Non-booking for antenatal care and risks for vertical HIV transmission among women in Chitungwiza, Zimbabwe: a cross-sectional study

Background: The success of prevention of mother to child transmission of HIV (PMTCT) programs dependents on pregnant women accessing antenatal care (ANC) services. Failure to access ANC throughout the course of pregnancy presents a missed opportunity to fully utilize PMTCT services and a high risk for vertical HIV transmission. Whilst not booking for ANC was about 6% in Zimbabwe, according to the 2015 Zimbabwe Demographic and Health Survey, it is important to determine the local burden of pregnant women both un-booked for ANC and living with HIV. in Chitungwiza city, to inform local response. This study aimed at determining the proportion of women un-booked for antenatal care and among them, the proportion of women who were with HIV and to identify risk factors associated with not-booking for ANC in Chitungwiza city in Zimbabwe

Pharmacokinetic-pharmacodynamic modelling of atazanavir in hair among adolescents on antiretroviral treatment in Zimbabwe

CITATION: Ngara, B., et al. 2021. Pharmacokinetic-pharmacodynamic modelling of atazanavir in hair among adolescents on antiretroviral treatment in Zimbabwe. BMC Pharmacology and Toxicology, 22:29, doi:10.1186/s40360-021-00497-8.The original publication is available at https://bmcpharmacoltoxicol.biomedcentral.comBackground: Drug potency is a pharmacological parameter defining dose or concentration of drug required to obtain 50% of the drug’s maximal effect. Pharmacokinetic-pharmacodynamic modelling and simulation allows estimation of potency and evaluate strategies improving treatment outcome. The objective of our study is to determine potency of atazanavir in hair, defined as atazanavir level in hair associated with 50% probability of failing to achieve viral load below 1000 copies/ml among adolescents, and explore the effect of participant specific variables on potency. Methods: A secondary analysis was performed on data from a previous study conducted in HIV-infected adolescents failing 2nd line ART from Harare central hospital, Zimbabwe, between 2015 and 2016. We simulated atazanavir concentrations in hair using NONMEM (version 7.3) ADVAN 13, based on a previously established pharmacokinetic model. Logistic regression methods were used for PKPD analysis. Simulations utilising PKPD model focused on estimation of potency and exploring the effect of covariates. Results: The potency of atazanavir in hair was found to be 4.5 ng/mg hair before adjusting for covariate effects. Participants at three months follow-up, reporting adequate adherence, having normal BMI-for-age, and cared for by mature guardians had increased potency of atazanavir in hair of 2.6 ng/mg, however the follow-up event was the only statistically significant factor at 5% level. Conclusion: Atazanavir in hair in the range 2.6 to 4.5 ng/mg is associated with above 50% probability of early viral load suppression. Adherence monitoring to adolescents with lower potency of atazanavir is recommended. The effect self-reported adherence level, BMI-for-age, and caregiver status require further evaluation.https://bmcpharmacoltoxicol.biomedcentral.com/articles/10.1186/s40360-021-00497-8Publisher's versio

Risk factors for COVID-19 among healthcare workers. A protocol for a systematic review and meta-analysis

Evidence on the spectrum of risk factors for infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among front-line healthcare workers (HCWs) has not been well-described. While several studies evaluating the risk factors associated with SARS-CoV-2 infection among patient-facing and non-patient-facing front-line HCWs have been reported since the outbreak of the coronavirus disease in 2019 (COVID-19), and several more are still underway. There is, therefore, an immediate need for an ongoing, rigorous systematic review that continuously assesses the risk factors of SARS-CoV-2 infection among front-line HCWs.Here, we outline a protocol to serve as a guideline for conducting a living systematic review and meta-analysis to examine the burden of COVID-19 on front-line HCWs and identify risk factors for SARS-CoV-2 infection in patient-facing and non-patient-facing front-line HCWs

Evaluation of the protective efficacy of Olyset®Plus ceiling net on reducing malaria prevalence in children in Lake Victoria Basin, Kenya: study protocol for a cluster-randomized controlled trial.

BACKGROUND: In the Lake Victoria Basin of western Kenya, malaria remains highly endemic despite high coverage of interventions such as insecticide-impregnated long-lasting insecticidal nets (LLIN). The malaria-protective effect of LLINs is hampered by insecticide resistance in Anopheles vectors and its repurposing by the community. Ceiling nets and LLIN with synergist piperonyl butoxide (PBO-LLIN) are novel tools that can overcome the problems of behavioral variation of net use and metabolic resistance to insecticide, respectively. The two have been shown to reduce malaria prevalence when used independently. Integration of these two tools (i.e., ceiling nets made with PBO-LLIN or Olyset®Plus ceiling nets) appears promising in further reducing the malaria burden. METHODS: A cluster-randomized controlled trial is designed to assess the effect of Olyset®Plus ceiling nets on reducing malaria prevalence in children on Mfangano Island in Homa Bay County, where malaria transmission is moderate. Olyset®Plus ceiling nets will be installed in 1315 residential structures. Malaria parasitological, entomological, and serological indicators will be measured for 12 months to compare the effectiveness of this new intervention against conventional LLIN in the control arm. DISCUSSION: Wider adoption of Olyset®Plus ceiling nets to complement existing interventions may benefit other malaria-endemic counties and be incorporated as part of Kenya's national malaria elimination strategy. TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000045079. Registered on 4 August 2021

COVID-19 prevalence among healthcare workers. A systematic review and meta-analysis

Understanding the burden of SARS-CoV-2 infections among healthcare workers is a critical component to inform occupational health policy and strategy. We conducted a systematic review and meta-analysis to map and analayse the available global evidence on the prevalence of SARS-CoV-2 infections among healthcare workers. The random-effects adjusted pooled prevalence of COVID-19 among those studies that conducted the test using the antibody (Ab) method was 7% [95% CI: 3 to 17%]. The random-effects adjusted pooled prevalence of COVID-19 among those studies that conducted the test using the PCR method was 11% [95% CI: 7 to 16%]. We found the burden of COVID-19 among healthcare workers to be quite significant and therefore a cause for global health concern. Furthermore, COVID-19 infections among healthcare workers affect service delivery through workers’ sick leave, the isolation of confirmed cases and quarantine of contacts, all of which place significant strain on an already shrunken health workforce.SUPPLEMENTARY MATERIALS : SUPPLEMENTARY FILE S1: PRISMA Flow Diagram, SUPPLEMENTARY FILE S2: List of full text articles reviewed, SUPPLEMENTARY FILE S3: Distribution of COVID-19 burden among health care workers in included studies, SUPPLEMENTARY FILE S4: Characteristics of included studies, SUPPLEMENTARY FILE S5: Egger’s plots for assessing the presence of publication bias for the meta-analysis, SUPPLEMENTARY FILE S6: Presentation of findings for assessing and accounting for small-study effects.https://www.mdpi.com/journal/ijerphSchool of Health Systems and Public Health (SHSPH

Risk factors for COVID-19 infection among healthcare workers. A first report from a living systematic review and meta-analysis

Health care workers (HCWs) are more than ten times more likely to be infected with coronavirus infectious disease 2019 (COVID-19) than the general population, thus demonstrating the burden of COVID- 19 among HCWs. Factors that expose HCWs to a differentially high-risk of COVID-19 acquisition are important to elucidate, enable appropriate public health interventions to mitigate against high risk and reduce adverse outcomes from the infection. We conducted a systematic review and meta-analysis to summarize and critically analyze the existing evidence on SARS-CoV-2 risk factors among HCWs. With no geographical limitation, we included studies, in any country, that reported (i) the PCR laboratory diagnosis of COVID-19 as an independent variable (ii) one or more COVID-19 risk factors among HCWs with risk estimates (relative risk, odds ratio, or hazard ratio) (iii) original, quantitative study design, and published in English or Mandarian. Our initial search resulted in 470 articles overall, however, only 10 studies met the inclusion criteria for this review. Out of the 10 studies included in the review, inadequate/ lack of protective personal equipment, performing tracheal intubation, and gender were the most common risk factors of COVID-19. Based on the random effects adjusted pooled relative risk, HCWs who reported the use of protective personal equipment were 29% (95% CI: 16% to 41%) less likely to test positive for COVID-19. The study also revealed that HCWs who performed tracheal intubations were 34% (95% CI: 14% to 57%) more likely to test positive for COVID-19. Interestingly, this study showed that female HCWs are at 11% higher risk (RR 1.11 95% CI 1.01e1.21) of COVID-19 than their male counterparts. This article presents initial findings from a living systematic review and meta-analysis, therefore, did not yield many studies; however, it revealed a significant insight into better understanding COVID-19 risk factors among HCWs; insights important for devising preventive strategies that protect them from this infection.http://www.e-shaw.netam2023School of Health Systems and Public Health (SHSPH

Risk factors for COVID-19 infection among healthcare workers. A first report from a living systematic review and meta-analysis

Health care workers (HCWs) are more than ten times more likely to be infected with COVID-19 compared to the general population, thus demonstrating the burden of COVID-19 among HCWs. Factors that expose HCWs to a differentially high-risk of COVID-19 acquisition are important to elucidate, to enable appropriate public health interventions to mitigate against high risk and reduce adverse outcomes from the infection. We conducted a systematic review and meta analysis to summarise and critically analyse the existing evidence on SARS-CoV-2 risk factors among HCWs. With no geographical limitation, we included studies, in any country, that reported (i) PCR laboratory diagnosis of COVID—19 as an independent variable (ii) one or more COVID-19 risk factors among health care workers with risk estimates (relative risk, odds ratio or harzard ratio) (iii) original, quantitative study design and published in English or Mandarian. Our initial search resulted in 470 articles overall, however, only 10 studies met the inclusion criteria for this review. Out of the 10 studies included in the review, inadequate/lack of protective personal equipment (PPE), performing tracheal intubation (PTI) and gender were the most common risk factors of COVID-19. Based on the random effects adjusted pooled relative risk, HCWs who reported use PPE were 29% (95% CI: 16% to 41%) less likely to test positive for COVID-19. The study also revealed that HCWs who performed tracheal intubations were 34% (95% CI: 14% to 57%) more likely to test positive for COVID-19. Interestingly, this study showed that female HCWs are at 11% higher risk (RR 1.11 95% CI 1.01-1.21) of COVID-19 than their male counterparts. This paper presents initial findings from a living systematic review and meta-analysis, therefore, did not yield many studies, however, it revealed a significant insight to better understand COVID-19 risk factors among HCWs; insights important for devising preventive strategies that protect them from this infection

Independent and combined effects of improved water, sanitation, and hygiene, and improved complementary feeding, on child stunting and anaemia in rural Zimbabwe: a cluster-randomised trial.

BACKGROUND: Child stunting reduces survival and impairs neurodevelopment. We tested the independent and combined effects of improved water, sanitation, and hygiene (WASH), and improved infant and young child feeding (IYCF) on stunting and anaemia in in Zimbabwe. METHODS: We did a cluster-randomised, community-based, 2 × 2 factorial trial in two rural districts in Zimbabwe. Clusters were defined as the catchment area of between one and four village health workers employed by the Zimbabwe Ministry of Health and Child Care. Women were eligible for inclusion if they permanently lived in clusters and were confirmed pregnant. Clusters were randomly assigned (1:1:1:1) to standard of care (52 clusters), IYCF (20 g of a small-quantity lipid-based nutrient supplement per day from age 6 to 18 months plus complementary feeding counselling; 53 clusters), WASH (construction of a ventilated improved pit latrine, provision of two handwashing stations, liquid soap, chlorine, and play space plus hygiene counselling; 53 clusters), or IYCF plus WASH (53 clusters). A constrained randomisation technique was used to achieve balance across the groups for 14 variables related to geography, demography, water access, and community-level sanitation coverage. Masking of participants and fieldworkers was not possible. The primary outcomes were infant length-for-age Z score and haemoglobin concentrations at 18 months of age among children born to mothers who were HIV negative during pregnancy. These outcomes were analysed in the intention-to-treat population. We estimated the effects of the interventions by comparing the two IYCF groups with the two non-IYCF groups and the two WASH groups with the two non-WASH groups, except for outcomes that had an important statistical interaction between the interventions. This trial is registered with ClinicalTrials.gov, number NCT01824940. FINDINGS: Between Nov 22, 2012, and March 27, 2015, 5280 pregnant women were enrolled from 211 clusters. 3686 children born to HIV-negative mothers were assessed at age 18 months (884 in the standard of care group from 52 clusters, 893 in the IYCF group from 53 clusters, 918 in the WASH group from 53 clusters, and 991 in the IYCF plus WASH group from 51 clusters). In the IYCF intervention groups, the mean length-for-age Z score was 0·16 (95% CI 0·08-0·23) higher and the mean haemoglobin concentration was 2·03 g/L (1·28-2·79) higher than those in the non-IYCF intervention groups. The IYCF intervention reduced the number of stunted children from 620 (35%) of 1792 to 514 (27%) of 1879, and the number of children with anaemia from 245 (13·9%) of 1759 to 193 (10·5%) of 1845. The WASH intervention had no effect on either primary outcome. Neither intervention reduced the prevalence of diarrhoea at 12 or 18 months. No trial-related serious adverse events, and only three trial-related adverse events, were reported. INTERPRETATION: Household-level elementary WASH interventions implemented in rural areas in low-income countries are unlikely to reduce stunting or anaemia and might not reduce diarrhoea. Implementation of these WASH interventions in combination with IYCF interventions is unlikely to reduce stunting or anaemia more than implementation of IYCF alone. FUNDING: Bill & Melinda Gates Foundation, UK Department for International Development, Wellcome Trust, Swiss Development Cooperation, UNICEF, and US National Institutes of Health.The SHINE trial is funded by the Bill & Melinda Gates Foundation (OPP1021542 and OPP113707); UK Department for International Development; Wellcome Trust, UK (093768/Z/10/Z, 108065/Z/15/Z and 203905/Z/16/Z); Swiss Agency for Development and Cooperation; US National Institutes of Health (2R01HD060338-06); and UNICEF (PCA-2017-0002)

A population pharmacokinetic model is beneficial in quantifying hair concentrations of ritonavir-boosted atazanavir : a study of HIV-infected Zimbabwean adolescents

CITATION:Ngara, B., et al. 2020. A population pharmacokinetic model is beneficial in quantifying hair concentrations of ritonavir-boosted atazanavir : a study of HIV-infected Zimbabwean adolescents. BMC Pharmacology and Toxicology, 21:58, doi:10.1186/s40360-020-00437-y.The original publication is available at https://bmcpharmacoltoxicol.biomedcentral.comBackground: Adolescents experience higher levels of non-adherence to HIV treatment. Drug concentration in hair promises to be reliable for assessing exposure to antiretroviral (ARV) drugs. Pharmacokinetic modelling can explore utility of drug in hair. We aimed at developing and validating a pharmacokinetic model based on atazanavir/ ritonavir (ATV/r) in hair and identify factors associated with variabilities in hair accumulation. Methods: We based the study on secondary data analysis whereby data from a previous study on Zimbabwean adolescents which collected hair samples at enrolment and 3 months follow-up was used in model development. We performed model development in NONMEM (version 7.3) ADVAN 13. Results: There is 16% / 18% of the respective ATV/r in hair as a ratio of steady-state trough plasma concentrations. At follow-up, we estimated an increase of 30% /42% of respective ATV/r in hair. We associated a unit increase in adherence score with 2% increase in hair concentration both ATV/r. Thinner participants had 54% higher while overweight had 21% lower atazanavir in hair compared to normal weight participants. Adolescents receiving care from fellow siblings had atazanavir in hair at least 54% less compared to other forms of care. Conclusion: The determinants of increased ATV/r concentrations in hair found in our analysis are monitoring at follow up event, body mass index, and caregiver status. Measuring drug concentration in hair is feasibly accomplished and could be more accurate for monitoring ARV drugs exposure.https://bmcpharmacoltoxicol.biomedcentral.com/articles/10.1186/s40360-020-00437-yPublisher's versio

Short Communication: Higher Tenofovir Concentrations in Hair Are Associated with Decreases in Viral Load and Not Self-Reported Adherence in HIV-Infected Adolescents with Second-Line Virological Treatment Failure

Objective methods of measuring antiretroviral adherence are limited. We assessed the relationship between tenofovir disoproxil fumarate (TDF) hair concentrations, self-reported adherence, and virological outcomes in HIV-infected adolescents in Harare, Zimbabwe. HIV-infected adolescents on atazanavir/ritonavir-based second-line treatment for >6 months with viral load (VL) ≥1,000 copies/mL were randomized to either modified directly administered antiretroviral therapy (mDAART) or standard of care. Hair and VL samples were collected at baseline and after 90 days. Treatment outcome was defined as TDF concentrations in hair. Virological suppression was defined as VL <1,000 copies/mL. Thirty-four adolescents had TDF concentrations measured at baseline and follow-up. Mean (median); range age was 16 (16); 13-18 years and 53% were females. Nineteen (56%) were randomized to mDAART. Mean (SD); range TDF concentrations were 0.03 (0.04); 0-0.17 ng/mg hair and 0.06 (0.06); 0-0.3 ng/mg hair at baseline and follow-up, respectively. Higher TDF concentrations were associated with decreased VL [regression coefficient (RC) 0.8; 95% confidence interval (CI) 0.7-1.0; p = .008] and mDAART (RC 0.5; 95% CI 0.3-1.0; p = .04), but were not associated with self-reported adherence and virological suppression (VL <1,000 copies/mL). Higher TDF hair concentrations were observed with virological decrease and an adherence intervention. Hair antiretroviral concentrations could be useful in triggering adherence interventions among adolescents with second-line virological failure