-income and middle-income countries

“…A diagnosis of cerebral malaria is contingent on the demonstration of asexual forms of P. falciparum in blood smears and the exclusion of alternative causes of a febrile coma. As asymptomatic peripheral blood parasitaemia is well known in SSA on account of immunity, the mere demonstration of the parasite in blood smears might not be sufficient to establish diagnosis 34 . An autopsy study from Malawi showed that seven of 31 children with clinically diagnosed cerebral malaria died from other causes 35 .…”

Polymorphism Analysis of pfmdr1 and pfcrt from Plasmodium falciparum Isolates in Northwestern Nigeria Revealed the Major Markers Associated with Antimalarial Resistance

“…In this study, the D1246Y mutation was not investigated since it is known to be present in approximately only 0.7–3% of the African isolates [ 10 , 30 , 31 ]. However, two studies have recorded 1246Y frequencies of 3.66 and 18.6%, respectively, in southeast and southwest Nigeria [ 24 , 30 ].…”

“…In this study, the D1246Y mutation was not investigated since it is known to be present in approximately only 0.7–3% of the African isolates [ 10 , 30 , 31 ]. However, two studies have recorded 1246Y frequencies of 3.66 and 18.6%, respectively, in southeast and southwest Nigeria [ 24 , 30 ]. A recently published study conducted in Lagos, southwest Nigeria, detected rare pfmdr1 mutations, N504K, N649D, F938Y and S967N, which were previously unreported [ 21 ], suggesting that the proactive surveillance of this gene and the validation of mutations discovered in it are necessary to ameliorate the menace of multidrug resistance.…”

“…While NH 2 -terminal mutations (N86Y and Y184F) are more commonly found in Asian and African parasites, the COOH-terminal mutations (S1034C, N1042D and D1246Y) are encountered more often in South American isolates [ 28 ]. However, the D1246Y mutation is also present in approximately 0.7–3% of the 1502 African genomes sequenced recently [ 10 , 30 , 31 ]. The 86 Y and 184 F replacements have been reported in several studies, the majority of which were conducted in southwest Nigeria [ 23 , 24 , 25 , 30 ], with 86 Y and 184 F mutations linked to amodiaquine, CQ and artemether resistance [ 13 , 15 , 19 ].…”

Plasmodium falciparum multidrug resistance gene-1 polymorphisms in Northern Nigeria: implications for the continued use of artemether-lumefantrine in the region

“…The prevalence of pfmdr1 polymorphisms in Nigeria was majorly reported from the Southern region, where a positive association between pfmdr1 N86, F184 and D1246 alleles and clinical failure was observed [ 36 ]. In contrast, a prevalence of 62.2% and 69.0% for pfmdr1 86Y and F184 allele, respectively, was also reported from the region [ 37 ] which was recently followed by another survey where the pfmdr1 86Y and 1246Y alleles had prevalence of 24% and 18.6%, respectively [ 38 ]. Yet, there is no valid baseline data involving pfmdr1 SNPs in both North-West and North–East Nigeria since the withdrawal of CQ and adoption of AL in Northern Nigeria.…”