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Publication The Challenges of HIV/AIDS Criminal Legislation in Botswana(2012-03-01) Kebonang, ZeinIn an attempt to halt the spread of the HIV epidemic, the Government of Botswana amended in 1998 the country’s criminal code to provide for stiffer penalties for those charged and convicted of the offence of rape. In particular, there was to be compulsory HIV testing of perpetrators and much stiffer sentences for those who tested positive to the HIV virus. In this paper, I argue that the amendment not only vitiates the right to voluntarily submit to an HIV test, it invades the right to privacy and leads to unwarranted disclosure of confidential information. In addition, I contend that the punitive criminal sentences that follow a positive HIV test are not an appropriate way of preventing transmission as these are not likely to encourage people to voluntarily test for HIV. Punitive sanctions are only justified where it can be shown that a person acted intentionally to transmit the disease.Publication Staphylococcus aureus Skin and Soft Tissue Infections at a Tertiary Hospital in Botswana(2011-05-25) Truong, Hong; Shah, Samir S; Ludmir, Johnathan; Tawanana, Ephraim O; Bafana, Margaret; Wood, Sarah M; Moffat, Howard; Steenhoff, Andrew PObjectives. To study the epidemiology of Staphylococcus aureus skin and soft-tissue infections (SSTIs) in hospitalised children and adults in Gaborone, Botswana, and to describe the changes in antimicrobial susceptibilities of S. aureus isolates over time. Methods. A retrospective cohort study evaluated SSTI isolates from January 2000 to December 2007 at Princess Marina Hospital (PMH), a large tertiary referral centre in Gaborone. Eligible subjects were those hospitalised at PMH during the study period who had a skin or soft-tissue culture yielding a bacterial or fungal pathogen. The primary outcome measure was a skin or soft-tissue culture yielding S. aureus. Secondary outcomes were the organism’s antimicrobial susceptibilities. Results. S. aureus was detected in 857 (35.8%) of single-organism SSTI cultures, and 194 (22.6%) of these isolates were methicillin resistant (MRSA). The proportion of MRSA isolates increased over time (linear test of trend: p=0.03 from 2000 to 2003), and MRSA isolates were more likely than methicillin-susceptible isolates to be resistant to commonly used antimicrobials recommended by the national SSTI treatment guideline. Conclusions. We report a high and increasing proportion of MRSA SSTIs in Gaborone. This high rate of MRSA resistance to currently recommended empiric antibiotics for SSTIs dictates the need for revising national guidelines and ongoing prospective surveillance of SSTIs in this setting.Publication CT Before Lumbar Puncture in Suspected Meningitis in Botswana: How Established Guidelines May Not Apply / Tomodensitométrie Avant Ponction Lombaire en Cas de Suspicion de Méningite au Botswana: Comment les Directives Classiques Peuvent ne Pas s’Appliquer(2013-09-27) Kestler, Andrew; Caruso, Ngaire; Chandra, Amit; Goldfarb, David; Haas, MichelleEnglish Introduction According to established guidelines from high-income countries, computed tomography of the head (CT) is indicated before lumbar puncture (LP) in the evaluation of suspected meningitis in HIV patients. In Botswana, meningitis in HIV-infected patients is common but CT is not widely available. Objective Develop a rational, evidence-based approach to CT use in the emergency evaluation of suspected meningitis in a population with high HIV prevalence. Methods Emergency center (EC) staff at Princess Marina Hospital in Gaborone, Botswana, reviewed indications for CT and LP in suspected meningitis. The authors considered existing evidence for CT before LP (mostly from high-income countries) and considered the epidemiology of central nervous system infections in Southern Africa. Draft guidelines were circulated to emergency center doctors and nurses, and to specialists in other hospital departments for review and comment before finalization. Result Available literature seems to indicate that in Botswana it would be possible to significantly limit the use of head CT before LP in HIV positive patients without increasing the incidence or risk of herniation. The guideline includes scenarios where an LP might be indicated in the presence of focal neurological findings and in the absence of a CT, in contradiction to established guidelines. Discussion The applicability of established guidelines for CT use in suspected meningitis is dependent on local epidemiology and resources. French Introduction Selon les directives classiques provenant des pays à revenu élevé, la tomodensitométrie (TDM) de la tête est indiquée avant une ponction lombaire (PL) pour l’évaluation d’une possible méningite chez les patients infectés par le VIH. Au Botswana, la méningite chez les patients infectés par le VIH est courante mais la TDM n’est pas souvent disponible. Objectif Développer une approche rationnelle fondée sur des preuves relative à l’utilisation de la TDM en cas d’évaluation d’urgence d’une possible méningite au sein d’une population à forte prévalence du VIH. Méthodes Le personnel du Centre d’Urgences (CU) de l’hôpital Princess Marina à Gaborone, Botswana, a examiné des prescriptions de TDM et de PL en cas de suspicion de méningite. Les auteurs se sont penchés sur les cas existants de TDM avant PL (la plupart provenant de pays à revenus élevés) et ont examiné l’épidémiologie des infections du système nerveux central en Afrique australe. Des directives provisoires ont été distribuées à des médecins et des infirmières de centres d’urgences et à des spécialistes dans d’autres services hospitaliers pour examen et commentaires avant finalisation. Résultat Les publications disponibles semblent indiquer qu’au Botswana, il serait possible de limiter fortement l’utilisation de la TDM de la tête avant une PL chez les patients séropositifs sans augmenter l’incidence ou le risque d’engagement cérébral. La directive comprend des scénarios dans lesquels une PL pourrait être indiquée en présence de signes neurologiques focaux et en l’absence d’une TDM, contrairement à ce que préconisent les directives classiques. Discussion L’applicabilité des directives classiques relatives à l’utilisation de la TDM dans des cas de suspicion de méningite dépend de l’épidémiologie et des ressources locales.Publication Risk Factors for Suboptimal Antiretroviral Therapy Adherence in HIV-Infected Adolescents in Gaborone, Botswana: A Pilot Cross-Sectional Study(2013-09-11) Ndiaye, Maimouna; Nyasulu, Peter; Lowenthal, Elizabeth D; Nguyen, Hoang; Gross, Robert; Mills, Edward J; Nachega, Jean BObjective: Little is known about factors associated with suboptimal antiretroviral treatment (ART) adherence among adolescents in Sub-Saharan Africa. Our objective was to determine the level of ART adherence and predictors of non-adherence among human immunodeficiency virus (HIV)-infected adolescents at the Botswana-Baylor Children's Clinical Centre of Excellence in Gaborone, Botswana. Methods: In a cross-sectional study, 82 HIV-infected adolescents receiving ART and their caregivers were administered a structured questionnaire. The patient's clinical information was retrieved from medical records. Outcome measures included excellent pill count ART adherence (>95%) and virologic suppression (HIV viral load <400 copies/mL). Multivariate logistic regression analysis was performed to identify independent predictors of ART non-adherence. Results: The overall median (interquartile range) ART adherence was 99% (96.5–100) (N = 82). Seventy-six percent of adolescents had excellent pill count ART adherence levels and 94% achieved virologic suppression. Male adolescents made up 65% of the non-adherent group (P = 0.02). Those who displayed suboptimal ART adherence were more likely to report having ever missed ART doses due to failure to pick up medication at the pharmacy (30.0% versus 9.7%, P = 0.03). In the multivariate logistic regression model, male sex (odds ratio [OR] 3.29, 95% confidence interval [CI] 1.13–9.54; P = 0.03) was the only factor which was independently associated with suboptimal ART adherence. Conclusions: A high proportion of HIV-infected adolescents studied had excellent ART adherence and virologic suppression, with male adolescents at higher risk of suboptimal adherence than females. Further research to investigate how gender relates to suboptimal adherence may aid in the design of targeted intervention strategies.Publication Diabetes Mellitus in HIV-Infected Patients Receiving Antiretroviral Therapy(2013-10-11) Moyo, D; Tanthuma, G; Mushisha, O; Cary, Mark S; Kwadiba, G; Steenhoff, Andrew P; Chikuse, F; Reid, Michael J. ABackground. There is little in the literature on HIV and diabetes mellitus (DM) in sub-Saharan Africa. Objective. To assess the characteristics of HIV and DM in patients receiving antiretroviral therapy (ART) in Botswana. Methods. A retrospective case-control study was conducted at 4 sites. Each HIV-infected patient with DM (n=48) was matched with 2 HIV-infected controls (n=108) by age (±2 years) and sex. Primary analysis was conditional logistic regression to estimate univariate odds and 95% confidence intervals (CIs) for each characteristic. Results. There was no significant association between co-morbid diseases, tuberculosis, hypertension or cancer and risk of diabetes. DM patients were more likely to have higher pre-ART weight (odds ratio (OR) 1.09; 95% CI 1.04 - 1.14). HIV-infected adults >70 kg were significantly more likely to have DM (OR 12.30; 95% CI 1.40 - 107.98). Participants receiving efavirenz (OR 4.58; 95% CI 1.44 - 14.57) or protease inhibitor therapy (OR 20.7; 95% CI 1.79 - 240.02) were more likely to have DM. Neither mean pre-ART CD4 cell count (OR 1.0; 95% CI 0.99 - 1.01) nor pre-ART viral load >100 000 copies/ml (OR 0.71; 95% CI 0.21 - 2.43) were associated with a significant risk of diabetes. Conclusions. These findings suggest a complex interrelation among traditional host factors and treatment-related metabolic changes in the pathogenesis of DM inpatients receiving ART. Notably, pre-ART weight, particularly if >70 kg, is associated with the diagnosis of diabetes in HIV-infected patients in Botswana.Publication Mobile Teledermatology in Sub-Saharan Africa: A Useful Tool in Supporting Health Workers in Low-Resource Centres(2012-03-26) Frühauf, Julia; Hofman-Wellenhof, Rainer; Kovarik, Carrie; Mulyowa, Grace; Alitwala, Caroline; Soyer, H. Peter; Kaddu, StevenIn developing countries, such as Uganda, skin problems are among the most common ailments seen in primary healthcare settings (1). Due to the dire lack of trained dermatologists, the vast majority of patients with skin diseases in these countries are treated by substitute auxiliary health workers with a limited education in skin disease management (1). To bridge this gap in access to dermatology services, we established a mobile teledermatology service and evaluated its applicability with regard to the impact of remote diagnoses on patient outcomes, as well as local health workers’ perception concerning this mode of dermatology consultation.Publication Mucosal Herpes Immunity and Immunopathology to Ocular and Genital Herpes Simplex Virus Infections(2012-11-20) Chentoufi, Aziz A; BenMohamed, LbachirHerpes simplex viruses type 1 and type 2 (HSV-1 and HSV-2) are amongst the most common human infectious viral pathogens capable of causing serious clinical diseases at every stage of life, from fatal disseminated disease in newborns to cold sores genital ulcerations and blinding eye disease. Primary mucocutaneous infection with HSV-1 & HSV-2 is followed by a lifelong viral latency in the sensory ganglia. In the majority of cases, herpes infections are clinically asymptomatic. However, in symptomatic individuals, the latent HSV can spontaneously and frequently reactivate, reinfecting the muco-cutaneous surfaces and causing painful recurrent diseases. The innate and adaptive mucosal immunities to herpes infections and disease remain to be fully characterized. The understanding of innate and adaptive immune mechanisms operating at muco-cutaneous surfaces is fundamental to the design of next-generation herpes vaccines. In this paper, the phenotypic and functional properties of innate and adaptive mucosal immune cells, their role in antiherpes immunity, and immunopathology are reviewed. The progress and limitations in developing a safe and efficient mucosal herpes vaccine are discussed.Publication Tenofovir-Associated Nephrotoxicity in Two HIV-Infected Adolescent Males(2009-02-01) Shah, Samir S; Steenhoff, Andrew P; Wood, Sarah M; Rutstein, Richard M; Meyers, Kevin E. C; Kaplan, Bernard SWe report two cases of tenofovir (TDF)-associated nephrotoxicity in perinatally HIV-infected adolescents. The first case, a 16-year-old African American male with an absolute CD4+ cell count of 314 cells/mm3, presented with an abrupt rise in serum creatinine leading to irreversible renal failure while on TDF-containing highly active antiretroviral therapy (HAART). While the patient had evidence of underlying kidney disease, the timing of his renal failure indicates that TDF played a central role. The second case, a 16-year-old African-American male with an absolute CD4+ cell count of 895 cells/mm3, presented with rickets and hypophosphatemia while receiving TDF-based HAART. To our knowledge, these cases represent the first reports of TDF-associated irreversible renal failure and rickets in pediatric patients. We believe these cases highlight important and potentially irreversible side effects of this agent and emphasize the need for further studies of the renal safety of TDF in pediatric patients.Publication Epidemiology of Methicillin‐Resistant Staphylococcus aureus Bacteremia in Gaborone, Botswana(2009-08-01) Shah, Samir S; Wood, Sarah; Meaney, Peter A; Bafana, Maragaret; Ratner, Adam J; Steenhoff, Andrew P; Malefho, Kolaatamo C.SThis cross‐sectional study at a tertiary‐care hospital in Botswana from 2000 to 2007 was performed to determine the epidemiologic characteristics of Staphylococcus aureus bacteremia. We identified a high prevalence (11.2% of bacteremia cases) of methicillin‐resistant S. aureus (MRSA) bacteremia. MRSA isolates had higher proportions of resistance to commonly used antimicrobials than did methicillin‐susceptible isolates, emphasizing the need to revise empiric prescribing practices in Botswana.Publication Pharmacy Refill Adherence Compared With CD4 Count Changes for Monitoring HIV-Infected Adults on Antiretroviral Therapy(2008-05-20) Bisson, Gregory P; Gross, Robert; Bellamy, Scarlett; Chittams, Jess; Frank, Ian; Hislop, Michael; Maartens, Gary; Nachega, Jean BBackground World Health Organization (WHO) guidelines for monitoring HIV-infected individuals taking combination antiretroviral therapy (cART) in resource-limited settings recommend using CD4+ T cell (CD4) count changes to monitor treatment effectiveness. In practice, however, falling CD4 counts are a consequence, rather than a cause, of virologic failure. Adherence lapses precede virologic failure and, unlike CD4 counts, data on adherence are immediately available to all clinics dispensing cART. However, the accuracy of adherence assessments for predicting future or detecting current virologic failure has not been determined. The goal of this study therefore was to determine the accuracy of adherence assessments for predicting and detecting virologic failure and to compare the accuracy of adherence-based monitoring approaches with approaches monitoring CD4 count changes. Methodology and Findings We conducted an observational cohort study among 1,982 of 4,984 (40%) HIV-infected adults initiating non-nucleoside reverse transcriptase inhibitor-based cART in the Aid for AIDS Disease Management Program, which serves nine countries in southern Africa. Pharmacy refill adherence was calculated as the number of months of cART claims submitted divided by the number of complete months between cART initiation and the last refill prior to the endpoint of interest, expressed as a percentage. The main outcome measure was virologic failure defined as a viral load > 1,000 copies/ml (1) at an initial assessment either 6 or 12 mo after cART initiation and (2) after a previous undetectable (i.e., < 400 copies/ml) viral load (breakthrough viremia). Adherence levels outperformed CD4 count changes when used to detect current virologic failure in the first year after cART initiation (area under the receiver operating characteristic [ROC] curves [AUC] were 0.79 and 0.68 [difference = 0.11; 95% CI 0.06 to 0.16; χ2 = 20.1] respectively at 6 mo, and 0.85 and 0.75 [difference = 0.10; 95% CI 0.05 to 0.14; χ2 = 20.2] respectively at 12 mo; p < 0.001 for both comparisons). When used to detect current breakthrough viremia, adherence and CD4 counts were equally accurate (AUCs of 0.68 versus 0.67, respectively [difference = 0.01; 95% CI −0.06 to 0.07]; χ2 = 0.1, p > 0.5). In addition, adherence levels assessed 3 mo prior to viral load assessments were as accurate for virologic failure occurring approximately 3 mo later as were CD4 count changes calculated from cART initiation to the actual time of the viral load assessments, indicating the potential utility of adherence assessments for predicting future, rather than simply detecting current, virologic failure. Moreover, combinations of CD4 count and adherence data appeared useful in identifying patients at very low risk of virologic failure. Conclusions Pharmacy refill adherence assessments were as accurate as CD4 counts for detecting current virologic failure in this cohort of patients on cART and have the potential to predict virologic failure before it occurs. Approaches to cART scale-up in resource-limited settings should include an adherence-based monitoring approach.