Perelman School of Medicine

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  • Publication
    Early Mortality and AIDS Progression Despite High Initial Antiretroviral Therapy Adherence and Virologic Suppression in Botswana
    (2011-06-15) Steele, Katherine; Steenhoff, Andrew P; Newcomb, Craige W; Rantleru, Tumelo; Nthobatsang, Rudo; Lesetedi, Gloria; Bellamy, Scarlett L; Nachega, Jean B; Gross, Robert; Bisson, Gregory P
    Background Adverse outcomes occurring early after antiretroviral therapy (ART) initiation are common in sub-Saharan Africa, despite reports of high levels of ART adherence in this setting. We sought to determine the relationship between very early ART adherence and early adverse outcomes in HIV-infected adults in Botswana. Methods This prospective cohort study of 402 ART-naïve, HIV-infected adults initiating ART at a public HIV clinic in Gaborone, Botswana evaluated the relationship between suboptimal early ART adherence and HIV treatment outcomes in the initial months after ART initiation. Early adherence during the interval between initial ART dispensation and first ART refill was calculated using pill counts. In the primary analysis patients not returning to refill and those with adherence <0.95 were considered to have suboptimal early adherence. The primary outcome was death or loss to follow-up during the first 6 months of ART; a secondary composite outcome included the primary outcome plus incident opportunistic illness (OIs) and virologic failure. We also calculated the percent of early adverse outcomes theoretically attributable to suboptimal early adherence using the population attributable risk percent (PAR%). Results Suboptimal early adherence was independently associated with loss to follow-up and death (adjusted OR 2.3, 95% CI 1.1–4.8) and with the secondary composite outcome including incident OIs and virologic failure (adjusted OR 2.6, 95% CI 1.4–4.7). However, of those with early adverse outcomes, less than one-third had suboptimal adherence and approximately two-thirds achieved virologic suppression. The PAR% relating suboptimal early adherence and primary and secondary outcomes were 14.7% and 17.7%, respectively. Conclusions Suboptimal early adherence was associated with poor outcomes, but most early adverse outcomes occurred in patients with optimal early adherence. Clinical care and research efforts should focus on understanding early adverse outcomes that occur despite optimal adherence.
  • 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, Michelle
    English 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
    Prevalence of Hypothyroidism Among MDR-TB Patients in Botswana
    (2012-11-01) Modongo, Chawangwa; Zetola, Nicola M
  • Publication
    Establishing Telepathology in Africa: Lessons From Botswana
    (2011-05-01) Fischer, Max K; Kayembe, Mukendi K; Scheer, Arnold J; Introcaso, Camille E; Binder, Scott W; Kovarik, Carrie L
    Few reports of telepathology in Africa exist in the medical literature. With the strong need for improvement in health care infrastructure and personnel training in many African nations, telepathology provides a rapid and versatile tool to improve clinical care and foster educational and research opportunities. We describe the challenges faced in establishing robotic telepathology (RT) services at a government referral center in Botswana and reflect on conditions under which such initiatives may be most likely to succeed in sub-Saharan Africa and other parts of the developing world.
  • Publication
    An Epidemiologic Review of Enteropathogens in Gaborone, Botswana: Shifting Patterns of Resistance in an HIV Endemic Region
    (2010-06-02) Rowe, Jack S; Shah, Samir S; Motlhagodi, Stephen; Bafana, Maragaret; Tawanana, Ephraim; Truong, Hong T; Wood, Sarah M; Zetola, Nicola M; Steenhoff, Andrew P
    Background The epidemiology of diarrheal disease in Botswana, an HIV endemic region, is largely unknown. Our primary objective was to characterize the prevalent bacterial and parasitic enteropathogens in Gaborone, Botswana. Secondary objectives included determining corresponding antimicrobial resistance patterns and the value of stool white and red blood cells for predicting bacterial and parasitic enteropathogens. Methodology/Principal Findings A retrospective cross-sectional study examined laboratory records of stool specimens analyzed by the Botswana National Health Laboratory in Gaborone, Botswana from February 2003 through July 2008. In 4485 specimens the median subject age was 23 [interquartile range 1.6–34] years. Overall, 14.4% (644 of 4485) of samples yielded a pathogen. Bacteria alone were isolated in 8.2% (367 of 4485), parasites alone in 5.6% (253 of 4485) and both in 0.5% (24 of 4485) of samples. The most common bacterial pathogens were Shigella spp. and Salmonella spp., isolated from 4.0% (180 of 4485) and 3.9% (175 of 4485) of specimens, respectively. Escherichia coli (22 of 4485) and Campylobacter spp. (22 of 4485) each accounted for 0.5% of pathogens. Comparing antimicrobial resistance among Shigella spp. and Salmonella spp. between two periods, February 2003 to February 2004 and July 2006 to July 2008, revealed an increase in ampicillin resistance among Shigella spp. from 43% to 83% (p<0.001). Among Salmonella spp., resistance to chloramphenicol decreased from 56% to 6% (p<0.001). The absence of stool white and red blood cells correlated with a high specificity and negative predictive value. Conclusions/Significance Most gastroenteritis stools were culture and microscopy negative suggesting that viral pathogens were the majority etiologic agents in this Botswana cohort. Shigella spp. and Salmonella spp. were the most common bacteria; Isospora spp. and Cryptosporidium spp. were the most common parasites. Resistance to commonly used antimicrobials is high and should be closely monitored.
  • Publication
    Overestimates of Survival After HAART: Implications for Global Scale-Up Efforts
    (2008-03-05) Bisson, Gregory P; Gaolathe, Tendani; Gross, Robert; Rollins, Caitlin; Bellamy, Scarlett; Mogorosi, Mpho; Avalos, Ava; Friedman, Harvey M; Dickinson, Diana; Frank, Ian; Ndwapi, Ndwapi
    Background Monitoring the effectiveness of global antiretroviral therapy scale-up efforts in resource-limited settings is a global health priority, but is complicated by high rates of losses to follow-up after treatment initiation. Determining definitive outcomes of these lost patients, and the effects of losses to follow-up on estimates of survival and risk factors for death after HAART, are key to monitoring the effectiveness of global HAART scale-up efforts. Methodology/Principal Findings A cohort study comparing clinical outcomes and risk factors for death after HAART initiation as reported before and after tracing of patients lost to follow-up was conducted in Botswana's National Antiretroviral Therapy Program. 410 HIV-infected adults consecutively presenting for HAART were evaluated. The main outcome measures were death or loss to follow-up within the first year after HAART initiation. Of 68 patients initially categorized as lost, over half (58.8%) were confirmed dead after tracing. Patient tracing resulted in reporting of significantly lower survival rates when death was used as the outcome and losses to follow-up were censored [1-year Kaplan Meier survival estimate 0.92 (95% confidence interval, 0.88–0.94 before tracing and 0.83 (95% confidence interval, 0.79–0.86) after tracing, log rank P<0.001]. In addition, a significantly increased risk of death after HAART among men [adjusted hazard ratio 1.74 (95% confidence interval, 1.05–2.87)] would have been missed had patients not been traced [adjusted hazard ratio 1.41 (95% confidence interval, 0.65–3.05)]. Conclusions/Significance Due to high rates of death among patients lost to follow-up after HAART, survival rates may be inaccurate and important risk factors for death may be missed if patients are not actively traced. Patient tracing and uniform reporting of outcomes after HAART are needed to enable accurate monitoring of global HAART scale-up efforts.
  • Publication
    New Models for Medical Education: Web-Based Conferencing to Support HIV Training in Sub-Saharan Africa
    (2012-09-01) Reid, Michael J. A; Flam, Robin; Tsiouris, Fatima
    Background: Healthcare workers in Africa managing human immunodeficiency virus (HIV)-infected patients often receive inadequate HIV-specific medical education. The acceptability and feasibility of Web-based distance learning tools to enhance HIV training in Africa have not been extensively evaluated. Materials and Methods: In this prospective observational study, we assessed the feasibility of Web-conferencing to deliver HIV-specific medical training to clinicians supporting HIV care and treatment across 12 Sub-Saharan African countries over a 10-month period. Webinar attendance, technical quality, and participant satisfaction were measured for each Webinar. Demographic details about participants were recorded. Results: Attendance increased from 40 participants in Month 1 to over 160 in Month 10. Thirty-six percent of participants were physicians, and 21% were in allied health professions. A mean of 95% of respondents found the content to be relevant. Participants reported that the opportunity to interact with HIV clinicians from other countries and expert teaching from leading scientists were major reasons for attendance. Audio quality was variable across countries and over time. Barriers to attendance included lack of information technology (IT) literacy and Internet connectivity. Conclusions: This analysis demonstrates that Webinars are feasible and acceptable to support HIV training. Significant impediments to scale up in use of Web-conferencing for HIV education in resource-limited settings include lack of IT hardware and limited IT literacy. Strengthening IT capacity and Internet infrastructure is necessary to support expanded use of Webinars as a tool for continuing HIV education.
  • Publication
    Randomized Trial of Time-Limited Interruptions of Protease Inhibitor-Based Antiretroviral Therapy (ART) vs. Continuous Therapy for HIV-1 Infection
    (2011-06-28) Firnhaber, Cynthia; Azzoni, Livio; Foulkes, Andrea S; Gross, Robert; Yin, Xiangan; Van Amsterdam, Desiree; Schulze, Doreen; Glencross, Deborah K; Stevens, Wendy; Hunt, Gillian; Morris, Lynn; Fox, Lawerence; Sanne, Ian; Montaner, Luis J
    Background The clinical outcomes of short interruptions of PI-based ART regimens remains undefined. Methods A 2-arm non-inferiority trial was conducted on 53 HIV-1 infected South African participants with viral load/ml and CD4 T cell count >450 cells/µl on stavudine (or zidovudine), lamivudine and lopinavir/ritonavir. Subjects were randomized to a) sequential 2, 4 and 8-week ART interruptions or b) continuous ART (cART). Primary analysis was based on the proportion of CD4 count >350 cells(c)/ml over 72 weeks. Adherence, HIV-1 drug resistance, and CD4 count rise over time were analyzed as secondary endpoints. Results The proportions of CD4 counts >350 cells/µl were 82.12% for the intermittent arm and 93.73 for the cART arm; the difference of 11.95% was above the defined 10% threshold for non-inferiority (upper limit of 97.5% CI, 24.1%; 2-sided CI: −0.16, 23.1). No clinically significant differences in opportunistic infections, adverse events, adherence or viral resistance were noted; after randomization, long-term CD4 rise was observed only in the cART arm. Conclusion We are unable to conclude that short PI-based ART interruptions are non-inferior to cART in retention of immune reconstitution; however, short interruptions did not lead to a greater rate of resistance mutations or adverse events than cART suggesting that this regimen may be more forgiving than NNRTIs if interruptions in therapy occur.
  • Publication
    Neurobehavioral Effects in HIV-Positive Individuals Receiving Highly Active Antiretroviral Therapy (HAART) in Gaborone, Botswana
    (2011-02-18) Lawler, Kathy A; Jeremiah, Kealeboga; Mosepele, Mosepele; Ratcliffe, Sarah; Cherry, Catherine; Seloilwe, Esther; Steenhoff, Andrew P
    Objective To explore the prevalence and features of HIV-associated neurocognitive disorders (HANDS) in Botswana, a sub-Saharan country at the center of the HIV epidemic. Design and Methods A cross sectional study of 60 HIV-positive individuals, all receiving highly active antiretroviral therapy (HAART), and 80 demographically matched HIV-seronegative control subjects. We administered a comprehensive neuropsychological test battery and structured psychiatric interview. The lowest 10th percentile of results achieved by control subjects was used to define the lower limit of normal performance on cognitive measures. Subjects who scored abnormal on three or more measures were classified as cognitively impaired. To determine the clinical significance of any cognitive impairment, we assessed medication adherence, employment, and independence in activities of daily living (ADL). Results HIV+ subjects were impaired for all cognitive-motor ability areas compared with matched, uninfected control subjects. Thirty seven percent of HIV+ patients met criteria for cognitive impairment. Conclusion These findings indicate that neurocognitive impairment is likely to be an important feature of HIV infection in resource-limited countries; underscoring the need to develop effective treatments for subjects with, or at risk of developing, cognitive impairment.
  • Publication
    Survey of Childhood Blindness and Visual Impairment in Botswana
    (2011-10-01) Nallasamy, Sudha; Anninger, William V; Quinn, Graham E; Kroener, Brian; Zetola, Nicola M; Nkomazana, Oathokwa
    Background/aims In terms of blind-person years, the worldwide burden of childhood blindness is second only to cataracts. In many developing countries, 30–72% of childhood blindness is avoidable. The authors conducted this study to determine the causes of childhood blindness and visual impairment (VI) in Botswana, a middle-income country with limited access to ophthalmic care. Methods This study was conducted over 4 weeks in eight cities and villages in Botswana. Children were recruited through a radio advertisement and local outreach programmes. Those ≤15 years of age with visual acuity <6/18 in either eye were enrolled. The WHO/Prevention of Blindness Eye Examination Record for Children with Blindness and Low Vision was used to record data. Results The authors enrolled 241 children, 79 with unilateral and 162 with bilateral VI. Of unilateral cases, 89% were avoidable: 23% preventable (83% trauma-related) and 66% treatable (40% refractive error and 31% amblyopia). Of bilateral cases, 63% were avoidable: 5% preventable and 58% treatable (33% refractive error and 31% congenital cataracts). Conclusion Refractive error, which is easily correctable with glasses, is the most common cause of bilateral VI, with cataracts a close second. A nationwide intervention is currently being planned to reduce the burden of avoidable childhood VI in Botswana.