Life-threatening bacteraemia in HIV-1 seropositive adults admitted to hospital in Nairobi, Kenya

Gilks, Charles F.; Brindle, Richard; Otieno, L S; Simani, P M; Newnham, Robert; Bhatt, Sunil; Gn, Lule; Okelo, G. B. A.; Watkins, William A.; Waiyaki, Peter

doi:10.1016/0140-6736(90)92096-z

Cited by 279 publications

(111 citation statements)

References 16 publications

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“…These data suggested that an important function of IL-17 is to orchestrate immune responses that limit bacterial dissemination from the intestinal mucosa. SIV selectively impaired this arm of the immune response, which provides an attractive explanation as to why people with HIV are at an increased risk of developing NTS bacteremia [35][36][37] . This SIV-mediated defect in mucosal barrier function may also help explain the presence of lipopolysaccharide in the circulation of people with HIV 38 .…”

Section: Discussionmentioning

confidence: 99%

Simian immunodeficiency virus–induced mucosal interleukin-17 deficiency promotes Salmonella dissemination from the gut

Raffatellu

Santos

Verhoeven

et al. 2008

Nat Med

510

557

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Salmonella typhimurium causes a localized enteric infection in immunocompetent individuals, whereas HIV-infected individuals develop a life-threatening bacteremia. Here we show that simian immunodeficiency virus (SIV) infection results in depletion of T helper type 17 (T H 17) cells in the ileal mucosa of rhesus macaques, thereby impairing mucosal barrier functions to S. typhimurium dissemination. In SIV-negative macaques, the gene expression profile induced by S. typhimurium in ligated ileal loops was dominated by T H 17 responses, including the expression of interleukin-17 (IL-17) and IL-22. T H 17 cells were markedly depleted in SIV-infected rhesus macaques, resulting in blunted T H 17 responses to S. typhimurium infection and increased bacterial dissemination. IL-17 receptor-deficient mice showed increased systemic dissemination of S. typhimurium from the gut, suggesting that IL-17 deficiency causes defects in mucosal barrier function. We conclude that SIV infection impairs the IL-17 axis, an arm of the mucosal immune response preventing systemic microbial dissemination from the gastrointestinal tract. A.G. served as consultant for the presentation of NTS bacteremia in African subjects. J.K.K. served as collaborator on studies with Il17ra −/− mice and provided useful comments on the experimental design. S.D. designed and supervised the SIV infections of rhesus macaques, blood sample scheduling, macaque protocols, processing and cell isolations for flow cytometry and DNA microarray analyses. A.J.B. was responsible for the experimental design and supervision of mouse studies, ligated ileal loop experiments in rhesus macaques, macaque protocols and analysis of host responses to Salmonella infection. A.J.B. collected tissue during the ligated ileal loop surgery and was responsible for the final manuscript preparation. A.J.B. and S.D. provided financial support for the study and equally contributed to the experimental design, supervision and data interpretation. Although nontyphoidal Salmonella serotypes (NTS) are common agents causing acute foodborne disease worldwide, it is unusual to isolate them from the blood of adults, because in immunocompetent individuals these pathogens remain localized to the intestine and cause a self-limiting gastroenteritis 1 . However, in people with underlying immunosuppression, NTS may spread beyond the intestine and reach the bloodstream, a serious complication known as NTS bacteremia2. The rise in the number of people with AIDS in sub-Saharan Africa has led to a dramatic increase in the frequency of NTS bacteremia3. In marked contrast to the pre-AIDS era4, NTS is currently a leading cause of hospital admission of adults and among the most common bacterial blood isolates from hospitalized adults in sub-Saharan Africa5, the vast majority of whom are HIV positive 3 . NTS infection in HIV-positive African adults is associated with high acute mortality rates (47%) 6 . Although the occurrence of NTS bacteremia in HIV-positive people is well documented, there are no reports inv...

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Section: Discussionmentioning

confidence: 99%

Simian immunodeficiency virus–induced mucosal interleukin-17 deficiency promotes Salmonella dissemination from the gut

Raffatellu

Santos

Verhoeven

et al. 2008

Nat Med

510

557

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“…Asymptomatic subjects with HIV-2 infection were found to be immunologically damaged, resulting in a depressed number of CD4 cells and low responses to immunization with KLH, a neoantigen. The poor antibody responses, which are also seen in the early stage of HIV-1 infection [21], may explain why asymptomatic subjects may be susceptible to bacterial septicaemia [8], Thus, if prophylactic immunization is to be considered in this group, pneumococcal or other vaccines should be given as early as possible after the diagnosis of HIV infection. It is also of interest that delayed hypersensitivity reactions, as manifest by positive skin tests, were intact in most asymptomatic subjects.…”

Section: Discussionmentioning

confidence: 99%

“…The virus infects and damages both CD4 [2] and antigen-processing eells [3]. The upshot of these effects is anergy to skin test antigens [4], low lymphocyte proiiferative responses to both mitogens and antigens, together with impaired production of cytokines [5], and poor control of viral [6] and bacterial pathogens such as Mycobacterium tuberculosis [7] and Streptococcus pneumoniae [8]. B cell responses are also deranged, resulting in high serum immunoglobulin levels [9] and abnormally low responses to some immunogens, including vaccines [10].…”

Section: Introductionmentioning

confidence: 99%

Immunological responses of Gambians in relation to clinical stage of HIV-2 disease

Whittle

Egboga

Todd

et al. 1993

Clinical and Experimental Immunology

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SUMMARYThis study describes a broad spectrum of cellular and antibody-mediated immune responses found in 28 asymptomatic and 37 symptomatic Gambian patients with HIV-2 infection. It shows that these responses vary according to the stage of infection as described by three clinical staging systems. The first system was a local one based on the signs used for the WHO Bangui clinical definition of AIDS, the second, suggested by WHO, was based on a performance scale, and the third was that used by the Centre for Disease Control. Asymptomatic patients had significantly lower mean CD4 counts, lymphoproliferative and interferon-gamma (IFN-y) responses and lower IgG and IgM antibody responses to keyhole limpet haemocyanin (KLH) than controls. These measurements and the size of the skin test reaction to purified protein derivative (PPD) or Candida antigen declined significantly according to the stage of infection. Mean values of the serological markers (82-microglobulin and neopterin and antibody titres to Epstein-Barr virus capsid antigen (EBVCA) rose significantly according to severity of disease. The Gambian or WHO clinical staging systems, which are easy and cheap to apply, may serve as an alternative to sophisticated and expensive immunological measurements when trying to stage disease and prediet prognosis.

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“…Further evidence for the importance of cellular immunity in protecting against Salmonella in man is shown by the high frequency of severe Salmonella infections in individuals with defects in the IL-12/23-IFN-γ axis (11,12), IFN-γ from CD4 + lymphocytes and NK cells being important for activating macrophages to produce an oxidative burst. Both in Africa and worldwide, individuals with HIV/AIDS, especially those with low CD4 + lymphocyte counts (13), are particularly vulnerable to fatal NTS infection (1,(14)(15)(16).…”

mentioning

confidence: 99%

Importance of antibody and complement for oxidative burst and killing of invasive nontyphoidalSalmonellaby blood cells in Africans

Gondwe

Molyneux

Goodall

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

118

133

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Bacteremia caused by nontyphoidal strains of Salmonella is endemic among African children. Case-fatality rates are high and antibiotic resistance increasing, but no vaccine is currently available. T cells are important for clearance of Salmonella infection within macrophages, but in Africa, invasive Salmonella disease usually manifests in the blood and affects children between 4 months and 2 y of age, when anti- Salmonella antibody is absent. We have previously found a role for complement-fixing bactericidal antibody in protecting these children. Here we show that opsonic activity of antibody and complement is required for oxidative burst and killing of Salmonella by blood cells in Africans. Induction of neutrophil oxidative burst correlated with anti- Salmonella IgG and IgM titers and C3 deposition on bacteria and was significantly lower in African children younger than 2 y compared with older children. Preopsonizing Salmonella with immune serum overcame this deficit, indicating a requirement for antibody and/or complement. Using different opsonization procedures, both antibody and complement were found to be necessary for optimal oxidative burst, phagocytosis and killing of nontyphoidal Salmonella by peripheral blood cells in Africans. Although most strains of African nontyphoidal Salmonella can be killed with antibody and complement alone, phagocytes in the presence of specific antibody and complement can kill strains resistant to killing by immune serum. These findings increase the likelihood that an antibody-inducing vaccine will protect against invasive nontyphoidal Salmonella disease in African children.

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Life-threatening bacteraemia in HIV-1 seropositive adults admitted to hospital in Nairobi, Kenya

Cited by 279 publications

References 16 publications

Simian immunodeficiency virus–induced mucosal interleukin-17 deficiency promotes Salmonella dissemination from the gut

Simian immunodeficiency virus–induced mucosal interleukin-17 deficiency promotes Salmonella dissemination from the gut

Immunological responses of Gambians in relation to clinical stage of HIV-2 disease

Importance of antibody and complement for oxidative burst and killing of invasive nontyphoidalSalmonellaby blood cells in Africans

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