Erratum: Prevalence and distribution of selected cervical human papillomavirus types in HIV infected and HIV uninfected women in South Africa, 1989-2021: A narrative review.

[This corrects the article DOI: 10.4102/sajid.v37i1.363.].

Prevalence and Molecular Epidemiology of Human Coronaviruses in Africa Prior to the SARS-CoV-2 Outbreak: A Systematic Review.

Coronaviruses, re-emerging in human populations, cause mild or severe acute respiratory diseases, and occasionally epidemics. This study systematically reviewed human coronavirus (HCoVs) infections in Africa prior to the SARS-CoV-2 outbreak. Forty studies on the prevalence or molecular epidemiology of HCoVs were available from 13/54 African countries (24%). The first published data on HCoV was from South Africa in 2008. Eight studies (20%) reported on HCoV molecular epidemiology. Endemic HCoV prevalence ranged from 0.0% to 18.2%. The prevalence of zoonotic MERS-CoV ranged from 0.0% to 83.5%. Two studies investigated SARS-CoV infection, for which a prevalence of 0.0% was reported. There was heterogeneity in the type of tests used in determining HCoV prevalence. Two studies reported that risk factors for HCoV include exposure to infected animals or humans. The quantity of virologic investigations on HCoV on the African continent was scant, and Africa was not prepared for SARS-CoV-2.

Early-Life Enteric Pathogen Exposure, Socioeconomic Status, and School-Age Cognitive Outcomes.

Early-life experiences of enteric infections and diarrheal illness are common in low-resource settings and are hypothesized to affect child development. However, longer-term associations of enteric infections with school-age cognitive outcomes are difficult to estimate due to lack of long-term studies. The objective of this study was to examine the relationship between enteropathogen exposure in the first 2 years of life with school-age cognitive skills in a cohort of children followed from birth until 6 to 8 years in low-resource settings in Brazil, Tanzania, and South Africa. The study included participants from three sites from the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health Study who were enrolled just after birth and followed for enteric infections, diarrheal illness, and cognitive development until 2 years of age. When the children were school-age, further data were collected on reasoning skills and semantic/phonemic fluency. We estimated associations between the burden of specific enteric pathogens and etiology-specific diarrhea from 0 to 2 years with cognitive test scores at 6 to 8 years using linear regression and adjusting for confounding variables. In this study, children who carried more enteric pathogens in the first 2 years of life showed overall decreases in school-age cognitive abilities, particularly children who carried protozoa, although this was not statistically significant in this sample. Socioeconomic factors such as maternal education and income were more closely associated with school-age cognitive abilities. Early-life enteric pathogens may have a small, lasting influence on school-age cognitive outcomes, although other socioeconomic factors likely contribute more significantly.

Spatiotemporal variation in risk of Shigella infection in childhood: a global risk mapping and prediction model using individual participant data.

BACKGROUND: Diarrhoeal disease is a leading cause of childhood illness and death globally, and Shigella is a major aetiological contributor for which a vaccine might soon be available. The primary objective of this study was to model the spatiotemporal variation in paediatric Shigella infection and map its predicted prevalence across low-income and middle-income countries (LMICs). METHODS: Individual participant data for Shigella positivity in stool samples were sourced from multiple LMIC-based studies of children aged 59 months or younger. Covariates included household-level and participant-level factors ascertained by study investigators and environmental and hydrometeorological variables extracted from various data products at georeferenced child locations. Multivariate models were fitted and prevalence predictions obtained by syndrome and age stratum. FINDINGS: 20 studies from 23 countries (including locations in Central America and South America, sub-Saharan Africa, and south and southeast Asia) contributed 66 563 sample results. Age, symptom status, and study design contributed most to model performance followed by temperature, wind speed, relative humidity, and soil moisture. Probability of Shigella infection exceeded 20% when both precipitation and soil moisture were above average and had a 43% peak in uncomplicated diarrhoea cases at 33°C temperatures, above which it decreased. Compared with unimproved sanitation, improved sanitation decreased the odds of Shigella infection by 19% (odds ratio [OR]=0·81 [95% CI 0·76-0·86]) and open defecation decreased them by 18% (OR=0·82 [0·76-0·88]). INTERPRETATION: The distribution of Shigella is more sensitive to climatological factors, such as temperature, than previously recognised. Conditions in much of sub-Saharan Africa are particularly propitious for Shigella transmission, although hotspots also occur in South America and Central America, the Ganges-Brahmaputra Delta, and the island of New Guinea. These findings can inform prioritisation of populations for future vaccine trials and campaigns. FUNDING: NASA, National Institutes of Health-The National Institute of Allergy and Infectious Diseases, and Bill & Melinda Gates Foundation.

Molecular epidemiology of SARS-CoV-2 in Northern South Africa: wastewater surveillance from January 2021 to May 2022.

Introduction: Wastewater-based genomic surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) provides a comprehensive approach to characterize evolutionary patterns and distribution of viral types in a population. This study documents the molecular epidemiology of SARS-CoV-2, in Northern South Africa, from January 2021 to May 2022. Methodology: A total of 487 wastewater samples were collected from the influent of eight wastewater treatment facilities and tested for SARS-CoV-2 RNA using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). SARS-CoV-2 positive samples with genome copies/mL ≥1,500 were subjected to allele-specific genotyping (ASG) targeting the Spike protein; 75 SARS-CoV-2 positive samples were subjected to whole genome sequencing (WGS) on the ATOPlex platform. Variants of concern (VoC) and lineages were assigned using the Nextclade and PangoLIN Software. Concordance for VoC between ASG and WGS analyses was determined. Sequence relationship was determined by phylogenetic analysis. Results: Seventy-five percent (365/487) of the influent samples were positive for SARS-CoV-2 RNA. Delta and Omicron VoC were more predominant at a prevalence of 45 and 32%, respectively, and they were detected as early as January and February 2021, while Beta VoC was least detected at a prevalence of 5%. A total of 11/60 (18%) sequences were assigned lineages and clades only, but not a specific VoC name. Phylogenetic analysis was used to investigate the relationship of these sequences to other study sequences, and further characterize them. Concordance in variant assignment between ASG and WGS was seen in 51.2% of the study sequences. There was more intra-variant diversity among Beta VoC sequences; mutation E484K was absent. Three previously undescribed mutations (A361S, V327I, D427Y) were seen in Delta VoC. Discussion and Conclusion: The detection of Delta and Omicron VoCs in study sites earlier in the outbreak than has been reported in other regions of South Africa highlights the importance of population-based approaches over individual sample-based approaches in genomic surveillance. Inclusion of non-Spike protein targets could improve the specificity of ASG, since all VoCs share similar Spike protein mutations. Finally, continuous molecular epidemiology with the application of sensitive technologies such as next generation sequencing (NGS) is necessary for the documentation of mutations whose implications when further investigated could enhance diagnostics, and vaccine development efforts.

Impact of Shigella infections and inflammation early in life on child growth and school-aged cognitive outcomes: Findings from three birth cohorts over eight years.

BACKGROUND: Shigella infections cause inflammation, which has been hypothesized to mediate the associations between Shigella and child development outcomes among children in low-resource settings. We aimed to assess whether early life inflammation and Shigella infections affect school-aged growth and cognitive outcomes from 6-8 years of age. METHODOLOGY/PRINCIPAL FINDINGS: We conducted follow-up assessments of anthropometry, reasoning skills, and verbal fluency in 451 children at 6-8 years of age in the Brazil, Tanzania, and South Africa sites of MAL-ED, a longitudinal birth cohort study. We estimated the associations between Shigella burden and inflammation with linear growth at 2, 5, and 6-8 years of age, and with the cognitive test scores using linear regression and adjusting for potential confounding variables. We also assessed whether inflammation mediated the associations between Shigella and school-aged outcomes using a regression-based approach to mediation analysis. A high prevalence of Shigella was associated with a 0.32 (95% CI: 0.08, 0.56) z-score lower height-for-age z-score (HAZ) at 6-8 years compared to a low prevalence of Shigella. Intestinal inflammation had a smaller association with HAZ at 6-8 years. Shigella burden had small and consistently negative associations with cognitive outcomes in Brazil and Tanzania, but not South Africa, and the estimates were not statistically significant. Systemic inflammation was strongly associated with lower verbal fluency scores in Brazil (semantic fluency z-score difference: -0.57, 95% CI: -1.05, -0.10; phonemic fluency z-score difference: -0.48, 95% CI: -0.93, -0.03). There was no evidence that intestinal inflammation mediated the association between Shigella and HAZ or cognitive outcomes. CONCLUSIONS/SIGNIFICANCE: While Shigella infections were consistently associated with long-term deficits in linear growth, the estimates of the negative associations between Shigella and cognitive outcomes were imprecise and only observed in the Brazil and Tanzania sites. Systemic inflammation was strongly associated with lower semantic and phonemic fluency scores in Brazil only, highlighting the site-specificity of effects.

Pharmacogenetic testing for NAT2 genotypes in a Tanzanian population across the lifespan to guide future personalized isoniazid dosing.

Despite updated recommendations for weight-based isoniazid dosing in children with drug-susceptible tuberculosis (TB) and higher dose isoniazid in regimens for adults with drug-resistant TB, individual pharmacokinetic variability can lead to sub-target isoniazid exposure. Host pharmacogenetics and isoniazid exposure remain understudied, especially in the East African population. We therefore employed a real-time polymerase chain reaction (qPCR) assay system to test genomic DNA extracted from saliva samples targeting the NAT2 gene responsible for isoniazid metabolism to describe the frequency of human single nucleotide polymorphisms in NAT2 within populations of children and adults in Tanzania, ascribe those polymorphisms to acetylator phenotype, and correlate to serum isoniazid exposures. In adults treated with higher dose isoniazid, genotypes with a predicted allelic phenotype of slow or intermediate acetylation were able to achieve a 0.41 µg/mL higher Cmax (p = 0.018) and a 2.9h*µg/mL higher AUC0-12 (p = 0.003) per mg/kg increase in isoniazid dosage versus adults with rapid acetylation phenotype. A similar relationship was not found in the younger age population as predicted by timing of NAT2 maturation. This saliva based qPCR assay was fieldable to guide personalized isoniazid dosing in adults but not young children that may not have full NAT2 maturation and activity.

Frequency of bystander exposure to antibiotics for enteropathogenic bacteria among young children in low-resource settings.

Children in low-resource settings carry enteric pathogens asymptomatically and are frequently treated with antibiotics, resulting in opportunities for pathogens to be exposed to antibiotics when not the target of treatment (i.e., bystander exposure). We quantified the frequency of bystander antibiotic exposures for enteric pathogens and estimated associations with resistance among children in eight low-resource settings. We analyzed 15,697 antibiotic courses from 1,715 children aged 0 to 2 y from the MAL-ED birth cohort. We calculated the incidence of bystander exposures and attributed exposures to respiratory and diarrheal illnesses. We associated bystander exposure with phenotypic susceptibility of E. coli isolates in the 30 d following exposure and at the level of the study site. There were 744.1 subclinical pathogen exposures to antibiotics per 100 child-years. Enteroaggregative Escherichia coli was the most frequently exposed pathogen, with 229.6 exposures per 100 child-years. Almost all antibiotic exposures for Campylobacter (98.8%), enterotoxigenic E. coli (95.6%), and typical enteropathogenic E. coli (99.4%), and the majority for Shigella (77.6%), occurred when the pathogens were not the target of treatment. Respiratory infections accounted for half (49.9%) and diarrheal illnesses accounted for one-fourth (24.6%) of subclinical enteric bacteria exposures to antibiotics. Bystander exposure of E. coli to class-specific antibiotics was associated with the prevalence of phenotypic resistance at the community level. Antimicrobial stewardship and illness-prevention interventions among children in low-resource settings would have a large ancillary benefit of reducing bystander selection that may contribute to antimicrobial resistance.

Burden, Clinical Characteristics, Risk Factors, and Seasonality of Adenovirus 40/41 Diarrhea in Children in Eight Low-Resource Settings.

Background: The application of molecular diagnostics has identified enteric group adenovirus serotypes 40 and 41 as important causes of diarrhea in children. However, many aspects of the epidemiology of adenovirus 40/41 diarrhea have not been described. Methods: We used data from the 8-site Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development Project birth cohort study to describe site- and age-specific incidence, risk factors, clinical characteristics, and seasonality. Results: The incidence of adenovirus 40/41 diarrhea was substantially higher by quantitative polymerase chain reaction than enzyme immunoassay and peaked at ∼30 episodes per 100 child-years in children aged 7-15 months, with substantial variation in incidence between sites. A significant burden was also seen in children 0-6 months of age, higher than other viral etiologies with the exception of rotavirus. Children with adenovirus 40/41 diarrhea were more likely to have a fever than children with norovirus, sapovirus, and astrovirus (adjusted odds ratio [aOR], 1.62; 95% CI, 1.16-2.26) but less likely than children with rotavirus (aOR, 0.66; 95% CI, 0.49-0.91). Exclusive breastfeeding was strongly protective against adenovirus 40/41 diarrhea (hazard ratio, 0.64; 95% CI, 0.48-0.85), but no other risk factors were identified. The seasonality of adenovirus 40/41 diarrhea varied substantially between sites and did not have clear associations with seasonal variations in temperature or rainfall. Conclusions: This study supports the situation of adenovirus 40/41 as a pathogen of substantial importance, especially in infants. Fever was a distinguishing characteristic in comparison to other nonrotavirus viral etiologies, and promotion of exclusive breastfeeding may reduce the high observed burden in the first 6 months of life.

Prevalence and distribution of selected cervical human papillomavirus types in HIV infected and HIV uninfected women in South Africa, 1989-2021: A narrative review.

Background: Human papillomavirus infection, a causative agent of cervical cancer, is of great concern, more so in populations with high HIV prevalence, such as South Africa. Aim: This review aimed to examine the prevalence and distribution of selected cervical human papillomavirus (HPV) types in HIV infected and HIV uninfected women in South Africa. Methods: PubMed and Web of Science databases were searched using key words. For data integrity, data was assessed by two authors independently. The study inclusion criteria comprised records on cervical HPV, HPV genotyping and HPV type distribution among South African women. Statistical analysis was performed using Social Science Statistics. Results: Sixty-nine articles met the inclusion criteria for analysis. Data on cervical HPV prevalence and type distribution was available only for five of the nine provinces of South Africa. Only 4/69 studies used sequencing as an approach to identify HPV types. In a general population, HPV type 16 was the most frequent (8.80%), followed by types 35 (4.86%), 18 (4.14%), 58 and 52 with the frequency of 3.65% and 3.62%, respectively. Furthermore, the least frequent type was HPV 70 (0.74%). Both HIV infected and HIV uninfected populations had a higher prevalence of high-risk human papillomavirus (hrHPV) types 16, 18 and 35 than other HPV types; while HPV types 6, 11 and 70 were the least frequent types from these populations. Lastly, HPV 16 was the most predominant type among women with normal (2.03%) and abnormal cervical cytology (6.60%). Conclusion: Expanding on HPV genotyping will improve the knowledge in patterns of HPV type distribution in South Africa that will further help in decision making to improve current diagnostics, and future vaccine development and assessment.

Epidemiology of Campylobacter infections among children of 0-24 months of age in South Africa.

BACKGROUND: Campylobacter spp. are one of the most frequent causes of diarrhoeal disease in humans throughout the world. This study aimed at determining the prevalence and the genotypic distribution of Campylobacter spp. and their association with diarrhoea and child growth in children of less than the age of two in the Limpopo Province of South Africa. METHODS: A total of 4280 diarrheal and non-diarrheal stool samples were collected on a monthly basis from children recruited at birth and followed up to 24 months. All stool samples were screened for the presence Campylobacter antigen using ELISA technique after which CAH 16S primer was used on the positive samples to confirm the presence of Campylobacter. Subsequently, the PCR positive samples were further characterised using species specific primers for Campylobacter jejuni and Campylobacter coli. RESULTS: Campylobacter antigen was detected in 564/4280 (13.2%). Campylobacter was more commonly found in diarrheal stools (20.4%) compared to non-diarrheal stools (12.4%) with a statistically significant difference (χ2 = 7.345; p = 0.006). Throughout the year there were two main peaks of Campylobacter infection one in December- January and the second peak in June. The prevalence of Campylobacter increased with the age of the children up to 11 months after which the prevalence decreased. Out of 564 positive ELISA samples, 257 (45.6%) were confirmed to have 16S rRNA gene for Campylobacter spp. Furthermore, C. jejuni was found to be more prevalent (232/257) than C. coli (25/257) with a prevalence of 90.3% and 9.7%, respectively. Both C. jejuni and C. coli were significantly associated with diarrhea with statistical values of (χ2 = 22.224; p < 0.001) and (χ2 = 81.682; p < 0.001) respectively. Sequences generated from the analysis of hip gene confirmed the PCR positives samples were C. jejuni positive. CONCLUSIONS: This study has delineated a high prevalence of Campylobacter spp. in the study cohort. Moreover, C. jejuni was found to be more prevalent than C. coli both of which were associated with diarrhea. These findings are of clinical and epidemiological significance.

Associations Between Eight Earth Observation-Derived Climate Variables and Enteropathogen Infection: An Independent Participant Data Meta-Analysis of Surveillance Studies With Broad Spectrum Nucleic Acid Diagnostics.

Diarrheal disease, still a major cause of childhood illness, is caused by numerous, diverse infectious microorganisms, which are differentially sensitive to environmental conditions. Enteropathogen-specific impacts of climate remain underexplored. Results from 15 studies that diagnosed enteropathogens in 64,788 stool samples from 20,760 children in 19 countries were combined. Infection status for 10 common enteropathogens-adenovirus, astrovirus, norovirus, rotavirus, sapovirus, Campylobacter, ETEC, Shigella, Cryptosporidium and Giardia-was matched by date with hydrometeorological variables from a global Earth observation dataset-precipitation and runoff volume, humidity, soil moisture, solar radiation, air pressure, temperature, and wind speed. Models were fitted for each pathogen, accounting for lags, nonlinearity, confounders, and threshold effects. Different variables showed complex, non-linear associations with infection risk varying in magnitude and direction depending on pathogen species. Rotavirus infection decreased markedly following increasing 7-day average temperatures-a relative risk of 0.76 (95% confidence interval: 0.69-0.85) above 28°C-while ETEC risk increased by almost half, 1.43 (1.36-1.50), in the 20-35°C range. Risk for all pathogens was highest following soil moistures in the upper range. Humidity was associated with increases in bacterial infections and decreases in most viral infections. Several virus species' risk increased following lower-than-average rainfall, while rotavirus and ETEC increased with heavier runoff. Temperature, soil moisture, and humidity are particularly influential parameters across all enteropathogens, likely impacting pathogen survival outside the host. Precipitation and runoff have divergent associations with different enteric viruses. These effects may engender shifts in the relative burden of diarrhea-causing agents as the global climate changes.

Full breastfeeding protection against common enteric bacteria and viruses: results from the MAL-ED cohort study.

BACKGROUND: Breastfeeding is known to reduce the risk of enteropathogen infections, but protection from specific enteropathogens is not well characterized. OBJECTIVE: The aim was to estimate the association between full breastfeeding (days fed breast milk exclusively or with nonnutritive liquids) and enteropathogen detection. METHODS: A total of 2145 newborns were enrolled at 8 sites, of whom 1712 had breastfeeding and key enteropathogen data through 6 mo. We focused on 11 enteropathogens: adenovirus 40/41, norovirus, sapovirus, astrovirus, and rotavirus, enterotoxigenic Escherichia coli (ETEC), Campylobacter spp., and typical enteropathogenic E. coli as well as entero-aggregative E. coli, Shigella and Cryptosporidium. Logistic regression was used to estimate the risk of enteropathogen detection in stools and survival analysis was used to estimate the timing of first detection of an enteropathogen. RESULTS: Infants with 10% more days of full breastfeeding within the preceding 30 d of a stool sample were less likely to have the 3 E. coli and Campylobacter spp. detected in their stool (mean odds: 0.92-0.99) but equally likely (0.99-1.02) to have the viral pathogens detected in their stool. A 10% longer period of full breastfeeding from birth was associated with later first detection of the 3 E. coli, Campylobacter, adenovirus, astrovirus, and rotavirus (mean HRs of 0.52-0.75). The hazards declined and point estimates were not statistically significant at 3 mo. CONCLUSIONS: In this large multicenter cohort study, full breastfeeding was associated with lower likelihood of detecting 4 important enteric pathogens in the first 6 mo of life. These results also show that full breastfeeding is related to delays in the first detection of some bacterial and viral pathogens in the stool. As several of these pathogens are risk factors for poor growth during childhood, this work underscores the importance of exclusive or full breastfeeding during the first 6 mo of life to optimize early health.

Drug Resistance Mutations in a Population Before Antiretroviral Therapy Initiation in Northern South Africa.

South Africa introduced the "diagnose and treat" universal HIV treatment program in September 2016. This program enables all identified HIV-positive patients to immediately start first-line antiretroviral therapy (ART). However, the presence of drug-resistant (DR) viruses in the drug-naive population complicates the choice of ART. We used next-generation sequencing (NGS) to determine the prevalence and diversity of HIV DR mutations in patients entering HIV treatment programs in northern South Africa. RNA was isolated from plasma of drug-naive HIV-1-infected patients. Using reverse transcriptase polymerase chain reaction, the HIV-1-pol gene comprising the complete protease (PR) and the first 900 bp of reverse transcriptase (RT) was amplified and sequenced on an Illumina MiniSeq platform. Consensus sequences were derived at >20% threshold and at >5% threshold using Geneious PRIME® software version 2020.1.2. HIV-1 surveillance drug resistance mutations (SDRM) were inferred using Calibrated Population Resistance tool in HIV Drug Resistance Database. Viral subtypes were determined using REGA and RIP genotyping tools. The HIV PR/RT region was successfully sequenced from 241 patients. From these, 23 (9.5%) had at least one SDRM detected at >20% threshold, with a prevalence of 9.5% (n = 18), 3% (n = 7), and 0.4% (n = 1) for non-nucleoside reverse transcriptase inhibitors (NNRTI), nucleoside reverse transcriptase inhibitors (NRTI), and protease inhibitors (PI), respectively. The number of patients with SDRM increased to 31 (12.9%) when minority variants were accounted for at >5% threshold. The most frequent SDRMs based on drug class were; K103N (7.9%-NNRTI), K65R (2.5%-NRTI), and D30N (0.8%-PI). Four cases of dual NRTI/NNRTI mutations were identified. All consensus sequences were subtype C, except three, which were C/A1, C/F1, and C/G recombinants. NGS analysis confirms that individuals entering HIV treatment programs in northern South Africa, habor moderate levels of SDRM, including cases of dual-class drug resistance. Further SDRM studies may be required to better understand resistance in the drug-naive population in the era of "diagnose and treat" in Limpopo Province, South Africa.

Influences on catch-up growth using relative versus absolute metrics: evidence from the MAL-ED cohort study.

BACKGROUND: Poor growth in early childhood has been considered irreversible after 2-3 years of age and has been associated with morbidity and mortality over the short-term and with poor economic and cognitive outcomes over the long-term. The MAL-ED cohort study was performed in eight low-income settings with the goal of evaluating relationships between the child's environment and experience (dietary, illness, and pathogen exposure, among others) and their growth and development. The goal of this analysis is to determine whether there are differences in the factors associated with growth from 24 to 60 months using two different metrics. METHODS: Across six MAL-ED sites, 942 children had anthropometry data at 24 and 60 months, as well as information about socioeconomic status, maternal height, gut permeability (lactulose-mannitol z-score (LMZ)), dietary intake from 9 to 24 months, and micronutrient status. Anthropometric changes were in height- or weight-for-age z-score (HAZ, WAZ), their absolute difference from the growth standard median (HAD (cm), WAD (kg)), as well as recovery from stunting/underweight. Outcomes were modeled using multivariate regression. RESULTS: At 24 months, almost half of the cohort was stunted (45%) and 21% were underweight. Among those who were stunted at 24 months (n = 426), 185 (43%) were no longer stunted at 60 months. Most children increased their HAZ from 24 to 60 months (81%), whereas fewer (33%) had positive changes in their HAD. Linear regression models indicate that girls improved less than boys from 24 to 60 months (HAZ: -0.21 (95% CI -0.27, -0.15); HAD: -0.75 (-1.07, -0.43)). Greater intestinal permeability (higher LMZ) at 0-24 months was associated with lower relative and absolute changes from 24 to 60 months (HAZ: -0.10 (-0.16, -0.04); HAD: -0.47 (-0.73, -0.21)). Maternal height (per 10 cm) was positively associated with changes (HAZ: 0.09 (0.03, 0.15); HAD: 0.45 (0.15, 0.75)). Similar relationships were identified for changes in WAZ and WAD. CONCLUSIONS: The study children demonstrated improved growth from 24 to 60 months of age, but only a subset had positive changes in HAD and WAD. The same environmental factors were associated with growth from 24 to 60 months regardless of metric used (change in HAZ or HAD, or WAZ and WAD).

Embedding Usage Sensors in Point-of-Use Water Treatment Devices: Sensor Design and Application in Limpopo, South Africa.

Health benefits from point-of-use (POU) water treatment devices come only with consistent use. Embedded sensors can measure the consistency of POU-device use and can provide insights about improving it. We demonstrate both potentials with data from SmartSpouts: accelerometer-based sensors embedded in spigot handles that record the duration and timing of use. In the laboratory, most sensor readings correlated well (>0.98) with manually timed water withdrawals. In the field, SmartSpouts measured >60,000 water withdrawals across 232 households in Limpopo, South Africa. Sensors proved critical to understanding consistent use; surveys overestimated it by 53 percentage points. Sensor data showed when households use POU devices (evening peaks and delayed weekend routines) and user preferences (safe storage over filters). We demonstrate analytically and with data that (i) consistent use (e.g., 7 continuous days) is extremely sensitive to single-day use prevalence and (ii) use prevalence affects the performance of contact-time-based POU devices, exemplified with silver tablets. Deployed SmartSpouts had limitations, including memory overflows and confounding device relocation with water withdrawal. Nevertheless, SmartSpouts provided useful and objective data on the prevalence of single-day and consistent use. Considerably less expensive than alternatives, SmartSpouts enable an order of magnitude increase in how many POU-device sensors can be deployed.

Undisclosed exposure to antiretrovirals prior to treatment initiation: An exploratory analysis.

BACKGROUND: The proportion of individuals with a history of exposure ('pre-exposure') to antiretrovirals (ARVs) prior to formal initiation into antiretroviral treatment (ART) is unknown. OBJECTIVES: This study describes the detection of ARVs in plasma and/or hair, of persons who self-reported no pre-exposure to ART at their first-time initiation onto ART in three clinics in the province of Limpopo, South Africa (SA). METHOD: Concentrations of tenofovir (TDF), emtricitabine (FTC) and efavirenz (EFV) in the plasma and hair of individuals initiating ART were analysed using a validated liquid chromatography tandem mass spectrometry (LC-MS/MS) method. Next generation sequences of HIV polymerase gene were analysed with Geneious software 11.15, and drug resistance (DR) mutations were determined according to the Stanford HIV Drug-Resistance database. Participants' demographic data were collected on a structured questionnaire. Data that describe prior exposure to ARV were also collected by this self-reporting method. RESULTS: Paired blood and hair samples were collected from 77 individuals newly initiated onto ART from 2017 to 2019. We detected at least one of the drugs in the plasma or hair of 41/77 (53.2%) patients who responded with a 'no' to the question 'have you received ARVs before initiation onto ART?' Thirty-one participants (n = 31/77, 40.3%) had TDF in either plasma or hair. Emtricitabine and EFV were found in the plasma or hair of 12/77 (15.6%) and 25/77 (32.4%) of participants respectively. Six (n = 6/77, 7.792%) had all three ARVs in plasma or hair. Prevalence of DR mutations at the > 5% significance threshold level in those known to have had ARV-exposure determined by LC-MS/MS prior to ART-initiation was not significant (χ2 = 0.798; p = 0.372), when compared to those who had no prior exposure but still showed DR. CONCLUSION: Antiretroviral levels in the hair of individuals initiating treatment imply prolonged prior-exposure to that ARV. The presence of ARV in plasma and hair of persons living with HIV (PLWH) who deny ARV-use, requires an explanation. A larger study at multiple sites and regular DR surveillance of ART-naïve PLWH will be necessary to confirm the generalisability of these findings to the wider South African population.

Community knowledge, attitudes and practices towards malaria in Ha-Lambani, Limpopo Province, South Africa: a cross-sectional household survey.

BACKGROUND: Malaria remains a global health concern and is endemic in Limpopo, Mpumalanga and KwaZulu Natal Provinces of South Africa, which aims to eliminate malaria by 2025. Community engagement plays a significant role in improving the acceptability and effectiveness of programmes aimed at reducing malaria transmission. The success of such intervention efforts depends on the knowledge, attitudes and practices (KAP) of the community, and understanding the KAP of community residents may support malaria control efforts in the locality. In this context, a cross-sectional household survey to assess community KAP on malaria transmission and prevention in the Ha-Lambani village, Vhembe District, Limpopo Province was conducted. METHODS: Data were collected between November 2018 and May 2019 by questionnaire of 261 consenting adults (213 females and 48 males, aged between 18 and 95 years) selected from different households. Also, a focus group discussion among 13 randomly selected participants was conducted. Pearson's Chi Square test was used to determine statistical differences by village. RESULTS: Study participants (100%, 261/261) were aware of the presence of malaria in their community and 95% associated it with mosquito bites. The local health clinic was the most prominent source of malaria information (85%). Only 22% correctly identified headache, chills and fever as the three most common symptoms of malaria. The majority of participants (98%) knew that effective medication for malaria is available and had a positive treatment-seeking behaviour. Knowledge of malaria prevention measures was high (82%); contrarily, 97% of respondents did not sleep under a bed net the previous night. The focus group data concurred with these results and also revealed that poor bed net use resulted from lack of access to bed nets because community residents could not afford them. CONCLUSIONS: The study demonstrates that participants have appropriate knowledge about malaria transmission and a positive treatment-seeking behaviour. However, economic barriers are responsible for the inadequate use of bed nets. Therefore, distribution of bed nets to the community should be considered to improve practice of malaria prevention measures. Furthermore, knowledge of signs and symptoms and appropriate malaria treatment was limited, and initiatives to improve awareness on these topics should be continued.

Potential challenges to sustained viral load suppression in the HIV treatment programme in South Africa: a narrative overview.

BACKGROUND: South Africa, with one of the highest HIV prevalences in the world, introduced the universal test and treat (UTT) programme in September 2016. Barriers to sustained viral suppression may include drug resistance in the pre-treated population, non-adherence, acquired resistance; pharmacokinetics and pharmacodynamics, and concurrent use of alternative treatments. OBJECTIVE: The purpose of this review is to highlight potential challenges to achieving sustained viral load suppression in South Africa (SA), a major expectation of the UTT initiative. METHODOLOGY: Through the PRISMA approach, published articles from South Africa on transmitted drug resistance; adherence to ARV; host genetic factors in drug pharmacokinetics and pharmacodynamics, and interactions between ARV and herbal medicine were searched and reviewed. RESULTS: The level of drug resistance in the pre-treated population in South Africa has increased over the years, although it is heterogeneous across and within Provinces. At least one study has documented a pre-treated population with moderate (> 5%) or high (> 15%) levels of drug resistance in eight of the nine Provinces. The concurrent use of ARV and medicinal herbal preparation is fairly common in SA, and may be impacting negatively on adherence to ARV. Only few studies have investigated the association between the genetically diverse South African population and pharmacokinetics and pharmacodynamics of ARVs. CONCLUSION: The increasing levels of drug resistant viruses in the pre-treated population poses a threat to viral load suppression and the sustainability of first line regimens. Drug resistance surveillance systems to track the emergence of resistant viruses, study the burden of prior exposure to ARV and the parallel use of alternative medicines, with the goal of minimizing resistance development and virologic failure are proposed for all the Provinces of South Africa. Optimal management of the different drivers of drug resistance in the pre-treated population, non-adherence, and acquired drug resistance will be beneficial in ensuring sustained viral suppression in at least 90% of those on treatment, a key component of the 90-90-90 strategy.