Adequate clinical and parasitologic cure by artemisinin combination therapies relies on the artemisinin component and the partner drug. Polymorphisms in the Plasmodium falciparum chloroquine resistance transporter (pfcrt) and P. falciparum multidrug resistance 1 (pfmdr1) genes are associated with decreased sensitivity to amodiaquine and lumefantrine, but effects of these polymorphisms on therapeutic responses to artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) have not been clearly defined. Individual patient data from 31 clinical trials were harmonized and pooled by using standardized methods from the WorldWide Antimalarial Resistance Network. Data for more than 7,000 patients were analyzed to assess relationships between parasite polymorphisms in pfcrt and pfmdr1 and clinically relevant outcomes after treatment with AL or ASAQ. Presence of the pfmdr1 gene N86 (adjusted hazards ratio = 4.74, 95% confidence interval = 2.29 – 9.78, P < 0.001) and increased pfmdr1 copy number (adjusted hazards ratio = 6.52, 95% confidence interval = 2.36–17.97, P < 0.001) were significant independent risk factors for recrudescence in patients treated with AL. AL and ASAQ exerted opposing selective effects on single-nucleotide polymorphisms in pfcrt and pfmdr1. Monitoring selection and responding to emerging signs of drug resistance are critical tools for preserving efficacy of artemisinin combination therapies; determination of the prevalence of at least pfcrt K76T and pfmdr1 N86Y should now be routine.

In this study, a rapid method for the detection of Central and West Africa clades of Monkeypox virus (MPXV) using recombinase polymerase amplification (RPA) assay targeting the G2R gene was developed. MPXV, an Orthopoxvirus, is a zoonotic dsDNA virus, which is listed as a biothreat agent. RPA was operated at a single constant temperature of 42°C and produced results within 3 to 10 minutes. The MPXV-RPA-assay was highly sensitive with a limit of detection of 16 DNA molecules/μl. The clinical performance of the MPXV-RPA-assay was tested using 47 sera and whole blood samples from humans collected during the recent MPXV outbreak in Nigeria as well as 48 plasma samples from monkeys some of which were experimentally infected with MPXV. The specificity of the MPXV-RPA-assay was 100% (50/50), while the sensitivity was 95% (43/45). This new MPXV-RPA-assay is fast and can be easily utilised at low resource settings using a solar powered mobile suitcase laboratory.

Anopheles mosquitoes are important vectors of malaria and lymphatic filariasis (LF), which are major public health diseases in Nigeria. Malaria is caused by infection with a protozoan parasite of the genus Plasmodium and LF by the parasitic worm Wuchereria bancrofti. Updating our knowledge of the Anopheles species is vital in planning and implementing evidence based vector control programs. To present a comprehensive report on the spatial distribution and composition of these vectors, all published data available were collated into a database. Details recorded for each source were the locality, latitude/longitude, time/period of study, species, abundance, sampling/collection methods, morphological and molecular species identification methods, insecticide resistance status, including evidence of the kdr allele, and P. falciparum sporozoite rate and W. bancrofti microfilaria prevalence. This collation resulted in a total of 110 publications, encompassing 484,747 Anopheles mosquitoes in 632 spatially unique descriptions at 142 georeferenced locations being identified across Nigeria from 1900 to 2010. Overall, the highest number of vector species reported included An. gambiae complex (65.2%), An. funestus complex (17.3%), An. gambiae s.s. (6.5%). An. arabiensis (5.0%) and An. funestus s.s. (2.5%), with the molecular forms An. gambiae M and S identified at 120 locations. A variety of sampling/collection and species identification methods were used with an increase in molecular techniques in recent decades. Insecticide resistance to pyrethroids and organochlorines was found in the main Anopheles species across 45 locations. Presence of P. falciparum and W. bancrofti varied between species with the highest sporozoite rates found in An. gambiae s.s, An. funestus s.s. and An. moucheti, and the highest microfilaria prevalence in An. gambiae s.l., An. arabiensis, and An. gambiae s.s. This comprehensive geo-referenced database provides an essential baseline on Anopheles vectors and will be an important resource for malaria and LF vector control programmes in Nigeria.

No abstract

Artemether, artemether-lumefantrine, or coartem and halofantrine are alternative antimalarial drugs to chloroquine. Their efficacy and potential to delay drug resistance in falciparum malaria had led to their increased use. Although these drugs have proven to be well tolerated, there are adverse effects associated with them. This study was designed to examine the toxic potential of acute administration of these drugs in rats. Twenty-four rats were divided into four groups: group I (control) received distilled water; group II received artemether for 5 days with an initial dose of 3.2 g/kg body weight on day 1 and 1.6 mg/kg body weight on days 2-5; group III received coartem (27 mg/kg body weight/day) for 3 days, which was divided into two equal portions per day; and group IV received halofantrine (24 mg/kg body weight/day) in three equal portions. Administration of artemether, coartem and halofantrine caused significant decrease (P < 0.05) in reduced glutathione levels in the liver by 29%, 21% and 26%, respectively. In contrast, there were no significant differences (P > 0.05) in the kidney glutathione levels. Furthermore, artemether, coartem and halofantrine decreased the liver-and kidney-enzymatic antioxidant status of the animals. Precisely, artemether, coartem and halofantrine decreased liver superoxide dismutase and catalase activities by 45%, 50% and 57%; and 20%, 29% and 23%, respectively. While the kidney catalase activities were decreased by 41%, 28% and 30%, respectively, the drugs however did not produce significant effect (P > 0.05) on the kidney superoxide dismutase activities. In addition, artemether, coartem and halofantrine decreased the hepatic levels of glutathione S-transferase by 64%, 51% and 53%, respectively. Administration of artemether, coartem and halofantrine significantly increased (P < 0.05) liver and kidney lipid peroxidation levels by 67%, 50% and 81%; and 58%, 43% and 31%, respectively. This indicates that the liver is considerably more affected than the kidneys. Similarly, halofantrine treatment caused significant elevation (P < 0.05) in the levels of serum creatinine, aspartate and alanine aminotransferases and blood urea nitrogen by 73%, 66%, 61% and 63%, respectively. These data indicate that oral administration of artemether, coartem and halofantrine has adverse effects on both enzymic and non-enzymatic antioxidant status of the animals.

BackgroundNigeria has a significant burden of lymphatic filariasis (LF) caused by the parasite Wuchereria bancrofti. A major concern to the expansion of the LF elimination programme is the risk of serious adverse events (SAEs) associated with the use of ivermectin in areas co-endemic with Loa filariasis. To better understand this, as well as other factors that may impact on LF elimination, we used Micro-stratification Overlap Mapping (MOM) to highlight the distribution and potential impact of multiple disease interventions that geographically coincide in LF endemic areas and which will impact on LF and vice versa.Methodology/Principal findingsLF data from the literature and Federal Ministry of Health (FMoH) were collated into a database. LF prevalence distributions; predicted prevalence of loiasis; ongoing onchocerciasis community-directed treatment with ivermectin (CDTi); and long-lasting insecticidal mosquito net (LLIN) distributions for malaria were incorporated into overlay maps using geographical information system (GIS) software. LF was prevalent across most regions of the country. The mean prevalence determined by circulating filarial antigen (CFA) was 14.0% (n = 134 locations), and by microfilaria (Mf) was 8.2% (n = 162 locations). Overall, LF endemic areas geographically coincided with CDTi priority areas, however, LLIN coverage was generally low (<50%) in areas where LF prevalence was high or co-endemic with L. loa.Conclusions/SignificanceThe extensive database and series of maps produced in this study provide an important overview for the LF Programme and will assist to maximize existing interventions, ensuring cost effective use of resources as the programme scales up. Such information is a prerequisite for the LF programme, and will allow for other factors to be included into planning, as well as monitoring and evaluation activities given the broad spectrum impact of the drugs used.

Abstract. The rate of malarial parasitemia in children and adults was assessed by microscopy and the polymerase chain reaction in a holoendemic area in Nigeria. A high rate of subpatent Plasmodium falciparum parasitemia (19.6%) was found. Plasmodium malariae and P. ovale infections were common in a rural area (26.1% and 14.8%) but were observed sporadically in individuals from an urban area. Simultaneous infections with P. falciparum, P. malariae, and P. ovale were frequent in the rural area (11.7% triple infections). The rate of triple infections was higher than expected from the prevalences of each species (P Ͻ 0.00001). Spleen enlargement was associated with mixed infections of P. falciparum and P. malariae (odds ratio [OR] ϭ 5.9, 95% confidence interval [CI] 3.0-11.7) and less frequently observed in individuals without detectable parasitemia (OR ϭ 0.06, 95% CI ϭ 0.01-0.3). Spleen enlargement and titers of antibodies to schizonts were positively correlated with parasite densities. The results also suggest that in some individuals a long-lasting subpatent parasitemia might occur.In areas holoendemic for Plasmodium falciparum infection, clinical malaria affects mostly young children. Adults have acquired a partial immunity after years of successive exposure to a variety of different parasite strains. An antidisease immunity evolves in early childhood, while an antiparasite immunity develops at the age of 15-20 years. 1 It is yet unclear to what extent subpatent parasitemia contributes to acquired immunity and whether clinically asymptomatic infections reflect effective parasite control or may eventually convert to manifest disease.The polymerase chain reaction (PCR) allows the detection of parasitemia below the threshold of conventional microscopy. 2 Re-evaluations of the epidemiology of unstable malaria have now shown that the prevalence of submicroscopic P. falciparum infections is far higher than has previously been expected. 3 Until the PCR came into use it had been difficult to assess correlations of submicroscopic parasitemia with particular features of malarial infections such as spleen size or antibody titers.Although simultaneous infections with different Plasmodium species have been described in humans, 4 detailed reports of prevalences in holoendemic areas were rare before species-specific PCR assays became available. 5 The extent of interspecies interactions in mixed infections is currently the subject of discussion. In a recent study, it has been suggested that cross-immunity between P. falciparum and P. vivax antigens might occur. 6 However, there is a controversy whether anti-disease-and anti-parasite immunity are in fact species-specific. 7 In a cross-sectional study in an urban and a rural setting of southwest Nigeria, we determined the rates of simultaneous P. falciparum, P. malariae, and P. ovale infections, including submicroscopic parasitemia. Furthermore, we looked at associations of different plasmodial infections with spleen size and with antibody titers against crude schizont antigen. P...

Glucose-6-phosphate dehydrogenase A- (G6PD A-) deficiency is a common enzymopathy in Africa that sporadically leads to manifest haemolytic anaemia. It is not exactly known how far the haematological status of individuals with either homozygous or heterozygous G6PD A- deficiency differs from that of individuals with normal G6PD activity. In a field study in Nigeria, we determined G6PD gene variants, the corresponding G6PD and pyruvate kinase (PK) activities, and basic haematological parameters in clinically healthy individuals, who were, in part, asymptomatically infected by malaria parasites. Red blood cell counts and haemoglobin levels were lower in G6PD A- deficient than in G6PD normal subjects. PK activities were higher in G6PD deficients, indicating a younger red cell population in these individuals. These findings suggest that G6PD A- deficiency is accompanied by chronic subclinical haemolysis. As a consequence, the reduced life span of red cells leads to an impaired diagnosis of G6PD heterozygosity when applying routine biochemical methods.