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SARS-CoV-2 infection during pregnancy was associated with maternal mortality and adverse birth outcomes in the pre-Omicron era, including a stillbirth rate of 5.6% in Botswana. We re-evaluated these outcomes in the Tsepamo Study during the Omicron era. We assessed maternal mortality and adverse birth outcomes for all singleton pregnancies from mid-November 2021 (the start of the Omicron era) to mid-August 2022 at nine Tsepamo sites, among individuals with documented SARS-CoV-2 screening PCR or antigen tests and known HIV status. Of 9,705 women routinely screened for SARS-CoV-2 infection at delivery (64% of deliveries at these sites), 373 (3.8%) tested positive. Women with HIV were as likely to test positive for SARS-CoV-2 (77/1833, 4.2%) as women without HIV (293/6981, 4.2%) (p = 1.0). There were 5 recorded maternal deaths (0.03%), one occurring in a woman with a positive SARS-CoV-2 test result. In contrast, maternal mortality was 3.7% and 0.1% in those with and without SARS-CoV-2, respectively, during the pre-Omicron era. In the Omicron era, there were no differences among infants exposed or unexposed to SARS-CoV-2 in overall adverse birth outcomes (28.1% vs 29.6%; aRR 1.0, 95%CI 0.8-1.1), severe adverse birth outcomes (11.9 vs 10.6%; aRR 1.1, 95%CI 0.8-1.5), preterm delivery (15.1% vs 14.9%; aRR 1.0, 95%CI 0.8-1.3), or stillbirth (1.9% vs 2.3%; aRR 0.8, 95%CI 0.4-1.7). Adverse outcomes among those exposed to both HIV and SARS-CoV-2 were similar to those exposed to HIV alone (31.2% vs. 33.1%; aRR 0.9, 95%CI 0.6-1.3; p = 0.5). Maternal mortality was far lower in Botswana during the Omicron era than in the pre-Omicron era, and adverse birth outcomes were no longer significantly impacted by exposure to SARS-CoV-2 either overall or with HIV co-exposure. Increased population immunity to SARS-CoV-2, less stress on the hospital systems in the Omicron era, and possible differences in viral pathogenicity may combine to explain these findings., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Banga 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.)

Objective: To evaluate the impact of screening and treating asymptomatic pregnant women for Chlamydia (C.) trachomatis and Neisseria (N.) gonorrhoeae infections on the frequency of preterm birth or low birthweight infants in Botswana., Design: Non-randomised, cluster-controlled trial., Setting: Four antenatal care clinics in Gaborone, Botswana., Population: Pregnant women aged ≥15 years, attending a first antenatal care visit, ≤27 weeks of gestation and without urogenital symptoms were eligible., Methods: Participants in the intervention clinics received screening (GeneXpert®, Cepheid) during pregnancy and at the postnatal visit. Participants in the standard-of-care clinics received screening at the postnatal visit only. We used multivariable logistic regression and post-estimation predictive margins analysis. Post-hoc analysis was conducted among sub-samples stratified by parity., Main Outcome Measures: Preterm birth (<37 weeks of gestation) and low birthweight (<2500 g)., Results: After controlling for parity, hypertension, antenatal care visits and clinic site, the predicted prevalence of preterm birth or low birthweight was lower in the intervention arm (11%) compared with the standard-of-care arm (16%) (adjusted odds ratio [aOR] 0.59; 95% confidence interval [CI] 0.28-1.24). In post-hoc analysis, the intervention was more effective than the standard-of-care (aOR 0.20; 95% CI 0.07-0.64) among nulliparous participants., Conclusion: A C. trachomatis and N. gonorrhoeae infection screening and treatment intervention among asymptomatic pregnant women may have reduced preterm birth or low birthweight outcomes, but results were not statistically significant. Post-hoc analysis found that the intervention reduced adverse outcomes among nulliparous participants., (© 2024 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Introduction: Studies have reported a higher risk of suboptimal neurodevelopment among children who are HIV-exposed uninfected (HEU) compared to children HIV-unexposed uninfected (HUU). Actual academic performance among school-aged children by HIV exposure status has not been studied., Methods: Academic performance in Mathematics, Science, English, Setswana and overall among children enrolled in the Botswana-based FLOURISH study who were attending public primary school and ranging in age from 7.1 to 14.6 years were compared by HIV exposure status using a Cochran-Mantel-Haenszel test. Lower academic performance was defined as a grade of "C" or lower (≤60%). Unadjusted and adjusted logistic regression models were fit to assess for an association between HIV exposure and lower academic performance., Results: Between April 2021 and December 2022, 398 children attending public primary school enrolled in the FLOURSH study, 307 (77%) were HEU. Median age was 9.4 years (IQR 8.9-10.2). Only 17.9% of children HEU were breastfeed versus 100% of children HUU. Among children HEU, 80.3% had foetal exposure to three-drug antiretroviral treatment, 18.7% to zidovudine only and 1.0% had no antiretroviral exposure. Caregivers of children HEU were older compared to caregivers of children HUU (median 42 vs. 36 years) and more likely to have no or primary education only (15.0% vs. 1.1%). In unadjusted analyses, children HEU were more likely to have lower overall academic performance compared to their children HUU (odds ratio [OR]: 1.96 [95% confidence interval (CI): 1.16, 3.30]), and lower performance in Mathematics, Science and English. The association was attenuated after adjustment for maternal education, caregiver income, breastfeeding, low birth weight and child sex (aOR: 1.86 [95% CI: 0.78, 4.43])., Conclusions: In this Botswana-based cohort, primary school academic performance was lower among children HEU compared to children HUU. Biological and socio-demographic factors, including child sex, appear to contribute to this difference. Further research is needed to identify modifiable contributors, develop screening tools to identify the risk of poor academic performance and design interventions to mitigate risk., (© 2023 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of International AIDS Society.)

Background: Chlamydia trachomatis ( C. trachomatis ) and Neisseria gonorrhoeae ( N. gonorrhoeae ) are curable sexually transmitted infections (STIs) that cause adverse pregnancy and neonatal outcomes. Most countries, including Botswana, do not offer C. trachomatis or N. gonorrhoeae screening during antenatal care (ANC) and instead use a syndromic approach for management of STIs., Methods: The Maduo Study is a prospective, cluster-controlled trial in Botswana evaluating the impact of diagnostic screening for antenatal C. trachomatis and N. gonorrhoeae infections to prevent adverse neonatal outcomes. Using baseline data from the Maduo Study (March 2021-March 2022), we determined the prevalence of C. trachomatis and N. gonorrhoeae infection among asymptomatic pregnant women in Botswana and correlates of infection using multivariable logistic regression., Results: Of 251 women who underwent C. trachomatis and N. gonorrhoeae screening at first ANC visit, 55 (21.9%, 95%CI 17.0-27.5) tested positive for C. trachomatis , 1 (0.4%, 95%CI 0-2.2) for N. gonorrhoeae ; and 2 (0.8%, 95%CI 0-2.8) for dual C. trachomatis and N. gonorrhoeae infection. Older age was associated with lower odds (aOR 0.93; 95%CI 0.88-0.98; p = 0.011) while any alcohol use during pregnancy was associated with higher odds (aOR = 3.53; 95%CI 1.22-10.16; p = 0.020) of testing positive for C. trachomatis or N. gonorrhoeae ., Conclusions: A high frequency of C. trachomatis infections was detected among asymptomatic pregnant women in Botswana indicating that many antenatal STIs are missed by the syndromic management approach. Our results highlight the need for diagnostic C. trachomatis screening during ANC in Botswana and other low- and middle-income countries that rely solely on the syndromic approach for management of STIs.

Objective: To evaluate the combined association of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and human immunodeficiency virus (HIV) infection on adverse birth outcomes in an HIV-endemic region., Methods: The Tsepamo Study abstracts data from antenatal and obstetric records in government maternity wards across Botswana. We assessed maternal mortality and adverse birth outcomes for all singleton pregnancies from September 2020 to mid-November 2021 at 13 Tsepamo sites among individuals with documented SARS-CoV-2 screening tests and known HIV status., Results: Of 20,410 individuals who gave birth, 11,483 (56.3%) were screened for SARS-CoV-2 infection; 4.7% tested positive. People living with HIV were more likely to test positive (144/2,421, 5.9%) than those without HIV (392/9,030, 4.3%) (P=.001). Maternal deaths occurred in 3.7% of those who had a positive SARS-CoV-2 test result compared with 0.1% of those who tested negative (adjusted relative risk [aRR] 31.6, 95% CI 15.4-64.7). Maternal mortality did not differ by HIV status. The offspring of individuals with SARS-CoV-2 infection experienced more overall adverse birth outcomes (34.5% vs 26.6%; aRR 1.2, 95% CI 1.1-1.4), severe adverse birth outcomes (13.6% vs 9.8%; aRR 1.2, 95% CI 1.0-1.5), preterm delivery (21.4% vs 13.4%; aRR 1.4, 95% CI 1.2-1.7), and stillbirth (5.6% vs 2.7%; aRR 1.7 95% CI 1.2-2.5). Neonates exposed to SARS-CoV-2 and HIV infection had the highest prevalence of adverse birth outcomes (43.1% vs 22.6%; aRR 1.7, 95% CI 1.4-2.0)., Conclusion: Infection with SARS-CoV-2 at the time of delivery was associated with 3.7% maternal mortality and 5.6% stillbirth in Botswana. Most adverse birth outcomes were worse among neonates exposed to both SARS-CoV-2 and HIV infection., Competing Interests: Financial Disclosure The authors did not report any potential conflicts of interest., (Copyright © 2022 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Until late 2015, Botswana recommended preventive treatment for pregnant women in malarial regions with chloroquine and proguanil (CP). The guideline change provided an opportunity to evaluate CP and adverse birth outcomes., Methods: The Tsepamo Study performed birth outcomes surveillance at large delivery centres throughout Botswana. We evaluated adverse birth outcomes from 2015 to 2017 at three hospitals where 93% of CP use was recorded. Outcomes included neonatal death (NND), small for gestational age (SGA), very SGA, stillbirth (SB), preterm delivery (PTD) and very PTD. Logistic regression analysis (unadjusted and adjusted) was conducted for each adverse birth outcome., Results: During the study period, 5883 (26%) of 23,033 deliveries were exposed to CP, with the majority (65%) in the most malaria-endemic region. At this site, there was a trend or an association between CP use and reduction of three adverse birth outcomes: PTD (aOR 0.85, 95% CI 0.76-0.96), vPTD (aOR 0.83, 95% CI 0.68-1.01) and NND (aOR 0.65, 95% CI 0.42-1.00). However, at the least malaria-endemic site, the association was in the opposite direction for SB (aOR 1.54, 95% CI 1.08-2.22), SGA (aOR 1.24, 95% CI 1.06-1.44) and vSGA (aOR 1.42, 95% CI 1.14-1.77). The association between CP and reduced PTD was present among women without HIV (aOR 0.77, 95% CI 0.67-0.89) but not among women with HIV (aOR 1.09, 95% CI 0.78-1.35)., Conclusions: Antimalarial prophylaxis was associated with improved birth outcomes in the most malaria-endemic region of Botswana, but not elsewhere. This finding supports current WHO guidance to use prophylaxis strategies among pregnant women in highly malaria-endemic regions. Further studies of the risks and benefits of specific antimalarial regimens in pregnancy are warranted, particularly in areas with lower incidence of malaria., (© 2022 The Authors Tropical Medicine & International Health Published by John Wiley & Sons Ltd.)

Background: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are extremely common sexually transmitted infections (STIs) that are associated with adverse birth and neonatal outcomes, and the risk of vertical transmission of CT and NG during delivery is high. The majority of CT and NG infections are asymptomatic and missed by the standard of care in most countries (treatment based on symptoms). Thus, it is likely that missed maternal CT and NG infections contribute to preventable adverse health outcomes among women and children globally. This study aims to assess the effectiveness of CT and NG testing for asymptomatic pregnant women to prevent adverse neonatal outcomes, understand the inflammatory response linking CT and NG infections to adverse neonatal outcomes, and conduct an economic analysis of the CT and NG testing intervention., Methods: The Maduo ("results" in Setswana) is a prospective, cluster-controlled trial in Gaborone, Botswana to compare a near point-of-care CT and NG testing and treatment intervention implemented in "study clinics" with standard antenatal care (World Health Organization-endorsed "syndromic management" strategy based on signs and symptoms without laboratory confirmation) implemented in "standard of care clinics" among asymptomatic pregnant women. The primary outcome is vertical transmission of CT/NG infection. Secondary outcomes include preterm birth (delivery < 37 completed weeks of gestation) and/or low birth weight (< 2500 g). The trial will also evaluate immunological and inflammatory markers of adverse neonatal outcomes, as well as the costs and cost-effectiveness of the intervention compared with standard care., Discussion: The Maduo study will improve our understanding of the effectiveness and cost-effectiveness of CT and NG testing among asymptomatic pregnant women. It will also increase knowledge about the CT/NG-related immune responses that might drive adverse neonatal outcomes. Further, results from this study could encourage expansion of STI testing during antenatal care in low resource settings and improve maternal and neonatal health globally., Trial Registration: This trial is registered with ClinicalTrials.gov (Identifier NCT04955717, First posted: July 9, 2021))., (© 2022. The Author(s).)

Introduction: Young women in sub-Saharan Africa are at particularly high risk of HIV acquisition. Recent shifts towards "test and treat" strategies have potential to reduce transmission in this age group but have not been widely studied outside of clinical trials. Using data from nationwide surveillance among pregnant women in Botswana, where a "test and treat" program was implemented in 2016, we describe trends in HIV prevalence over time and highlight opportunities for targeted prevention., Methods: The Tsepamo study abstracted data from obstetric records of all women delivering at eight government hospitals in Botswana between 2015 and 2019, accounting for 45% of all births in the country (n = 120,755). We used a stratified analysis to identify prevalence trends and evaluated decreases in HIV prevalence over time using the Cochrane-Armitage test for linear trend. A multivariable logistic regression analysis was also performed to identify factors associated with declines in HIV prevalence., Results: Overall HIV prevalence was 24.1% among 120,755 women who delivered during the study period. Prevalence differed by site of delivery, ranging from 16.1% to 28.2%, and increased markedly with age. Lower educational attainment (adjusted odds ratio [aOR] = 3.28; 95% confidence interval [CI] 3.07-3.50) and being unmarried (aOR = 1.98; 95% CI 1.88-2.08) were associated with HIV infection. HIV prevalence was 10.0% with a first pregnancy, 21.0% with a second and 39.2% with a third or greater (aOR = 2.20; for any prior pregnancy; 95% CI 2.10-2.29). The same age-adjusted trends were seen when data were limited to women aged 15-24, with a two- to three-fold increase in HIV prevalence between a first and third pregnancy. Prevalence decreased linearly during the 5-year study period from 25.8% to 22.7% (p <0.001). Among age-specific strata, the greatest absolute decline occurred in those aged 35-39, with an 8.7% absolute decrease in HIV prevalence from 2015 to 2019. Minimal declines were seen in those 15-24, with a decrease of only 1.5% over the same period., Conclusions: While overall trends in Botswana show HIV prevalence declining among pregnant women, prevalence among the youngest age group has remained stagnant. Preventative interventions utilizing pre-exposure prophylaxis should be prioritized during the high-risk period surrounding a woman's first pregnancy., (© 2022 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Background: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are common sexually transmitted infections (STIs) associated with adverse outcomes, yet most countries do not test and conduct syndromic management, which lacks sensitivity and specificity. Innovations allow for expanded STI testing; however, cost is a barrier., Methods: Using inputs from a pilot program in Botswana, we developed a model among a hypothetical population of 50,000 pregnant women to compare 1-year costs and outcomes associated with 3 antenatal STI testing strategies: (1) point-of-care, (2) centralized laboratory, and (3) a mixed approach (point of care at high-volume sites, and hubs elsewhere), and syndromic management., Results: Syndromic management had the lowest delivery cost but was associated with the most infections at delivery, uninfected women treated, CT/NG-related low-birth-weight infants, disability-adjusted life years, and low birth weight hospitalization costs. Point-of-care CT/NG testing would treat and cure the most infections but had the highest delivery cost. Among the testing scenarios, the mixed scenario had the most favorable cost per woman treated and cured ($534/cure). Compared with syndromic management, the mixed approach resulted in a mean incremental cost-effectiveness ratio of $953 per disability-adjusted life years averted, which is cost-effective under World Health Organization's one-time per-capita gross domestic product willingness-to-pay threshold., Conclusions: As countries consider new technologies to strengthen health services, there is an opportunity to determine how to best deploy resources. Compared with point-of-care, centralized laboratory, and syndromic management, the mixed approach offered the lowest cost per infection averted and is cost-effective if policy makers' willingness to pay is informed by the World Health Organization's gross domestic product/capita threshold., Competing Interests: Conflict of Interest and Sources of Funding: None declared., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Sexually Transmitted Diseases Association.)

We describe a cluster of six SARS-CoV-2 infections occurring in a crowded neonatal unit in Botswana, including presumed transmission among mothers, postnatal mother-to-neonate transmission and three neonate-to-healthcare worker transmissions. The affected neonate, born at 25 weeks' gestation weighing 785 g, had a positive SARS-CoV-2 test at 3 weeks of age which coincided with new onset of hypoxaemia and worsening respiratory distress. Because no isolation facility could accommodate both patient and mother, they were separated for 10 days, during which time the patient was switched from breastmilk to formula. Her subsequent clinical course was marked by several weeks of supplemental oxygen, sepsis-like presentations requiring additional antibiotics and bronchopulmonary dysplasia. Despite these complications, adequate growth was achieved likely due to early initiation of nutrition. This nosocomial cluster highlights the vulnerabilities of neonates, caregivers and healthcare workers in an overcrowded environment, and underscores the importance of uninterrupted bonding and breast feeding, even during a pandemic., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Women with vertically acquired HIV (VHIV) may have a greater risk of adverse birth outcomes than women with horizontally acquired HIV (HHIV)., Methods: The Tsepamo study performed birth outcomes surveillance at 8 government delivery sites in Botswana from July 2014 through March 2019. Pregnant women diagnosed with HIV before their 11th birthday received VHIV status, and other women had HHIV. Small for gestational age (SGA), preterm delivery (PTD), stillbirth, and neonatal death were compared using χ2 and Fisher's exact tests. Log-binomial regression models determined risk ratios (RRs)., Results: VHIV women (n = 402) aged 15-27 years were identified over 4 years of surveillance and compared with HHIV women (n = 8465) of the same age. VHIV women were more likely to use nevirapine (NVP)-based antiretroviral treatment (ART) in pregnancy and to have SGA and very SGA infants, but less likely to have very PTD infants. In unadjusted analyses, VHIV women had a higher risk of any adverse birth outcome combined (RR = 1.21, 95% confidence interval [CI], 1.08-1.36). After adjusting for potential confounders, particularly use of NVP-based regimens, the risk of adverse birth outcomes among VHIV and HHIV women was similar., Conclusions: NVP-based ART is a primary and modifiable risk factor for adverse birth outcomes. Updating ART regimens could improve birth outcomes for women with HIV., (Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society 2020.)

Objectives: To determine the prevalence and sociodemographic predictors of HIV among pregnant women in Botswana., Methods: This was a cross-sectional study of randomly enrolled women aged 18 to 49 years, attending 7 health facilities in Botswana. Data were gathered from November 2017 to March 2018 and analyzed using SPSS version 24., Result: Of the 429 women enrolled, 407 (96.4%) were included in the analysis. The HIV prevalence was 17%; 69 of 407 (95% CI: 13.4- 21.0). Women aged 35 to 49 years had higher HIV prevalence than those 18 to 24 years (adjusted odds ratio [AOR] = 6.2; 95% CI: 2.7-14.4). Illiterate and elementary school educated women had higher HIV prevalence than those with a tertiary education (AOR = 8.5; 95% CI: 1.8-39.1). Those with a history of alcohol intake had a higher HIV prevalence than those without (AOR = 2.6; 95% CI: 1.3-5.3)., Conclusion: HIV prevalence was lower than it was in 2011. Age, level of education, and history of alcohol intake were strong predictors for HIV infection calling for targeted behavioral change interventions.

Background: A preliminary safety signal for neural-tube defects was previously reported in association with dolutegravir exposure from the time of conception, which has affected choices of antiretroviral treatment (ART) for human immunodeficiency virus (HIV)-infected women of reproductive potential. The signal can now be evaluated with data from follow-up of additional pregnancies., Methods: We conducted birth-outcomes surveillance at hospitals throughout Botswana, expanding from 8 to 18 sites in 2018. Trained midwives performed surface examinations of all live-born and stillborn infants. Research assistants photographed abnormalities after maternal consent was obtained. The prevalence of neural-tube defects and major external structural defects according to maternal HIV infection and ART exposure status was determined. In the primary analyses, we used the Newcombe method to evaluate differences in prevalence with 95% confidence intervals., Results: From August 2014 through March 2019, surveillance captured 119,477 deliveries; 119,033 (99.6%) had an infant surface examination that could be evaluated, and 98 neural-tube defects were identified (0.08% of deliveries). Among 1683 deliveries in which the mother was taking dolutegravir at conception, 5 neural-tube defects were found (0.30% of deliveries); the defects included two instances of myelomeningocele, one of anencephaly, one of encephalocele, and one of iniencephaly. In comparison, 15 neural-tube defects were found among 14,792 deliveries (0.10%) in which the mother was taking any non-dolutegravir ART at conception, 3 among 7959 (0.04%) in which the mother was taking efavirenz at conception, 1 among 3840 (0.03%) in which the mother started dolutegravir treatment during pregnancy, and 70 among 89,372 (0.08%) in HIV-uninfected mothers. The prevalence of neural-tube defects was higher in association with dolutegravir treatment at conception than with non-dolutegravir ART at conception (difference, 0.20 percentage points; 95% confidence interval [CI], 0.01 to 0.59) or with other types of ART exposure. Major external structural defects were found in 0.95% of deliveries among women exposed to dolutegravir at conception and 0.68% of those among women exposed to non-dolutegravir ART at conception (difference, 0.27 percentage points; 95% CI, -0.13 to 0.87)., Conclusions: The prevalence of neural-tube defects was slightly higher in association with dolutegravir exposure at conception than with other types of ART exposure at conception (3 per 1000 deliveries vs. 1 per 1000 deliveries). (Funded by the National Institutes of Health.)., (Copyright © 2019 Massachusetts Medical Society.)

Background: Minimal data exist related to neurodevelopment after in utero exposure to Efavirenz (EFV). We sought to compare neurodevelopmental outcomes in HIV-exposed/uninfected (HEU) children with in utero exposure to EFV-based triple antiretroviral treatment (ART) versus non-EFV-based ART, and to examine whether timing of initial EFV exposure is associated with neurodevelopment deficits., Methods: Women living with HIV who had received EFV-based ART during pregnancy and whose HEU newborn participated in a prior study were reconsented for their HEU toddler to undergo neurodevelopmental testing at 24 months old. We administered the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III), Developmental Milestones Checklist (DMC) and Profile of Social Emotional Development (PSED). We compared outcomes to previously-collected data from a cohort of 24-month-old HEU children with in utero exposure to non-EFV-based ART. Adjusted general linear models were used to compare mean outcomes., Results: Our analysis included 493 HEU children (126 EFV-exposed, 367 EFV-unexposed). Adjusted mean scores for the EFV-exposed group were worse than the EFV-unexposed group on BSID-III Receptive Language (adjusted means = 21.5 vs. 22.5, P = 0.05), DMC Locomotor (30.7 vs. 32.0, P < 0.01) and Fine Motor scales (17.8 vs. 19.2, P < 0.01); and PSED (11.7 vs. 9.9, P = 0.02); but better on the DMC Language scale (17.6 vs. 16.5, P = 0.01). Earlier (vs. later) EFV exposure was associated with worse scores on the BSID-III Receptive Language scale (20.7 vs. 22.2, P = 0.02)., Conclusions: HEU children exposed in utero to EFV-based ART may be at higher risk for neurodevelopmental and social-emotional deficits than HEU children exposed to non-EFV-based ART.

Background: Partner notification is an essential component of sexually transmitted infection (STI) management. The process involves identifying exposed sex partner(s), notifying these partner(s) about their exposure to a curable STI, and offering counselling and treatment for the STI as a part of syndromic management or after results from an STI test. When implemented effectively, partner notification services can prevent the index patient from being reinfected with a curable STI from an untreated partner, reduce the community burden of curable STIs, and prevent adverse health outcomes in both the index patient and his or her sex partner(s). However, partner notification and treatment rates are often low. This study seeks to explore experiences and preferences related to partner notification and treatment for curable STIs among pregnant women receiving care in an antenatal clinic with integrated HIV and curable STI testing. Results are intended to inform efforts to improve partner notification and treatment rates in Southern Africa., Methods: We conducted qualitative interviews among women diagnosed with Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and/or Trichomonas vaginalis (TV) infection while seeking antenatal care in Gaborone, Botswana. Semi-structured interviews were used to obtain women's knowledge about STIs and their experiences and preferences regarding partner notification., Results: Fifteen women agreed to participate in the study. The majority of women had never heard of CT, NG, or TV infections prior to testing. Thirteen out of 15 participants had notified partners about the STI diagnosis. The majority of notified partners received some treatment; however, partner treatment was often delayed. Most women expressed a preference for accompanying partners to the clinic for treatment. Experiences and preferences did not differ by HIV infection status., Conclusions: The integration of STI, HIV, and antenatal care services may have contributed to most women's willingness to notify partners. However, logistical barriers to partner treatment remained. More research is needed to identify effective and appropriate strategies for scaling-up partner notification services in order to improve rates of partners successfully contacted and treated, reduce rates of STI reinfection during pregnancy, and ultimately reduce adverse maternal and infant outcomes attributable to antenatal STIs.

Maternal rectovaginal colonization is the major risk factor for early-onset neonatal sepsis due to Group B Streptococcus (GBS), a major cause of early life morbidity and mortality. Transmission generally occurs perinatally from colonized mothers to infants. Vaccines targeting a subset of GBS serotypes are under development, but GBS epidemiology remains poorly understood in many African nations. We performed a cross-sectional study of GBS colonization among pregnant women at two sites in Botswana, a country with minimal prior GBS carriage data. We found a rectovaginal colonization rate of 19%, comparable with studies in other regions; however, we also noted a striking predominance of serotype V (> 45% of strains). Although further studies are required to delineate the burden of invasive GBS disease in Botswana and the generalizability of type V epidemiology, these data provide a useful baseline for understanding the potential local impact of GBS prevention strategies, including vaccines.

Background: Human immunodeficiency virus-exposed but uninfected (HIV-EU) children have a higher mortality rate than the children of HIV-negative mothers (HIV-unexposed). Causal mediators of the poor health outcomes of HIV-EU children remain poorly defined., Methods: We conducted a hospital-based prospective cohort study of children aged 1 to 23 months with clinically defined pneumonia. The children were recruited at a referral hospital in Gaborone, Botswana, between April 2012 and June 2016. The primary outcome, treatment failure at 48 hours, was assessed by an investigator blinded to the children's HIV-exposure status. We examined associations between HIV exposure and pneumonia outcomes in HIV-uninfected children. We next determined whether the effect of HIV exposure on outcomes was mediated by low-birth-weight status, nonbreastfeeding, malnutrition, in utero exposure to combination antiretroviral therapy, or pneumonia severity., Results: A total of 352 HIV-uninfected children were included in these analyses, including 245 (70%) HIV-unexposed and 107 (30%) HIV-EU children. Their median age was 7.4 months, and 57% were male. Treatment failure occurred in 111 (32%) children, and 19 (5.4%) children died. HIV-EU children were more likely to fail treatment (risk ratio [RR], 1.57 [95% confidence interval (CI), 1.19-2.07]; P = .002) and had a higher in-hospital mortality rate (RR, 4.50 [95% CI, 1.86-10.85]; P = .001) than HIV-unexposed children. Nonbreastfeeding mediated 47% of the effect of HIV exposure on the risk of in-hospital death., Conclusions: HIV-EU children have worse pneumonia outcomes than HIV-unexposed children. Nonbreastfeeding mediates nearly half of the effect of HIV exposure on pneumonia mortality. Our findings provide additional evidence for a mortality benefit of breastfeeding by HIV-EU children., (© The Author(s) 2017. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: To prospectively assess rates and detailed predictors of morbidity and mortality among HIV-exposed uninfected children and HIV-unexposed children in Botswana in a more recent era., Study Design: We enrolled HIV-infected and HIV-uninfected mothers and their children in the prospective observational Tshipidi study at 2 sites (1 city and 1 village) in Botswana from May 2010-July 2012. Live-born children and their mothers were followed for 24 months postpartum. Detailed sociodemographic data, health, and psychosocial characteristics were collected at baseline and prospectively, and health outcomes ascertained. Mothers chose infant feeding method with counselling., Results: A total of 893 live-born HIV-uninfected children (436 HIV-exposed uninfected, 457 HIV-unexposed) were followed. HIV-infected mothers had a median CD4 count of 410 cells/mm 3 , 32% took 3-drug antiretroviral treatment during pregnancy, 67% took only zidovudine, and 1% took <2 weeks of any antiretrovirals antepartum. Twenty four-month vital status was available for 888 (99.4%) children. HIV-exposed uninfected children had a significantly higher risk of death compared with children of HIV-uninfected mothers (5.0% vs 1.8%) (adjusted hazard ratio 3.27, 95% CI 1.44-7.40). High collinearity between maternal HIV status and child feeding method precluded analysis of these factors as independent predictors of mortality. Preterm birth, low birth weight, and congenital anomaly were also associated with mortality (in separate analyses), but maternal socioeconomic factors, depression, substance use, and social support were not significant predictors., Conclusions: The strongest predictors of 24-month mortality among children in Botswana were HIV exposure and formula feeding, although the relative contribution of these factors to child health could not be separated., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Global rollout of dolutegravir-based antiretroviral therapy (ART) has been hampered in part by insufficient safety data in pregnancy. We compared birth outcomes among women initiating dolutegravir-based ART with those among women initiating efavirenz-based ART in pregnancy in Botswana., Methods: In this observational study, we captured birth outcome data at eight government hospitals throughout Botswana (~45% of all deliveries in the country) in an ongoing study that started on Aug 15, 2014. In 2016, Botswana changed first-line ART from efavirenz-tenofovir-emtricitabine to dolutegravir-tenofovir-emtricitabine, including for pregnant women. This analysis includes women starting either efavirenz-based ART or dolutegravir-based ART during singleton pregnancy (regimen started and delivery occurring between Aug 15, 2014, and Aug 15, 2016, for efavirenz-based ART and between Nov 1, 2016, and Sept 30, 2017, for dolutegravir-based ART). We excluded births to mothers who had switched regimen or stopped ART. The primary outcomes were the combined endpoints of any adverse outcome (stillbirth, preterm birth [<37 weeks' gestation], small for gestational age [SGA; less than the tenth percentile of birthweight by gestational age], or neonatal death [within 28 days of age]) and severe adverse outcomes (stillbirth, neonatal death, very preterm birth [<32 weeks' gestation], and very SGA [less than the third percentile of birthweight by gestational age]). We fitted log-binomial regression models, controlling for maternal age, gravidity, and education, to estimate adjusted risk ratios (aRRs)., Findings: Our analysis included 1729 pregnant women who initiated dolutegravir-based ART and 4593 who initiated efavirenz-based ART. The risk for any adverse birth outcome among women on dolutegravir versus efavirenz was similar (33·2% vs 35·0%; aRR 0·95, 95% CI 0·88-1·03), as was the risk of any severe birth outcome (10·7% vs 11·3%; 0·94, 0·81-1·11). We found no significant differences by regimen in the individual outcomes of stillbirth, neonatal death, preterm birth, very preterm birth, SGA, or very SGA., Interpretation: Adverse birth outcomes were similar among pregnant women who initiated dolutegravir-based and efavirenz-based ART. Dolutegravir-based ART can be safely initiated in pregnancy., Funding: National Institutes of Health., (Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Chlamydia trachomatis (CT) , Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV) are curable, mostly asymptomatic, STIs that cause adverse maternal and perinatal outcomes. Most countries do not test for those infections during antenatal care. We implemented a CT, NG and TV testing and treatment programme in an antenatal clinic in Gaborone, Botswana., Methods: We conducted a prospective study in the antenatal clinic at Princess Marina Hospital in Gaborone, Botswana. We offered pregnant women who were 18 years or older and less than 35 weeks of gestation, CT, NG and TV testing using self-collected vaginal swabs. Testing was conducted using a GeneXpert® CT/NG and TV system. Those who tested positive were given directly observed antibiotic therapy and asked to return for a test of cure. We determined the prevalence of infections, uptake of treatment and proportion cured. The relationships between positive STI test and participant characteristics were assessed., Results: We enrolled 400 pregnant women. Fifty-four (13.5%) tested positive for CT, NG and/or TV: 31 (8%) for CT, 5 (1.3%) for NG and 21 (5%) for TV. Among those who tested positive, 74% (40) received same-day, in person results and treatment. Among those who received delayed results (6), 67% (4) were treated. Statistical comparisons showed that being unmarried and HIV infected were positively association CT, NG and/or TV infection. Self-reported STI symptoms were not associated with CT, NG and/or TV infection., Conclusion: The prevalence of CT, NG and/or TV was high, particularly among women with HIV infection. Among women with CT, NG and/or TV infection, those who received same-day results were more likely to be treated than those who received delayed results. More research is needed on the costs and benefits of integrating highly sensitive and specific STI testing into antenatal care in Southern Africa., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Trichomonas vaginalis (TV) are sexually transmitted infections (STIs) associated with adverse birth outcomes. Untreated partners contribute to high rates of STI reinfection; thus, partner notification and treatment remain important components of STI care and control. A prospective cohort study was conducted among 300 pregnant women presenting to the antenatal clinic at Princess Marina Hospital in Gaborone, Botswana who enrolled in an STI screening study. Following informed consent and sample collection for CT/NG/TV testing, participants were asked if they were willing to disclose their STI result and to deliver medications to their partner(s). Those who tested positive were asked at a follow-up appointment if they notified their partners. Among the 300 participants, 294 (98%) said they would be willing to tell their partner(s) about their test results if they tested positive, and 284 (95%) said they would be willing to give their partner(s) medication if the option was available. Of those who tested positive and returned for a test of cure, 27 of 32 (84%) reported that they told their partner about the results, and 20 of 32 (63%) reported that their partner received treatment. Almost all pregnant women reported willingness to tell their partner the STI test result and give their partner medications. At test of cure, most women reported informing their partner, although actual treatment receipt was lower. Our findings suggest that pregnant women are willing to utilize patient-based partner notification, but actual partner treatment might be lower than intended.

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 co-trimoxazole 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., Funding: US National Institutes of Health., (Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND license. Published by Elsevier Ltd.. All rights reserved.)

Mortality in the postpartum period may be impacted by antiretroviral therapy (ART) received in pregnancy, and whether ART is continued in the postpartum period. HIV-infected and HIV-uninfected mothers were enrolled within 48 h of delivery at five public hospital maternity wards throughout Botswana and followed for 24 months. Maternal deaths were reported by one of the approved contacts given by the mother at enrollment. Detailed information on the cause of death was not available. Risk factors for 24-month mortality were assessed using Cox proportional hazard models. From February 2012 to March 2013, 3000 mothers (1499 HIV infected and 1501 HIV uninfected) were enrolled, and 2985 (99.5%) were followed to 24 months or death, or until the death of their child. There were 26 total maternal deaths through 24 months postpartum [439 per 100,000 person-years (p-y)], 22 among HIV-infected women (758 per 100,000 p-y) and 4 among HIV-uninfected women (132 per 100,000 p-y). Maternal HIV-infection (aHR 5.0, 95% CI 1.6-15.2) and infant birth injury (aHR 3.8, 95% CI 1.3-11.4) were independent risk factors for maternal death. Universal ART in pregnancy became the standard-of-care after June 2012, and 978 (65%) women received ART in pregnancy; by 24 months postpartum or end of follow-up, 1148 (79%) had started ART overall. There was no significant difference in 24-month mortality among HIV-infected women who took ART in pregnancy and continued throughout the follow-up period compared with HIV-infected women who took ART or zidovudine in pregnancy and stopped postpartum (aHR 0.6, 95% CI 0.2-1.7). Despite high uptake of ART in pregnancy and postpartum, women with HIV infection in Botswana are five times more likely to die than HIV-uninfected women in the 24 months postpartum., Competing Interests: Author Disclosure Statement No competing financial interests exist.

In perinatal epidemiology, birth outcomes such as small for gestational age (SGA) may not be observed for a pregnancy ending with a stillbirth. It is then said that SGA is truncated by stillbirth, which may give rise to survival bias when evaluating the effects on SGA of an exposure known also to influence the risk of a stillbirth. In this article, we consider the causal effects of maternal infection with human immunodeficiency virus (HIV) on the risk of SGA, in a sample of pregnant women in Botswana. We hypothesize that previously estimated effects of HIV on SGA may be understated because they fail to appropriately account for the over-representation of live births among HIV negative mothers, relative to HIV positive mothers. A simple yet novel regression-based approach is proposed to adjust effect estimates for survival bias for an outcome that is either continuous or binary. Under certain straightforward assumptions, the approach produces an estimate that may be interpreted as the survivor average causal effect of maternal HIV, which is, the average effect of maternal HIV on SGA among births that would be live irrespective of maternal HIV status. The approach is particularly appealing, because it recovers an exposure effect which is robust to survival bias, even if the association between the risk of SGA and that of a stillbirth cannot be completely explained by adjusting for observed shared risk factors. The approach also gives a formal statistical test of the null hypothesis of no survival bias in the regression framework.

Background: The Mahalapye district health management team (DHMT) conducts regular audits to evaluate the standard of services delivered to patients, one of which is the prevention of mother-to-child-transmission (PMTCT) programme. Xhosa clinic is one of the facilities in Mahalapye which provides a PMTCT programme., Aim: This audit aimed to identify gaps between the current PMTCT clinical practice in Xhosa clinic and the Botswana PMTCT national guidelines., Setting: This audit took place in Xhosa clinic in the urban village of Mahalapye, in the Central District of Botswana., Methods: This was a retrospective audit using PMTCT Xhosa clinic records of pregnant mothers and HIV-exposed babies seen from January 2013 to June 2013., Results: One hundred and thirty-three pregnant women registered for antenatal care. Twenty-five (19%) knew their HIV-positive status as they had been tested before their pregnancy or had tested HIV positive at their first antenatal clinic visit. More than two-thirds of the 115 pregnant women (69%) were seen at a gestational age of between 14 and 28 weeks. About two-thirds of the pregnant women (67%) took antiretroviral drugs. Of the 44 HIV-exposed infants, 39 (89%) were HIV DNA PCR negative at 6 weeks. Thirty-two (73%) children were given cotrimoxazole prophylaxis between 6 and 8 weeks., Conclusion: The PMTCT programme service delivery was still suboptimal and could potentially increase the mother-to-child transmission of HIV. Daily monitoring mechanism to track those eligible could help to close the gap.

Background: It is unknown whether adverse birth outcomes are associated with maternal highly active antiretroviral therapy (HAART) in pregnancy, particularly in resource-limited settings., Methods: We abstracted obstetrical records at 6 sites in Botswana for 24 months. Outcomes included stillbirths (SBs), preterm delivery (PTD), small for gestational age (SGA), and neonatal death (NND). Among human immunodeficiency virus (HIV)-infected women, comparisons were limited to HAART exposure status at conception, and those with similar opportunities for outcomes. Comparisons were adjusted for CD4(+) lymphocyte cell count., Results: Of 33,148 women, 32,113 (97%) were tested for HIV, of whom 9504 (30%) were HIV infected. Maternal HIV was significantly associated with SB, PTD, SGA, and NND. Compared with all other HIV-infected women, those continuing HAART from before pregnancy had higher odds of PTD (adjusted odds ratio [AOR], 1.2; 95% confidence interval [CI], 1.1, 1.4), SGA (AOR, 1.8; 95% CI, 1.6, 2.1) and SB (AOR, 1.5; 95% CI, 1.2, 1.8). Among women initiating antiretroviral therapy in pregnancy, HAART use (vs zidovudine) was associated with higher odds of PTD (AOR, 1.4; 95% CI, 1.2, 1.8), SGA (AOR, 1.5; 95% CI, 1.2, 1.9), and SB (AOR, 2.5; 95% CI, 1.6, 3.9). Low CD4(+) was independently associated with SB and SGA, and maternal hypertension during pregnancy with PTD, SGA, and SB., Conclusions: HAART receipt during pregnancy was associated with increased PTD, SGA, and SB.

Background: Standard values for birth weight by gestational age are not available for sub-Saharan Africa, but are needed to evaluate incidence and risk factors for intrauterine growth retardation in settings where HIV, antiretrovirals, and other in utero exposures may impact birth outcomes., Methods: Birth weight data were collected from six hospitals in Botswana. Infants born to HIV-negative women between 26-44 weeks gestation were analyzed to construct birth weight for gestational age charts. These data were compared with published norms for black infants in the United States., Results: During a 29 month period from 2007-2010, birth records were reviewed in real-time from 6 hospitals and clinics in Botswana. Of these, 11,753 live infants born to HIV-negative women were included in the analysis. The median gestational age at birth was 39 weeks (1st quartile 38, 3rd quartile 40 weeks), and the median birth weight was 3100 grams (1st quartile 2800, 3rd quartile 3400 grams). We constructed estimated percentile curves for birth weight by gestational age which demonstrate increasing slope during the third trimester and leveling off beyond 40 weeks. Compared with black infants in the United States, Botswana-born infants had lower median birth weight for gestational age from weeks 37 through 42 (p < .02)., Conclusions: We present birth weight for gestational age norms for Botswana, which are lower at term than norms for black infants in the United States. These findings suggest the importance of regional birth weight norms to identify and define risk factors for higher risk births. These data serve as a reference for Botswana, may apply to southern Africa, and may help to identify infants at risk for perinatal complications and inform comparisons among infants exposed to HIV and antiretrovirals in utero.

Objective: To evaluate risk factors for very preterm delivery (VPTD) and very-small-for-gestational-age (VSGA) births in a country with a high HIV prevalence., Methods: Obstetric records at 6 hospitals across Botswana were reviewed at delivery; VPTD was defined as birth before 32 weeks of pregnancy and VSGA as birth weight below the 3rd percentile for Botswana-specific norms., Results: Of 16219 live births born after 26 weeks of pregnancy, 701 (4.3%) were delivered very preterm and 607 (3.7%) were VSGA; 4347 (28.4%) were documented as HIV-exposed. In a multivariable analysis, HIV infection and hypertension during pregnancy were associated with a VPTD (adjusted odds ratio [AOR]: HIV 1.65, hypertension 1.75) and a VSGA birth (AOR: HIV infection 1.90, hypertension 3.44). Among HIV-infected women, the continuation of highly active antiretroviral therapy (HAART) from before conception was associated with a VSGA birth (AOR 1.75) but not with a VPTD (AOR 0.78). In a secondary analysis, HAART continuation was associated with hypertension during pregnancy (AOR 1.34)., Conclusion: Hypertension and HIV infection were risk factors for a VPTD and a VSGA birth. Continuation of HAART from before conception was associated with a VSGA birth but not with a VPTD., (Copyright © 2011 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.)

Background: Maternal highly-active antiretroviral therapy (HAART) reduces mother-to-child HIV transmission but may increase the risk for infant anemia., Methods: The incidence of first severe anemia (grade 3 or 4, Division of AIDS 2004 Toxicity Table) was assessed among HIV-uninfected infants in the Mashi and Mma Bana mother-to-child HIV transmission prevention trials in Botswana. Severe anemia rates were compared between 3 groups: infants exposed to maternal HAART in utero and during breastfeeding (BF) and 1 month of postnatal zidovudine (ZDV) (HAART-BF); infants exposed to maternal ZDV in utero, 6 months of postnatal ZDV, and BF (ZDV-BF); and infants exposed to maternal ZDV in utero, 1 month of postnatal ZDV, and formula-feeding (ZDV-FF)., Results: A total of 1719 infants were analyzed-691 HAART-BF, 503 ZDV-BF, and 525 ZDV-FF. Severe anemia was detected in 118 infants (7.4%). By 6 months, 12.5% of HAART-BF infants experienced severe anemia, compared with 5.3% of ZDV-BF (P < 0.001) and 2.5% of ZDV-FF infants (P < 0.001). In adjusted analysis, HAART-BF infants were at greater risk of severe anemia than ZDV-BF or ZDV-FF infants (adjusted odds ratios 2.6 and 5.8, respectively; P < 0.001). Most anemias were asymptomatic and improved with iron/multivitamin supplementation and cessation of ZDV exposure. However, 11 infants (0.6% of all infants) required transfusion for symptomatic anemia. Microcytosis and hypochromia were common among infants with severe anemia., Conclusions: Exposure to maternal HAART starting in utero was associated with severe infant anemia. Confirmation of this finding and possible strategies to mitigate hematologic toxicity warrant further study.

Objective: This study identified factors contributing to pregnancies in HIV-positive women who were on a prevention of HIV from mother-to-child transmission (PMTCT) programme in Letlhakeng Subdistrict, Botswana., Method: A cross-sectional descriptive survey was employed using an interviewer administered (face-to-face) questionnaire to obtain information from 35 HIV-positive pregnant women registered for a PMTCT programme. Use was made of a non-probability sampling method to obtain information from all the pregnant women who sought antenatal care (ANC) during the survey period., Results: The age of the participants ranged between 18 and 37 years with a modal age of 30 years and a mean of 29.02 years (standard deviation of 5.29). The majority of the participants were single (66%) and had two or more children (74%). About half of the participants (49%) had secondary school education and a high proportion of them knew their HIV-positive status for more than one year prior to the interview day (77%) while the same number of them were unemployed. Pregnant participants seemed to know their HIV status prior to pregnancy. Sharing information about the HIV status of their partners and the participant's financial dependence on their partners did not show any significant association with their pregnancy status. However the partner's desire for parenthood (p < 0.05, 95% CI), the age difference between them and their partners (p < 0.05, 95%CI) and the use of condoms (p < 0.05, 95% CI) indicated significant associations between decision-making and the pregnancies., Conclusion: Pregnancy is common among HIV-positive women who are on a PMTCT at Letlhakeng sub-district as was shown by this study and this may constitute a serious health risk to the child and to the population in general.

In Francistown, Botswana, approximately 40% of pregnant women are HIV positive. PMTCT has been available since 1999, antiretroviral (ARV) therapy since 2001, and 95% of women have antenatal care (ANC) and deliver in hospital. However, in 2002, only 33% of ANC clients were tested for HIV, and not all women with HIV received services. In 2003, we conducted a survey of 504 pregnant and postpartum women to explore reasons for poor program uptake, and interviewed 82 health providers about PMTCT. Most women (95%) believed that all pregnant women should be tested for HIV. In multivariate analysis, factors associated with having an HIV test included being interviewed at an urban site, having a high PMTCT knowledge score, knowing someone receiving PMTCT or ARV therapy, and having a partner who had been tested for HIV. Neither fear of stigma nor resistance from partners were frequent reasons for refusing an HIV test. Providers of HIV services reported discomfort with their knowledge and skills, and 84% believed HIV testing should be routine. Ensuring adequate knowledge about HIV and PMTCT, creating systems whereby HIV-positive women receiving care can educate and support other women, and making HIV testing routine for pregnant women may improve the uptake of HIV testing.

Background: Millions of HIV-infected women in developing countries are in need of safe and highly effective antiretroviral therapy. Pregnancy rates are usually high in developing countries, and efavirenz (EFV) use in women of childbearing age is of concern because of its potential teratogenicity., Methods: As part of a prospective study comparing 6 initial highly active antiretroviral therapy (HAART) regimens, 3 of which contained EFV, pregnancy and birth outcomes were evaluated among female participants enrolled in a randomized clinical trial in Botswana. Before enrollment, all female participants indicated a willingness to avoid pregnancy for the 3-year duration of the study. Monthly urine pregnancy testing and regular contraceptive education and counseling were given to all women on study., Results: Four hundred fifty-one (69.4%) of 650 enrolled study participants were female and experienced 71 pregnancies, for a rate of 7.9 per 100 person-years during the study. The mean time from HAART initiation to time of first pregnancy was 385 days. The median birth weight of babies was 2950 g (interquartile range: 2700-3250 g); the gender of babies (24 female and 15 male) and occurrence of early pregnancy loss (42%) and stillbirths (3%) did not differ between EFV- and non-EFV-exposed pregnancies (P=0.7). First-trimester EFV exposure occurred in 38 (53.5%) of the 71 pregnancies; 22 (57.9%) of these 38 pregnancies resulted in live births. One infant (4.5%) of the 22 EFV-exposed live births had a congenital abnormality with right limb shortening that was assessed to be unrelated to EFV exposure., Conclusions: The restoration of health and longevity in many HAART-treated women is often accompanied by childbearing, as evidenced by the large fraction of women in our cohort who became pregnant despite their initial statements of intent to avoid pregnancy. Of 22 first-trimester EFV-exposed live births, 1 neonate was found to have a major congenital abnormality; however, this defect was unrelated to EFV exposure. The small sample size is insufficient to estimate accurately the underlying risk of congenital malformation after exposure to EFV in early pregnancy, underscoring the importance of reporting to the existing international Antiretroviral Pregnancy Registry. In addition to accessing safe and effective HAART regimens, HIV-infected women require access to comprehensive family planning services, including contraception and procreation counseling.

Background: Chlamydia and gonorrhoea are major causes of morbidity among women in developing countries. Both infections have been associated with pregnancy-related complications, and case detection and treatment in pregnancy is essential. In countries without laboratory support, the diagnosis and treatment of cervical infections is based on the syndromic approach. In this study we measured the prevalence of chlamydia and gonorrhoea among antenatal care attendees in Botswana. We evaluated the syndromic approach for the detection of cervical infections in pregnancy, and determined if risk scores could improve the diagnostic accuracy., Methods: In a cross-sectional study, 703 antenatal care attendees in Botswana were interviewed and examined, and specimens were collected for the identification of C trachomatis, N gonorrhoeae and other reproductive tract infections. Risk scores to identify attendees with cervical infections were computed based on identified risk factors, and their sensitivities, specificities, likelihood ratios and predictive values were calculated., Results: The prevalence of chlamydia was 8%, and gonorrhoea was found in 3% of the attendees. Symptoms and signs of vaginal discharge did not predict cervical infection, and a syndromic approach failed to identify infected women. Age (youth) risk factor most strongly associated with cervical infection. A risk score with only sociodemographic factors had likelihood ratios equivalent to risk scores which incorporated clinical signs and microscopy results. However, all the evaluated risk scores were of limited value in the diagnosis of chlamydia and gonorrhoea. A cut-off set at an acceptable sensitivity to avoid infected antenatal care attendees who remained untreated would inevitably lead to considerable over-treatment., Conclusion: Although in extensive use, the syndromic approach is unsuitable for diagnosing cervical infections in antenatal care attendees in Botswana. None of the evaluated risk scores can replace this management. Without diagnostic tests, there are no adequate management strategies for C trachomatis and N gonorrhoeae in pregnant women in Botswana, a situation which is likely to apply to other countries in sub-Saharan Africa. Screening for cervical infections in pregnant women is an essential public health measure, and rapid tests will hopefully be available in developing countries within a few years.

Objective: To measure the prevalence of Trichomonas vaginalis (TV) infection and bacterial vaginosis (BV) among pregnant women in Botswana, and to evaluate the syndromic approach and alternative management strategies for these conditions in pregnancy., Methods: In a cross-sectional study, 703 antenatal care attendees were interviewed and examined, and specimens were collected to identify TV, BV, Candida species, Chlamydia trachomatis and Neisseria gonorrhoeae. Information on reproductive tract infections earlier in pregnancy was obtained from a structured interview and the antenatal record., Findings: TV was found in 19% and BV in 38% of the attendees. Three-fourths of women with TV or BV were asymptomatic. Syndromic management according to the vaginal discharge algorithm would lead to substantial under-diagnosis and over-treatment of TV and BV. Signs of vaginal discharge were more predictive of the presence of these conditions than were symptoms. Among the 546 attendees on a repeat antenatal visit, 142 (26%) had been diagnosed with vaginal discharge earlier in their pregnancy--14 of them twice. In 143 cases, an attendee was diagnosed with vaginal discharge in the second or third trimester; however, metronidazole had been prescribed only 17 times (12%)., Conclusion: Diagnosis and treatment of TV and BV among pregnant women in sub-Saharan Africa presents major challenges. Half the pregnant women in this study were diagnosed with TV or BV, but these conditions were not detected and treated during antenatal care with syndromic management. Also, health workers did not adhere to treatment guidelines. These results indicate that management guidelines for TV and BV in antenatal care should be revised.

Objectives: To evaluate trends in syphilis prevalence among antenatal women in a high HIV prevalence setting in northern Botswana., Methods: Laboratory logbooks of antenatal syphilis testing for 1992-2003 in Francistown, Botswana's second largest city, were reviewed, and a consecutive sample of 750 women per year from 1992-2003 were analysed. VDRL result and age were recorded. A positive result was considered a case., Results: Overall syphilis prevalence (VDRL positive) among pregnant women in Francistown decreased from 12.4% in 1992 to 4.3% in 2003 (p< or =0.001). The downward trend in overall syphilis prevalence began in 1997. There was no change in syphilis prevalence from 1992-6. Beginning in 1997, there has been a significant decrease in syphilis prevalence in all age groups., Conclusions: Syphilis in pregnant women in Francistown has been decreasing for the last 6 years, despite extremely high HIV prevalence (stable at > or =40% since 1996) in the same population. Reasons contributing to the decline in syphilis rates may include nationwide implementation of syndromic management of sexually transmitted diseases (STDs) in 1992, improved access to health care, and less risky sexual behaviour. There is evidence from other sources indicating that risky sexual behaviour in Botswana has decreased during the HIV epidemic.

This study examined the extent to which women accessing antenatal-care services in Botswana were offered HIV-related information and counselling and an opportunity to take an HIV test as part of the Prevention of Mother-to-Child Transmission of infection, and how these women responded. Data for this study were drawn from the Botswana AIDS Impact Survey 2001, a nationally-representative sample survey. The survey successfully interviewed over 4,494 of 4,728 eligible women on various issues relating to HIV/AIDS at both household and individual levels. Frequencies, cross tabulations, and logistic regression were used for data analysis. Over half (57.9%) of the women were offered HIV/AIDS-related information, counselling, or testing. Age, education, and residence were important predictors of being offered HIV counselling or testing. Younger and more-educated women and those residing in towns were more likely to be offered both HIV counselling and testing than older, less-educated, and rural women. Seventy-nine percent of the women who were offered HIV testing agreed to undergo the test regardless of their background characteristics. The number of pregnant women who underwent HIV testing during antenatal care accounted for only a fifth (21%) of all antenatal-care attendees in 2001. Lack of capacity to deliver voluntary counselling and testing services to all pregnant women attending antenatal care is one of the biggest challenges to increased use of voluntary counselling and testing services.