Integrating noncommunicable disease services into primary health care, Botswana.

Despite the rising burden of noncommunicable diseases, access to quality decentralized noncommunicable disease services remain limited in many low- and middle-income countries. Here we describe the strategies we employed to drive the process from adaptation to national endorsement and implementation of the 2016 Botswana primary healthcare guidelines for adults. The strategies included detailed multilevel assessment with broad stakeholder inputs and in-depth analysis of local data; leveraging academic partnerships; facilitating development of supporting policy instruments; and embedding noncommunicable disease guidelines within broader primary health-care guidelines in keeping with the health ministry strategic direction. At facility level, strategies included developing a multimethod training programme for health-care providers, leveraging on the experience of provision of human immunodeficiency virus care and engaging health-care implementers early in the process. Through the strategies employed, the country's first national primary health-care guidelines were endorsed in 2016 and a phased three-year implementation started in August 2017. In addition, provision of primary health-care delivery of noncommunicable disease services was included in the country's 11th national development plan (2017-2023). During the guideline development process, we learnt that strong interdisciplinary skills in communication, organization, coalition building and systems thinking, and technical grasp of best-practices in low- and middle-income countries were important. Furthermore, misaligned agendas of stakeholders, exaggerated by a siloed approach to guideline development, underestimation of the importance of having policy instruments in place and coordination of the processes initially being led outside the health ministry caused delays. Our experience is relevant to other countries interested in developing and implementing guidelines for evidence-based noncommunicable disease services.

Malgré la charge de morbidité croissante des maladies non transmissibles, l'accès à des services décentralisés de qualité pour lutter contre ces maladies reste limité dans de nombreux pays à revenu faible ou intermédiaire. Dans cet article, nous décrivons les stratégies qui ont été employées pour mener les étapes d'adaptation, de validation et de mise en œuvre à l'échelle nationale des Lignes directrices 2016 du Botswana sur les soins de santé primaires pour l'adulte. Ces stratégies ont inclus: une évaluation multiniveau détaillée avec une large implication des parties prenantes et une analyse approfondie des données locales; le recours à des partenariats universitaires; la promotion de l'élaboration d'instruments politiques propices; l'intégration de lignes directrices portant spécifiquement sur les maladies non transmissibles dans les lignes directrices générales sur les soins primaires, en écho à l'orientation stratégique du ministère de la Santé. Au niveau des établissements de santé, les stratégies ont inclus: la création d'un programme de formation multiméthode à destination des prestataires de soins; l'exploitation de l'expérience acquise dans la prise en charge du virus de l'immunodéficience humaine et l'implication des prestataires de soins très tôt dans le processus. Grâce aux stratégies employées, les premières lignes directrices nationales sur les soins de santé primaires ont été validées en 2016, et une étape de mise en œuvre graduelle, sur trois ans, a commencé en août 2017. De plus, la prestation de soins de santé primaires contre les maladies non transmissibles a été incluse dans le 11e plan national de développement du pays (2017-2023). Pendant la phase d'élaboration des lignes directrices, nous avons constaté toute l'importance, dans les pays à revenu faible et intermédiaire, de pouvoir compter sur de solides compétences interdisciplinaires en matière de communication, d'organisation, de création de coalitions et de réflexion systémique et d'obtenir une bonne compréhension technique des meilleures pratiques. Nous avons par ailleurs observé des retards provoqués par des problèmes d'incompatibilité d'agendas entre les différentes parties prenantes, exagérés par des approches cloisonnées lors de la phase d'élaboration des lignes directrices, par la sous-estimation de l'importance d'avoir des outils politiques déjà en place et par des difficultés de coordination des processus initialement pilotés hors du ministère de la Santé. Notre expérience peut être utile pour d'autres pays qui souhaiteraient élaborer et mettre en œuvre des lignes directrices pour des services de soins contre les maladies non transmissibles fondés sur des données probantes.

A pesar de la creciente carga de las enfermedades no transmisibles, el acceso a servicios de calidad descentralizados para estas enfermedades sigue siendo limitado en muchos países de bajos y medianos ingresos. A continuación, describimos las estrategias que empleamos para impulsar el proceso desde la adaptación a la aprobación nacional y la implementación de las directrices de atención primaria de la salud para adultos de Botswana de 2016. Las estrategias incluían una evaluación detallada a varios niveles con amplias aportaciones de las partes interesadas y un análisis a fondo de los datos locales; el aprovechamiento de las asociaciones académicas; la facilidad para elaborar instrumentos normativos de apoyo; la incorporación de directrices sobre las enfermedades no transmisibles en las directrices más amplias sobre la atención primaria de la salud, de conformidad con la dirección estratégica del Ministerio de Salud. A nivel de los centros de salud, las estrategias incluían la elaboración de un programa de capacitación multimétodo para los proveedores de servicios de salud, el aprovechamiento de la experiencia en la prestación de servicios de atención del virus de la inmunodeficiencia humana y la participación de los encargados de la ejecución de los servicios de salud en las primeras etapas del proceso. Gracias a las estrategias empleadas, en 2016 se aprobaron las primeras directrices nacionales de atención primaria de la salud del país y en agosto de 2017 se inició una aplicación por etapas de tres años. Además, la prestación de servicios de atención primaria de la salud para las enfermedades no transmisibles se incluyó en el 11º plan nacional de desarrollo del país (2017-2023). Durante el proceso de desarrollo de las directrices, aprendimos que eran importantes las buenas habilidades interdisciplinarias en comunicación, organización, formación de coaliciones y pensamiento sistémico, así como la comprensión técnica de las mejores prácticas en los países de ingresos bajos y medios. Por otra parte, las agendas desalineadas de las partes interesadas, exageradas por el enfoque aislado del desarrollo de las directrices, la subestimación de la importancia de contar con instrumentos de política y la coordinación de los procesos que inicialmente se llevaban a cabo fuera del ministerio de salud causaron retrasos. Nuestra experiencia es relevante para otros países interesados en desarrollar e implementar directrices para servicios de enfermedades no transmisibles basados en la evidencia.

Effectiveness of Monovalent Rotavirus Vaccine After Programmatic Implementation in Botswana: A Multisite Prospective Case-Control Study.

BACKGROUND: Botswana introduced monovalent G1P rotavirus vaccine (RV1) in July 2012, providing one of the first opportunities to assess the effectiveness of routine RV1 vaccination in a high-burden setting in Africa. We sought to determine the effectiveness of RV1 against rotavirus diarrhea hospitalization using a case-control evaluation. METHODS: Vaccine age-eligible children <5 years of age admitted with diarrhea at 4 hospitals in Botswana were enrolled from June 2013 to April 2015. Card-confirmed vaccine history was compared between case patients (children with laboratory-confirmed rotavirus diarrhea) and nonrotavirus "test-negative" diarrhea controls. Vaccine effectiveness (VE) was computed using unconditional logistic regression models adjusting for age, birth month/year, and hospital. Sequence-based genotyping was performed on antigen-positive samples. RESULTS: Among 242 case patients and 368 controls, 82% (199/242) and 92% (339/368), respectively, had received ≥1 doses of RV1. Effectiveness of a full series (2 doses) of RV1 against rotavirus diarrhea requiring hospitalization was 54% (95% confidence interval [CI], 23%-73%); 1 dose of RV1 was 48% (95% CI, 1%-72%) effective. Effectiveness was 59% (95% CI, 4%-83%) against rotavirus caused by G2P, the most common (37%) circulating genotype. However, the effectiveness of 2 RV1 doses was significantly higher in children with no undernutrition (VE, 75% [95% CI, 41%-89%]), compared to those with moderate or severe undernutrition (VE, -28% [95% CI, -309% to 60%]) (P= .02). CONCLUSIONS: Routine RV1 vaccination in Botswana showed effectiveness similar to that in clinical trials in Africa, including against a serotype fully heterotypic to the vaccine. Undernutrition may in part explain the lower rotavirus VE in low-income settings.

Yield of screening for TB and HIV among children failing to thrive in Botswana.

BACKGROUND: Failure to thrive (FTT) is a sign of tuberculosis (TB) and human immunodeficiency virus (HIV) infection. We assessed TB and HIV prevalence in children with FTT at one clinic in Botswana. METHODS: In July 2010, we screened all children attending a 'Well Child' clinic for FTT. Children with FTT were referred to a paediatrician who: (i) assessed causes of FTT, (ii) evaluated for HIV and TB and (iii) reviewed the patient chart for evaluations for TB and HIV. RESULTS: Of 919 children screened, 176 (19%) had FTT. One hundred eighteen (67%) children saw a paediatrician, and of these, 95 (81%) completed the TB evaluation. TB was newly diagnosed in 6 of 95 (6%). At review, HIV status was known in 23 of 118 (19%). Ninety-five had an unknown HIV status. Forty-five (47%) tested for HIV; all tested HIV-negative. CONCLUSION: TB and HIV screening among children with FTT diagnosed TB in 6% of cases completing an evaluation, but no new HIV infections.

Malaria control in Botswana, 2008-2012: the path towards elimination.

BACKGROUND: Botswana has made substantial progress towards malaria elimination across the country. This work assessed interventions and epidemiological characteristics of malaria in Botswana, during a period of decreasing transmission intensity. METHODS: National passive malaria surveillance data for five years (2008-2012) were analysed. A district-level, random effects model with Poisson regression was used to explore the association between malaria cases and coverage with long-lasting insecticide-treated nets (LLINs) and indoor residual spraying (IRS). Malaria cases were mapped to visualize spatio-temporal variation in malaria for each year. RESULTS: Within five years, a reduction in malaria prevalence (approximately 98%) and number of deaths (12 to three) was observed. Between 2008 and 2012, 237,050 LLINs were distributed and 596,979 rooms were sprayed with insecticides. Coverage with LLINs and IRS was not uniformly distributed over the study period and only targeted the northern districts with a high malaria burden. The coverage of IRS was associated with a reduction in malaria cases. CONCLUSIONS: Botswana has made significant strides towards its goal of country-wide elimination of malaria. A major challenge in the future will be prevention and management of imported malaria infections from neighbouring countries. In order to accurately monitor progress towards the elimination goal, the malaria control programme (NMP) should strengthen the reporting and capturing of data at household and individual level. Systematic, periodic operational research to feedback the NMP will help to guide and achieve elimination.

Evaluation of the effectiveness of an outreach clinical mentoring programme in support of paediatric HIV care scale-up in Botswana.

Clinical mentoring by providers skilled in HIV management has been identified as a cornerstone of scaling-up antiretroviral treatment in Africa, particularly in settings where expertise is limited. However, little data exist on its effectiveness and impact on improving the quality-of-care and clinical outcomes, especially for HIV-infected children. Since 2008, the Botswana-Baylor Children's Clinical Centre of Excellence (COE) has operated an outreach mentoring programme at clinical sites around Botswana. This study is a retrospective review of 374 paediatric charts at four outreach mentoring sites (Mochudi, Phutadikobo, Molepolole and Thamaga) evaluating the effectiveness of the programme as reflected in a number of clinically-relevant areas. Charts from one visit prior to initiation of mentoring and from one visit after approximately one year of mentoring were assessed for statistically-significant differences (p<0.05) in the documentation of clinically-relevant indicators. Mochudi showed notable improvements in all indicators analysed, with particular improvements in documentation of pill count, viral load (VL) results, correct laboratory monitoring and correct antiretroviral therapy (ART) dosing (p<0.0001, p<0.0001, p<0.0001 and p<0.0001, respectively). Broad and substantial improvements were also seen in Molepolole, with the most improvement in disclosure documentation of all four sites. At Thamaga, improvements were restricted to CD4 documentation (p<0.001), recent VL and documented pill count (p<0.05 and p<0.05, respectively). Phuthadikobo showed the least amount of improvement across indicators, with only VL documentation and correct ART dosing showing statistically-significant improvements (p<0.05 and p<0.0001, respectively). These findings suggest that clinical mentoring may assist improvements in a number of important areas, including ART dosing and monitoring; adherence assessment and assurance; and disclosure. Clinical mentoring may be a valuable tool in scale-up of quality paediatric HIV care-and-treatment outside specialised centres. Further study will help refine approaches to clinical mentoring, including assuring mentoring translates into improved clinical outcomes for HIV-infected children.

Knowledge acquisition and retention following Saving Children's Lives course for healthcare providers in Botswana: a longitudinal cohort study.

OBJECTIVES: Millions of children die every year from serious childhood illnesses. Most deaths are avertable with access to quality care. Saving Children's Lives (SCL) includes an abbreviated high-intensity training (SCL-aHIT) for providers who treat serious childhood illnesses. The objective of this study was to examine the impact of SCL-aHIT on knowledge acquisition and retention of providers. SETTING: 76 participating centres who provide primary and secondary care in Kweneng District, Botswana. PARTICIPANTS: Doctors and nurses expected by the District Health Management Team to provide initial care to seriously ill children, completed SCL-aHIT between January 2014 and December 2016, submitted demographic data, course characteristics and at least one knowledge assessment. METHODS: Retrospective, cohort study. Planned and actual primary outcome was adjusted acquisition (change in total knowledge score immediately after training) and retention (change in score at 1, 3 and 6 months), secondary outcomes were pneumonia and dehydration subscores. Descriptive statistics and linear mixed models with random intercept and slope were conducted. Relevant institutional review boards approved this study. RESULTS: 211 providers had data for analysis. Cohort was 91% nurses, 61% clinic/health postbased and 45% pretrained in Integrated Management of Childhood Illness (IMCI). A strong effect of SCL-aHIT was seen with knowledge acquisition (+24.56±1.94, p<0.0001), and loss of retention was observed (-1.60±0.67/month, p=0.018). IMCI training demonstrated no significant effect on acquisition (+3.58±2.84, p=0.211 or retention (+0.20±0.91/month, p=0.824) of knowledge. On average, nurses scored lower than physicians (-19.39±3.30, p<0.0001). Lost to follow-up had a significant impact on knowledge retention (-3.03±0.88/month, p=0.0007). CONCLUSIONS: aHIT for care of the seriously ill child significantly increased provider knowledge and loss of knowledge occurred over time. IMCI training did not significantly impact overall knowledge acquisition nor retention, while professional status impacted overall score and lost to follow-up impacted retention.

Pediatric Neurodevelopmental Functioning After In Utero Exposure to Triple-NRTI vs. Dual-NRTI + PI ART in a Randomized Trial, Botswana.

BACKGROUND: In utero exposure to nucleoside reverse transcriptase inhibitor (NRTI)-containing antiretroviral treatment (ART) regimens may be associated with poor neurodevelopmental functioning in children of HIV-infected mothers. We investigated neurodevelopmental outcomes of HIV-exposed uninfected (HEU) children of HIV-infected women enrolled in a randomized trial of abacavir/zidovudine/lamivudine (triple-NRTI regimen) vs. lopinavir/ritonavir/zidovudine/lamivudine [dual-NRTI + protease inhibitor (PI) regimen]. SETTING: The Mma Bana randomized trial was conducted in urban and rural sites in Botswana. METHODS: The Mma Bana study randomized HIV-infected pregnant women with CD4 ≥200 cells per mm to a triple-NRTI vs. dual-NRTI + PI regimen from 26- to 34-week gestation through planned weaning at 6-month postpartum. Partway through the study, neurodevelopmental assessments were added at 24 months of age, including the Developmental Milestones Checklist, the Bayley Scales of Infant and Toddler Development third edition, Ten Questions Questionnaire, and Profile of Social Emotional Development. We evaluated differences in mean scores between the 2 arms using unadjusted and adjusted linear regression. RESULTS: A total of 197 HEU infants (48% male) completed a neurodevelopmental assessment (101 in triple-NRTI arm and 96 in dual-NRTI + PI-exposed arm). Mean values for all neurodevelopmental outcomes were similar for children of mothers randomized to either ART regimen, with no significant differences in either unadjusted or adjusted models (estimated effect sizes ranging from -0.12 to 0.14). CONCLUSIONS: Neurodevelopmental outcomes in 24-month-old HEU children of HIV-infected mothers with baseline CD4 ≥200 were similar in those randomized to a dual-NRTI + PI-based vs. a triple-NRTI-based ART regimen, suggestive of lack of short-term toxicity. Monitoring of long-term toxicity and newer regimens is warranted.

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.

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

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.

Neurodevelopment of HIV-Exposed and HIV-Unexposed Uninfected Children at 24 Months.

BACKGROUND: We sought to determine if HIV-exposed uninfected (HEU) children had worse neurodevelopmental outcomes at 24 months compared with HIV-unexposed uninfected (HUU) children in Botswana. METHODS: HIV-infected and uninfected mothers enrolled in a prospective observational study ("Tshipidi") in Botswana from May 2010 to July 2012. Child neurodevelopment was assessed at 24 months with the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III: cognitive, gross motor, fine motor, expressive language, and receptive language domains) and the Development Milestones Checklist (DMC), a caregiver-completed questionnaire (locomotor, fine motor, language and personal-social domains). We used linear regression models to estimate the association of in-utero HIV exposure with neurodevelopment, adjusting for socioeconomic and maternal health characteristics. RESULTS: We evaluated 670 children (313 HEU, 357 HUU) with ≥1 valid Bayley-III domain assessed and 723 children (337 HEU, 386 HUU) with a DMC. Among the 337 HEU children with either assessment, 122 (36%) were exposed in utero to maternal 3-drug antiretroviral treatment and 214 (64%) to zidovudine. Almost all HUU children (99.5%) breastfed, compared with only 9% of HEU children. No domain score was significantly lower among HEU children in adjusted analyses. Bayley-III cognitive and DMC personal-social domain scores were significantly higher in HEU children than in HUU children, but differences were small. CONCLUSIONS: HEU children performed equally well on neurodevelopmental assessments at 24 months of age compared with HUU children. Given the global expansion of the HEU population, results suggesting no adverse impact of in-utero HIV and antiretroviral exposure on early neurodevelopment are reassuring.

Malaria elimination in Botswana, 2012-2014: achievements and challenges.

BACKGROUND: Botswana significantly reduced its malaria burden between 2000 and 2012. Incidence dropped from 0.99 to 0.01 % and deaths attributed to malaria declined from 12 to 3. The country initiated elimination strategies in October 2012. We examine the progress and challenges during implementation and identify future needs for a successful program in Botswana. METHODS: A national, rapid notification and response strategy was developed. Cases detected through the routine passive surveillance system at health facilities were intended to initiate screening of contacts around a positive case during follow up. Positive cases were reported to district health management teams to activate district rapid response teams (DRRT). The health facility and the DRRT were to investigate the cases, and screen household members within 100 m of case households within 48 h of notification using rapid diagnostic tests (RDT) and microscopy. Positive malaria cases detected in health facilities were used for spatial analysis. RESULTS: There were 1808 malaria cases recorded in Botswana during 26 months from October, 2012 to December, 2014. Males were more frequently infected (59%) than females. Most cases (60%) were reported from Okavango district which experienced an outbreak in 2013 and 2014. Among the factors creating challenges for malaria eradication, only 1148 cases (63.5%) were captured by the required standardized notification forms. In total, 1080 notified cases were diagnosed by RDT. Of the positive malaria cases, only 227 (12.6%) were monitored at the household level. One hundred (8.7%) cases were associated with national or transnational movement of patients. Local movements of infected individuals within Botswana accounted for 31 cases while 69 (6.01%) cases were imported from other countries. Screening individuals in and around index households identified 37 additional, asymptomatic infections. Oscillating, sporadic and new malaria hot-spots were detected in Botswana during the study period. CONCLUSION: Botswana's experience shows some of the practical challenges of elimination efforts. Among them are the substantial movements of human infections within and among countries, and the persistence of asymptomatic reservoir infections. Programmatically, challenges include improving the speed of communicating and improving the thoroughness when responding to newly identified cases. The country needs further sustainable interventions to target infections if it is to successfully achieve its elimination goal.

Cotrimoxazole prophylaxis and risk of severe anemia or severe neutropenia in HAART-exposed, HIV-uninfected infants.

BACKGROUND: Prophylactic cotrimoxazole is recommended for infants born to HIV-infected mothers. However, cotrimoxazole may increase the risk of severe anemia or neutropenia. METHODS: We compared the proportion of HIV-exposed uninfected (HIV-EU) infants experiencing incident severe anemia (and separately, severe neutropenia) between a prospective cohort receiving prophylactic cotrimoxazole from 1 to 6 months vs. infants from two prior trials who did not receive cotrimoxazole. Infants were from rural and urban communities in southern Botswana. RESULTS: A total of 1705 HIV-EU infants were included. Among these 645 (37.8%) were fed with iron-supplemented formula from birth. Severe anemia developed in 87 (5.1%) infants, and severe neutropenia in 164 (9.6%) infants. In an analysis stratified by infant feeding method, there were no significant differences in the risk of severe anemia by prophylactic cotrimoxazole exposure-risk difference, -0.69% (95% confidence interval [CI] -2.1 to 0.76%). Findings were similar in multivariable analysis, adjusted odds ratio (aOR) 0.35 (95% CI 0.07 to 1.65). There were also no significant differences observed for severe neutropenia by cotrimoxazole exposure, risk difference 2.0% (95% CI -1.3 to 5.2%) and aOR 0.80 (95% CI 0.33 to 1.93). CONCLUSIONS: Severe anemia and severe neutropenia were infrequent among HIV-exposed uninfected infants receiving cotrimoxazole from 1-6 months of age. Concerns regarding hematologic toxicity should not limit the use of prophylactic cotrimoxazole in HIV-exposed uninfected infants. CLINICALTRIAL.SGOV REGISTRATION NUMBERS: NCT01086878 (http://clinicaltrials.gov/show/NCT01086878), NCT00197587 (http://clinicaltrials.gov/show/NCT00197587), and NCT00270296 (http://clinicaltrials.gov/show/NCT00270296).

Etiology of meningitis among patients admitted to a tertiary referral hospital in Botswana.

This retrospective review evaluated records of cerebrospinal fluid samples between 2000 and 2008 at Princess Marina Hospital in Gaborone, Botswana. Of the 7501 cerebrospinal fluid samples reviewed, Streptococcus pneumoniae (n = 125) and Haemophilus influenzae (n = 60) were the most common bacteria cultured. There were also 1018 cryptococcal and 44 tuberculous meningitis cases. Antimicrobial susceptibilities are described. Public health interventions could decrease the burden of meningitis in Botswana.

Highly active antiretroviral therapy versus zidovudine for prevention of mother-to-child transmission in a programmatic setting, Botswana.

Few studies have compared the programmatic effectiveness of the recommended strategies of antenatal highly active antiretroviral therapy (HAART) and zidovudine for prevention of mother-to-child transmission. We prospectively followed infants (93% formula fed) whose mothers who took either HAART (258 infants) or zidovudine (170 infants) during pregnancy in the Botswana national program. Overall, 10 infants (2.5%) acquired HIV--9 infants in the zidovudine group (5.5%, 95% confidence interval: 2.6% to 10.2%) and 1 infant in the HAART group (0.4%, 95% confidence interval: 0.0% to 2.2%). Maternal HAART was associated with decreased prevention of mother-to-child transmission (P = 0.001) and improved HIV-free survival (P = 0.040) compared with zidovudine (with or without single-dose nevirapine) in a programmatic setting.

Antibiotic use in pediatric patients admitted to a referral hospital in Botswana.

Inappropriate antimicrobial drug use is well described for hospitalized patients in the United States. Antibiotic use in hospitals in developing countries is less well documented. We evaluated the antibiotics prescribed to 91 pediatric inpatients in Botswana. The results showed that the duration of prescribed therapy can be excessive. Recommendations for potential interventions to reduce antibiotic overuse in this setting are necessary.