Etiology of Fever and Associated Outcomes Among Adults Receiving Chemotherapy for the Treatment of Solid Tumors in Uganda.

Background: Little is known about the microbiology and outcomes of chemotherapy-associated febrile illness among patients in sub-Saharan Africa. Understanding the microbiology of febrile illness could improve antibiotic selection and infection-related outcomes. Methods: From September 2019 through June 2022, we prospectively enrolled adult inpatients at the Uganda Cancer Institute who had solid tumors and developed fever within 30 days of receiving chemotherapy. Evaluation included blood cultures, malaria rapid diagnostic tests, and urinary lipoarabinomannan testing for tuberculosis. Serum cryptococcal antigen was evaluated in participants with human immunodeficiency virus (HIV). The primary outcome was the mortality rate 40 days after fever onset, which we estimated using Cox proportional hazards models. Results: A total of 104 febrile episodes occurred among 99 participants. Thirty febrile episodes (29%) had ≥1 positive microbiologic result. The most frequently identified causes of infection were tuberculosis (19%) and bacteremia (12%). The prevalence of tuberculosis did not differ by HIV status. The 40-day case fatality ratio was 25%. There was no difference in all-cause mortality based on HIV serostatus, presence of neutropenia, or positive microbiologic results. A universal vital assessment score of >4 was associated with all-cause mortality (hazard ratio, 14.5 [95% confidence interval, 5-42.7]). Conclusions: The 40-day mortality rate among Ugandan patients with solid tumors who developed chemotherapy-associated febrile illness was high, and few had an identified source of infection. Tuberculosis and bacterial bloodstream infections were the leading diagnoses associated with fever. Tuberculosis should be included in the differential diagnosis for patients who develop fever after receiving chemotherapy in tuberculosis-endemic settings, regardless of HIV serostatus.

A prospective study of clinical outcomes of HIV-associated and HIV-negative Kaposi sarcoma in Uganda.

OBJECTIVE: Improved understanding of the effect of HIV infection on Kaposi sarcoma (KS) presentation and outcomes will guide development of more effective KS staging and therapeutic approaches. We enrolled a prospective cohort of epidemic (HIV-positive; HIV + KS) and endemic (HIV-negative; HIV - KS) KS patients in Uganda to identify factors associated with survival and response. METHODS: Adults with newly diagnosed KS presenting for care at the Uganda Cancer Institute (UCI) in Kampala, Uganda, between October 2012 and December 2019 were evaluated. Participants received chemotherapy per standard guidelines and were followed over 1 year to assess overall survival (OS) and treatment response. RESULTS: Two hundred participants were enrolled; 166 (83%) had HIV + KS, and 176 (88%) were poor-risk tumor (T1) stage. One-year OS was 64% (95% confidence interval [CI] 57-71%), with the hazard of death nearly threefold higher for HIV + KS (hazard ratio [HR] = 2.93; P  = 0.023). Among HIV + KS, abnormal chest X-ray (HR = 2.81; P  = 0.007), lower CD4 + T-cell count (HR = 0.68 per 100 cells/µl; P  = 0.027), higher HIV viral load (HR = 2.22 per log 10  copies/ml; P  = 0.026), and higher plasma Kaposi sarcoma-associated herpesvirus (KSHV) copy number (HR = 1.79 per log 10  copies/ml; P  = 0.028) were associated with increased mortality. Among HIV - KS, factors associated with mortality included Karnofsky score <70 (HR = 9.17; P  = 0.045), abnormal chest X-ray (HR = 8.41; P  = 0.025), and higher plasma KSHV copy number (HR = 6.21 per log 10  copies/ml; P  < 0.001). CONCLUSIONS: Although survival rates were better for HIV - KS than HIV + KS, the high mortality rate seen in both groups underscores the urgent need to identify new staging and therapeutic approaches. Factors associated with mortality, including high plasma KSHV, may serve as important targets of therapy.

Effect of Empiric Anti-Mycobacterium tuberculosis Therapy on Survival Among Human Immunodeficiency Virus-Infected Adults Admitted With Sepsis to a Regional Referral Hospital in Uganda.

BACKGROUND: Mycobacterium tuberculosis is the leading cause of bloodstream infection among human immunodeficiency virus (HIV)-infected patients with sepsis in sub-Saharan Africa and is associated with high mortality rates. METHODS: We conducted a retrospective study of HIV-infected adults with sepsis at the Mbarara Regional Referral Hospital in Uganda to measure the proportion who received antituberculosis therapy and to determine the relationship between antituberculosis therapy and 28-day survival. RESULTS: Of the 149 patients evaluated, 74 (50%) had severe sepsis and 48 (32%) died. Of the 55 patients (37%) who received antituberculosis therapy, 19 (35%) died, compared with 29 of 94 (31%) who did not receive such therapy (odds ratio, 1.34; 95% confidence interval [CI], .56-3.18; P = .64). The 28-day survival rates did not differ significantly between these 2 groups (log-rank test, P = .21). Among the 74 patients with severe sepsis, 9 of 26 (35%) who received antituberculosis therapy died, versus 23 of 48 (48%) who did not receive such therapy (odds ratio, 0.58; 95% CI, .21-1.52; P = .27). In patients with severe sepsis, antituberculosis therapy was associated with an improved 28-day survival rate (log-rank test P = .01), and with a reduced mortality rate in a Cox proportional hazards model (hazard ratio, 0.32; 95% CI, .13-.80; P = .03). CONCLUSIONS: Empiric antituberculosis therapy was associated with improved survival rates among patients with severe sepsis, but not among all patients with sepsis.