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
- Global Health Programs
- Medical Physics Programs
PublicationDiabetes Mellitus in HIV-Infected Patients Receiving Antiretroviral Therapy(2013-10-11) Moyo, D; Tanthuma, G; Mushisha, O; Kwadiba, G; Chikuse, F; Cary, Mark S; Steenhoff, Andrew P; 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. PublicationBartonella Infection in Immunocompromised Hosts: Immunology of Vascular Infection and Vasoproliferation(2012-01-01) Mosepele, Mosepele; Mazo, Dana; Cohn, JenniferMost infections by genus Bartonella in immunocompromised patients are caused by B. henselae and B. quintana. Unlike immunocompetent hosts who usually develop milder diseases such as cat scratch disease and trench fever, immunocompromised patients, including those living with HIV/AIDS and posttransplant patients, are more likely to develop different and severe life-threatening disease. This paper will discuss Bartonella's manifestations in immunosuppressed patients and will examine Bartonella's interaction with the immune system including its mechanisms of establishing infection and immune escape. Gaps in current understanding of the immunology of Bartonella infection in immunocompromised hosts will be highlighted. PublicationLeveraging a Rapid, Round-the-Clock HIV Testing System to Screen for Acute HIV Infection in a Large Urban Public Medical Center(2013-02-01) Christopoulos, Katerina A; Zetola, Nicola M; Klausner, Jeffrey D; Haller, Barbara; Louie, Brian; Hare, Bradley; Pandori, Mark; Nassos, Patricia; Roemer, Marguerite; Pilcher, Christopher DMethods The hospital laboratory performed round-the-clock rapid HIV antibody testing on venipuncture specimens from patients undergoing HIV testing in hospital and community clinics, inpatient settings, and the emergency department. For patients with negative results, a public health laboratory conducted pooled HIV RNA testing for acute HIV infection. The laboratories communicated positive results from the hospital campus to a linkage team. Linkage was defined as one outpatient HIV-related visit. Results Among 7,927 patients, 8,550 rapid tests resulted in 137 cases of HIV infection (1.7%, 95% CI 1.5%–2.0%), of whom 46 were new HIV diagnoses (0.58%, 95% CI 0.43%–0.77%). Pooled HIV RNA testing of 6,704 specimens (78.4%) resulted in 3 cases of acute HIV infection (0.05%, 95% CI 0.01%–0.14) and increased HIV case detection by 3.5%. Half of new HIV diagnoses and 2/3 of acute infections were detected in the emergency department and urgent care clinic. Rapid test sensitivity was 98.9% (95% CI 93.8%– 99.8%); specificity was 99.9% (95% CI 99.7%–99.9%). Over 95% of newly diagnosed and out-of-care HIV-infected patients were linked to care. Conclusions Patients undergoing HIV testing in emergency departments and urgent care clinics may benefit from being simultaneously screened for acute HIV infection. PublicationSubtype Distribution of Human Papillomavirus in HIV-Infected Women With Cervical Intraepithelial Neoplasia Stages 2 and 3 in Botswana(2011-11-01) Ramogola-Masire, Doreen; McGrath, Cindy M; Barnhart, Kurt T; Friedman, Harvey M; Zetola, Nicola MHuman papillomavirus (HPV) vaccines containing types 16 and 18 are likely to be effective in preventing cervical cancer associated with these HPV types. No information currently exists in Botswana concerning the HPV types causing precancerous or cancerous lesions. Our goal was to determine the prevalence of HPV types associated with precancerous cervical intraepithelial neoplasia (CIN) stages 2 and 3 in HIV-infected women in Gaborone, Botswana. HIV-infected women referred to our clinic with high-grade intraepithelial lesion on the Pap smear were enrolled in the study. HPV typing was only performed if the histopathology results showed CIN stage 2 or 3 disease using linear array genotyping (CE-IVD, Roche Diagnostics).One hundred HIV-infected women were identified with CIN stages 2 or 3 between August 11, 2009 and September 29, 2010. Eighty-two of 100 women enrolled had coinfection by multiple HPV subtypes (range, 2 to 12). Of the remaining 18 women, 14 were infected with a single high-risk subtype and 4 had no HPV detected. Overall, 92 (92%) women were infected with at least 1 high-risk HPV subtype, and 56 were coinfected with more than 1 high-risk HPV type (range, 2 to 5). Fifty-one (51%) women had HPV subtypes 16, 18, or both. HPV 16 and 18 are the most common types in HIV-infected women with CIN 2 or 3 in Gaborone, Botswana, suggesting that the implementation of HPV vaccination programs could have a significant impact on the reduction of cervical cancer incidence. However, given the relative lack of knowledge on the natural history of cervical cancer in HIV-infected women and the significant prevalence of infection and coinfection with other high-risk HPV types in our sample, the true impact and cost-effectiveness of such vaccination programs need to be evaluated. PublicationThe 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. PublicationHIV-Positive Patients in Botswana State That Mobile Teledermatology Is an Acceptable Method for Receiving Dermatology Care(2011-09-01) Azfar, Rahat S; Weinberg, Jennifer L; Cavric, Gordana; Lee-Keltner, Ivy A; Bilker, Warren B.; Gelfand, Joel M; Kovarik, Carrie PublicationA Simple Novel Method for Determining Mortality Rates in HIV Treatment Programs Worldwide(2011-01-18) Bisson, Gregory P PublicationReview of Causes of Maternal Deaths in Botswana in 2010(2013-06-05) Ray, S.; Madzimbamuto, F. D; Ramagola-Masire, Doreen; Phillips, Raina; Mogobe, K. D; Haverkamp, Miriam; Mokatedi, M.; Montana, M.Background. In Botswana the maternal mortality ratio in 2010 was 163 per 100 000 live births. It is a priority to reduce this ratio to meet Millennium Development Goal 5 target of 21 per 100 000 live births. Objective. To investigate the underlying circumstances of maternal deaths in Botswana. Method. Fifty-six case notes from the 80 reported maternal deaths in 2010 were reviewed. Five clinicians reviewed each case independently and then together to achieve a consensus on diagnosis and underlying cause(s) of death. Results. Sixty-six percent of deaths occurred in Botswana’s two referral hospitals. Cases in which death had direct obstetric causes were fewer than cases in which cause of death was indirect. The main direct causes were haemorrhage (39%), hypertension (22%), and pregnancy-related sepsis (13%). Thirty-six (64%) deaths were in HIV-positive women, of whom 21 (58%) were receiving antiretroviral (ARV) therapy. Nineteen (34%) deaths were attributable to HIV, including 4 from complications of ARVs. Twenty-nine (52%) deaths were in the postnatal period, 19 (66%) of these in the first week. Case-note review revealed several opportunities for improved quality of care: better teamwork, communication and supportive supervision of health professionals; earlier recognition of the seriousness of complication(s) with more aggressive case-management; joint management between HIV and obstetric clinicians; screening for, and treatment of, opportunistic infections throughout the antenatal to postnatal periods; and better supply management of medications, fluids, blood for transfusion and laboratory tests. Conclusion. Integrating HIV management into maternal healthcare is essential to reduce maternal deaths in the region, alongside greater efforts to improve quality of care to avoid direct and indirect causes of death. PublicationPerinatally Acquired HIV Infection in Adolescents From Sub-Saharan Africa: A Review of Emerging Challenges(2014-07-01) Lowenthal, Elizabeth D; Bakeera-Kitaka, Sabrina; Marukutira, Tafireyi; Chapman, Jennifer; Goldrath, Kathryn; Ferrand, Rashida AWorldwide, more than three million children are infected with HIV, 90% of whom live in sub-Saharan Africa. As the HIV epidemic matures and antiretroviral treatment is scaled up, children with HIV are reaching adolescence in large numbers. The growing population of adolescents with perinatally acquired HIV infection living within this region presents not only unprecedented challenges but also opportunities to learn about the pathogenesis of HIV infection. In this Review, we discuss the changing epidemiology of paediatric HIV and the particular features of HIV infection in adolescents in sub-Saharan Africa. Longstanding HIV infection acquired when the immune system is not developed results in distinctive chronic clinical complications that cause severe morbidity. As well as dealing with chronic illness, HIV-infected adolescents have to confront psychosocial issues, maintain adherence to drugs, and learn to negotiate sexual relationships, while undergoing rapid physical and psychological development. Context-specific strategies for early identification of HIV infection in children and prompt linkage to care need to be developed. Clinical HIV care should integrate age-appropriate sexual and reproductive health and psychological, educational, and social services. Health-care workers will need to be trained to recognise and manage the needs of these young people so that the increasing numbers of children surviving to adolescence can access quality care beyond specialist services at low-level health-care facilities. PublicationGenetic Analysis of Human Immunodefiency Virus Type I Strains in Kenya: A Comparison Using Phylogenetic Analysis and a Combinatorial Melting Assay(1999-11-04) Robbins, Kenneth E; Kostrikis, Leondios G; Brown, Teresa M; Anzala, Omu; Shin, Sunny; Plummer, Francis A; Kalish, Marcia LWe surveyed human immunodeficiency virus (HIV) subtype distribution from peripheral blood mononuclear cells (PBMCs) collected in 1995 from 24 HIV-1-infected Kenyan residents (specimens from predominantly male truck drivers and female sex workers near Mombasa and Nairobi). Processed lysates from the PBMC samples were used for env amplification, directly sequenced, and analyzed by phylogenetic analysis. Envelope amplification products were also used for analysis in a polymerase chain reaction (PCR)-based assay, called the combinatorial melting assay (COMA). Results of the two tests were compared for assignment of subtype for this Kenyan cohort. The COMA, a PCR capture technique with colorimetric signal detection, was used with HIV reference subtype strains as well as regional (East Africa) HIV strains for subtype identification. Performance of the COMA was at 100% concordance (24 of 24) as compared with DNA sequencing analysis. Phylogenetic analysis showed 17 isolates to be subtype A, 3 subtype D, and 4 subtype C viruses. This may represent an increase in subtype C presence in Kenya compared with previously documented reports. The COMA can offer advantages for rapid HIV-1 subtype screening of large populations, with the use of previously identified regional strains to enhance the identification of local strains. When more detailed genetic information is desired, DNA sequencing and analysis may be required.