Feasibility of Rapid Case Ascertainment for Cancer in East Africa: An Investigation of Community-Representative Kaposi Sarcoma in the Era of Antiretroviral Therapy.

BACKGROUND: Rapid case ascertainment (RCA) refers to the expeditious and detailed examination of patients with a potentially rapidly fatal disease shortly after diagnosis. RCA is frequently performed in resource-rich settings to facilitate cancer research. Despite its utility, RCA is rarely implemented in resource-limited settings and has not been performed for malignancies. One cancer and context that would benefit from RCA in a resource-limited setting is HIV-related Kaposi sarcoma (KS) in sub-Saharan Africa. METHODS: To determine the feasibility of RCA for KS, we searched for all potential newly diagnosed KS among HIV-infected adults attending three community-based facilities in Uganda and Kenya. Searching involved querying of electronic medical records, pathology record review, and notification by clinicians. Upon identification, a team verified eligibility and attempted to locate patients to perform RCA, which included epidemiologic, clinical and laboratory measurements. RESULTS: We identified 593 patients with suspected new KS. Of the 593, 171 were ineligible, mainly because biopsy failed to confirm KS (65%) or KS was not new (30%). Among the 422 remaining, RCA was performed within 1 month for 56% of patients and within 3 months for 65% (95% confidence interval: 59 to 70%). Reasons for not performing RCA included intervening death (47%), inability to contact (44%), refusal/unsuitable to consent (8.3%), and patient re-location (0.7%). CONCLUSIONS: We found that RCA - an important tool for cancer research in resource-rich settings - is feasible for the investigation of community-representative KS in East Africa. Feasibility of RCA for KS suggests feasibility for other cancers in Africa.

Beyond T Staging in the "Treat-All" Era: Severity and Heterogeneity of Kaposi Sarcoma in East Africa.

BACKGROUND: Although many patients with Kaposi sarcoma (KS) in sub-Saharan Africa are diagnosed with AIDS Clinical Trials Group (ACTG) T1 disease, T1 staging insufficiently captures clinical heterogeneity of advanced KS. Using a representative community-based sample, we detailed disease severity at diagnosis to inform KS staging and treatment in sub-Saharan Africa. METHODS: We performed rapid case ascertainment on people living with HIV, aged 18 years or older, newly diagnosed with KS from 2016 to 2019 at 3 clinic sites in Kenya and Uganda to ascertain disease stage as close as possible to diagnosis. We reported KS severity using ACTG and WHO staging criteria and detailed measurements that are not captured in the current staging systems. RESULTS: We performed rapid case ascertainment within 1 month for 241 adults newly diagnosed with KS out of 389 adult patients with suspected KS. The study was 68% men with median age 35 years and median CD4 count 239. Most of the patients had advanced disease, with 82% qualifying as ACTG T1 and 64% as WHO severe/symptomatic KS. The most common ACTG T1 qualifiers were edema (79%), tumor-associated ulceration (24%), extensive oral KS (9%), pulmonary KS (7%), and gastrointestinal KS (4%). There was marked heterogeneity within T1 KS, with 25% of patients having 2 T1 qualifying symptoms and 3% having 3 or more. CONCLUSION: Most of the patients newly diagnosed with KS had advanced stage disease, even in the current antiretroviral therapy "treat-all" era. We observed great clinical heterogeneity among advanced stage patients, leading to questions about whether all patients with advanced KS require the same treatment strategy.

The diagnostic accuracy of Th1 (IFN-γ, TNF-α, and IL-2) and Th2 (IL-4, IL-6 and IL-10) cytokines response in AFB microscopy smear negative PTB- HIV co-infected patients.

Acid Fast Bacilli (AFB) microscopy smear remains the most widely used laboratory diagnostic technique for Pulmonary Tuberculosis (PTB) in low-and-middle income countries. Although it is highly specific, the sensitivity varies between 20-80% in immune-competent people, with only 50% case detection among HIV/TB co-infected patients, hence the need to determine the diagnostic accuracy of Th1 and Th2 cytokine response in AFB microscopy smear negative PTB-HIV co-infected patients. A total of 86 participants were recruited; 70 (81.4%) AFB microscopy smear negative and 16 (18.6%) AFB microscopy smear positive. The AFB microscopy smear negative samples were then cultured using Lowenstein Jensen Medium with 46 being culture-negative and 24 being culture-positive. Blood samples were also collected, cultured using QFT-GIT and the supernatant (plasma) harvested to evaluate cytokine profiles using Enzyme-Linked Immunosorbent Assay. IFN-γ (P < 0.001), TNF-α (P = 0.004), IL-2 (P = 0.004) and IL-4 (P = 0.009) median levels were elevated in PTB culture-positive (AFB microscopy smear negative) as compared to PTB culture-negative (AFB microscopy smear negative) participants. Finally, when Th1 cytokines (IFN-γ, TNF-α and IL-2), Th2 cytokines (IL-6 and IL-10) and T cells were included in the logistic regression fit for PTB outcome, the predictive power of discriminating between those who were AFB smear negative in the diagnosis of PTB was good with cross validated area under the curve (AUC) being 0.87 (95% CI: 0.78, 0.96). This study provides evidence for the ability of Th1 and Th2 cytokines to determine PTB status in AFB microscopy smear negative patients co-infected with HIV.

The role of Mycobacterium tuberculosis antigen specific cytokines in determination of acid fast bacilli culture status in pulmonary tuberculosis patients co-infected with human immunodeficiency virus.

INTRODUCTION: The interaction between Mycobacterium tuberculosis and HIV leads to rapid progression of tuberculosis (TB) and human immunodeficiency virus (HIV)-induced immunosuppression. Diagnosis of TB in these patients is more difficult due to its atypical presentations giving contradicting results. The overall aim of this study was to evaluate the ability of pro-inflammatory cytokine (Th1) and anti-inflammatory cytokine (Th2) to discriminate between culture-positive and -negative smear status in HIV-TB co-infected patients. METHODS: In a prospective cohort, a total of 86 study participants were recruited: 46 culture-negative and 40 culture-positive. Blood and sputum samples were collected from all participants. The blood was then analyzed using FACSCalibur flow cytometer to immunophenotype the cells and ELISA performed for cytokine profiles. Sputum samples were analyzed to determine smear status using direct microscopy and Lowenstein Jensen medium. Statistical analyses were performed using R software. Independent samples t-test was used to compare means between the two groups, while the medians were compared using two-sample Wilcoxon rank sum test. Pearson's Chi-square test was used to compare the proportion of male and female participants across the culture and AFB smear status. In order to determine the predictive power of Th1 and Th2 in discriminating Pulmonary Tuberculosis status (PTB) (culture status was used as a confirmatory test), binary logistic regression models were fitted for Th1 covariates [IFN-γ, TNF-α, IL-2 and IL-12(p70)] and Receiver Operating Characteristic (ROC) curves plotted. RESULTS: The overall mean age of the participants was 39 years (SD=12), 42% being male. Although, lymphocytes counts were higher in culture-positive relative to culture-negative, the CD8, CD19, and CD16/CD56 were comparable in the two groups. The CD4 counts differed between the two groups (P=0.012). The Th1 showed a better discrimination between culture-positive and -negative PTB individuals; IFN-γ (P=0.001), TNF-α (P=0.001), IL-2 (P=0.001) and IL-12(p70) (P=0.016). The Th2 cytokines (IL-4, IL-6 and IL-10) were comparable between the culture-positive and -negative groups. However, when the combination of Th1 cytokines [IFN-γ, TNF-α, IL-2 and IL-12(p70)] was fitted in binary logistic regression models, the predictive power was high with area under curve (AUC) being 89.7% in discriminating PTB. CONCLUSION: This study provides evidence for the ability of a combination of Th1 cytokines in discriminating against culture-positive and culture-negative PTB.

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.

Screening by Clinical Breast Examination in Western Kenya: Who Comes?

PURPOSE: More than 80% of women with breast cancer in Kenya present to medical care with established late-stage disease. We sought to understand why women might not participate in breast cancer screening when it is offered by comparing the views of a cohort of those who attended a screening special event with those of community controls who did not attend. METHODS: All residents living close to three health centers in western Kenya were invited to participate in screening. Participants (attendees) underwent clinical breast examination by trained physician oncologists. In addition, women who consented were interviewed by using a modified Breast Cancer Awareness Module questionnaire. Nonattendees were interviewed in their homes the following day. RESULTS: A total of 1,511 attendees (1,238 women and 273 men) and 467 nonattendee women participated in the study. Compared with nonattendees, the women attendees were older, more often employed, knew that breast cancer presented as a lump, and were more likely to have previously felt a lump in a breast. In addition, they were more likely to report previously participating in screening activities, were more likely to have performed breast self-examination, and were less concerned about wasting a doctor's time. Almost all those surveyed (attendees and nonattendees) expressed interest in future breast cancer screening opportunities. CONCLUSION: The women who volunteer for breast cancer screening in western Kenya are more aware of breast cancer than those who do not volunteer. Screening recruitment should seek to close these knowledge gaps to increase participation.

Lay perceptions of breast cancer in Western Kenya.

AIM: To explore lay perceptions of causes, severity, presenting symptoms and treatment of breast cancer. METHODS: In October-November 2012, we recruited men and women (18 years and older) from households and health facilities in three different parts of Western Kenya, chosen for variations in their documented burdens of breast cancer. A standardized and validated tool, the breast cancer awareness measure (BCAM), was administered in face-to-face interviews. Survey domains covered included socio-demographics, opinions about causes, symptoms, severity, and treatment of breast cancer. Descriptive analyses were done on quantitative data while open-ended answers were coded, and emerging themes were integrated into larger categories in a qualitative analysis. The open-ended questions had been added to the standard BCAM for the purposes of learning as much as the investigators could about underlying lay beliefs and perceptions. RESULTS: Most respondents were female, middle-aged (mean age 36.9 years), married, and poorly educated. Misconceptions and lack of knowledge about causes of breast cancer were reported. The following (in order of higher to lower prevalence) were cited as potential causes of the condition: Genetic factors or heredity (n = 193, 12.3%); types of food consumed (n = 187, 11.9%); witchcraft and curses (n = 108, 6.9%); some family planning methods (n = 56, 3.6%); and use of alcohol and tobacco (n = 46, 2.9%). When asked what they thought of breast cancer's severity, the most popular response was "it is a killer disease" (n = 266, 19.7%) a lethal condition about which little or nothing can be done. While opinions about presenting symptoms and signs of breast cancer were able to be elicited, such as an increase in breast size and painful breasts, early-stage symptoms and signs were not widely recognized. Some respondents (14%) were ignorant of available treatment altogether while others felt breast cancer treatment is both dangerous and expensive. A minority reported alternative medicine as providing relief to patients. CONCLUSION: The impoverished knowledge in these surveys suggests that lay education as well as better screening and treatment should be part of breast cancer control in Kenya.