Antiretroviral regimens in pregnancy and breast-feeding in Botswana.

BACKGROUND: The most effective highly active antiretroviral therapy (HAART) to prevent mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) in pregnancy and its efficacy during breast-feeding are unknown. METHODS: We randomly assigned 560 HIV-1-infected pregnant women (CD4+ count, > or = 200 cells per cubic millimeter) to receive coformulated abacavir, zidovudine, and lamivudine (the nucleoside reverse-transcriptase inhibitor [NRTI] group) or lopinavir-ritonavir plus zidovudine-lamivudine (the protease-inhibitor group) from 26 to 34 weeks' gestation through planned weaning by 6 months post partum. A total of 170 women with CD4+ counts of less than 200 cells per cubic millimeter received nevirapine plus zidovudine-lamivudine (the observational group). Infants received single-dose nevirapine and 4 weeks of zidovudine. RESULTS: The rate of virologic suppression to less than 400 copies per milliliter was high and did not differ significantly among the three groups at delivery (96% in the NRTI group, 93% in the protease-inhibitor group, and 94% in the observational group) or throughout the breast-feeding period (92% in the NRTI group, 93% in the protease-inhibitor group, and 95% in the observational group). By 6 months of age, 8 of 709 live-born infants (1.1%) were infected (95% confidence interval [CI], 0.5 to 2.2): 6 were infected in utero (4 in the NRTI group, 1 in the protease-inhibitor group, and 1 in the observational group), and 2 were infected during the breast-feeding period (in the NRTI group). Treatment-limiting adverse events occurred in 2% of women in the NRTI group, 2% of women in the protease-inhibitor group, and 11% of women in the observational group. CONCLUSIONS: All regimens of HAART from pregnancy through 6 months post partum resulted in high rates of virologic suppression, with an overall rate of mother-to-child transmission of 1.1%. (ClinicalTrials.gov number, NCT00270296.)

'That's when I struggle' Exploring challenges faced by care givers of children with tuberculosis in Botswana.

SETTING: Government-funded public health clinics in and around Gaborone, Botswana. OBJECTIVE: To explore the challenges faced by care givers of children on treatment for tuberculosis (TB) to inform a more child-friendly approach to Botswana's National TB Programme (NTP) strategy. DESIGN: Qualitative study using 28 in-depth interviews with care givers of children receiving anti-tuberculosis treatment. RESULTS: Care givers identified five main challenges: long delays in their child's diagnosis, difficulty attending clinic for daily treatment, difficulty administering TB medications, stock-outs of TB medications leading to treatment interruptions, and inadequate TB education. Care givers prioritized these same five areas to improve the overall management of their child's TB. CONCLUSION: Our findings suggest that despite accessing care through an NTP that adheres to World Health Organization guidelines, care givers for children on treatment in Botswana continue to encounter significant challenges. While each of these represents a potential threat to successful treatment, they can be addressed with relatively small systematic and programmatic adjustments. These results will inform the next version of the Botswana NTP guidelines towards a more child- and care giver-centered approach.

Nasopharyngeal carriage and antimicrobial resistance in isolates of Streptococcus pneumoniae and Haemophilus influenzae type b in children under 5 years of age in Botswana.

OBJECTIVES: A prospective survey was conducted to determine the prevalence of asymptomatic nasopharyngeal carriage of Streptococcus pneumoniae and Haemophilus influenzae type b in children under 5 years of age in Botswana and to determine the antibiotic resistance patterns of these organisms to commonly used antimicrobial agents. METHODS: Children 2 months to 5 years of age (n = 249) were recruited from outpatient clinics in Gaborone and Francistown, and 29 were sampled from the pediatric wards at Princess Marina (Gaborone) and Nyangabgwe (Francistown) Hospitals. Nasopharyngeal specimens were collected and the carriage and antibiotic resistance of S. pneumoniae and H. influenzae type b were determined. Analyses of risk factors associated with carriage and resistance were performed. RESULTS: Streptococcus pneumoniae was isolated from 69% of the outpatient children in Gaborone and 85% of the children in Francistown; the carriage rate in hospitalized children was 36% and 33% in Gaborone and Francistown, respectively. Approximately half of the isolates at both sites were resistant to at least one antibiotic, the most common being cotrimoxazole and penicillin. Resistance to three or more antibiotics (multiple resistance) was found in less than 10% of the isolates. Most penicillin resistance at both sites was at the intermediate level; however, almost 20% of the isolates demonstrated high-level resistance to cotrimoxazole. The most prevalent serogroups or serotypes of antibiotic-resistant isolates were 14, 19F, 19A, 6A, 6B, and 4. No risk factors for antibiotic resistance were identified. Haemophilus influenzae type b was isolated from 8% of the children in Gaborone and from 3% of the children in Francistown. Almost a third of the isolates were resistant to ampicillin. CONCLUSIONS: The high levels of antibiotic resistance in pneumococci isolated from children in Botswana suggest that the clinical management of meningitis and otitis media with a b-lactam antibiotic may fail in a significant proportion of cases and that empiric first-line use of cefotaxime or ceftriaxone for meningitis and higher dose amoxicillin (90 mg/kg/day) for otitis media is recommended. The levels of penicillin resistance in this study would not impact on the management of pneumonia with amoxicillin.

Yield of contact tracing from pediatric tuberculosis index cases in Gaborone, Botswana.

SETTING: Contact tracing using pediatric index cases has not been adequately investigated in high tuberculosis (TB) and human immunodeficiency virus (HIV) prevalence settings. OBJECTIVE: To determine the yield of contact tracing in household contacts of pediatric TB index cases in Botswana. DESIGN: Index cases included all pediatric (age ≤ 13 years) TB admissions from January 2009 to December 2011 to Botswana's largest referral hospital. A contact tracing team identified cases, conducted home visits, symptom-screened contacts and referred those with ≥ 1 TB symptoms. The primary outcome was newly diagnosed TB in a contact. RESULTS: From 163 pediatric index cases, 548 contacts were screened (median 3 contacts/case, interquartile range [IQR] 2-4). Of these, 49 (9%) were referred for positive symptoms on screening and 27/49 (55%) were evaluated for active TB. Twelve new TB cases were diagnosed (12/548, 2.2%); the median age was 31 years (IQR 23-38); 11 (92%) were smear-positive. Ten (83%) had known HIV status: 7 (70%) were HIV-positive. To find one new TB case, the number needed to contact trace (index cases/new cases) was 13.6, and the number needed to screen (contacts/new cases) was 46. CONCLUSION: This yield of contact tracing using pediatric index cases is similar to the traditional adult index case approach. Improving the proportion of symptomatic contacts evaluated may increase yield.

Noncovalent inhibitors of sickle hemoglobin gelation: effects of tetrasubstituted ammonium salts.

The effects of various tetrasubstituted ammonium compounds on the solubility of deoxygenated sickle hemoglobin were evaluated. These conclusions were drawn from the slopes of the solubility profiles obtained: (1) for the homologous series of tetraalkylammonium chloride salts (R4NCl), antigelling potency increased with increasing chain length of the R group: Ch3 less than C2H5 less than C3H7 less than C4H9; (2) for halide salts of the tetrabutylammonium cation there was no difference in effectiveness among the anions examined (Br-, Cl-, F-), presumably because of the extremely potent salting-in effect of this cation; (3) substitution of a benzyl for an alkyl group in three tetraalkylammonium chloride salts, C6H5CH2(R)3NCl, where R = CH3, C2H5, or C4H9, potentiated the antigelling capacity by as much as eight-fold. Because they are substantially more water soluble than any other class of noncovalent inhibitors examined to date, further manipulation of the aryl substituent on these compounds may contribute to the design of an effective antisickling agent.