Search

Background: The World Health Organization (WHO) declared the COVID-19 pandemic a public health emergency of international concern. South Africa, like many other countries, initiated a multifaceted national response to the pandemic. Self-isolation and quarantine are essential components of the public health response in the country. This paper examined perceptions and preparedness for self-isolation or quarantine during the initial phase of the pandemic in South Africa., Methods: The analysis used data obtained from an online quantitative survey conducted in all nine provinces using a data-free platform. Descriptive statistics and multivariable logistic regression models were used to analyse the data., Results: Of 55,823 respondents, 40.1% reported that they may end up in self-isolation or quarantine, 32.6% did not think that they would and 27.4% were unsure. Preparedness for self-isolation or quarantine was 59.0% for self, 53.8% for child and 59.9% for elderly. The odds of perceived possibility for self-isolation or quarantine were significantly higher among Coloureds, Whites, and Indians/Asians than Black Africans, and among those with moderate or high self-perceived risk of contracting COVID-19 than those with low risk perception. The odds were significantly lower among older age groups than those aged 18-29 years, and those unemployed than fully employed. The odds of preparedness for self-isolation or quarantine were significantly less likely among females than males. Preparedness for self, child and elderly isolation or quarantine was significantly more likely among other population groups than Black Africans and among older age groups than those aged 18-29 years. Preparedness for self, child and elderly isolation or quarantine was significantly less likely among those self-employed than fully employed and those residing in informal dwellings than formal dwellings. In addition, preparedness for self-isolation or quarantine was significantly less likely among those with moderate and high self-perceived risk of contracting COVID-19 than low risk perception., Conclusion: The findings highlight the challenge of implementing self-isolation or quarantine in a country with different and unique social contexts. There is a need for public awareness regarding the importance of self-isolation or quarantine as well as counter measures against contextual factors inhibiting this intervention, especially in impoverished communities.

Background: In South Africa, age-disparate to sexual relationships where the age difference between partners is 5 years or greater is an important contributor to the spread of HIV. However, little is known about the predictors of age-disparate sexual relationships. This study investigates factors associated with age-disparate sexual relationships among males and females in South Africa., Methods: This analysis used the 2012 nationally representative population-based household survey conducted using multi-stage stratified cluster sampling design. Multivariate multinomial stepwise logistic regression models were used to determine factors associated with age-disparate sexual relationships., Results: Of 15,717 participants, who responded to the question on age-disparate sexual relationships, 62% males versus 58.5% females had partners within 5 years older or younger, 34.7% of males versus 2.7% of females had partners at least 5 years younger and 3.3% of males versus 38.8% of females had partners at least 5 years older. Among both males and females predictors of age-disparate sexual relationships were education, employment, socioeconomic status, locality type, age at sexual debut, condom use at last sexual act and HIV status while race was also an additional predictor for among females. Including unprotected sex and risk of HIV infection among adolescent girls and young women with sexual partners 5 years older their age., Conclusions: This study suggest that there is a need for reprioritizing the combination of behavioural and structural interventions to address risky sexual behaviours, unprotected sex, poverty, limited education and gender inequitable norms related to age-disparate sexual relationships and HIV.

Background: HIV drug resistance (HIVDR) testing was included in the 2017 South African national HIV household survey. We describe the prevalence of HIVDR by drug class, age, sex and antiretroviral drugs (ARV) status., Methods: Dried blood were spots tested for HIV, with Viral load (VL), exposure to ARVs and HIVDR testing among those HIV positive. HIVDR testing was conducted on samples with VL ≥1000 copies/ml using Next Generation Sequencing. Weighted percentages of HIVDR are reported., Results: 697/1,105 (63%) of HIV positive samples were sequenced. HIVDR was detected in samples from 200 respondents (27.4% (95% confidence interval (CI) 22.8-32.6)). Among these 130 (18.9% (95% CI 14.8-23.8)), had resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) only, 63 (7.8% (95% CI 5.6-10.9)) resistance to NNRTIs and nucleoside reverse transcriptase inhibitors, and 3 (0.5% (95% CI 0.1-2.1)) resistance to protease inhibitors. Sixty-five (55.7% (95% CI 42.6-67.9) of ARV-positive samples had HIVDR compared to 112 (22.8% (95% CI 17.7-28.7)), in ARV-negative samples. HIVDR was found in 75.6% (95% CI 59.2-87.3), n = 27, samples from respondents who reported ARV use but tested ARV-negative, and in 15.3% (95% CI 6.3-32.8), n = 7, respondents who reported no ARV use and tested ARV-negative. There were no significant age and sex differences in HIVDR., Conclusion: 27% of virally unsuppressed respondents had HIVDR, increasing to 75% among those who had discontinued ARV. Our findings support strengthening first-line ARV regimens by including drugs with a higher resistance barrier and treatment adherence strategies, and close monitoring of HIVDR., Competing Interests: The authors have declared that no competing interests exist

Background: To optimally allocate limited health resources in responding to the HIV epidemic, South Africa has undertaken to generate local epidemiological profiles identifying high disease burden areas. Central to achieving this, is the need for readily available quality health data linked to both large and small geographic areas. South Africa has relied on national population-based surveys: the Household HIV Survey and the National Antenatal Sentinel HIV and Syphilis Prevalence Survey (ANC) amongst others for such data for informing policy decisions. However, these surveys are conducted approximately every 2 and 3 years creating a gap in data and evidence required for policy. At subnational levels, timely decisions are required with frequent course corrections in the interim. Routinely collected HIV testing data at public health facilities have the potential to provide this much needed information, as a proxy measure of HIV prevalence in the population, when survey data is not available. The South African District health information system (DHIS) contains aggregated routine health data from public health facilities which is used in this article. Methods: Using spatial interpolation methods we combine three "types" of data: (1) 2015 gridded high-resolution population data, (2) age-structure data as defined in South Africa mid-year population estimates, 2015; and (3) georeferenced health facilities HIV-testing data from DHIS for individuals (15-49 years old) who tested in health care facilities in the district in 2015 to delineate high HIV disease burden areas using density surface of either HIV positivity and/or number of people living with HIV (PLHIV). For validation, we extracted interpolated values at the facility locations and compared with the real observed values calculating the residuals. Lower residuals means the Inverse Weighted Distance (IDW) interpolator provided reliable prediction at unknown locations. Results were adjusted to provincial published HIV estimates and aggregated to municipalities. Uncertainty measures map at municipalities is provided. Data on major cities and roads networks was only included for orientation and better visualization of the high burden areas. Results: Results shows the HIV burden at local municipality level, with high disease burden in municipalities in eThekwini, iLembe and uMngundgudlovu; and around major cities and national routes. Conclusion: The methods provide accurate estimates of the local HIV burden at the municipality level. Areas with high population density have high numbers of PLHIV. The analysis puts into the hand of decision makers a tool that they can use to generate evidence for HIV programming. The method allows decision makers to routinely update and use facility level data in understanding the local epidemic., (Copyright © 2019 Wabiri, Naidoo, Mungai, Samuel and Ngwenya.)

Objective: To assess changes and equity in antiretroviral therapy (ART) use in Kenya and South Africa., Methods: We analysed national population-based household surveys conducted in Kenya and South Africa between 2007 and 2012 for factors associated with lack of ART use among people living with HIV (PLHIV) aged 15-64 years. We considered ART use to be inequitable if significant differences in use were found between groups of PLHIV (e.g. by sex)., Findings: ART use among PLHIV increased from 29.3% (95% confidence interval [CI]: 22.8-35.8) to 42.5% (95%CI: 37.4-47.7) from 2007 to 2012 in Kenya and 17.4% (95%CI: 14.2-20.9) to 30.3% (95%CI: 27.2-33.6) from 2008 to 2012 in South Africa. In 2012, factors independently associated with lack of ART use among adult Kenyan PLHIV were rural residency (adjusted odds ratio [aOR] 1.98, 95%CI: 1.23-3.18), younger age (15-24 years: aOR 4.25, 95%CI: 1.7-10.63, and 25-34 years: aOR 5.16, 95%CI: 2.73-9.74 versus 50-64 years), nondisclosure of HIV status to most recent sex partner (aOR 2.41, 95%CI: 1.27-4.57) and recent recreational drug use (aOR 2.50, 95%CI: 1.09-5.77). Among South African PLHIV in 2012, lack of ART use was significantly associated with younger age (15-24 years: aOR 4.23, 95%CI: 2.56-6.70, and 25-34 years: aOR 2.84, 95%CI: 1.73-4.67, versus 50-64 years), employment status (aOR 1.61, 95%CI: 1.16-2.23 in students versus unemployed), and recent recreational drug use (aOR 4.56, 95%CI: 1.79-11.57)., Conclusion: Although we found substantial increases in ART use in both countries over time, we identified areas needing improvement including among rural Kenyans, students in South Africa, and among young people and drug users in both countries., Competing Interests: The authors have declared no competing interests exist.

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., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

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.

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; I 2 = 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; I 2 = 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.

Intermittent preventive treatment of infants (IPTi) with sulphadoxine pyrimethamine (SP) is recommended as an additional malaria control intervention in high transmission areas of sub-Saharan Africa, provided its protective efficacy is not compromised by SP resistance. A significant obstacle in implementing SP-IPTi, is in establishing the degree of resistance in an area. Since SP monotherapy is discontinued, no contemporary measures of in vivo efficacy can be made, so the World Health Organisation has recommended a cut-off based upon molecular markers, stating that SP-IPTi should not be implemented when the prevalence of the dhps 540E mutation among infections exceeds 50%. We created a geo-referenced database of SP resistance markers in Africa from published literature. By selecting surveys of malaria infected blood samples conducted since 2004 we have mapped the contemporary prevalence of dhps 540E. Additional maps are freely available in interactive form at http://www.drugresistancemaps.org/ipti/. Eight countries in East Africa are classified as unsuitable for SP-IPTi when data are considered at a national level. Fourteen countries in Central and West Africa were classified as suitable while seven countries had no available contemporary data to guide policy. There are clear deficiencies in molecular surveillance data coverage. We discuss requirements for ongoing surveillance of SP resistance markers in support of the use of SP-IPTi.

Chloroquine resistant malaria (CQR) emerged in East Africa during the late 1970s and then spread westward. A molecular marker only became available in the late 1990s, and by that time CQR had permeated throughout Africa. By contrast, resistance to sulphadoxine-pyrimethamine (SPR) has emerged during an era of molecular surveillance, and the changing prevalence of SPR conferred by point mutations in the dhfr and dhps genes has been recorded in hundreds of sites across Africa. We have collated and mapped reports of the dhps K540E mutation, a uniquely informative marker of SPR, and used these to describe the geography of its dispersal through time. Like CQR, dhps K540E appeared first in East Africa and spread west. We discuss whether there are common principles governing resistance dispersal in Africa and how these might guide surveillance in future., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Background: Although the molecular basis of resistance to a number of common antimalarial drugs is well known, a geographic description of the emergence and dispersal of resistance mutations across Africa has not been attempted. To that end we have characterised the evolutionary origins of antifolate resistance mutations in the dihydropteroate synthase (dhps) gene and mapped their contemporary distribution., Methods and Findings: We used microsatellite polymorphism flanking the dhps gene to determine which resistance alleles shared common ancestry and found five major lineages each of which had a unique geographical distribution. The extent to which allelic lineages were shared among 20 African Plasmodium falciparum populations revealed five major geographical groupings. Resistance lineages were common to all sites within these regions. The most marked differentiation was between east and west African P. falciparum, in which resistance alleles were not only of different ancestry but also carried different resistance mutations., Conclusions: Resistant dhps has emerged independently in multiple sites in Africa during the past 10-20 years. Our data show the molecular basis of resistance differs between east and west Africa, which is likely to translate into differing antifolate sensitivity. We have also demonstrated that the dispersal patterns of resistance lineages give unique insights into recent parasite migration patterns.

Background: Sulphadoxine-pyrimethamine (SP) a widely used treatment for uncomplicated malaria and recommended for intermittent preventive treatment of malaria in pregnancy, is being investigated for intermittent preventive treatment of malaria in infants (IPTi). High levels of drug resistance to SP have been reported from north-eastern Tanzania associated with mutations in parasite genes. This study compared the in vivo efficacy of SP in symptomatic 6-59 month children with uncomplicated malaria and in asymptomatic 2-10 month old infants., Methodology and Principal Findings: An open label single arm (SP) standard 28 day in vivo WHO antimalarial efficacy protocol was used in 6 to 59 months old symptomatic children and a modified protocol used in 2 to 10 months old asymptomatic infants. Enrolment was stopped early (87 in the symptomatic and 25 in the asymptomatic studies) due to the high failure rate. Molecular markers were examined for recrudescence, re-infection and markers of drug resistance and a review of literature of studies looking for the 581G dhps mutation was carried out. In symptomatic children PCR-corrected early treatment failure was 38.8% (95% CI 26.8-50.8) and total failures by day 28 were 82.2% (95% CI 72.5-92.0). There was no significant difference in treatment failures between asymptomatic and symptomatic children. 96% of samples carried parasites with mutations at codons 51, 59 and 108 in the dhfr gene and 63% carried a double mutation at codons 437 and 540. 55% carried a third mutation with the addition of a mutation at codon 581 in the dhps gene. This triple: triple haplotype maybe associated with earlier treatment failure., Conclusion: In northern Tanzania SP is a failed drug for treatment and its utility for prophylaxis is doubtful. The study found a new combination of parasite mutations that maybe associated with increased and earlier failure., Trial Registration: ClinicalTrials.gov NCT00361114.

The S108N, C59R, and N51I mutations in the Plasmodium falciparum gene that encodes dihydrofolate reductase, dhfr, confer resistance to pyrimethamine and are common in Africa. However, the I164L mutation, which confers high-level resistance, is rarely seen. We found a 14% prevalence of the I164L mutation among a sample of 51 patients with malaria in Kabale District in southwest Uganda in 2005 and a 4% prevalence among 72 patients with malaria in the neighboring district of Rukungiri during the same year. Surveillance at 6 sites across Uganda during 2002-2004 reported a single case of infection involving an I164L mutant, also in the southwest, suggesting that this is a regional hot spot. The spatial clustering and increasing prevalence of the I164L mutation is indicative of local transmission of the mutant. Targeted surveillance is needed to confirm the extent of the spread of the I164L mutation and to monitor the impact of I164L on the efficacy of antifolates for intermittent preventive treatment of pregnant women and/or infants with falciparum malaria.

The proliferation of antimalarial drug trials in the last ten years provides the opportunity to launch a concerted global surveillance effort to monitor antimalarial drug efficacy. The diversity of clinical study designs and analytical methods undermines the current ability to achieve this. The proposed World Antimalarial Resistance Network (WARN) aims to establish a comprehensive clinical database from which standardised estimates of antimalarial efficacy can be derived and monitored over time from diverse geographical and endemic regions. The emphasis of this initiative is on five key variables which define the therapeutic response. Ensuring that these data are collected at the individual patient level in a consistent format will facilitate better data management and analytical practices, and ensure that clinical data can be readily collated and made amenable for pooled analyses. Such an approach, if widely adopted will permit accurate and timely recognition of trends in drug efficacy. This will guide not only appropriate interventions to deal with established multidrug resistant strains of malaria, but also facilitate prompt action when new strains of drug resistant plasmodia first emerge. A comprehensive global database incorporating the key determinants of the clinical response with in vitro, molecular and pharmacokinetic parameters will bring together relevant data on host, drug and parasite factors that are fundamental contributors to treatment efficacy. This resource will help guide rational drug policies that optimize antimalarial drug use, in the hope that the emergence and spread of resistance to new drugs can be, if not prevented, at least delayed.

Molecular markers for drug resistant malaria represent public health tools of great but mostly unrealized potential value. A key reason for the failure of molecular resistance markers to live up to their potential is that data on the their prevalence is scattered in disparate databases with no linkage to the clinical, in vitro and pharmacokinetic data that are needed to relate the genetic data to relevant phenotypes. The ongoing replacement of older monotherapies for malaria by new, more effective combination therapies presents an opportunity to create an open access database that brings together standardized data on molecular markers of drug resistant malaria from around the world. This paper presents a rationale for creating a global database of molecular markers for drug resistant malaria and for linking it to similar databases containing results from clinical trials of drug efficacy, in vitro studies of drug susceptibility, and pharmacokinetic studies of antimalarial drugs, in a World Antimalarial Resistance Network (WARN). This database will be a global resource, guiding the selection of first line drugs for treating uncomplicated malaria, for preventing malaria in travelers and for intermittent preventive treatment of malaria in pregnant women, infants and other vulnerable groups. Perhaps most important, a global database for molecular markers of drug resistant malaria will accelerate the identification and validation of markers for resistance to artemisinin-based combination therapies and, thereby, potentially prolong the useful therapeutic lives of these important new drugs.