Loeto Mazhani

HIV transmission and 24-month survival in a randomized trial of HAART to prevent MTCT during pregnancy and breastfeeding in Botswana.

Objectives:HAART for prevention of mother-to-child HIV transmission (MTCT) may impact long-term survival of women and children. Design:Randomized clinical trial. Methods:HIV-infected pregnant women with CD4+ cell count at least 200 cells/&mgr;l were randomly assigned to abacavir, zidovudine, lamivudine (arm A) or lopinavir–ritonavir, zidovudine–lamivudine (arm B) from week 26 to 34 gestation through planned weaning by 6 months postpartum. Women with baseline CD4+ cell count less than 200 cells/&mgr;l received nevirapine–zidovudine–lamivudine indefinitely (Obs arm), as did randomized women later qualifying for treatment. Results:Among 560 randomized and 170 observational women enrolled, there were 14 deaths (1.9%) – one antenatally (Obs), three from delivery to 6 months postpartum (1 arm A, 2 Obs), and 10 from 6 to 24 months postpartum (5 arm A, 3 arm B, 2 Obs). Time to death or CD4+ cell count below 200 cells/&mgr;l was shorter in arm A vs. B (P = 0.03). Of the 709 live-born children, 97% breastfed for a median of 5.8 months. Of 37 (5.2%) deaths by 24 months, nine were before breastfeeding initiated (3 arm A, 2 arm B, 4 Obs); six while breastfeeding (1 arm A, 2 arm B, 3 Obs); and 22 after weaning (9 arm A, 11 arm B, 2 Obs). Only eight children (1.1%) were HIV-infected at 24 months (6 arm A, 1 arm B, 1 Obs), all before 6 months. Conclusion:Low MTCT was maintained through extended follow-up in all arms. Disease progression appeared slower after discontinuing protease inhibitor-based HAART, but a concerning number of maternal deaths occurred after stopping either regimen. Strategies to improve maternal and child survival in the postintervention period are required.

Training hospital providers in basic CPR skills in Botswana: Acquisition, retention and impact of novel training techniques

OBJECTIVE Globally, one third of deaths each year are from cardiovascular diseases, yet no strong evidence supports any specific method of CPR instruction in a resource-limited setting. We hypothesized that both existing and novel CPR training programs significantly impact skills of hospital-based healthcare providers (HCP) in Botswana. METHODS HCP were prospectively randomized to 3 training groups: instructor led, limited instructor with manikin feedback, or self-directed learning. Data was collected prior to training, immediately after and at 3 and 6 months. Excellent CPR was prospectively defined as having at least 4 of 5 characteristics: depth, rate, release, no flow fraction, and no excessive ventilation. GEE was performed to account for within subject correlation. RESULTS Of 214 HCP trained, 40% resuscitate ≥ 1/month, 28% had previous formal CPR training, and 65% required additional skills remediation to pass using AHA criteria. Excellent CPR skill acquisition was significant (infant: 32% vs. 71%, p<0.01; adult 28% vs. 48%, p<0.01). Infant CPR skill retention was significant at 3 (39% vs. 70%, p<0.01) and 6 months (38% vs. 67%, p<0.01), and adult CPR skills were retained to 3 months (34% vs. 51%, p=0.02). On multivariable analysis, low cognitive score and need for skill remediation, but not instruction method, impacted CPR skill performance. CONCLUSIONS HCP in resource-limited settings resuscitate frequently, with little CPR training. Using existing training, HCP acquire and retain skills, yet often require remediation. Novel techniques with increased student: instructor ratio and feedback manikins were not different compared to traditional instruction.

Evaluation of Anatomically Designed Flocked Rectal Swabs for Molecular Detection of Enteric Pathogens in Children Admitted to Hospital with Severe Gastroenteritis in Botswana

ABSTRACT Two-hundred eighty matched bulk stool and anatomically designed flocked rectal swab samples were collected from children admitted to the hospital with acute diarrhea in Botswana. Their parents were asked about the acceptability of the swab collection method compared with bulk stool sampling. All samples underwent identical testing with a validated 15-target (9 bacterial, 3 viral, and 3 parasite) commercial multiplex PCR assay. The flocked swabs had a 12% higher yield for bacterial pathogen targets (241 versus 212; P = 0.003) compared with that of stool samples, as well as similar yields for viral targets (110 versus 113; P = 0.701) and parasite targets (59 versus 65; P = 0.345). One hundred sixty-four of the flocked swab-stool pairs were also tested with separate laboratory-developed bacterial and viral multiplex assays, and the flocked rectal swabs had a performance that was similar to that seen with commercial assay testing. Almost all parents/guardians found the swabs acceptable. Flocked rectal swabs significantly facilitate the molecular diagnosis of diarrheal disease in children.

Vitamin D₃ Supplementation in Batswana Children and Adults with HIV: A Pilot Double Blind Randomized Controlled Trial

Objectives Since vitamin D insufficiency is common worldwide in people with HIV, we explored safety and efficacy of high dose cholecalciferol (D₃) in Botswana, and evaluated potential modifiers of serum 25 hydroxy vitamin D change (Δ25D). Design Prospective randomized double-blind 12-week pilot trial of subjects ages 5.0–50.9 years. Methods Sixty subjects randomized within five age groups to either 4000 or 7000IU per day of D₃ and evaluated for vitamin D, parathyroid hormone, HIV, safety and growth status. Efficacy was defined as serum 25 hydroxy vitamin D (25D) ≥32ng/mL, and safety as no simultaneous elevation of serum calcium and 25D. Also assessed were HIV plasma viral RNA viral load (VL), CD4%, anti-retroviral therapy (ART) regime, and height-adjusted (HAZ), weight-adjusted (WAZ) and Body Mass Index (BMIZ) Z scores. Results Subjects were 50% male, age (mean±SD) 19.5±11.8 years, CD4% 31.8±10.4, with baseline VL log₁₀ range of <1.4 to 3.8 and VL detectable (>1.4) in 22%. From baseline to 12 weeks, 25D increased from 36±9ng/ml to 56±18ng/ml (p<0.0001) and 68% and 90% had 25D ≥32ng/ml, respectively (p = 0.02). Δ25D was similar by dose. No subjects had simultaneously increased serum calcium and 25D. WAZ and BMIZ improved by 12 weeks (p<0.04). HAZ and CD4% increased and VL decreased in the 7000IU/d group (p<0.04). Younger (5–13y) and older (30–50y) subjects had greater Δ25D than those 14–29y (26±17 and 28±12 vs. 11±11ng/ml, respectively, p≤0.001). Δ25D was higher with efavirenz or nevirapine compared to protease inhibitor based treatment (22±12, 27±17, vs. 13±10, respectively, p≤0.03). Conclusions In a pilot study in Botswana, 12-week high dose D₃ supplementation was safe and improved vitamin D, growth and HIV status; age and ART regimen were significant effect modifiers. Trial Registration ClinicalTrials.gov NCT02189902

Impact of contextualized pediatric resuscitation training on pediatric healthcare providers in Botswana

BACKGROUND Worldwide, 6.6 million children die each year, partly due to a failure to recognize and treat acutely ill children. Programs that improve provider recognition and treatment initiation may improve child survival. OBJECTIVES Describe provider characteristics and hospital resources during a contextualized pediatric resuscitation training program in Botswana and determine if training impacts provider knowledge retention. DESIGN/METHODS The American Heart Associations Pediatric Emergency Assessment Recognition and Stabilization (PEARS) course was contextualized to Botswana resources and practice guidelines in this observational study. A cohort of facility-based nurses (FBN) was assessed prior to and 1-month following training. Survey tools assessed provider characteristics, cognitive knowledge and confidence and hospital pediatric resources. Data analysis utilized Fishers exact, Chi-square, Wilcoxon rank-sum and linear regression where appropriate. RESULTS 61 healthcare providers (89% FBNs, 11% physicians) successfully completed PEARS training. Referral facilities had more pediatric specific equipment and high-flow oxygen. Median frequency of pediatric resuscitation was higher in referral compared to district level FBNs (5 [3,10] vs. 2 [1,3] p=0.007). While 50% of FBNs had previous resuscitation training, none was pediatric specific. Median provider confidence improved significantly after training (3.8/5 vs. 4.7/5, p<0.001), as did knowledge of correct management of acute pneumonia and diarrhea (44% vs. 100%, p<0.001, 6% vs. 67%, p<0.001, respectively). CONCLUSION FBNs in Botswana report frequent resuscitation of ill children but low baseline training. Provider knowledge for recognition and initial treatment of respiratory distress and shock is low. Contextualized training significantly increased FBN provider confidence and knowledge retention 1-month after training.

Hospital-based surveillance for rotavirus gastroenteritis using molecular testing and immunoassay during the 2011 season in Botswana.

We describe rotavirus testing and clinical characteristics for children admitted with acute gastroenteritis during Botswanas 2011 rotavirus season. The rotavirus season extended from June to October with rotavirus-specific case fatality being 2.8%. Using molecular testing as reference, the immunochromatographic test had a sensitivity of 76.5% and specificity of 68.0%. Rotavirus vaccine may significantly reduce childhood morbidity and mortality in Botswana.

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

BACKGROUND Co-trimoxazole prophylaxis reduces mortality among HIV-infected children, but efficacy in HIV-exposed but uninfected (HEU) children in a non-malarial, low-breastfeeding setting with a low risk of mother-to-child transmission of HIV is unclear. METHODS HEU children in Botswana were randomly assigned to receive co-trimoxazole (100 mg/20 mg once daily until age 6 months and 200 mg/40 mg once daily thereafter) or placebo from age 14-34 days to age 15 months. Mothers chose whether to breastfeed or formula feed their children. Breastfed children were randomly assigned to breastfeeding for 6 months (Botswana guidelines) or 12 months (WHO guidelines). The primary outcome, analysed by a modified intention-to-treat approach, was cumulative child mortality from treatment assignment to age 18 months. We also assessed HIV-free survival by duration of breastfeeding. This trial is registered with ClinicalTrials.gov, number NCT01229761. FINDINGS From June 7, 2011, to April 2, 2015, 2848 HEU children were randomly assigned to receive co-trimoxazole (n=1423) or placebo (n=1425). The data and safety monitoring board stopped the study early because of a low likelihood of benefit with co-trimoxazole. Only 153 (5%) children were lost to follow-up (76 in the co-trimoxazole group and 77 in the placebo group), and 2053 (72%) received treatment continuously to age 15 months, death, or study closure. Mortality after the start of study treatment was similar in the two study groups: 30 children died in the co-trimoxazole group, compared with 34 in the placebo group (estimated mortality at 18 months 2·4% vs 2·6%; difference -0·2%, 95% CI -1·5 to 1·0, p=0·70). We saw no difference in hospital admissions between groups (12·5% in the 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.

Partnerships for Global Child Health

This literature-based expert consensus review presents the definition, scope, genesis, evolution, and models of GCH partnerships, including benefits and challenges, guiding principles and core practices. Child mortality remains a global health challenge and has resulted in demand for expanding the global child health (GCH) workforce over the last 3 decades. Institutional partnerships are the cornerstone of sustainable education, research, clinical service, and advocacy for GCH. When successful, partnerships can become self-sustaining and support development of much-needed training programs in resource-constrained settings. Conversely, poorly conceptualized, constructed, or maintained partnerships may inadvertently contribute to the deterioration of health systems. In this comprehensive, literature-based, expert consensus review we present a definition of partnerships for GCH, review their genesis, evolution, and scope, describe participating organizations, and highlight benefits and challenges associated with GCH partnerships. Additionally, we suggest a framework for applying sound ethical and public health principles for GCH that includes 7 guiding principles and 4 core practices along with a structure for evaluating GCH partnerships. Finally, we highlight current knowledge gaps to stimulate further work in these areas. With awareness of the potential benefits and challenges of GCH partnerships, as well as shared dedication to guiding principles and core practices, GCH partnerships hold vast potential to positively impact child health.

Rapid enteric testing to permit targeted antimicrobial therapy, with and without Lactobacillus reuteri probiotics, for paediatric acute diarrhoeal disease in Botswana: A pilot, randomized, factorial, controlled trial

Introduction Diarrhoeal disease is the second-leading cause of death in young children. Current guidelines recommend treating children with acute non-bloody diarrhea with oral rehydration solutions and zinc, but not antimicrobials. However, in many resource-limited settings, infections with treatable enteric bacterial and protozoan pathogens are common. Probiotics have shown promise as an adjunct treatment for diarrhoea but have not been studied in sub-Saharan Africa. Methods We conducted a pilot, factorial, randomized, placebo-controlled trial of children aged 2–60 months hospitalized in Botswana for acute non-bloody diarrhoea. A rapid test-and-treat intervention, consisting of multiplex PCR testing of rectal swabs taken at enrolment, accompanied by targeted antimicrobial therapy if treatable pathogens were detected, was compared to the reference standard of no stool testing. Additionally, Lactobacillus reuteri DSM 17938 x 60 days was compared to placebo treatment. The main objective of this pilot study was to assess feasibility. The primary clinical outcome was the increase in age-standardized height (HAZ) at 60 days adjusted for baseline HAZ. Results Seventy-six patients were enrolled over a seven-month study period. We judged that the recruitment rate, lab processing times, communication protocols, provision of specific antimicrobials, and follow-up rates were acceptable. Compared to the reference arm (no stool testing and placebo treatment), the combination of the rapid test-and-treat strategy plus L. reuteri DSM 17938 was associated with an increase of 0.61 HAZ (95% CI 0.09–1.13) and 93% lower odds of recurrent diarrhoea (OR 0.07, 95%CI 0.01–0.61) at 60 days. Discussion We demonstrated that it was feasible to evaluate the study interventions in Botswana. Despite the small sample size, we observed a statistically significant increase in HAZ at 60 days and significantly lower odds of recurrent diarrhoea in children receiving both rapid test-and-treat and L. reuteri. There is sufficient evidence to warrant proceeding with a larger follow-up trial in a similar setting.

Relationship of Training to Self-Reported Competency and Care of Adolescents in an African Health Care Setting

PURPOSE Adolescent medicine is not a recognized specialty in most African countries and African healthcare providers receive little adolescent-specific training. We explored the association between training, self-reported competence, and clinical practice related to adolescent health in an African setting. METHODS A total of 119 healthcare providers of various disciplines who work with adolescent patients in Francistown, Botswana were surveyed regarding their adolescent-specific training, self-reported competence, and counseling practices. Self-reported competence and practices related to counseling adolescents about sexual activity, alcohol and/or drug use, human immunodeficiency virus (HIV)-specific issues, and mental health were explored. RESULTS In all, 50.4% of respondents had received HIV training with an adolescent-specific component. Fewer had received adolescent-specific training outside the context of HIV prevention and management. Respondents were significantly more likely to report higher competence for all items except for counseling adolescents about depression and anxiety if they had received any adolescent-specific training. Respondents who reported higher competence were significantly more likely to report more frequent counseling of their adolescent clients. CONCLUSIONS Our study suggests that adolescent-focused training is important for ensuring that adolescents receive counseling when presenting for routine healthcare in our setting. The mental health needs of adolescents do not seem to be adequately addressed by current training.