Ten Years of Surveillance for Invasive Streptococcus pneumoniae during the Era of Antiretroviral Scale-Up and Cotrimoxazole Prophylaxis in Malawi

OBJECTIVE: To document trends in invasive pneumococcal disease (IPD) in a central hospital in Malawi during the period of national scale-up of antiretroviral therapy (ART) and cotrimoxazole prophylaxis. METHODS: Between 1 January 2000 and 31 December 2009 almost 100,000 blood cultures and 40,000 cerebrospinal fluid (CSF) cultures were obtained from adults and children admitted to the Queen Elizabeth Central Hospital, Blantyre, Malawi with suspected severe bacterial infection. RESULTS: 4,445 pneumococcal isolates were obtained over the 10 year period. 1,837 were from children: 885 (19.9%) from blood and 952 (21.4%) from CSF. 2,608 were from adults: 1,813 (40.8%) from blood and 795 (17.9%) from CSF. At the start of the surveillance period cotrimoxazole resistance was 73.8% and at the end was 92.6%. Multidrug resistance (MDR) was present in almost one third of isolates and was constant over time. Free ART was introduced in Malawi in 2004. From 2005 onwards there was a decline in invasive pneumococcal infections with a negative correlation between ART scale-up and the decline in IPD (Pearson's correlation r = -0.91; p<0.001). CONCLUSION: During 2004-2009, national ART scale-up in Malawi was associated with a downward trend in IPD at QECH. The introduction of cotrimoxazole prophylaxis in HIV-infected groups has not coincided with a further increase in pneumococcal cotrimoxazole or multidrug resistance. These data highlight the importance of surveillance for high disease burden infections such as IPD in the region, which will be vital for monitoring pneumococcal conjugate vaccine introduction into national immunisation programmes

High Prevalence of Tuberculosis and Serious Bloodstream Infections in Ambulatory Individuals Presenting for Antiretroviral Therapy in Malawi

Background Tuberculosis (TB) and serious bloodstream infections (BSI) may contribute to the high early mortality observed among patients qualifying for antiretroviral therapy (ART) with unexplained weight loss, chronic fever or chronic diarrhea. Methods and Findings A prospective cohort study determined the prevalence of undiagnosed TB or BSI among ambulatory HIV-infected adults with unexplained weight loss and/or chronic fever, or diarrhea in two routine program settings in Malawi. Subjects with positive expectorated sputum smears for AFB were excluded. Investigations Bacterial and mycobacterial blood cultures, cryptococcal antigen test (CrAg), induced sputum (IS) for TB microscopy and solid culture, full blood count and CD4 lymphocyte count. Among 469 subjects, 52 (11%) had microbiological evidence of TB; 50 (11%) had a positive (non-TB) blood culture and/or positive CrAg. Sixty-five additional TB cases were diagnosed on clinical and radiological grounds. Nontyphoidal Salmonellae (NTS) were the most common blood culture pathogens (29 cases; 6% of participants and 52% of bloodstream isolates). Multivariate analysis of baseline clinical and hematological characteristics found significant independent associations between oral candidiasis or lymphadenopathy and TB, marked CD4 lymphopenia and NTS infection, and severe anemia and either infection, but low positive likelihood ratios (<2 for all combinations). Conclusions We observed a high prevalence of TB and serious BSI, particularly NTS, in a program cohort of chronically ill HIV-infected outpatients. Baseline clinical and hematological characteristics were inadequate predictors of infection. HIV clinics need better rapid screening tools for TB and BSI. Clinical trials to evaluate empiric TB or NTS treatment are required in similar populations

Malawians permit research bronchoscopy due to perceived need for healthcare.

OBJECTIVES: Bronchoalveolar lavage obtained at bronchoscopy is useful for research on pulmonary defence mechanisms. Bronchoscopy involves some discomfort and risk to subjects. We audited the process of consent, experienced adverse effects and reasons for participation among research bronchoscopy volunteers. DESIGN: 100 consecutive volunteer research subjects attending for bronchoscopy, repeat bronchoscopy or routine recruitment clinic were interviewed. Information was gathered about volunteer motivation, perception of the consent process and adverse effects of bronchoscopy. Suggestions for improvement were requested. Responses were themed by a second investigator prior to data analysis. RESULTS: 81 bronchoscopy-experienced subjects (total of 263 procedures) and 19 new volunteers were interviewed. 19 subjects (21%) reported adverse symptoms during or after bronchoscopy, but no symptoms were of sufficient severity that they would not repeat the procedure. The frequency of symptoms was not related to gender, the quality of the lavage or the HIV status of the subject. 76 subjects (94%) reported that the information given pre-procedure was useful and adequate but 43 (56%) had further questions mostly relating to their own results. The reasons given for research participation were access to health assessment (75 subjects), access to treatment when ill (61 subjects), desire to participate in research (15 subjects) and remuneration (6 subjects). 7 subjects complained that the remuneration was inadequate. CONCLUSIONS: The main incentive to participation in research bronchoscopy was access to healthcare. Informed consent and procedure technique were adequate but subjects would value more feedback about individual and project results