Defective Pneumococcal-Specific Th1 Responses in HIV-Infected Adults Precedes a Loss of Control of Pneumococcal Colonization

Glennie, Sarah; Banda, Dominic H.; Gould, Kate; Hinds, Jason; Kamng’ona, Arox W; Everett, Dean; Williams, Neil; Heyderman, Robert S.

doi:10.1093/cid/cis842

Cited by 49 publications

(68 citation statements)

References 44 publications

(69 reference statements)

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“…Moreover, despite few studies describing higher levels of isotype switched B cells in treated patients compared to naive [27] and differentiate from HIV negative individuals [28], our study confirmed more recent authors [29], underlining the need for further investigation on this specific memory subset.…”

Section: Discussionsupporting

confidence: 85%

Alterations in memory B cell subsets upon immunization against Streptococcus pneumoniae in HIV-1 infected adults

et al. 2015

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Section: Discussionsupporting

confidence: 85%

Alterations in memory B cell subsets upon immunization against Streptococcus pneumoniae in HIV-1 infected adults

et al. 2015

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“…NK cells, the main producers of IFN-γ, were previously shown to be less responsive to ex vivo stimulation with E. coli or NTS in HIV-positive patients [18]. Furthermore, IFN-γ production in response to pneumococcal antigens was reduced in CD4 T cells from HIV patients [19]. Our findings extend the relevance of these findings to a whole blood stimulation model and a wider range of bacterial agonists.…”

Section: Discussionsupporting

confidence: 78%

The impact of HIV infection on blood leukocyte responsiveness to bacterial stimulation in asymptomatic patients and patients with bloodstream infection

Huson

Hoogendijk

Vos

et al. 2016

Journal of the International AIDS Society

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IntroductionHIV-induced changes in cytokine responses to bacteria may influence susceptibility to bacterial infections and the consequent inflammatory response.MethodsWe examined the impact of HIV on whole blood responsiveness to bacterial stimulation in asymptomatic subjects and patients with bacterial bloodstream infection (BSI). Whole blood was stimulated ex vivo with two bacterial Toll-like receptor agonists (lipopolysaccharide and lipoteichoic acid) and two pathogens (Streptococcus pneumoniae and non-typhoidal Salmonella), which are relevant in HIV-positive patients. Production of interferon-γ, tumour necrosis factor-α, interleukin-1β and interleukin-6 was used as a read-out.ResultsIn asymptomatic subjects, HIV infection was associated with reduced interferon-γ, release after stimulation and priming of the pro-inflammatory cytokine response to non-typhoidal Salmonella. In patients with BSI, we found no such priming effect, nor was there evidence for more profound sepsis-induced immunosuppression in BSI patients with HIV co-infection.ConclusionsThese results suggest a complex effect of HIV on leukocyte responses to bacteria. However, in patients with sepsis, leukocyte responses were equally blunted in patients with and without HIV infection.

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“…HIV infected adults in our setting have higher rates of pneumococcal carriage than HIV uninfected individuals [Kamng’ona et al 2013 unpublished]. The high rates of bacterial meningitis in HIV positive adults may be potentially related to increased susceptibility to S.pneumoniae infection via altered mucosal and cell-mediated immunity [28]. Immunocompromise has been associated with ABM in adults, but HIV has not to date been proven to be an independent risk factor [9], [23], [24], [29].…”

Section: Discussionmentioning

confidence: 99%

High Mortality amongst Adolescents and Adults with Bacterial Meningitis in Sub-Saharan Africa: An Analysis of 715 Cases from Malawi

et al. 2013

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Mortality from bacterial meningitis in African adults is significantly higher than those in better resourced settings and adjunctive therapeutic interventions such as dexamethasone and glycerol have been shown to be ineffective. We conducted a study analysing data from clinical trials of bacterial meningitis in Blantyre, Malawi to investigate the clinical parameters associated with this high mortality.MethodsWe searched for all clinical trials undertaken in Blantyre investigating bacterial meningitis from 1990 to the current time and combined the data from all included trial datasets into one database. We used logistic regression to relate individual clinical parameters to mortality. Adults with community acquired bacterial meningitis were included if the CSF culture isolate was consistent with meningitis or if the CSF white cell count was >100 cells/mm3 (>50% neutrophils) in HIV negative participants and >5 cells/mm3 in HIV positive participants. Outcome was measured by mortality at discharge from hospital (after 10 days of antibiotic therapy) and community follow up (day 40).ResultsSeven hundred and fifteen episodes of bacterial meningitis were evaluated. The mortality rate was 45% at day 10 and 54% at day 40. The most common pathogens were S.pneumoniae (84% of positive CSF isolates) and N.meningitidis (4%). 607/694 (87%) participants tested were HIV antibody positive. Treatment delays within the hospital system were marked. The median presenting GCS was 12/15, 17% had GCS<8 and 44.9% had a seizure during the illness. Coma, seizures, tachycardia and anaemia were all significantly associated with mortality on multivariate analysis. HIV status and pneumococcal culture positivity in the CSF were not associated with mortality. Adults with community acquired bacterial meningitis in Malawi present with a severe clinical phenotype. Predictors of high mortality are different to those seen in Western settings. Optimising in-hospital care and minimising treatment delays presents an opportunity to improve outcomes considerably.

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Defective Pneumococcal-Specific Th1 Responses in HIV-Infected Adults Precedes a Loss of Control of Pneumococcal Colonization

Cited by 49 publications

References 44 publications

Alterations in memory B cell subsets upon immunization against Streptococcus pneumoniae in HIV-1 infected adults

Alterations in memory B cell subsets upon immunization against Streptococcus pneumoniae in HIV-1 infected adults

The impact of HIV infection on blood leukocyte responsiveness to bacterial stimulation in asymptomatic patients and patients with bloodstream infection

High Mortality amongst Adolescents and Adults with Bacterial Meningitis in Sub-Saharan Africa: An Analysis of 715 Cases from Malawi

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