A retrospective review of patients with Kaposi's sarcoma in Botswana.

BACKGROUND: Despite widespread antiretroviral coverage in Botswana, Kaposi's sarcoma (KS) remains among the most common malignancies. To date, adult KS in Botswana is not well characterized. The diagnosis relies on clinical suspicion that is often confirmed by histopathology given the implications of treatment; however, this poses a significant resource burden. METHODS: We conducted a retrospective review of the cohort of patients biopsied for possible KS at Princess Marina Hospital, the main dermatology referral site in Botswana, from September 2008 through June 2015 to describe the demographics, human immunodeficiency virus (HIV) characteristics, and clinical presentations of these patients. Histopathologic diagnoses were reviewed, and positive predictive value (PPV) was used to characterize the accuracy of clinical suspicion of KS. RESULTS: A total of 441 patients received 450 biopsies where KS was on the differential diagnosis, and 239 patients (54%) were ultimately diagnosed with KS. The KS cohort was more likely to be male (58% vs. 37%, P < 0.001), HIV positive (94% vs. 85%, P < 0.05), and have lower CD4 counts at the time of biopsy (274 cells/µl vs. 362 cells/µl, P < 0.05). The PPV of clinical suspicion of KS was 58%. When KS was not histopathologically diagnosed, clinically benign diseases were found in 17%, medically significant conditions requiring alternative therapies in 78%, and life-threatening diseases in 5%. DISCUSSION: Our study reinforces the risk factors in development of KS. The poor PPV supports the important role of histology in KS diagnosis to both ensure appropriate treatment and prevent overtreatment. Improved accessibility to biopsy and augmentation of local dermatopathologic services would likely improve diagnostic accuracy and treatment.

Predictors of Timely Access of Oncology Services and Advanced-Stage Cancer in an HIV-Endemic Setting.

BACKGROUND: Three-quarters of cancer deaths occur in resource-limited countries, and delayed presentation contributes to poor outcome. In Botswana, where more than half of cancers arise in HIV-infected individuals, we sought to explore predictors of timely oncology care and evaluate the hypothesis that engagement in longitudinal HIV care improves access. METHODS: Consenting patients presenting for oncology care from October 2010 to September 2014 were interviewed and their records were reviewed. Cox and logistic models were used to examine the effect of HIV and other predictors on time to oncology care and presentation with advanced cancer (stage III or IV). RESULTS: Of the 1,146 patients analyzed, 584 (51%) had HIV and 615 (54%) had advanced cancer. The initial clinic visit occurred a mean of 144 days (median 29, interquartile range 0-185) after symptom onset, but subsequent mean time to oncology care was 406 days (median 160, interquartile range 59-653). HIV status was not significantly associated with time to oncology care (adjusted hazard ratio [aHR] 0.91, 95% confidence interval [CI] 0.79-1.06). However, patients who reported using traditional medicine/healers engaged in oncology care significantly faster (aHR 1.23, 95% CI 1.09-1.40) and those with advanced cancer entered care earlier (aHR 1.48, 95% CI 1.30-1.70). Factors significantly associated with advanced cancer included income <$50 per month (adjusted odds ratio [aOR] 1.35, 95% CI 1.05-1.75), male sex (aOR 1.45, 95% CI 1.12-1.87), and pain as the presenting symptom (aOR 1.39, 95% CI 1.03-1.88). CONCLUSION: Longitudinal HIV care did not reduce the substantial delay to cancer treatment. Research focused on reducing health system delay through coordination and navigation is needed. IMPLICATIONS FOR PRACTICE: The majority (54%) of patients in this large cohort from Botswana presented with advanced-stage cancer despite universal access to free health care. Median time from first symptom to specialized oncology care was 13 months. For HIV-infected patients (51% of total), regular longitudinal contact with the health system, through quarterly doctor visits for HIV management, was not successful in providing faster linkages into oncology care. However, patients who used traditional medicine/healers engaged in cancer care faster, indicating potential for leveraging traditional healers as partners in early cancer detection. New strategies are urgently needed to facilitate diagnosis and timely treatment of cancer in low- and middle-income countries.

Establishing and Delivering Quality Radiation Therapy in Resource-Constrained Settings: The Story of Botswana.

There is a global cancer crisis, and it is disproportionately affecting resource-constrained settings, especially in low- and middle-income countries (LMICs). Radiotherapy is a critical and cost-effective component of a comprehensive cancer control plan that offers the potential for cure, control, and palliation of disease in greater than 50% of patients with cancer. Globally, LMICs do not have adequate access to quality radiation therapy and this gap is particularly pronounced in sub-Saharan Africa. Although there are numerous challenges in implementing a radiation therapy program in a low-resource setting, providing more equitable global access to radiotherapy is a responsibility and investment worth prioritizing. We outline a systems approach and a series of key questions to direct strategy toward establishing quality radiation services in LMICs, and highlight the story of private-public investment in Botswana from the late 1990s to the present. After assessing the need and defining the value of radiation, we explore core investments required, barriers that need to be overcome, and assets that can be leveraged to establish a radiation program. Considerations addressed include infrastructure; machine choice; quality assurance and patient safety; acquisition, development, and retention of human capital; governmental engagement; public-private partnerships; international collaborations; and the need to critically evaluate the program to foster further growth and sustainability.

Cotrimoxazole prophylaxis and risk of severe anemia or severe neutropenia in HAART-exposed, HIV-uninfected infants.

BACKGROUND: Prophylactic cotrimoxazole is recommended for infants born to HIV-infected mothers. However, cotrimoxazole may increase the risk of severe anemia or neutropenia. METHODS: We compared the proportion of HIV-exposed uninfected (HIV-EU) infants experiencing incident severe anemia (and separately, severe neutropenia) between a prospective cohort receiving prophylactic cotrimoxazole from 1 to 6 months vs. infants from two prior trials who did not receive cotrimoxazole. Infants were from rural and urban communities in southern Botswana. RESULTS: A total of 1705 HIV-EU infants were included. Among these 645 (37.8%) were fed with iron-supplemented formula from birth. Severe anemia developed in 87 (5.1%) infants, and severe neutropenia in 164 (9.6%) infants. In an analysis stratified by infant feeding method, there were no significant differences in the risk of severe anemia by prophylactic cotrimoxazole exposure-risk difference, -0.69% (95% confidence interval [CI] -2.1 to 0.76%). Findings were similar in multivariable analysis, adjusted odds ratio (aOR) 0.35 (95% CI 0.07 to 1.65). There were also no significant differences observed for severe neutropenia by cotrimoxazole exposure, risk difference 2.0% (95% CI -1.3 to 5.2%) and aOR 0.80 (95% CI 0.33 to 1.93). CONCLUSIONS: Severe anemia and severe neutropenia were infrequent among HIV-exposed uninfected infants receiving cotrimoxazole from 1-6 months of age. Concerns regarding hematologic toxicity should not limit the use of prophylactic cotrimoxazole in HIV-exposed uninfected infants. CLINICALTRIAL.SGOV REGISTRATION NUMBERS: NCT01086878 (http://clinicaltrials.gov/show/NCT01086878), NCT00197587 (http://clinicaltrials.gov/show/NCT00197587), and NCT00270296 (http://clinicaltrials.gov/show/NCT00270296).

Acceptability of male circumcision among adolescent boys and their parents, Botswana.

Little is known of the acceptability of male circumcision (MC) to adolescent boys, a key target group for HIV prevention. We conducted a cluster design survey among adolescent boys and their parents/guardians in two villages in Botswana. Of 1300 households visited, 398 boys were eligible; 269 boys and 210 parents/guardians participated. MC was described correctly by 80% of boys, and 76% identified that MC reduces the risk of male HIV acquisition. After a brief informational session, 75% of boys stated that they would definitely want to be circumcised and 96% of parents/guardians would want their boy circumcised. Boys most frequently reported pain (49%) and possible health problems (19%) as concerns undergoing MC; concerns about peer or partner acceptance, sexual function, or cultural appropriateness were uncommon. Adolescent MC is likely to be highly acceptable in Botswana if done safely, for free and with adequate pain control in a hospital setting.

Increased risk of severe infant anemia after exposure to maternal HAART, Botswana.

BACKGROUND: Maternal highly-active antiretroviral therapy (HAART) reduces mother-to-child HIV transmission but may increase the risk for infant anemia. METHODS: The incidence of first severe anemia (grade 3 or 4, Division of AIDS 2004 Toxicity Table) was assessed among HIV-uninfected infants in the Mashi and Mma Bana mother-to-child HIV transmission prevention trials in Botswana. Severe anemia rates were compared between 3 groups: infants exposed to maternal HAART in utero and during breastfeeding (BF) and 1 month of postnatal zidovudine (ZDV) (HAART-BF); infants exposed to maternal ZDV in utero, 6 months of postnatal ZDV, and BF (ZDV-BF); and infants exposed to maternal ZDV in utero, 1 month of postnatal ZDV, and formula-feeding (ZDV-FF). RESULTS: A total of 1719 infants were analyzed-691 HAART-BF, 503 ZDV-BF, and 525 ZDV-FF. Severe anemia was detected in 118 infants (7.4%). By 6 months, 12.5% of HAART-BF infants experienced severe anemia, compared with 5.3% of ZDV-BF (P < 0.001) and 2.5% of ZDV-FF infants (P < 0.001). In adjusted analysis, HAART-BF infants were at greater risk of severe anemia than ZDV-BF or ZDV-FF infants (adjusted odds ratios 2.6 and 5.8, respectively; P < 0.001). Most anemias were asymptomatic and improved with iron/multivitamin supplementation and cessation of ZDV exposure. However, 11 infants (0.6% of all infants) required transfusion for symptomatic anemia. Microcytosis and hypochromia were common among infants with severe anemia. CONCLUSIONS: Exposure to maternal HAART starting in utero was associated with severe infant anemia. Confirmation of this finding and possible strategies to mitigate hematologic toxicity warrant further study.