Complement Factor H Levels Associate With Plasmodium falciparum Malaria Susceptibility and Severity.

BACKGROUND: Plasmodium falciparum may evade complement-mediated host defense by hijacking complement Factor H (FH), a negative regulator of the alternative complement pathway. Plasma levels of FH vary between individuals and may therefore influence malaria susceptibility and severity. METHODS: We measured convalescent FH plasma levels in 149 Gambian children who had recovered from uncomplicated or severe P. falciparum malaria and in 173 healthy control children. We compared FH plasma levels between children with malaria and healthy controls, and between children with severe (n = 82) and uncomplicated malaria (n = 67). We determined associations between FH plasma levels and laboratory features of severity and used multivariate analyses to examine associations with FH when accounting for other determinants of severity. RESULTS: FH plasma levels differed significantly between controls, uncomplicated malaria cases, and severe malaria cases (mean [95% confidence interval], 257 [250 to 264], 288 [268 to 309], and 328 [313 to 344] µg/mL, respectively; analysis of variance P < .0001). FH plasma levels correlated with severity biomarkers, including lactate, parasitemia, and parasite density, but did not correlate with levels of PfHRP2, which represent the total body parasite load. Associations with severity and lactate remained significant when adjusting for age and parasite load. CONCLUSIONS: Natural variation in FH plasma levels is associated with malaria susceptibility and severity. A prospective study will be needed to strengthen evidence for causation, but our findings suggest that interfering with FH binding by P. falciparum might be useful for malaria prevention or treatment.

Publisher Correction: Non-tuberculous Mycobacteria isolated from Pulmonary samples in sub-Saharan Africa - A Systematic Review and Meta Analyses.

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Non-tuberculous Mycobacteria isolated from Pulmonary samples in sub-Saharan Africa - A Systematic Review and Meta Analyses.

Pulmonary non-tuberculous mycobacterial (NTM) disease epidemiology in sub-Saharan Africa is not as well described as for pulmonary tuberculosis. Earlier reviews of global NTM epidemiology only included subject-level data from one sub-Saharan Africa country. We systematically reviewed the literature and searched PubMed, Embase, Popline, OVID and Africa Wide Information for articles on prevalence and clinical relevance of NTM detection in pulmonary samples in sub-Saharan Africa. We applied the American Thoracic Society/Infectious Disease Society of America criteria to differentiate between colonisation and disease. Only 37 articles from 373 citations met our inclusion criteria. The prevalence of pulmonary NTM colonization was 7.5% (95% CI: 7.2%-7.8%), and 75.0% (2325 of 3096) occurred in males, 16.5% (512 of 3096) in those previously treated for tuberculosis and Mycobacterium avium complex predominated (27.7% [95% CI: 27.2-28.9%]). In seven eligible studies, 27.9% (266 of 952) of participants had pulmonary NTM disease and M. kansasii with a prevalence of 69.2% [95% CI: 63.2-74.7%] was the most common cause of pulmonary NTM disease. NTM species were unidentifiable in 29.2% [2,623 of 8,980] of isolates. In conclusion, pulmonary NTM disease is a neglected and emerging public health disease and enhanced surveillance is required.

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.

Enhanced anti-mycobacterial immunity in children with erythema nodosum and a positive tuberculin skin test.

Erythema nodosum (EN) may follow a variety of infections, but in regions with a high prevalence of tuberculosis, is frequently associated with a positive tuberculin skin test (TST) and tuberculosis infection. We aimed to investigate the immunological differences between patients with EN as a manifestation of primary tuberculosis, and those with progressive pulmonary tuberculosis (PTB) or asymptomatic infection. We studied the inflammatory response to both mycobacterial and non-mycobacterial antigens in 11 children with EN associated with a positive TST, 22 children with culture-confirmed tuberculosis, and 53 healthy skin test-positive children. In addition, we evaluated functional anti-mycobacterial immunity using an ex vivo assay of mycobacterial growth restriction in five children with EN and 15 with PTB. Patients with EN were distinguished by enhanced mycobacterial growth restriction on the functional assay, which was associated with a markedly increased production of IFNgamma in response to stimulation with purified protein derivative of Mycobacterium tuberculosis. Children presenting with EN and a positive TST show evidence of responses associated with enhanced anti-mycobacterial immunity.