High prevalence of molecular markers for resistance to chloroquine and pyrimethamine in Plasmodium falciparum from Zimbabwe

Chloroquine has been the first line drug of treatment for malaria in Zimbabwe until a recent adoption of an interim policy to treat using a combination of chloroquine (CQ) and sulfadoxine/pyrimethamine (SP). We examined the prevalence of parasites with mutations associated with resistance to the drug combination in three areas that have been previously described to differ in malaria endemicity. Our results show that the parasite population from the three areas had a high prevalence of molecular markers of resistance to chloroquine and pyrimethamine. The prevalence of crt (K76T) was 64, 82, and 92% for Chiredzi, Kariba, and Bindura, respectively. On the dhfr locus, the presence of triple mutations (codons 51, 59, and 108) was approximately 50% for all the three locations. On the other hand, the prevalence of dhps mutations (codons 436, 437, and 540) was low accounting for less than 20% in all the areas. Studies reported here demonstrate widespread prevalence of molecular markers associated with chloroquine and pyrimethamine resistance and should be taken into consideration for further refinement of malaria control strategies in Zimbabwe. The design and implementation of successful control strategies would benefit from understanding the prevalence of mutations associated with drug resistance in parasite populations. © 2007 Springer-Verlag

Antibody responses to Plasmodium falciparum vaccine candidate antigens in three areas distinct with respect to altitude.

Antibody levels against malaria antigens were measured among patients presenting with uncomplicated malaria at health centers from three locations in Zimbabwe (Bindura, Chiredzi and Kariba) that are distinct with regard to altitude and climatic conditions. Antibody levels were determined by ELISA using the antigens, apical membrane antigen 1 (AMA-1), erythrocyte binding antigen 175 (EBA-175), circumsporozoite surface protein (CSP), merozoite surface protein 1 (MSP-1) and Pfg27. For all the antigens tested, IgG and IgM levels were higher for Bindura (altitude 1100 m) compared to Kariba (<600 m, altitude) and Chiredzi (approximately 600 m, altitude) with the exception of IgG and IgM to AMA-1 and EBA-175 which were similar between Chiredzi and Bindura. Plasma samples were further analyzed for their functional activity by testing their ability to inhibit the growth of Plasmodium falciparum in culture. Our results, determined by microscopy and verified by the LDH assay revealed that plasma from the three locations had similar inhibitory activity against the growth of P. falciparum in vitro. Our data revealed that highest growth inhibition correlated with the highest levels of MSP-1 antibody values

Antibody responses to Plasmodium falciparum vaccine candidate antigens in three areas distinct with respect to altitude

Antibody levels against malaria antigens were measured among patients presenting with uncomplicated malaria at health centers from three locations in Zimbabwe (Bindura, Chiredzi and Kariba) that are distinct with regard to altitude and climatic conditions. Antibody levels were determined by ELISA using the antigens, apical membrane antigen 1 (AMA-1), erythrocyte binding antigen 175 (EBA-175), circumsporozoite surface protein (CSP), merozoite surface protein 1 (MSP-1) and Pfg27. For all the antigens tested, IgG and IgM levels were higher for Bindura (altitude 1100 m) compared to Kariba (\u3c600 m, altitude) and Chiredzi (∼600 m, altitude) with the exception of IgG and IgM to AMA-1 and EBA-175 which were similar between Chiredzi and Bindura. Plasma samples were further analyzed for their functional activity by testing their ability to inhibit the growth of Plasmodium falciparum in culture. Our results, determined by microscopy and verified by the LDH assay revealed that plasma from the three locations had similar inhibitory activity against the growth of P. falciparum in vitro. Our data revealed that highest growth inhibition correlated with the highest levels of MSP-1 antibody values. © 2006

Inclusion of edaphic predictors for enhancement of models to determine distribution of soil-transmitted helminths: the case of Zimbabwe

Abstract Background Reliable mapping of soil-transmitted helminth (STH) parasites requires rigorous statistical and machine learning algorithms capable of integrating the combined influence of several determinants to predict distributions. This study tested whether combining edaphic predictors with relevant environmental predictors improves model performance when predicting the distribution of STH, Ascaris lumbricoides and hookworms at a national scale in Zimbabwe. Methods Geo-referenced parasitological data obtained from a 2010/2011 national survey indicating a confirmed presence or absence of STH among school children aged 10–15 years was used to calibrate ten species distribution models (SDMs). The performance of SDMs calibrated with a set of environmental and edaphic variables was compared to that of SDMs calibrated with environmental variables only. Model performance was evaluated using the true skill statistic and receiver operating characteristic curve. Results Results show a significant improvement in model performance for both A. lumbricoides and hookworms for all ten SDMs after edaphic variables were combined with environmental variables in the modelling of the geographical distribution of the two STHs at national scale. Using the top three performing models, a consensus prediction was developed to generate the first continuous maps of the potential distribution of the two STHs in Zimbabwe. Conclusions The findings from this study demonstrate significant model improvement if relevant edaphic variables are included in model calibration resulting in more accurate mapping of STH. The results also provide spatially-explicit information to aid targeted control of STHs in Zimbabwe and other countries with STH burden

Analysis of genetic polymorphism in select vaccine candidate antigens and microsatellite loci in Plasmodium falciparum from endemic areas at varying altitudes

Plasmodium falciparum parasites obtained from symptomatic patients attending clinics in Bindura (altitude 1100 m), Chiredzi (600 m) and Kariba (\u3c600 m), previously reported to differ in malaria endemicity were genotyped on the msp-1, msp-2 and glurp loci to examine the extent of parasite genetic diversity. While the parasites were monomorphic for msp-1 allele RO33 from the three locations, the K1 allele was over-represented in Kariba (p = 0.02) and Mad20 alleles occurred at a higher frequency in Bindura. A similar PCR analysis for glurp and the two main allelic families of msp-2, i.e. IC/3D7 and FC-27 revealed minimal differences in the parasite population. A total of 8 msp-1 Block 2 and 11 msp-2 genotypes were identified from the three locations combined. On the glurp locus, 13 different genotypes ranging in size from 660 to 1160 bp were detected in parasites obtained from Bindura and Kariba. To gain further insight into P. falciparum genetic diversity in the three different geographical locations, parasites were examined for neutral microsatellite markers (C4M8, C13M30 and TA81). The number of microsatellite alleles ranged from 8 to 17 and the average expected heterozygosity (HE) for the three areas combined was 0.83 suggesting that the parasite population of Zimbabwe is genetically heterogeneous. These findings have implications in understanding the impact of genetic variation on immunity and possibly emergence of drug resistance. © 2007 Elsevier B.V. All rights reserved