Naftali Busakhala

Impact of antiretroviral therapy on the incidence of Kaposi's sarcoma in resource-rich and resource-limited settings.

Purpose of review Given the recent availability of antiretroviral therapy (ART) in resource-limited settings and the significant burden exacted by Kaposis sarcoma in these areas, we reviewed data regarding the impact of ART on Kaposis sarcoma incidence. We summarized the sizeable literature in resource-rich settings as well as emerging data from resource-limited regions. Importantly, we delineated ways impact can be defined, including individual patient-level effectiveness; population-level effectiveness; change in population-level incidence; and residual risk of Kaposis sarcoma. Recent findings In resource-rich settings, there are now ample data demonstrating beneficial individual patient-level and population-level effects of ART on Kaposis sarcoma incidence. There is, however, considerable variability between studies and important methodologic shortcomings. Data from resource-limited settings are much more limited; although they preliminarily indicate individual patient-level effectiveness, they do not yet provide insight on population-level effects. Summary ART has had a substantial impact on Kaposis sarcoma incidence in resource-rich settings, but more attention is needed on validly quantifying this effect in order to determine whether additional interventions are needed. Emerging data from resource-limited regions also suggest beneficial impact of ART on Kaposis sarcoma incidence, but – given the scope of Kaposis sarcoma in these settings – more data are needed to understand the breadth and magnitude of the effect.

The oncology pharmacy in cancer care delivery in a resource-constrained setting in western Kenya

The movement to deliver cancer care in resource-limited settings is gaining momentum, with particular emphasis on the creation of cost-effective, rational algorithms utilizing affordable chemotherapeutics to treat curable disease. The delivery of cancer care in resource-replete settings is a concerted effort by a team of multidisciplinary care providers. The oncology pharmacy, which is now considered integral to cancer care in resourced medical practice, developed over the last several decades in an effort to limit healthcare provider exposure to workplace hazards and to limit risk to patients. In developing cancer care services in resource-constrained settings, creation of oncology pharmacies can help to both mitigate the risks to practitioners and patients, and also limit the costs of cancer care and the environmental impact of chemotherapeutics. This article describes the experience and lessons learned in establishing a chemotherapy pharmacy in western Kenya.

Accuracy of Clinical Suspicion and Pathologic Diagnosis of Kaposi Sarcoma in East Africa.

Background:HIV-associated Kaposi sarcoma (KS) is one of the most common malignancies in sub-Saharan Africa. The diagnosis is often based on clinical suspicion, without histopathologic confirmation. When biopsies are performed, the accuracy of interpretation by local pathologists is poorly understood. We assessed the accuracy of clinical suspicion and pathologic diagnosis of KS in 2 East African countries. Methods:At 2 large HIV care sites in Uganda and Kenya, we evaluated consecutive biopsies performed from October 2008 to January 2013 on HIV-infected adults with clinically suspected KS. Biopsies were interpreted by both local African pathologists and a group of US-based dermatopathologists from a high volume medical center. For the purpose of this analysis, the US-based dermatopathologist interpretation was used as the gold standard. Positive predictive value was used to characterize accuracy of local African clinical suspicion of KS, and concordance, sensitivity, and specificity were used to characterize accuracy of local pathologic diagnosis. Results:Among 1106 biopsies, the positive predictive value of clinical suspicion of KS was 77% (95% confidence interval: 74% to 79%). When KS was not histopathologically diagnosed, clinically banal conditions were found in 35%, medically significant disorders which required different therapy in 59% and life-threatening diseases in 6%. Concordance between African pathologists and US-based dermatopathologists was 69% (95% confidence interval: 66% to 72%). Sensitivity and specificity of African pathologic diagnoses were 68% and 89%, respectively. Conclusions:Among East African HIV-infected patients, we found suboptimal positive predictive value of clinical suspicion of KS and specific, but not sensitive, histopathologic interpretation. The findings call for abandonment of isolated clinical diagnosis of KS in the region and augmentation of local dermatopathologic services.

Retrospective Analysis of the Efficacy of Gemcitabine for Previously Treated AIDS-Associated Kaposi's Sarcoma in Western Kenya

Objectives: Evaluation of outcomes in the use of single-agent gemcitabine for the treatment of AIDS-associated Kaposi’s sarcoma (KS) in a western Kenyan cancer treatment program. Methods: Retrospective chart review of all patients with KS treated with single agent gemcitabine following failure of first-line Adriamycin, bleomycin, and vincristine (ABV). Baseline demographics were collected, and clinicians’ assessments of response were utilized to fill out objective criteria for both response as well as symptom benefit assessment. Results: Twenty-three patients with KS who had previously failed first-line therapy with ABV were evaluated. Following treatment, 22 of the 23 patients responded positively to treatment with stable disease or better. Of the 18 patients who had completed therapy, with a median follow-up of 5 months, 12 patients had no documented progression. Conclusions: Treatment options in the resource-constrained setting are limited, both by financial constraints as well as the need to avoid myelotoxicity, which is associated with high morbidity in this treatment setting. This work shows that gemcitabine has promising activity in KS, with both objective responses and clinical benefit observed in this care setting. Gemcitabine as a single agent merits further investigation for AIDS-associated KS.

A prospective ascertainment of cancer incidence in sub-Saharan Africa: The case of Kaposi sarcoma.

In resource‐limited areas, such as sub‐Saharan Africa, problems in accurate cancer case ascertainment and enumeration of the at‐risk population make it difficult to estimate cancer incidence. We took advantage of a large well‐enumerated healthcare system to estimate the incidence of Kaposi sarcoma (KS), a cancer which has become prominent in the HIV era and whose incidence may be changing with the rollout of antiretroviral therapy (ART). To achieve this, we evaluated HIV‐infected adults receiving care between 2007 and 2012 at any of three medical centers in Kenya and Uganda that participate in the East Africa International Epidemiologic Databases to Evaluate AIDS (IeDEA) Consortium. Through IeDEA, clinicians received training in KS recognition and biopsy equipment. We found that the overall prevalence of KS among 102,945 HIV‐infected adults upon clinic enrollment was 1.4%; it declined over time at the largest site. Among 140,552 patients followed for 319,632 person‐years, the age‐standardized incidence rate was 334/100,000 person‐years (95% CI: 314–354/100,000 person‐years). Incidence decreased over time and was lower in women, persons on ART, and those with higher CD4 counts. The incidence rate among patients on ART with a CD4 count >350 cells/mm3 was 32/100,000 person‐years (95% CI: 14–70/100,000 person‐years). Despite reductions over time coincident with the expansion of ART, KS incidence among HIV‐infected adults in East Africa equals or exceeds the most common cancers in resource‐replete settings. In resource‐limited settings, strategic efforts to improve cancer diagnosis in combination with already well‐enumerated at‐risk denominators can make healthcare systems attractive platforms for estimating cancer incidence.

Task Shifting and Skin Punch for the Histologic Diagnosis of Kaposi's Sarcoma in Sub-Saharan Africa: A Public Health Solution to a Public Health Problem

Fueled by HIV, sub-Saharan Africa has the highest incidence of Kaposis sarcoma (KS) in the world. Despite this, KS diagnosis in the region is based mostly on clinical grounds. Where biopsy is available, it has traditionally been excisional and performed by surgeons, resulting in multiple appointments, follow-up visits for suture removal, and substantial costs. We hypothesized that a simpler approach - skin punch biopsy - would make histologic diagnosis more accessible. To address this, we provided training and equipment for skin punch biopsy of suspected KS to three HIV clinics in East Africa. The procedure consisted of local anesthesia followed by a disposable cylindrical punch blade to obtain specimens. Hemostasis is facilitated by Gelfoam®. Patients removed the dressing after 4 days. From 2007 to 2013, 2,799 biopsies were performed. Although originally targeted to be used by physicians, biopsies were performed predominantly by nurses (62%), followed by physicians (15%), clinical officers (12%) and technicians (11%). There were no reports of recurrent bleeding or infection. After minimal training and provision of inexpensive equipment (USD 3.06 per biopsy), HIV clinics in East Africa can integrate same-day skin punch biopsy for suspected KS. Task shifting from physician to non-physician greatly increases access. Skin punch biopsy should be part of any HIV clinics essential procedures. This example of task shifting may also be applicable to the diagnosis of other cancers (e.g., breast) in resource-limited settings.

Medical Education and Training: Building In-Country Capacity at All Levels

Poorly trained workers and limited workforce capacity contribute immensely to barriers in cancer control in low- and middle-income countries (LMICs). Because of an increasing disease burden and the gap in trained personnel, it is critical that LMICs must develop appropriate in-country training programs at all levels to adequately address their cancer-related outcomes. The training in LMICs of cancer health personnel should address priority cancer diseases in the specific country by developing caregivers, trainers, researchers, and administrators at all levels of health care and all cadres of staff, from the community level to the national level. The Academic Model of Providing Access to Health care is a representative model of how a public tertiary hospital like the Moi Teaching and Referral Hospital in an LMIC setting can leverage its resources, collaborate with partners from high-resource countries, and assist in the development of a training center to spearhead a sustainable education program.

Bacillary Angiomatosis Masquerading as Kaposi’s Sarcoma in East Africa

Background: Bacillary angiomatosis (BA) is a rare manifestation of infection caused by Bartonella species, which leads to vasoproliferative lesions of skin and other organs. Bacillary angiomatosis affects individuals with advanced HIV disease or other immunocompromised individuals. In sub-Saharan Africa, despite the high prevalence of HIV infection and documentation of the causative Bartonella species in humans, mammalian hosts, and arthropod vectors, BA has only rarely been described. Methods: Three adult patients from Uganda and Kenya with deep purple dome-shaped papules or nodules of the skin underwent punch biopsies for histopathologic diagnosis. The biopsies of all 3 patients were sent to a local pathologist as well as to a dermatopathologist at the University of California, San Francisco. Results: All 3 patients were clinically suspected to have Kaposi’s sarcoma (KS), and local pathologists had interpreted the lesions as KS in 2 of the cases and nonspecific inflammation in the third. Histologic examination by dermatopathologists in the United States revealed nodular dermal proliferations of irregular capillaries lined by spindled to epithelioid endothelial cells. The surrounding stroma contained a mixed inflammatory infiltrate with lymphocytes, eosinophils, and neutrophils. Extracellular deposits of pale amphophilic granular material were noted in the surrounding stroma. A Warthin-Starry stain highlighted clumps of bacilli, confirming the diagnosis of BA. Conclusions: These 3 cases, to our knowledge, are the first reports of BA in East Africa in the biomedical literature. Each had been originally incorrectly diagnosed as KS. We speculate BA is underdiagnosed and underreported in resource-poor regions, such as sub-Saharan Africa, that have high endemic rates of HIV infection.

Factors Associated with Uptake of Visual Inspection with Acetic Acid (VIA) for Cervical Cancer Screening in Western Kenya

Purpose Cervical cancer screening has been successful in reducing the rates of cervical cancer in developed countries, but this disease remains the leading cause of cancer deaths among women in sub-Saharan Africa. We sought to understand factors associated with limited uptake of screening services in our cervical cancer-screening program in Western Kenya. Participants and Methods Using items from a previously validated cancer awareness questionnaire repurposed for use in cervical cancer and culturally adapted for use in Kenya, we interviewed 2,505 women aged 18–55 years receiving care in gynecology clinics or seeking other services in 4 health facilities in Western Kenya between April 2014 and September 2014. We used logistic regression modeling to assess factors associated with uptake (or non-uptake), associated odds ratios (ORs) and the 95% confidence intervals (95% CI). Results Only two hundred and seventy-three women out of 2505 (11%) accepted VIA cervical cancer screening. Knowledge of just how women are screened for cervical cancer was significantly associated with reduced uptake of cervical cancer screening (OR: 0.53; CI 0.38–0.73) as was fear that screening would reveal a cancer (OR 0.70; CI 0.63–0.77), and reliance on prayer with the onset of illness (OR 0.43; CI 0.26–0.71). Participants who thought that one should get cervical cancer screening even if there were no symptoms were more than twice as likely to accept cervical cancer screening (OR 2.21; 95% CI 1.24–3.93). Older patients, patients living with HIV and women who do not know if bleeding immediately after sex might be a sign of cervical cancer were also more likely to accept screening (OR 1.03, CI 1.02–1.04; OR 1.78, CI 1.01–3.14; OR 2.39, CI 1.31–4.39, respectively). Conclusions In our population, a high percent of women knew that it is appropriate for all women to get cervical cancer screening, but only a small proportion of women actually got screening. There may be an opportunity to design educational materials for this population that will not only encourage participation in cervical cancer screening but also remediate misconceptions. The discussion illustrates how our findings could be used in such an effort.

A Review of the Ingredients Contained in Over the Counter (OTC) Cough Syrup Formulations in Kenya. Are They Harmful to Infants

Background Cough syrups are widely used in the developing world, but safety of their use in infants and children less than two years has not been well documented. Some syrups contain multiple combinations of such drugs as promethazine, diphenhydramine and ephedrine; which are individually now contraindicated in children less than two years. Despite this, the syrups are available as over the counter drugs and may be dispensed to mothers who are unaware of the potentially hazardous effects to their infants. A descriptive cross-sectional study was used to investigate suitability of cough syrups sold within Eldoret municipality for use in children less than two years of age based on their formulations and available literature. Methods Two semi-structured questionnaires were administered to pharmacy attendants and mothers attending sick child clinic at a referral hospital to establish whether cough syrups containing more than one active ingredient of compounds, now contraindicated in children are administered to infants, and awareness of potential serious adverse effects. Data from labeled contents of cough syrups from retail pharmacies was recorded and corroborated with information from literature to determine those deemed to contain the ingredients. The second questionnaire was administered to mothers with children less than two years to ascertain whether they had used the identified syrups. A total of 260 mothers and 55 pharmacy attendants were interviewed. Results There was widespread use of the syrups in children, including infants, with 192 (74%) of the respondents having used identified syrups and over 90% of these on children less than 2 years including those less than three months.146 (76%) mothers had administered the syrup at double the recommended dose. Conclusion The regulatory authorities should make concerted efforts to discourage use of cough syrups containing ingredients that pose adverse events to infants, including campaigns to educate pharmacy workers and mothers.