Matemba M.,Karonga Prevention Study |
French N.,Karonga Prevention Study |
French N.,London School of Hygiene and Tropical Medicine
Emerging Infectious Diseases | Year: 2011
To determine whether an association exists between group B streptococcus carriage and HIV infection, we recruited 1,857 pregnant women (21.7% HIV positive) from Queen Elizabeth Central Hospital, Blantyre, Malawi. Overall, group B streptococcus carriage was 21.2% and did not differ by HIV status. However, carriage was increased among HIV-positive women with higher CD4 counts. Source
Jahn A.,London School of Hygiene and Tropical Medicine |
Floyd S.,London School of Hygiene and Tropical Medicine |
McGrath N.,London School of Hygiene and Tropical Medicine |
McGrath N.,University of KwaZulu - Natal |
And 6 more authors.
PLoS ONE | Year: 2010
Background: As HIV-related deaths increase in a population the usual association between low socioeconomic status and child mortality may change, particularly as death rates from other causes decline. Methods/Principal Findings: As part of a demographic surveillance system in northern Malawi in 2002-6, covering a population of 32,000, information was collected on socio-economic status of the households. Deaths were classified as HIV/AIDS-related or not by verbal autopsy. Poisson regression models were used to assess the association of socio-economic indicators with all-cause mortality, AIDS-mortality and non-AIDS mortality among children. There were 195 deaths in infants, 109 in children aged 1-4 years, and 38 in children aged 5-15. All-cause child mortality in infants and 1-4 year olds was similar in households with higher and lower socio-economic status. In infants 13% of deaths were attributed to AIDS, and there were no clear trends with socio-economic status for AIDS or non-AIDS causes. For 1-4 year olds 27% of deaths were attributed to AIDS. AIDS mortality was higher among those with better built houses, and lowest in those with income from farming and fishing, whereas non-AIDS mortality was higher in those with worse built houses, lowest in those with income from employment, and decreased with increasing household assets. Conclusions/Significance: In this population, since HIV infection among adults was initially more common among the less poor, childhood mortality patterns have changed. The usual gap in survival between the poor and the less poor has been lost, but because the less poor have been disproportionately affected by HIV, rather than because of relative improvement in the survival of the poorest. © 2010 Jahn et al. Source
Floyd S.,London School of Hygiene and Tropical Medicine |
Marston M.,London School of Hygiene and Tropical Medicine |
Baisley K.,London School of Hygiene and Tropical Medicine |
Wringe A.,London School of Hygiene and Tropical Medicine |
And 9 more authors.
Tropical Medicine and International Health | Year: 2012
Objective To provide a broad and up-to-date picture of the effect of antiretroviral therapy (ART) provision on population-level mortality in Southern and East Africa. Methods Data on all-cause, AIDS and non-AIDS mortality among 15-59year olds were analysed from demographic surveillance sites (DSS) in Karonga (Malawi), Kisesa (Tanzania), Masaka (Uganda) and the Africa Centre (South Africa), using Poisson regression. Trends over time from up to 5years prior to ART roll-out, to 4-6years afterwards, are presented, overall and by age and sex. For Masaka and Kisesa, trends are analysed separately for HIV-negative and HIV-positive individuals. For Karonga and the Africa Centre, trends in AIDS and non-AIDS mortality are analysed using verbal autopsy data. Results For all-cause mortality, overall rate ratios (RRs) comparing the period 2-6years following ART roll-out with the pre-ART period were 0.58 (5.9 vs. 10.2 deaths per 1000 person-years) in Karonga, 0.79 (7.2 vs. 9.1 deaths per 1000 person-years) in Kisesa, 0.61 (6.7 compared with 11.0 deaths per 1000 person-years) in Masaka and 0.79 (14.8 compared with 18.6 deaths per 1000 person-years) in the Africa Centre DSS. The mortality decline was seen only in HIV-positive individuals/AIDS mortality, with no decline in HIV-negative individuals/non-AIDS mortality. Less difference was seen in Kisesa where ART uptake was lower. Conclusions Falls in all-cause mortality are consistent with ART uptake. The largest falls occurred where ART provision has been decentralised or available locally, suggesting that this is important. © 2012 Blackwell Publishing Ltd. Source
Hur Y.-G.,London School of Hygiene and Tropical Medicine |
Hur Y.-G.,Yonsei University |
Crampin A.C.,London School of Hygiene and Tropical Medicine |
Chisambo C.,Karonga Prevention Study |
And 15 more authors.
Clinical and Vaccine Immunology | Year: 2014
A positive gamma interferon (IFN-γ) response to Mycobacterium tuberculosis early secretory antigenic target-6 (ESAT-6)/culture filtrate protein-10 (CFP-10) has been taken to indicate latent tuberculosis (TB) infection, but it may also be due to exposure to environmental nontuberculous mycobacteria in which ESAT-6 homologues are present. We assessed the immune responses to M. tuberculosis ESAT-6 and cross-reactive responses to ESAT-6 homologues of Mycobacterium avium and Mycobacterium kansasii. Archived culture supernatant samples from children at 3 years post-BCG vaccination were tested for cytokine/chemokine responses to M. tuberculosis antigens. Furthermore, the IFN-γ responses to M. tuberculosis antigens were followed up for 40 children at 8 years post-BCG vaccination, and 15 TB patients were recruited as a control group for the M. tuberculosis ESAT-6 response in Malawi. IFN-γ enzyme-linked immunosorbent assays (ELISAs) on supernatants from diluted whole-blood assays, IFN-γ enzyme-linked immunosorbent spot (ELISpot) assays, QuantiFERON TB Gold-In Tube tests, and multiplex bead assays were performed. More than 45% of the responders to M. tuberculosis ESAT-6 showed IFN-γ responses to M. avium and M. kansasii ESAT-6. In response to M. tuberculosis ESAT-6/CFP-10, interleukin 5 (IL-5), IL-9, IL-13, and IL-17 differentiated the stronger IFN-γ responders to M. tuberculosis ESAT-6 from those who preferentially responded to M. kansasii and M. avium ESAT-6. A cytokine/chemokine signature of IL-5, IL-9, IL-13, and IL-17 was identified as a putative immunological biosignature to differentiate latent TB infection from exposure to M. avium and M. kansasii in Malawian children, indicating that this signature might be particularly informative in areas where both TB and exposure to environmental nontuberculous mycobacteria are endemic. Copyright © 2014, American Society for Microbiology. All Rights Reserved. Source
Kaforou M.,Imperial College London |
Wright V.J.,Imperial College London |
Oni T.,Imperial College London |
Oni T.,University of Cape Town |
And 27 more authors.
PLoS Medicine | Year: 2013
Background:A major impediment to tuberculosis control in Africa is the difficulty in diagnosing active tuberculosis (TB), particularly in the context of HIV infection. We hypothesized that a unique host blood RNA transcriptional signature would distinguish TB from other diseases (OD) in HIV-infected and -uninfected patients, and that this could be the basis of a simple diagnostic test.Methods and Findings:Adult case-control cohorts were established in South Africa and Malawi of HIV-infected or -uninfected individuals consisting of 584 patients with either TB (confirmed by culture of Mycobacterium tuberculosis [M.TB] from sputum or tissue sample in a patient under investigation for TB), OD (i.e., TB was considered in the differential diagnosis but then excluded), or healthy individuals with latent TB infection (LTBI). Individuals were randomized into training (80%) and test (20%) cohorts. Blood transcriptional profiles were assessed and minimal sets of significantly differentially expressed transcripts distinguishing TB from LTBI and OD were identified in the training cohort. A 27 transcript signature distinguished TB from LTBI and a 44 transcript signature distinguished TB from OD. To evaluate our signatures, we used a novel computational method to calculate a disease risk score (DRS) for each patient. The classification based on this score was first evaluated in the test cohort, and then validated in an independent publically available dataset (GSE19491).In our test cohort, the DRS classified TB from LTBI (sensitivity 95%, 95% CI [87-100]; specificity 90%, 95% CI [80-97]) and TB from OD (sensitivity 93%, 95% CI [83-100]; specificity 88%, 95% CI [74-97]). In the independent validation cohort, TB patients were distinguished both from LTBI individuals (sensitivity 95%, 95% CI [85-100]; specificity 94%, 95% CI [84-100]) and OD patients (sensitivity 100%, 95% CI [100-100]; specificity 96%, 95% CI [93-100]).Limitations of our study include the use of only culture confirmed TB patients, and the potential that TB may have been misdiagnosed in a small proportion of OD patients despite the extensive clinical investigation used to assign each patient to their diagnostic group.Conclusions:In our study, blood transcriptional signatures distinguished TB from other conditions prevalent in HIV-infected and -uninfected African adults. Our DRS, based on these signatures, could be developed as a test for TB suitable for use in HIV endemic countries. Further evaluation of the performance of the signatures and DRS in prospective populations of patients with symptoms consistent with TB will be needed to define their clinical value under operational conditions.Please see later in the article for the Editors' Summary. © 2013 Kaforou et al. Source