Rationale: In the context of rapid antiretroviral therapy rollout and an increasing burden of noncommunicable diseases, there are few contemporary data describing the etiology and outcome of community-acquired pneumonia (CAP) in sub-Saharan Africa. Objectives: To describe the current etiology of CAP in Malawi and identify risk factors for mortality. Methods: We conducted a prospective observational study of adults hospitalized with CAP to a teaching hospital in Blantyre, Malawi. Etiology was defined by blood culture, Streptococcus pneumoniae urinary antigen detection, sputum mycobacterial culture and Xpert MTB/RIF, and nasopharyngeal aspirate multiplex PCR. Measurements and Main Results: In 459 patients (285 [62.1%] males; median age, 34.7 [interquartile range, 29.4-41.9] yr), 30-day mortality was 14.6% (64/439) and associated with male sex (adjusted odds ratio, 2.60 [95% confidence interval, 1.17-5.78]), symptom duration greater than 7 days (2.78 [1.40-5.54]), tachycardia (2.99 [1.48-6.06]), hypoxemia (4.40 [2.03-9.51]), and inability to stand (3.59 [1.72-7.50]). HIV was common (355/453; 78.4%), frequently newly diagnosed (124/355; 34.9%), but not associated with mortality. S. pneumoniae (98/458; 21.4%) and Mycobacterium tuberculosis (75/326; 23.0%) were the most frequently identified pathogens. Viral infection occurred in 32.6% (148/454) with influenza (40/454; 8.8%) most common. Bacterial-viral coinfection occurred in 9.1% (28/307). Detection of M. tuberculosis was associated with mortality (adjusted odds ratio, 2.44 [1.19-5.01]). Conclusions: In the antiretroviral therapy era, CAP in Malawi remains predominantly HIV associated, with a large proportion attributable to potentially vaccine-preventable pathogens. Strategies to increase early detection and treatment of tuberculosis and improve supportive care, in particular the correction of hypoxemia, should be evaluated in clinical trials to address CAP-associated mortality.

Background:The impact of human immunodeficiency virus (HIV) infection on influenza incidence and severity in adults in sub-Saharan Africa is unclear. Seasonal influenza vaccination is recommended for HIV-infected persons in developed settings but is rarely implemented in Africa. Methods:We conducted a prospective cohort study to compare the incidence of laboratory-confirmed influenza illness between HIV-infected and HIV-uninfected adults in Blantyre, Malawi. In a parallel case-control study, we explored risk factors for severe influenza presentation of severe (hospitalized) lower respiratory tract infection, and mild influenza (influenza-like illness [ILI]). Results:The cohort study enrolled 608 adults, of whom 360 (59%) were HIV infected. Between April 2013 and March 2015, 24 of 229 ILI episodes (10.5%) in HIV-infected and 5 of 119 (4.2%) in HIV-uninfected adults were positive for influenza by means of polymerase chain reaction (incidence rate, 46.0 vs 14.5 per 1000 person-years; incidence rate ratio, 2.75; 95% confidence interval, 1.02-7.44; P = .03; adjusted for age, sex, household crowding, and food security). In the case-control study, influenza was identified in 56 of 518 patients (10.8%) with hospitalized lower respiratory tract infection, and 88 or 642 (13.7%) with ILI. The HIV prevalence was 69.6% and 29.6%, respectively, among influenza-positive case patients and controls. HIV was a significant risk factor for severe influenza (odds ratio, 4.98; 95% confidence interval, 2.09-11.88; P < .001; population-attributable fraction, 57%; adjusted for season, sanitation facility, and food security). Conclusions:HIV is an important risk factor for influenza-associated ILI and severe presentation in this high-HIV prevalence African setting. Targeted influenza vaccination of HIV-infected African adults should be reevaluated, and the optimal mechanism for vaccine introduction in overstretched health systems needs to be determined.

BackgroundAlthough annual vaccination of at-risk groups is the cornerstone of influenza prevention in many developed settings, it is unavailable in most sub-Saharan African countries. Since 70% of the estimated total population of HIV-infected persons reside in these countries, they might be an important group for whom policy makers could target influenza control strategies. This study aimed to determine the impact of HIV on the burden and severity of influenza illness in adults in a setting with high HIV prevalence.MethodsAt the Queen Elizabeth Central Hospital, Blantyre, Malawi, we conducted a prospective cohort study between April 1, 2013, and March 31, 2015, to compare influenza incidence between HIV-infected and HIV-uninfected adults. We also did a case-control study of adults with mild influenza (influenza-like illness) and severe influenza (admission to hospital with lower respiratory tract infection) to explore risk factors for severe influenza presentation. Poisson and unconditional logistic regression models, respectively, were performed.Findings608 adults were enrolled in the cohort study, of whom 360 (59%) were HIV-reactive (median CD4 count 390 cells per μL [IQR 244–547]). 24 (11%) of 229 episodes of influenza-like illness in HIV-infected and five (4%) of 119 in HIV-uninfected adults were influenza PCR positive (incidence rates 46 vs 15 per 1000 person-years, incidence rate ratio 2·75 [95% CI 1·02–7·44]). In the case-control study, 56 (11%) of 518 patients admitted with lower respiratory tract infection and 88 (14%) of 642 patients with influenza-like illness were influenza PCR positive. HIV prevalence in the influenza-positive cases and controls were 70% (39/56) and 30% (26/88), respectively. HIV was a significant risk factor for severe influenza presentation (odds ratio 4·98 [95% CI 2·09–11·88], population attributable fraction 57%). There was a tendency towards increased incidence and severity in individuals with CD4 count less than 200 cells per μL.InterpretationIn a setting with high HIV prevalence, HIV infection is an important risk factor for acquiring influenza infection and for severe presentation. Individuals with advanced immunosuppression can be particularly vulnerable. These results present a strong case to policy makers to consider targeted vaccination policy in HIV-infected adults in sub-Saharan Africa. However, the optimum mechanism for vaccine introduction and evaluation in overstretched health systems will need to be determined.FundingWellcome Trust.

Introduction: The impact of HIV infection on influenza incidence and presentation in adults in sub-Saharan Africa is unclear. Although seasonal influenza vaccination is recommended for HIV-infected persons in developed settings, it is not part of routine HIV care in Africa.