Our multidisciplinary approach can be a model for strong pathology services that provide direct, real-time support to clinical care and research in SSA.

There are no prospective studies of aggressive non-Hodgkin lymphoma (NHL) treated with CHOP in sub-Saharan Africa. We enrolled adults with aggressive NHL in Malawi between June 2013 and May 2015. Chemotherapy and supportive care were standardized, and HIV+ patients received antiretroviral therapy (ART). Thirty-seven of 58 patients (64%) were HIV+. Median age was 47 years (IQR 39–56), and 35 (60%) were male. Thirty-five patients (60%) had stage III/IV, 43 (74%) B symptoms, and 28 (48%) performance status ≥2. B-cell NHL predominated among HIV+ patients, and all T-cell NHL occurred among HIV- individuals. Thirty-one HIV+ patients (84%) were on ART for a median 9.9 months (IQR 1.1–31.7) before NHL diagnosis, median CD4 was 121 cells/μL (IQR 61–244), and 43% had suppressed HIV RNA. HIV+ patients received a similar number of CHOP cycles compared to HIV- patients, but more frequently developed grade 3/4 neutropenia (84% vs 31%, p = 0.001), resulting in modestly lower cyclophosphamide and doxorubicin doses with longer intervals between cycles. Twelve-month overall survival (OS) was 45% (95% CI 31–57%). T-cell NHL (HR 3.90, p = 0.017), hemoglobin (HR 0.82 per g/dL, p = 0.017), albumin (HR 0.57 per g/dL, p = 0.019), and IPI (HR 2.02 per unit, p<0.001) were associated with mortality. HIV was not associated with mortality, and findings were similar among patients with diffuse large B-cell lymphoma. Twenty-three deaths were from NHL (12 HIV+, 11 HIV-), and 12 from CHOP (9 HIV+, 3 HIV-). CHOP can be safe, effective, and feasible for aggressive NHL in Malawi with and without HIV.

Background Contemporary descriptions of classical Hodgkin lymphoma (cHL) are lacking from sub-Saharan Africa where human immunodeficiency virus (HIV) and Epstein–Barr virus (EBV) are prevalent. Methods We describe a prospective cHL cohort in Malawi enrolled from 2013 to 2015. Patients received standardized treatment and evaluation, including HIV status and EBV testing of tumors and plasma. Results Among 31 patients with confirmed cHL, the median age was 19 years (range, 2–51 years) and 22 (71%) were male. Sixteen patients (52%) had stage III/IV, 25 (81%) B symptoms, and 16 (52%) performance status impairment. Twenty-three patients (74%) had symptoms >6 months, and 11 of 29 (38%) had received empiric antituberculosis treatment. Anemia was common with median hemoglobin 8.2 g/dL (range, 3.1–17.1 g/dL), which improved during treatment. No children and 5 of 15 adults (33%)were HIV+. All HIV+ patients were on antiretroviral therapy for a median 15 months (range, 2–137 months), with median CD4 count 138 cells/μL (range, 23–329 cells/μL) and four (80%) having undetectable HIV. EBV was present in 18 of 24 (75%) tumor specimens, including 14 of 20 (70%) HIV− and 4 of 4 (100%) HIV+. Baseline plasma EBV DNA was detected in 25 of 28 (89%) patients, with median viral load 4.7 (range, 2.0–6.7) log10copies/mL, and subsequently declined in most patients. At 12 months, overall survival was 75% (95% confidence interval [CI], 55%–88%) and progression-free survival 65% (95% CI, 42%–81%). Baseline plasma EBV DNA and persistent viremia during treatment were associated with poorer outcomes. Conclusion cHL in Malawi is characterized by delayed diagnosis and advanced disease. Most cases were EBV associated and one-third of adults were HIV+. Despite resource limitations, 12-month outcomes were good.

Point-of-care tools are needed in sub-Saharan Africa (SSA) to improve pediatric Burkitt lymphoma (BL) diagnosis and treatment. We evaluated plasma Epstein-Barr virus (pEBV) DNA as a pediatric BL biomarker in Malawi. Prospectively enrolled children with BL were compared to classical Hodgkin lymphoma (cHL) and non-lymphoma diagnoses. Pediatric BL patients received standardized chemotherapy and supportive care. pEBV DNA was measured at baseline, mid-treatment, and treatment completion. Of 121 assessed children, pEBV DNA was detected in 76/88 (86%) with BL, 16/17 (94%) with cHL, and 2/16 (12%) with non-lymphoma, with proportions higher in BL versus non-lymphoma (p<0.001) and similar in BL versus cHL (p=0.69). If detected, median pEBV DNA was 6.1 log10copies/mL for BL, 4.8 log10copies/mL for cHL, and 3.4 log10copies/mL for non-lymphoma, with higher levels in BL versus cHL (p=0.029), and a trend toward higher levels in BL versus non-lymphoma (p=0.062). pEBV DNA declined during treatment in the cohort overall and increased in several children before clinical relapse. Twelve-month overall survival was 40% in the cohort overall, and for children with baseline pEBV detected, survival was worse if baseline pEBV DNA was ≥6 log10copies/mL versus <6 log10copies/mL (p=0.0002), and also if pEBV DNA was persistently detectable at mid-treatment versus undetectable (p=0.041). Among children with baseline pEBV DNA detected, viremia was the only significant risk factor for death by 12 months in multivariate analyses (adjusted hazard ratio 1.35 per log10copies/mL, 95% CI 1.04–1.75, p=0.023). Quantitative pEBV DNA has potential utility for diagnosis, prognosis, and response assessment for pediatric BL in SSA.

Pregnancy-associated Plasmodium falciparum infection impacts the health of mothers and newborns, but little is known about the effects of these infections on infant susceptibility to malaria. We followed 473 mother-infant pairs during pregnancy and through 2 years of age. We observed that children born to mothers with placental malaria, but not those born to mothers with peripheral infection without evidence of placental sequestration, had increased risk of malaria during the first year of life compared with children born to mothers with no malaria during pregnancy. Malaria infections with placental sequestration have long-lasting impact on infant susceptibility to malaria infection.

Plasmablastic lymphoma (PBL) clinical descriptions are scarce from sub-Saharan Africa (SSA) where both HIV and EBV are highly endemic. We identified 12 patients with pathologically confirmed PBL from a prospective cohort in Lilongwe, Malawi. Median age was 46 (range 26–71), seven (58%) were male, and six (50%) were HIV-positive. Eight patients were treated with CHOP and four with a modified EPOCH regimen. One-year overall survival was 56% (95% CI 24–79%), without clear differences based on HIV status. PBL occurs in Malawi in HIV-positive and HIV-negative individuals and can be treated successfully with curative intent, even in a low-resource setting in SSA.

Across much of Africa, there is a critical shortage of pathology services necessary for clinical care. Even in settings where specialty-level clinical care, such as medical oncology, is available, access to anatomic pathology services has often lagged behind. Pathology laboratories in the region are challenging to establish and maintain. This article describes the successful implementation of telepathology services in Malawi and reviews other successful programs developed to support diagnostic pathology in resource-limited settings.

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