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Appleton C.C.,University of KwaZulu - Natal | Naidoo I.,Malaria Research Unit
South African Journal of Science | Year: 2012

We reviewed the early literature and maps of the occurrence of urogenital schistosomiasis (bilharzia) in the Eastern Cape, South Africa from the 1860s until its decline from about 1900 and reappearance in 2002. Although this decline in transmission has received little attention to date, clinical descriptions of the disease over this period indicate that infection was common, probably patchy, although sometimes with severe morbidity. The long period of quiescence between 1900 and 2002 is thought to be as a result of several factors, but primarily because of the impact of the area's cold winters and drought-prone climate on the survival and reproduction of both the snail intermediate host Bulinus africanus and the intramolluscan stages of the parasite. The concept of an outbreak area is invoked to describe the occurrence of intense urogenital schistosomiasis transmission in localised areas for relatively short periods of up to 35 years in this the southernmost part of its range in Africa, a suboptimal environment for transmission. © 2012. The Authors. Source


Flegg J.A.,University of Oxford | Patil A.P.,University of Oxford | Venkatesan M.,Howard Hughes Medical Institute | Venkatesan M.,University of Maryland Baltimore County | And 5 more authors.
Malaria Journal | Year: 2013

Background: Plasmodium falciparum has repeatedly evolved resistance to first-line anti-malarial drugs, thwarting efforts to control and eliminate the disease and in some period of time this contributed largely to an increase in mortality. Here a mathematical model was developed to map the spatiotemporal trends in the distribution of mutations in the P. falciparum dihydropteroate synthetase (dhps) gene that confer resistance to the anti-malarial sulphadoxine, and are a useful marker for the combination of alleles in dhfr and dhps that is highly correlated with resistance to sulphadoxine-pyrimethamine (SP). The aim of this study was to present a proof of concept for spatiotemporal modelling of trends in anti-malarial drug resistance that can be applied to monitor trends in resistance to components of artemisinin combination therapy (ACT) or other anti-malarials, as they emerge or spread. Methods. Prevalence measurements of single nucleotide polymorphisms in three codon positions of the dihydropteroate synthetase (dhps) gene from published studies of dhps mutations across Africa were used. A model-based geostatistics approach was adopted to create predictive surfaces of the dhps540E mutation over the spatial domain of sub-Saharan Africa from 1990-2010. The statistical model was implemented within a Bayesian framework and hence quantified the associated uncertainty of the prediction of the prevalence of the dhps540E mutation in sub-Saharan Africa. Conclusions: The maps presented visualize the changing prevalence of the dhps540E mutation in sub-Saharan Africa. These allow prediction of space-time trends in the parasite resistance to SP, and provide probability distributions of resistance prevalence in places where no data are available as well as insight on the spread of resistance in a way that the data alone do not allow. The results of this work will be extended to design optimal sampling strategies for the future molecular surveillance of resistance, providing a proof of concept for similar techniques to design optimal strategies to monitor resistance to ACT. © 2013 Flegg et al.; licensee BioMed Central Ltd. Source


Kayentao K.,Child and Reproductive Health Group | Kayentao K.,University of Bamako | Garner P.,Child and Reproductive Health Group | Van Eijk A.M.,Child and Reproductive Health Group | And 8 more authors.
JAMA - Journal of the American Medical Association | Year: 2013

Importance: Intermittent preventive therapy with sulfadoxine-pyrimethamine to control malaria during pregnancy is used in 37 countries in sub-Saharan Africa, and 31 of those countries use the standard 2-dose regimen. However, 2 doses may not provide protection during the last 4 to 10 weeks of pregnancy, a pivotal period for fetal weight gain. Objective: To perform a systematic review and meta-analysis of trials to determine whether regimens containing 3 or more doses of sulfadoxine-pyrimethamine for intermittent preventive therapy during pregnancy are associated with a higher birth weight or lower risk of low birth weight (LBW) (<2500 g) than standard 2-dose regimens. Data Sources and Study Selection: ISI Web of Knowledge, EMBASE, SCOPUS, PubMed, LILACS, the Malaria in Pregnancy Library, Cochrane CENTRAL, and trial registries from their inception to December 2012, without language restriction. Eligible studies included randomized and quasi-randomized trials of intermittent preventive therapy during pregnancy with sulfadoxine-pyrimethamine monotherapy. Data Extraction: Data were independently abstracted by 2 investigators. Relative risk (RR), mean differences, and 95% CIs were calculated with random-effects models. Results: Of 241 screened studies, 7 trials of 6281 pregnancies were included. The median birth weight in the 2-dose group was 2870 g (range, 2722-3239 g) and on average 56 g higher (95% CI, 29-83 g; I2=0%) in the ≥3-dose group. Three or more doses were associated with fewer LBW births (RR, 0.80; 95% CI, 0.69-0.94; I2=0%), with a median LBW risk per 1000 women in the 2-dose group (assumed control group risk) of 167 per 1000 vs 134 per 1000 in the ≥3-dose group (absolute risk reduction, 33 per 1000 [95% CI, 10-52]; number needed to treat=31). The association was consistent across a wide range of sulfadoxine-pyrimethamine resistance (0% to 96% dihydropteroate-synthase K540E mutations). There was no evidence of small-study bias. The ≥3-dose group had less placental malaria (RR, 0.51; 95% CI, 0.38-0.68; I2=0%, in 6 trials, 63 vs 32 per 1000; absolute risk reduction, 31 per 1000 [95% CI, 20-39]). In primigravid plus secundigravid women, the risk of moderate to severe maternal anemia was lower in the ≥3-dose group (RR, 0.60; 95% CI, 0.36-0.99; I2=20%; in 6 trials, 36 vs 22 per 1000; absolute risk reduction, 14 per 1000 [95% CI, 0.4-23]). There were no differences in rates of serious adverse events. Conclusions and Relevance: Among pregnant women in sub-Saharan Africa, intermittent preventive therapy with 3 or more doses of sulfadoxine-pyrimethamine was associated with a higher birth weight and lower risk of LBW than the standard 2-dose regimens. These data provide support for the new WHO recommendations to provide at least 3 doses of intermittent preventive therapy during pregnancy at each scheduled antenatal care visit in the second and third trimester. ©2013 American Medical Association. All rights reserved. Source


Vaughan-Williams C.H.,Umkhanyakude Health District Office | Vaughan-Williams C.H.,University of KwaZulu - Natal | Raman J.,Malaria Research Unit | Raswiswi E.,Umkhanyakude Health District Office | And 4 more authors.
Malaria Journal | Year: 2012

Background: Recent malaria epidemics in KwaZulu-Natal indicate that effective anti-malarial therapy is essential for malaria control. Although artemether-lumefantrine has been used as first-line treatment for uncomplicated Plasmodium falciparum malaria in northern KwaZulu-Natal since 2001, its efficacy has not been assessed since 2002. The objectives of this study were to quantify the proportion of patients treated for uncomplicated P. falciparum malaria with artemether-lumefantrine who failed treatment after 28 days, and to determine the prevalence of molecular markers associated with artemether-lumefantrine and chloroquine resistance. Methods. An observational cohort of 49 symptomatic patients, diagnosed with uncomplicated P. falciparum malaria by rapid diagnostic test, had blood taken for malaria blood films and P. falciparum DNA polymerase chain reaction (PCR). Following diagnosis, patients were treated with artemether-lumefantrine (Coartem®) and invited to return to the health facility after 28 days for repeat blood film and PCR. All PCR P. falciparum positive samples were analysed for molecular markers of lumefantrine and chloroquine resistance. Results: Of 49 patients recruited on the basis of a positive rapid diagnostic test, only 16 were confirmed to have P. falciparum by PCR. At follow-up, 14 were PCR-negative for malaria, one was lost to follow-up and one blood specimen had insufficient blood for a PCR analysis. All 16 with PCR-confirmed malaria carried a single copy of the multi-drug resistant (mdr1) gene, and the wild type asparagine allele mdr1 codon 86 (mdr1 86N). Ten of the 16 samples carried the wild type haplotype (CVMNK) at codons 72-76 of the chloroquine resistance transporter gene (pfcrt); three samples carried the resistant CVIET allele; one carried both the resistant and wild type, and in two samples the allele could not be analysed. Conclusions: The absence of mdr1 gene copy number variation detected in this study suggests lumefantrine resistance has yet to emerge in KwaZulu-Natal. In addition, data from this investigation implies the possible re-emergence of chloroquine-sensitive parasites. Results from this study must be viewed with caution, given the extremely small sample size. A larger study is needed to accurately determine therapeutic efficacy of artemether-lumefantrine and resistance marker prevalence. The high proportion of rapid diagnostic test false-positive results requires further investigation. © 2012 Vaughan-Williams et al.; licensee BioMed Central Ltd. Source


Naidoo I.,London School of Hygiene and Tropical Medicine | Naidoo I.,Malaria Research Unit | Roper C.,London School of Hygiene and Tropical Medicine
Trends in Parasitology | Year: 2013

Sulfadoxine-pyrimethamine (SP) is used throughout Africa for intermittent preventive treatment (IPT) of malaria, but resistance threatens its efficacy. We found marked regional differences in the genotypes responsible for SP resistance when mapping recent surveys of dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) mutations. In West Africa, a 'partially resistant' combination of dhfr N51I, N59R, and S108N with dhps A437G predominates, whereas in East Africa the 'fully resistant' combination of dhfr N51I, N59R, and S108N with dhps A437G. +. K540E is found. There are three East African foci where 'fully resistant' populations have additionally acquired dhps 581G and/or dhfr 164L to become 'super resistant'. SP-IPT in infants and pregnant women is reported to have failed in super resistant areas prompting review of SP-IPT use in affected areas. © 2013 Elsevier Ltd. Source

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