A case of massive splenomegaly due to chronic myeloproliferative neoplasm

A 34-year-old female, HIV non-reactive, presented to Kamuzu Central Hospital (KCH) in Lilongwe, Malawi, complaining of 7 months abdominal pain. She endorsed shortness of breath and early satiety for the same duration, but denied fever, chills, night sweats, and weight loss. The remainder of her review of systems was negative. She had no significant past medical history. There were no identifiable risk factors for myeloproliferative disorders, including family history, known genetic syndromes, chemical exposure, or history of ionizing radiation. On physical exam, she was noted to have a visible spleen (figure 1) which crossed into the right upper quadrant as well as the pelvis, and was non-tender to palpation. There was no cervical or axillary lymphadenopathy. The remainder of her exam was unremarkable

Salvage chemotherapy for adults with relapsed or refractory lymphoma in Malawi

Abstract Background Lymphoma is highly associated with HIV in sub-Saharan Africa (SSA), which contributes to worse outcomes relative to resource-rich settings, and frequent failure of first-line chemotherapy. However, there are no second-line treatment descriptions for adults with relapsed or refractory lymphoma (RRL) in SSA. Methods We describe HIV+ and HIV- patients with RRL receiving salvage chemotherapy in Malawi. Patients were prospectively treated at a national teaching hospital in Lilongwe, with the modified EPIC regimen (etoposide, prednisolone, ifosfamide, cisplatin) between June 2013 and May 2016, after failing prior first-line chemotherapy. Results Among 21 patients (18 relapsed, 3 refractory), median age was 40 years (range 16–78), 12 (57%) were male. Thirteen patients (62%) were HIV+, of whom 12 (92%) were on antiretroviral therapy (ART) at initiation of salvage chemotherapy, with median CD4 cell count 139 cells/μL (range 12–529) and 11 (85%) with suppressed HIV RNA. Median number of EPIC cycles was 3 (range 1–6), and the commonest toxicity was grade 3/4 neutropenia in 19 patients (90%). Fifteen patients responded (3 complete, 12 partial, overall response rate 71%), but durations were brief. Median overall survival was 4.5 months [95% confidence interval (CI) 2.4–5.6]. However, three patients, all HIV+, experienced sustained remissions. Tolerability, response, and survival did not differ by HIV status. Conclusions The appropriateness and cost-effectiveness of this approach in severely resource-limited environments is uncertain, and multifaceted efforts to improve first-line lymphoma treatment should be emphasized, to reduce frequency with which patients require salvage chemotherapy. Trial registration NCT02835911 . Registered 19 January 2016

Tobacco and other risk factors for esophageal squamous cell carcinoma in Lilongwe Malawi: Results from the Lilongwe esophageal cancer case: Control study

Objective Esophageal cancer is the second commonest cancer in Malawi, and 95% of all cases are esophageal squamous cell carcinoma (ESCC). Very little is known about the epidemiology of ESCC in Malawi including risk factors. The main objective of the study was to evaluate and describe risk factors of ESCC in Malawi. Methods We conducted a case-control study from 2017 to 2020 at two hospitals in Lilongwe, Malawi and consenting adults were eligible for inclusion. Endoscopy was conducted on all cases and biopsies were obtained for histological confirmation. Controls were selected from patients or their guardians in orthopedic, dental and ophthalmology wards and they were frequency matched by sex, age, and region of origin to cases. An electronic structured questionnaire was delivered by a trained interviewer. Multivariate conditional logistic regression models were used to assess the associations between subject characteristics, habits, and medical history and risk of ESCC. Results During the study period, 300 cases and 300 controls were enrolled into the study. Median age of cases and controls was 56 years and 62% of the cases were male. Among cases, 30% were ever cigarette smokers as were 22% of controls. Smoking cigarettes had an adjusted odds ratio of 2.4 (95% CI 1.4–4.2 p = 0.003). HIV+ status was present in 11% of cases and 4% controls, which resulted in an adjusted odds ratio was 4.0 (95% CI 1.8–9.0 p = 0.001). Drinking hot tea was associated with an adjusted odd ratio of 2.9 (95% CI 1.3–6.3 p = 0.007). Mold on stored grain has an adjusted odd ratio of 1.6 (95% CI 1.1–2.5 p = 0.021). Conclusion Reducing smoking cigarettes, consumption of scalding hot tea, and consumption of contaminated grain, could potentially help reduce the burden of ESCC in Malawi. Further investigation of the association between HIV status and ESCC are warranted

High pretreatment plasma Epstein-Barr virus (EBV) DNA level is a poor prognostic marker in HIV-associated, EBV-negative diffuse large B-cell lymphoma in Malawi

Plasma Epstein-Barr virus (EBV) DNA measurement has established prognostic utility in EBV-driven lymphomas, where it serves as a circulating tumor DNA marker. The value of plasma EBV measurement may be amplified in sub-Saharan Africa (SSA), where advanced imaging and molecular technologies for risk stratification are not typically available. However, its utility in diffuse large B-cell lymphoma (DLBCL) is less certain, given that only a subset of DLBCLs are EBV-positive. To explore this possibility, we measured plasma EBV DNA at diagnosis in a cohort of patients with DLBCL in Malawi. High plasma EBV DNA at diagnosis (≥3.0 log10 copies/mL) was associated with decreased overall survival (OS) (P =.048). When stratified by HIV status, the prognostic utility of baseline plasma EBV DNA level was restricted to HIV-positive patients. Unexpectedly, most HIV-positive patients with high plasma EBV DNA at diagnosis had EBV-negative lymphomas, as confirmed by multiple methods. Even in these HIV-positive patients with EBV-negative DLBCL, high plasma EBV DNA remained associated with shorter OS (P =.014). These results suggest that EBV reactivation in nontumor cells is a poor prognostic finding even in HIV-positive patients with convincingly EBV-negative DLBCL, extending the potential utility of EBV measurement as a valuable and implementable prognostic marker in SSA

CHOP Chemotherapy for Aggressive Non-Hodgkin Lymphoma with and without HIV in the Antiretroviral Therapy Era in Malawi

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

Outcomes for paediatric Burkitt lymphoma treated with anthracycline-based therapy in Malawi

Burkitt lymphoma (BL) is the most common paediatric cancer in sub-Saharan Africa (SSA). Anthracyline-based treatment is standard in resource-rich settings, but has not been described in SSA. Children ≤ 18 years of age with newly diagnosed BL were prospectively enrolled from June 2013 to May 2015 in Malawi. Staging and supportive care were standardized, as was treatment with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) for six cycles. Among 73 children with BL, median age was 9.2 years (interquartile range 7.7–11.8), 48 (66%) were male and two were positive for human immunodeficiency virus. Twelve (16%) had stage I/II disease, 36 (49%) stage III and 25 (34%) stage IV. Grade 3/4 neutropenia occurred in 17 (25%), and grade 3/4 anaemia in 29 (42%) of 69 evaluable children. Eighteen-month overall survival was 29% (95% confidence interval [CI] 18–41%) overall. Mortality was associated with age >9 years [hazard ratio [HR] 2.13, 95% CI 1.15–3.94], female gender (HR 2.12, 95% CI 1.12–4.03), stage (HR 1.52 per unit, 95% CI 1.07–2.17), lactate dehydrogenase (HR 1.03 per 100 iu/l, 95% CI 1.01–1.05), albumin (HR 0. 96 per g/l, 95% CI 0.93–0.99) and performance status (HR 0.78 per 10-point increase, 95% CI 0.69–0.89). CHOP did not improve outcomes in paediatric BL compared to less intensive regimens in Malawi

Plasmablastic lymphoma in Malawi

Abstract 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

Road Traffic Crashes and Fatalities in Japan 2000-2010 With Special Reference to the Elderly Road User

Objective: To investigate comparative road user crash and fatality rates in Japan between 2000 and 2010 in the elderly and young. Methods: Data from the Japan Ministry of Health, Labor and Welfare Vital Statistics Database and the Institute for Traffic Accident Research and Data Analysis were used to calculate crash rates by age group, vehicle, and license category. Results: Fatal crash rates per 100,000 licensed drivers for 4-wheeled motor vehicle drivers decreased by 53, 56, and 42 percent among the 65-69, 70-74, and >= 75 age groups between 2000 and 2010, respectively, compared to 66 and 60 percent among the 16-19 and 20-24 age groups, respectively. Fatal crash rates per 100,000 licensed riders for 2-wheeled motor vehicles decreased by 64, 23, and 33 percent in the 65-69, 70-74, and >= 75 age groups, respectively. Similarly, fatal crash rates per million population among bicyclists and pedestrians decreased in all age groups but were highest in the elderly age group in all years; the annual fatal crash rate for elderly pedestrians was 3 to 10 times higher than that for younger pedestrians. Conclusions: Despite the overall decrease in the elderly crash and fatal crash rates in all road use categories, elderly pedestrians are more susceptible to road traffic crashes and are more likely to be killed than younger persons. Further research may reduce this risk

Salvage chemotherapy for adults with relapsed or refractory lymphoma in Malawi

Abstract Background Lymphoma is highly associated with HIV in sub-Saharan Africa (SSA), which contributes to worse outcomes relative to resource-rich settings, and frequent failure of first-line chemotherapy. However, there are no second-line treatment descriptions for adults with relapsed or refractory lymphoma (RRL) in SSA. Methods We describe HIV+ and HIV- patients with RRL receiving salvage chemotherapy in Malawi. Patients were prospectively treated at a national teaching hospital in Lilongwe, with the modified EPIC regimen (etoposide, prednisolone, ifosfamide, cisplatin) between June 2013 and May 2016, after failing prior first-line chemotherapy. Results Among 21 patients (18 relapsed, 3 refractory), median age was 40 years (range 16–78), 12 (57%) were male. Thirteen patients (62%) were HIV+, of whom 12 (92%) were on antiretroviral therapy (ART) at initiation of salvage chemotherapy, with median CD4 cell count 139 cells/μL (range 12–529) and 11 (85%) with suppressed HIV RNA. Median number of EPIC cycles was 3 (range 1–6), and the commonest toxicity was grade 3/4 neutropenia in 19 patients (90%). Fifteen patients responded (3 complete, 12 partial, overall response rate 71%), but durations were brief. Median overall survival was 4.5 months [95% confidence interval (CI) 2.4–5.6]. However, three patients, all HIV+, experienced sustained remissions. Tolerability, response, and survival did not differ by HIV status. Conclusions The appropriateness and cost-effectiveness of this approach in severely resource-limited environments is uncertain, and multifaceted efforts to improve first-line lymphoma treatment should be emphasized, to reduce frequency with which patients require salvage chemotherapy. Trial registration NCT02835911 . Registered 19 January 2016