Perelman School of Medicine
Perelman School of Medicine's mission is to advance knowledge and improve health through research, patient care, and the education of trainees in an inclusive culture that embraces diversity, fosters innovation, stimulates critical thinking, supports lifelong learning, and sustains our legacy of excellence.
- Center for Public Health Initiatives
- Department of Biostatistics, Epidemiology and Informatics
- Department of Family Medicine and Community Health
- Department of Medical Ethics and Health Policy
- Department of Microbiology Papers
- Department of Obstetrics and Gynecology
- Department of Psychiatry
- Department of Systems Pharmacology and Translational Therapeutics
- Botswana-UPenn Partnership
- Center for Cognitive Neuroscience
- FM Kirby Center for Molecular Ophthalmology
- Global Health Programs
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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 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 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 Microbiology of Urinary Tract Infections in Gaborone, Botswana(2013-03-04) Renuart, Andrew J; Goldfarb, David M; Mokomane, Margaret; Tawanana, Ephraim O; Steenhoff, Andrew P; Narasimhamurthy, Mohan; Silverman, Jonathan AObjective The microbiology and epidemiology of UTI pathogens are largely unknown in Botswana, a high prevalence HIV setting. Using laboratory data from the largest referral hospital and a private hospital, we describe the major pathogens causing UTI and their antimicrobial resistance patterns. Methods This retrospective study examined antimicrobial susceptibility data for urine samples collected at Princess Marina Hospital (PMH), Bokamoso Private Hospital (BPH), or one of their affiliated outpatient clinics. A urine sample was included in our dataset if it demonstrated pure growth of a single organism and accompanying antimicrobial susceptibility and subject demographic data were available. Results A total of 744 samples were included. Greater than 10% resistance was observed for amoxicillin, co-trimoxazole, amoxicillin-clavulanate, and ciprofloxacin. Resistance of E. coli isolates to ampicillin and co-trimoxazole was greater than 60% in all settings. HIV status did not significantly impact the microbiology of UTIs, but did impact antimicrobial resistance to co-trimoxazole. Conclusions Data suggests that antimicrobial resistance has already emerged to most oral antibiotics, making empiric management of outpatient UTIs challenging. Ampicillin, co-trimoxazole, and ciprofloxacin should not be used as empiric treatment for UTI in this context. Nitrofurantoin could be used for simple cystitis; aminoglycosides for uncomplicated UTI in inpatients.Publication A Cross-Sectional Study of HPV Vaccine Acceptability in Gaborone, Botswana(2011-10-25) DiAngi, Yumi Taylor; Ramogola-Masire, Doreen; Steenhoff, Andrew P; Panozzo, Catherine A; Brewer, Noel TBackground Cervical cancer is the most common cancer among women in Botswana and elsewhere in Sub-Saharan Africa. We sought to examine whether HPV vaccine is acceptable among parents in Botswana, which recently licensed the vaccine to prevent cervical cancer. Methods and Findings We conducted a cross-sectional survey in 2009, around the time the vaccine was first licensed, with adults recruited in general medicine and HIV clinics in Gaborone, the capital of Botswana. Although only 9% (32/376) of respondents had heard of HPV vaccine prior to the survey, 88% (329/376) said they definitely will have their adolescent daughters receive HPV vaccine. Most respondents would get the vaccine for their daughters at a public or community clinic (42%) or a gynecology or obstetrician's office (39%), and 74% would get it for a daughter if it were available at her school. Respondents were more likely to say that they definitely will get HPV vaccine for their daughters if they had less education (OR = 0.20, 95% CI = 0.07–0.58) or lived more than 30 kilometers from the capital, Gaborone (OR = 2.29, 95% CI = 1.06–4.93). Other correlates of acceptability were expecting to be involved in the decision to get HPV vaccine, thinking the vaccine would be hard to obtain, and perceiving greater severity of HPV-related diseases. Conclusions HPV vaccination of adolescent girls would be highly acceptable if the vaccine became widely available to the daughters of healthcare seeking parents in Gaborone, Botswana. Potential HPV vaccination campaigns should provide more information about HPV and the vaccine as well as work to minimize barriers.Publication Neurobehavioral Effects in HIV-Positive Individuals Receiving Highly Active Antiretroviral Therapy (HAART) in Gaborone, Botswana(2011-02-18) Lawler, Kathy A; Ratcliffe, Sarah; Jeremiah, Kealeboga; Mosepele, Mosepele; Steenhoff, Andrew P; Cherry, Catherine; Seloilwe, EstherObjective 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 Early Mortality and AIDS Progression Despite High Initial Antiretroviral Therapy Adherence and Virologic Suppression in Botswana(2011-06-15) Steenhoff, Andrew P; Newcomb, Craige W; Steele, Katherine; Bellamy, Scarlett L; Rantleru, Tumelo; Gross, Robert; Nthobatsang, Rudo; Bisson, Gregory P; Lesetedi, Gloria; Nachega, Jean BBackground 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 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 PBackground 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 Association Between Efavirenz-Based Compared With Nevirapine-Based Antiretroviral Regimens and Virological Failure in HIV-Infected Children(2013-05-01) Lowenthal, Elizabeth D; Ellenberg, Jonas H; Steenhoff, Andrew P; Rutstein, Richard M; Machine, Edwin; Sagdeo, Aditi; Gross, Robert; Boiditswe, Sefelani; Anabwani, GabrielImportance Worldwide, the nonnucleoside reverse transcriptase inhibitors (NNRTIs) efavirenz and nevirapine are commonly used in first-line antiretroviral regimens in both adults and children with human immunodeficiency virus (HIV) infection. Data on the comparative effectiveness of these medications in children are limited. Objective To investigate whether virological failure is more likely among children who initiated 1 or the other NNRTI-based HIV treatment. Design, Setting, and Participants Retrospective cohort study of children (aged 3–16 years) who initiated efavirenz-based (n=421) or nevirapine-based (n=383) treatment between April 2002 and January 2011 at a large pediatric HIV care setting in Botswana. Main Outcomes and Measures The primary outcome was time from initiation of therapy to virological failure. Virological failure was defined as lack of plasma HIV RNA suppression to less than 400 copies/mL by 6 months or confirmed HIV RNA of 400 copies/mL or greater after suppression. Cox proportional hazards regression analysis compared time to virological failure by regimen. Multivariable Cox regression controlled for age, sex, baseline immunologic category, baseline clinical category, baseline viral load, nutritional status, NRTIs used, receipt of single-dose nevirapine, and treatment for tuberculosis. Results With a median follow-up time of 69 months (range, 6–112 months; interquartile range, 23–87 months), 57 children (13.5%; 95% CI, 10.4%–17.2%) initiating treatment with efavirenz and 101 children (26.4%; 95% CI, 22.0%–31.1%) initiating treatment with nevirapine had virological failure. There were 11 children (2.6%; 95% CI, 1.3%–4.6%) receiving efavirenz and 20 children (5.2%; 95% CI, 3.2%–7.9%) receiving nevirapine who never achieved virological suppression. The Cox proportional hazard ratio for the combined virological failure end point was 2.0 (95% CI, 1.4–2.7; log rank P Conclusions and Relevance Among children aged 3 to 16 years infected with HIV and treated at a clinic in Botswana, the use of efavirenz compared with nevirapine as initial antiretroviral treatment was associated with less virological failure. These findings may warrant additional research evaluating the use of efavirenz and nevirapine for pediatric patients.