Follow-up of infants diagnosed with HIV - Early Infant Diagnosis Program, Francistown, Botswana, 2005-2012.

The 2011 prevalence of human immunodeficiency virus (HIV) among pregnant women in Botswana was 30.4%. High coverage rates of HIV testing and antiretroviral prophylaxis have reduced the rate of mother-to-child transmission of HIV in Botswana from as high as 40% with no prophylaxis to <4% in 2011. In June 2005, the national Early Infant Diagnosis (EID) Program began testing HIV-exposed infants (i.e., those born to HIV-infected mothers) for HIV using polymerase chain reaction (PCR) at 6 weeks postpartum. During 2005-2012, follow-up of all HIV-infected infants diagnosed in all 13 postnatal care facilities in Francistown, Botswana, was conducted to ascertain patient outcomes. A total of 202 infants were diagnosed with HIV. As of September 2013, 82 (41%) children were alive and on antiretroviral therapy (ART), 79 (39%) had died, and 41 (20%) were either lost to follow-up, had transferred, or their mothers declined ART. Despite success in preventing mother-to-child transmission in Botswana, results of the EID program highlight the need for early diagnosis of HIV-infected infants, prompt initiation of ART, and retention in care.

6-month versus 36-month isoniazid preventive treatment for tuberculosis in adults with HIV infection in Botswana: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: In accordance with WHO guidelines, people with HIV infection in Botswana receive daily isoniazid preventive therapy against tuberculosis without obtaining a tuberculin skin test, but duration of prophylaxis is restricted to 6 months. We aimed to assess effectiveness of extended isoniazid therapy. METHODS: In our randomised, double-blind, placebo-controlled trial we enrolled adults infected with HIV aged 18 years or older at government HIV-care clinics in Botswana. Exclusion criteria included current illness such as cough and an abnormal chest radiograph without antecedent tuberculosis or pneumonia. Eligible individuals were randomly allocated (1:1) to receive 6 months' open-label isoniazid followed by 30 months' masked placebo (control group) or 6 months' open-label isoniazid followed by 30 months' masked isoniazid (continued isoniazid group) on the basis of a computer-generated randomisation list with permuted blocks of ten at each clinic. Antiretroviral therapy was provided if participants had CD4-positive lymphocyte counts of fewer than 200 cells per µL. We used Cox regression analysis and the log-rank test to compare incident tuberculosis in the groups. Cox regression models were used to estimate the effect of antiretroviral therapy. The trial is registered at ClinicalTrials.gov, number NCT00164281. FINDINGS: Between Nov 26, 2004, and July 3, 2009, we recorded 34 (3·4%) cases of incident tuberculosis in 989 participants allocated to the control group and 20 (2·0%) in 1006 allocated to the continued isoniazid group (incidence 1·26% per year vs 0·72%; hazard ratio 0·57, 95% CI 0·33-0·99, p=0·047). Tuberculosis incidence in those individuals receiving placebo escalated approximately 200 days after completion of open-label isoniazid. Participants who were tuberculin skin test positive (ie, ≥5 mm induration) at enrolment received a substantial benefit from continued isoniazid treatment (0·26, 0·09-0·80, p=0·02), whereas participants who were tuberculin skin test-negative received no significant benefit (0·75, 0·38-1·46, p=0·40). By study completion, 946 (47%) of 1995 participants had initiated antiretroviral therapy. Tuberculosis incidence was reduced by 50% in those receiving 360 days of antiretroviral therapy compared with participants receiving no antiretroviral therapy (adjusted hazard ratio 0·50, 95% CI 0·26-0·97). Severe adverse events and death were much the same in the control and continued isoniazid groups. INTERPRETATION: In a tuberculosis-endemic setting, 36 months' isoniazid prophylaxis was more effective for prevention of tuberculosis than was 6-month prophylaxis in individuals with HIV infection, and chiefly benefited those who were tuberculin skin test positive. FUNDING: US Centers for Disease Control and Prevention and US Agency for International Development.

Case-control study to determine risk factors for diarrhea among children during a large outbreak in a country with a high prevalence of HIV infection.

OBJECTIVES: Between January and March of 2006, over 35 000 diarrhea cases and 532 deaths were reported among children aged <5 years in Botswana. We conducted an investigation to characterize the outbreak, identify risk factors for diarrhea, and recommend control strategies. METHODS: We enrolled children <5 years of age presenting to the emergency department between March 2 and March 20, 2006. Cases had ≥3 loose stools per day and no antecedent diarrhea among household members. Controls had had no diarrhea since January 1, 2006. We conducted a multivariate logistic regression analysis controlling for socioeconomic status, age, and maternal HIV status. RESULTS: Forty-nine cases with median age of 12 months (range 0-45 months) and 61 controls with median age of 24 months (range 0-59 months) were enrolled; 33 (30%) were born to HIV-positive mothers. Case-parents were more likely to report storing household drinking water (adjusted odds ratios (AOR) 3.9, 95% confidence interval (CI) 1.2-15.7). Lack of hand washing after using the toilet or latrine (AOR 4.2, 95% CI 1.1-20.4) was more likely to be reported by case-parents. Case-children were less likely to be currently breastfeeding (AOR 30.3, 95% CI 2.0-1000.0). Five (10%) case-patients and no control-patients died. Multiple causal pathogens were identified. CONCLUSIONS: During this diarrhea outbreak in a country with a national program to prevent mother-to-child transmission of HIV, ill children were less likely to be breastfed and more likely to have been exposed to environmental factors associated with fecal contamination. These findings underscore the importance of adequate access to safe water, sanitation, hygiene, and nutrition education among populations using breast milk substitutes.

Hospitalization and mortality among primarily nonbreastfed children during a large outbreak of diarrhea and malnutrition in Botswana, 2006.

BACKGROUND: In 2006, a pediatric diarrhea outbreak occurred in Botswana, coinciding with heavy rains. Surveillance recorded a 3 times increase in cases and a 25 fold increase in deaths between January and March. Botswana has high HIV prevalence among pregnant women (33.4% in 2005), and an estimated 35% of all infants under the age of 6 months are not breastfed. METHODS: We followed all children <5 years old with diarrhea in the country's second largest referral hospital at the peak of the outbreak by chart review, interviewed mothers, and conducted laboratory testing for HIV and enteric pathogens. RESULTS: Of 153 hospitalized children with diarrhea, 97% were <2 years old; 88% of these were not breastfeeding. HIV was diagnosed in 18% of children and 64% of mothers. Cryptosporidium and enteropathogenic Escherichia coli were common; many children had multiple pathogens. Severe acute malnutrition (kwashiorkor or marasmus) developed in 38 (25%) patients, and 33 (22%) died. Kwashiorkor increased risk for death (relative risk 2.0; P = 0.05); only one breastfeeding child died. Many children who died had been undersupplied with formula. CONCLUSIONS: Most of the severe morbidity and mortality in this outbreak occurred in children who were HIV negative and not breastfed. Feeding and nutritional factors were the most important determinants of severe illness and death. Breastfeeding is critical to infant survival in the developing world, and support for breastfeeding among HIV-negative women, and HIV-positive women who cannot formula feed safely, may prevent further high-mortality outbreaks.

Early diagnosis of human immunodeficiency virus in infants using polymerase chain reaction on dried blood spots in Botswana's national program for prevention of mother-to-child transmission.

BACKGROUND: Botswana has high antenatal human immunodeficiency virus (HIV) prevalence (33.4%). The public health system provides free services for prevention of mother to child transmission of HIV (PMTCT) and antiretroviral therapy, which can reduce vertical HIV transmission from 35% to <5%. Infant HIV diagnosis is challenging in resource-limited settings, and HIV prevalence among HIV-exposed infants in Botswana is unknown. Dried blood spot (DBS) polymerase chain reaction (PCR) provides a feasible method to assess PMTCT programs and identify HIV-infected children. METHODS: We trained staff in 15 clinics and a hospital to obtain DBS on HIV-exposed infants age 6 weeks to 17 months receiving routine care. Samples were sent to the national HIV reference laboratory. Roche Amplicor 1.5 DNA PCR testing was performed. RESULTS: Between June-December 2005, 1931 HIV-exposed infants age 6 weeks to 17 months were tested for HIV, of whom 136 (7.0%) were HIV infected. Among infants

Assessment of infant feeding: the validity of measuring milk intake.

Accurate assessment of infant feeding is needed for clinical practice and research. We identified 32 studies that evaluated the validity of direct observation, test weighing, or doubly labeled water methods. Correlations with validation standards were highest for doubly labeled water and test weighing, and lowest for observation. Cost and availability of isotope may limit the doubly labeled water method to research studies, whereas observation may be useful for clinical practice. Test weighing could be applied to either setting, but it may be practical to sample less frequently over 24 hours. Validity results and intended use of the measurement should be considered when selecting a method.

Tracking the Prevalence of FAS.

Surveillance programs allow the tracking of the prevalence of a condition over time. Tracking the prevalence of FAS poses particular problems, however, as there is no "gold standard" of diagnosis. To evaluate the effectiveness of prevention efforts, surveillance techniques must be refined.