Effect of co-trimoxazole on mortality in HIV-exposed but uninfected children in Botswana (the Mpepu Study): a double-blind, randomised, placebo-controlled trial

Background Co-trimoxazole prophylaxis reduces mortality among HIV-infected children, but efficacy in HIV-exposed but uninfected (HEU) children in a non-malarial, low-breastfeeding setting with a low risk of mother-to-child transmission of HIV is unclear. Methods HEU children in Botswana were randomly assigned to receive co-trimoxazole (100 mg/20 mg once daily until age 6 months and 200 mg/40 mg once daily thereafter) or placebo from age 14–34 days to age 15 months. Mothers chose whether to breastfeed or formula feed their children. Breastfed children were randomly assigned to breastfeeding for 6 months (Botswana guidelines) or 12 months (WHO guidelines). The primary outcome, analysed by a modified intention-to-treat approach, was cumulative child mortality from treatment assignment to age 18 months. We also assessed HIV-free survival by duration of breastfeeding. This trial is registered with ClinicalTrials.gov, number NCT01229761. Findings From June 7, 2011, to April 2, 2015, 2848 HEU children were randomly assigned to receive co-trimoxazole (n=1423) or placebo (n=1425). The data and safety monitoring board stopped the study early because of a low likelihood of benefit with co-trimoxazole. Only 153 (5%) children were lost to follow-up (76 in the co-trimoxazole group and 77 in the placebo group), and 2053 (72%) received treatment continuously to age 15 months, death, or study closure. Mortality after the start of study treatment was similar in the two study groups: 30 children died in the co-trimoxazole group, compared with 34 in the placebo group (estimated mortality at 18 months 2·4% vs 2·6%; difference –0·2%, 95% CI –1·5 to 1·0, p=0·70). We saw no difference in hospital admissions between groups (12·5% in the cotrimoxazole group vs 17·4% in the placebo group, p=0·19) or grade 3–4 clinical adverse events (16·5% vs 18·4%, p=0·18). Grade 3–4 anaemia did not differ between groups (8·1% vs 8·3%, p=0·93), but grade 3–4 neutropenia was more frequent in the co-trimoxazole group than in the placebo group (8·1% vs 5·8%, p=0·03). More co-trimoxazole resistance in commensal Escherichia coli isolated from stool samples was seen in children aged 3 or 6 months in the co-trimoxazole group than in the placebo group (p=0·001 and p=0·01, respectively). 572 (20%) children were breastfed. HIV infection and mortality did not differ significantly by duration of breastfeeding (3·9% for 6 months vs 1·9% for 12 months, p=0·21). Interpretation Prophylactic co-trimoxazole seems to offer no survival benefit among HEU children in non-malarial, low-breastfeeding areas with a low risk of mother-to-child transmission of HIV

Will Africans take COVID-19 vaccination?

The economic and humanistic impact of COVID-19 pandemic is enormous globally. No definitive treatment exists, hence accelerated development and approval of COVID-19 vaccines, offers a unique opportunity for COVID-19 prevention and control. Vaccine hesitancy may limit the success of vaccine distribution in Africa, therefore we assessed the potentials for coronavirus vaccine hesitancy and its determinants among Africans. An online crosssectional African-wide survey was administered in Arabic, English, and French languages. Questions on demographics, self-reported health status, vaccine literacy, knowledge and perception on vaccines, past experience, behavior, infection risk, willingness to receive and affordability of the SARS-COV-2 vaccine were asked. Data were subjected to descriptive and inferential statistics. A total of 5,416 individuals completed the survey. Approximately, 94% were residents of 34 African countries while the other Africans live in the Diaspora. Only 63% of all participants surveyed were willing to receive the COVID-19 vaccination as soon as possible and 79% were worried about its side effects. Thirty-nine percent expressed concerns of vaccine-associated infection. The odds of vaccine hesitancy was 0.28 (95% CI: 0.22, 0.30) among those who believed their risk of infection was very high, compared to those who believed otherwise. The odds of vaccine hesitancy was one-fifth (OR = 0.21, 95% CI: 0.16, 0.28) among those who believed their risk of falling sick was very high, compared to those who believed their risk of falling very sick was very low. The OR of vaccine hesitancy was 2.72 (95% CI: 2.24, 3.31) among those who have previously refused a vaccine for themselves or their child compared to counterparts with no self-reported history of vaccine hesitancy. Participants want the vaccines to be mandatory (40%), provided free of charge (78%) and distributed in homes and offices (44%). COVID-19 vaccine hesitancy is substantial among Africans based on perceived risk of coronavirus infection and past experiences.http://www.plosone.orgam2022Veterinary Tropical Disease

Will Africans take COVID-19 vaccination?

The economic and humanistic impact of COVID-19 pandemic is enormous globally. No definitive treatment exists, hence accelerated development and approval of COVID-19 vaccines, offers a unique opportunity for COVID-19 prevention and control. Vaccine hesitancy may limit the success of vaccine distribution in Africa, therefore we assessed the potentials for coronavirus vaccine hesitancy and its determinants among Africans. An online cross-sectional African-wide survey was administered in Arabic, English, and French languages. Questions on demographics, self-reported health status, vaccine literacy, knowledge and perception on vaccines, past experience, behavior, infection risk, willingness to receive and affordability of the SARS-COV-2 vaccine were asked. Data were subjected to descriptive and inferential statistics. A total of 5,416 individuals completed the survey. Approximately, 94% were residents of 34 African countries while the other Africans live in the Diaspora. Only 63% of all participants surveyed were willing to receive the COVID-19 vaccination as soon as possible and 79% were worried about its side effects. Thirty-nine percent expressed concerns of vaccine-associated infection. The odds of vaccine hesitancy was 0.28 (95% CI: 0.22, 0.30) among those who believed their risk of infection was very high, compared to those who believed otherwise. The odds of vaccine hesitancy was one-fifth (OR = 0.21, 95% CI: 0.16, 0.28) among those who believed their risk of falling sick was very high, compared to those who believed their risk of falling very sick was very low. The OR of vaccine hesitancy was 2.72 (95% CI: 2.24, 3.31) among those who have previously refused a vaccine for themselves or their child compared to counterparts with no self-reported history of vaccine hesitancy. Participants want the vaccines to be mandatory (40%), provided free of charge (78%) and distributed in homes and offices (44%). COVID-19 vaccine hesitancy is substantial among Africans based on perceived risk of coronavirus infection and past experiences

Correction: Youth and healthcare workers' perspectives on the feasibility and acceptability of self-testing for HIV, Hepatitis and Syphilis among young people: Qualitative findings from a pilot study in Gaborone, Botswana.

[This corrects the article DOI: 10.1371/journal.pone.0288971.]

Decreased diarrheal and respiratory disease in HIV exposed uninfected children following vaccination with rotavirus and pneumococcal conjugate vaccines.

BackgroundRotavirus vaccine (RV) and pneumococcal vaccine (PCV) decrease diarrheal and respiratory disease incidence and severity, but there are few data about the effects of these vaccines among HIV-exposed uninfected (HEU) children.MethodsWe recorded RV and PCV vaccination history in a placebo-controlled trial that studied the need for cotrimoxazole among HEU infants in Botswana (the Mpepu Study). We categorized infants by enrollment before or after the simultaneous April 2012 introduction of RV and PCV, and compared diagnoses of diarrhea and pneumonia (grade 3/4), hospitalizations, and deaths from both disease conditions through the 12-month study visit by vaccine era/status across two sites (a city and a village) by Kaplan-Meier estimates.ResultsTwo thousand six hundred and thirty-five HEU infants were included in this secondary analysis, of these 1689 (64%) were enrolled in Gaborone (344 pre-vaccine, 1345 vaccine) and 946 (36%) in Molepolole (209 pre-vaccine, 737 vaccine). We observed substantial reduction in hazard of hospitalization or death for reason of diarrhea and pneumonia in the vaccine era versus the pre-vaccine era in Molepolole (hazard ratio, HR = 0.44, 95% confidence interval, CI = 0.28, 0.71) with smaller reduction in Gaborone (HR = 0.91, 95% CI = 0.57, 1.45). Similar downward trends were observed for diagnoses of diarrhea and pneumonia separately during the vaccine versus pre-vaccine era.ConclusionsAlthough temporal confounding cannot be excluded, significant declines in the burden of diarrheal and respiratory illness were observed among HEU children in Botswana following the introduction of RV and PCV. RV and PCV may maximally benefit HEU children in rural areas with higher disease burden

Youth and healthcare workers' perspectives on the feasibility and acceptability of self-testing for HIV, Hepatitis and Syphilis among young people: Qualitative findings from a pilot study in Gaborone, Botswana

Nambusi K, Gbolahan A, Maureen S-M, et al. Youth and healthcare workers' perspectives on the feasibility and acceptability of self-testing for HIV, Hepatitis and Syphilis among young people: Qualitative findings from a pilot study in Gaborone, Botswana. PLoS ONE. 2023;18(7): e0288971.INTRODUCTION: Little is known regarding the attitudes and perspectives of young people and healthcare workers in Botswana about dual self-testing for HIV and STIs including its acceptability, or their perceptions of the opportunities and limitations of this approach.; METHODS: From July to November 2021, 25 young people and 6 healthcare workers were purposively sampled for in-depth telephone interviews conducted in English or Setswana. The interviews followed a semi-structured topic guide, were audio recorded, transcribed, and analysed thematically using deviant case and constant comparative techniques. The study was part of a pilot project evaluating dual self-testing for HIV and STIs among young people in Gaborone.; RESULTS: We found that most of the young people were already aware of their HIV status and were motivated to participate in self-testing mainly because they were interested in learning their STI status. Whilst most were excited about the autonomy and convenience offered by self-testing, some participants expressed nervousness particularly of the finger-prick process, and preferred healthcare worker-administered tests. Both young people and healthcare workers raised concerns about the potential negative mental health outcomes of unexpected test results and emphasized the importance of pre- and post-test counselling and seamless linkage to care.; CONCLUSION: Dual self-testing for HIV and STIs has the potential to empower young people to take control of their sexual health. However, it is crucial to ensure that proper support and counselling services are in place, along with effective mechanisms for linkage to care. This study emphasizes the importance of integrating pre- and post-test counselling into self-testing programs to ensure that young people feel adequately supported throughout the testing process. By doing so, self-testing can become a valuable tool for improving the sexual health outcomes of young people in Botswana. Copyright: © 2023 Nambusi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Detecting congenital malformations - Lessons learned from the Mpepu study, Botswana

Introduction: A large and increasing number of HIV-infected women are conceiving on antiretroviral treatment (ART). While most antiretrovirals are considered safe in pregnancy, monitoring for rare pregnancy and infant adverse outcomes is warranted. Methods: We conducted a retrospective secondary analysis nested within a clinical trial of infant cotrimoxazole vs. placebo prophylaxis in Botswana (the Mpepu Study). Infants were examined at birth, and at least every 3 months through 18 months of age. Abnormal physical findings and diagnostic testing revealing malformations were documented. Post hoc, a geneticist classified all reported malformations based on available documentation. Structural malformations with surgical, medical or cosmetic importance were classified as major malformations. We present a descriptive analysis of identified malformations. Results: Between 2011 and 2014, 2,933 HIV-infected women who enrolled in the Mpepu study delivered 2,971 live-born infants. Study staff conducted 2,944 (99%) newborn exams. One thousand eighty-eight (38%) women were taking ART at conception; 1,147 (40%) started ART during pregnancy; 442 (15%) received zidovudine monotherapy; and 223 (7%) received no antiretroviral during pregnancy. Of 33 reported anomalies, 25 (76%) met congenital malformations criteria, 10 (30%) were classified as major malformations, 4 (40%) of which were identified after the birth exam. Discussion Our results highlight the importance of staff training on identification of congenital malformations, programmatic monitoring beyond the birth examination and the value of geneticist involvement in the malformations classification process in resource-limited settings. These elements will be important to fully define antiretroviral drug safety in pregnancy. Significance Surveillance systems for monitoring the safety of antiretroviral use during pregnancy among HIV-infected women in resource-limited setting are lacking. The World Health Organization’s published programmatic recommendations for such surveillance systems represents the gold standard. We employed data from a clinical trial in Botswana, a country with a generalized HIV epidemic and high antiretroviral uptake by HIV-infected women, to highlight practical opportunities to strengthen congenital malformation surveillance systems in these settings where over 1 million HIV infected pregnant women reside. Trial registration Clinical Trials.gov NCT0122976

Cotrimoxazole prophylaxis was associated with enteric commensal bacterial resistance among HIV‐exposed infants in a randomized controlled trial, Botswana

Abstract Introduction: Despite declining risk of vertical HIV transmission, prophylactic cotrimoxazole (CTX) remains widely used to reduce morbidity and mortality in the event of HIV infection among exposed infants, with an inherent risk of conferring commensal antimicrobial resistance. Using data from a randomized, placebo‐controlled trial of infant CTX prophylaxis, we sought to quantify emergence of antibiotic resistance. Methods: HIV‐exposed uninfected infants enrolled in the Botswana Mpepu study were randomized to prophylactic CTX or placebo between 14 and 34 days of life and continued through 15 months. Stool samples were collected from a subset of participating infants at randomization, three, and six months, and stored at −70°C prior to culture. Specimens that grew Escherichia coli (E. coli) or Klebsiella species (Klebsiella spp.) underwent antibiotic susceptibility testing by Kirby Bauer method using CTX (CTX 1.25/23.75 μg) and Amoxicillin (10 μg) in Mueller Hinton agar. Fisher's exact testing was used to compare prevalence of resistance by randomization arm (CTX/placebo). Results and Discussion A total of 381 stool samples from 220 infants were cultured: 118 at randomization, 151 at three months, and 112 at six‐months. E. coli was isolated from 206 specimens and Klebsiella spp. from 138 specimens. Resistance to CTX was common in both E. coli and Klebsiella spp. at the randomization visit (52.2% and 37.7% respectively) and did not differ by study arm. E. Coli isolates from CTX recipients at three and six months had 94.9% and 84.2% CTX resistance, as compared with 51.4% and 57.5% CTX resistance in isolates from placebo recipients (p=0.01). Klebsiella spp. isolates from CTX recipients had 79.0% and 68.8% CTX resistance at three and six months, as compared with 19.1% and 14.3% in isolates from placebo recipients (p<0.01). Conclusions: HIV‐exposed infants randomized to CTX prophylaxis had increased CTX‐resistant commensal gastrointestinal bacteria compared with placebo recipients. Additional research is needed to determine the longer‐term clinical, microbiologic, and public health consequences of antimicrobial resistance selected by infant CTX prophylaxis

Hepatitis B virus prevalence and vaccine antibody titers in children HIV exposed but uninfected in Botswana.

BackgroundBotswana introduced the HBV vaccine at birth for all newborns in 2000. To the best of our knowledge, since the introduction of HBV vaccination, there have been limited data for vaccine response to HBV and its impact on early childhood HBV infections among children HIV exposed but uninfected in Botswana.AimsTo determine the prevalence of hepatitis B surface antigen (HBsAg) and HBV vaccine response in 18 months old children HIV exposed but uninfected in Botswana.MethodsStored plasma samples from 304 children at 18 months of age and 287 mothers from delivery were tested for HBsAg. Mothers with positive HBsAg had HBV DNA level tested, and their HBV genotypes were determined by amplifying a 415-base pair (bp) region of the surface gene. Plasma samples from children exposed to HIV were tested for hepatitis B surface antibody (anti-HBs) titers.ResultsNo children (0 of 304) were positive for HBsAg at 18 months while 5 (1.74%) of 287 HIV-positive mothers were HBsAg positive. Four of the HBsAg positive mothers were infected with genotype A1, while 1 was infected with genotype E. The median anti-HBs titer in children was 174 mIU/mL [QR: 70, 457]. Three (1.1%) of 269 children had an inadequate vaccine response (ConclusionNo HBsAg positivity was identified in a cohort of children HIV exposed but uninfected. The absence of HBsAg positives was associated with good HBV vaccine responses and low maternal HBsAg prevalence in Botswana

Similar HIV protection from four weeks of zidovudine versus nevirapine prophylaxis among formula-fed infants in Botswana

Background: The World Health Organization HIV guidelines recommend either infant zidovudine (ZDV) or nevirapine (NVP) prophylaxis for the prevention of intrapartum mother-to-child HIV transmission (MTCT) among formula-fed infants. No study has evaluated the comparative efficacy of infant prophylaxis with twice daily ZDV versus once daily NVP in exclusively formula-fed HIV-exposed infants. Methods: Using data from the Mpepu Study, a Botswana-based clinical trial investigating whether prophylactic co-trimoxazole could improve infant survival, retrospective analyses of MTCT events and Division of AIDS (DAIDS) Grade 3 or Grade 4 occurrences of anaemia or neutropenia were performed among infants born full-term (≥ 37 weeks gestation), with a birth weight ≥ 2500 g and who were formula-fed from birth. ZDV infant prophylaxis was used from Mpepu Study inception. A protocol modification mid-way through the study led to the subsequent use of NVP infant prophylaxis. Results: Among infants qualifying for this secondary retrospective analysis, a total of 695 (52%) infants received ZDV, while 646 (48%) received NVP from birth for at least 25 days but no more than 35 days. Confirmed intrapartum HIV infection occurred in two (0.29%) ZDV recipients and three (0.46%) NVP recipients (p = 0.68). Anaemia occurred in 19 (2.7%) ZDV versus 12 (1.9%) NVP (p = 0.36) recipients. Neutropenia occurred in 28 (4.0%) ZDV versus 21 (3.3%) NVP recipients (p = 0.47). Conclusions: Both ZDV and NVP resulted in low intrapartum transmission rates and no significant differences in severe infant haematologic toxicity (DAIDS Grade 3 or Grade 4) among formula-fed full-term infants with a birthweight ≥ 2500 g