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  1. Article ; Online: Interventions to reduce deaths in people living with HIV admitted to hospital in low- and middle-income countries

    Rachael M Burke / Hussein H Twabi / Cheryl Johnston / Marriott Nliwasa / Ankur Gupta-Wright / Katherine Fielding / Nathan Ford / Peter MacPherson / Elizabeth L Corbett

    PLOS Global Public Health, Vol 3, Iss 2, p e

    A systematic review.

    2023  Volume 0001557

    Abstract: People living with HIV (PLHIV) admitted to hospital have a high risk of death. We systematically appraised evidence for interventions to reduce mortality among hospitalised PLHIV in low- and middle-income countries (LMICs). Using a broad search strategy ... ...

    Abstract People living with HIV (PLHIV) admitted to hospital have a high risk of death. We systematically appraised evidence for interventions to reduce mortality among hospitalised PLHIV in low- and middle-income countries (LMICs). Using a broad search strategy with terms for HIV, hospitals, and clinical trials, we searched for reports published between 1 Jan 2003 and 23 August 2021. Studies of interventions among adult HIV positive inpatients in LMICs were included if there was a comparator group and death was an outcome. We excluded studies restricted only to inpatients with a specific diagnosis (e.g. cryptococcal meningitis). Of 19,970 unique studies identified in search, ten were eligible for inclusion with 7,531 participants in total: nine randomised trials, and one before-after study. Three trials investigated systematic screening for tuberculosis; two showed survival benefit for urine TB screening vs. no urine screening, and one which compared Xpert MTB/RIF versus smear microscopy showed no difference in survival. One before-after study implemented 2007 WHO guidelines to improve management of smear negative tuberculosis in severely ill PLHIV, and showed survival benefit but with high risk of bias. Two trials evaluated complex interventions aimed at overcoming barriers to ART initiation in newly diagnosed PLHIV, one of which showed survival benefit and the other no difference. Two small trials evaluated early inpatient ART start, with no difference in survival. Two trials investigated protocol-driven fluid resuscitation for emergency-room attendees meeting case-definitions for sepsis, and showed increased mortality with use of a protocol for fluid administration. In conclusion, ten studies published since 2003 investigated interventions that aimed to reduce mortality in hospitalised adults with HIV, and weren't restricted to people with a defined disease diagnosis. Inpatient trials of diagnostics, therapeutics or a package of interventions to reduce mortality should be a research priority. Trial registration: ...
    Keywords Public aspects of medicine ; RA1-1270
    Subject code 610
    Language English
    Publishing date 2023-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Impact of active case-finding for tuberculosis on case-notifications in Blantyre, Malawi

    Helena R A Feasey / McEwen Khundi / Rebecca Nzawa Soko / Christian Bottomley / Lingstone Chiume / Helen E D Burchett / Marriott Nliwasa / Hussein H Twabi / James A Mpunga / Peter MacPherson / Elizabeth L Corbett

    PLOS Global Public Health, Vol 3, Iss 12, p e

    A community-based cluster-randomised trial (SCALE).

    2023  Volume 0002683

    Abstract: Active case-finding (ACF) for tuberculosis can help find the "missing millions" with undiagnosed tuberculosis. In a cluster-randomised trial, we investigated impact of ACF on case-notifications in Blantyre, Malawi, where ACF has been intensively ... ...

    Abstract Active case-finding (ACF) for tuberculosis can help find the "missing millions" with undiagnosed tuberculosis. In a cluster-randomised trial, we investigated impact of ACF on case-notifications in Blantyre, Malawi, where ACF has been intensively implemented following 2014 estimates of ~1,000 per 100,000 adults with undiagnosed TB. Following a pre-intervention prevalence survey (May 2019 to March 2020), constrained randomisation allocated neighbourhoods to either door-to-door ACF (sputum microscopy for reported cough >2 weeks) or standard-of-care (SOC). Implementation was interrupted by COVID-19. Cluster-level bacteriologically-confirmed case-notification rate (CNR) ratio within 91 days of ACF was our redefined primary outcome; comparison between arms used Poisson regression with random effects. Secondary outcomes were 91-day CNR ratios comparing all tuberculosis registrations and all non-ACF registrations. Interrupted time series (ITS) analysis of CNRs in the SOC arm examined prevalence survey impact. (ISRCTN11400592). 72 clusters served by 10 study-supported tuberculosis registration centres were randomised to ACF (261,244 adults, 58,944 person-years follow-up) or SOC (256,713 adults, 52,805 person-years). Of 1,192 ACF participants, 13 (1.09%) were smear-positive. Within 91 days, 113 (42 bacteriologically-confirmed) and 108 (33 bacteriologically-confirmed) tuberculosis patients were identified as ACF or SOC cluster residents, respectively. There was no difference by arm, with adjusted 91-day CNR ratios 1.12 (95% CI: 0.61-2.07) for bacteriologically-confirmed tuberculosis; 0.93 (95% CI: 0.68-1.28) for all tuberculosis registrations; and 0.86 (95%CI: 0.63-1.16) for non-ACF (routinely) diagnosed. Of 7,905 ACF and 7,992 SOC pre-intervention survey participants, 12 (0.15%) and 17 (0.21%), respectively, had culture/Xpert-confirmed tuberculosis. ITS analysis showed no survey impact on SOC CNRs. Despite residual undiagnosed tuberculosis of 150 per 100,000 population, there was no increase in tuberculosis ...
    Keywords Public aspects of medicine ; RA1-1270
    Subject code 310
    Language English
    Publishing date 2023-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Prevalence of bacteriologically-confirmed pulmonary tuberculosis in urban Blantyre, Malawi 2019-20

    Helena R A Feasey / McEwen Khundi / Rebecca Nzawa Soko / Emily Nightingale / Rachael M Burke / Marc Y R Henrion / Mphatso D Phiri / Helen E Burchett / Lingstone Chiume / Marriott Nliwasa / Hussein H Twabi / James A Mpunga / Peter MacPherson / Elizabeth L Corbett

    PLOS Global Public Health, Vol 3, Iss 10, p e

    Substantial decline compared to 2013-14 national survey.

    2023  Volume 0001911

    Abstract: Recent evidence shows rapidly changing tuberculosis (TB) epidemiology in Southern and Eastern Africa, with need for subdistrict prevalence estimates to guide targeted interventions. We conducted a pulmonary TB prevalence survey to estimate current TB ... ...

    Abstract Recent evidence shows rapidly changing tuberculosis (TB) epidemiology in Southern and Eastern Africa, with need for subdistrict prevalence estimates to guide targeted interventions. We conducted a pulmonary TB prevalence survey to estimate current TB burden in Blantyre city, Malawi. From May 2019 to March 2020, 115 households in middle/high-density residential Blantyre, were randomly-selected from each of 72 clusters. Consenting eligible participants (household residents ≥ 18 years) were interviewed, including for cough (any duration), and offered HIV testing and chest X-ray; participants with cough and/or abnormal X-ray provided two sputum samples for microscopy, Xpert MTB/Rif and mycobacterial culture. TB disease prevalence and risk factors for prevalent TB were calculated using complete-case analysis, multiple imputation, and inverse probability weighting. Of 20,899 eligible adults, 15,897 (76%) were interviewed, 13,490/15,897 (85%) had X-ray, and 1,120/1,394 (80%) sputum-eligible participants produced at least one specimen, giving 15,318 complete cases (5,895, 38% men). 29/15,318 had bacteriologically-confirmed TB (189 per 100,000 complete-case (cc) / 150 per 100,000 with inverse weighting (iw)). Men had higher burden (cc: 305 [95% CI:144-645] per 100,000) than women (cc: 117 [95% CI:65-211] per 100,000): cc adjusted odds ratio (aOR) 2.70 (1.26-5.78). Other significant risk factors for prevalent TB on complete-case analysis were working age (25-49 years) and previous TB treatment, but not HIV status. Multivariable analysis of imputed data was limited by small numbers, but previous TB and age group 25-49 years remained significantly associated with higher TB prevalence. Pulmonary TB prevalence for Blantyre was considerably lower than the 1,014 per 100,000 for urban Malawi in the 2013-14 national survey, at 150-189 per 100,000 adults, but some groups, notably men, remain disproportionately affected. TB case-finding is still needed for TB elimination in Blantyre, and similar urban centres, but should focus on ...
    Keywords Public aspects of medicine ; RA1-1270
    Subject code 331
    Language English
    Publishing date 2023-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Design and protocol for a cluster randomised trial of enhanced diagnostics for tuberculosis screening among people living with HIV in hospital in Malawi (CASTLE study).

    Rachael M Burke / Saulos Nyirenda / Hussein H Twabi / Marriott Nliwasa / Elizabeth Joekes / Naomi Walker / Rose Nyirenda / Ankur Gupta-Wright / Katherine Fielding / Peter MacPherson / Elizabeth L Corbett

    PLoS ONE, Vol 17, Iss 1, p e

    2022  Volume 0261877

    Abstract: Background People living with HIV (PLHIV) have a high risk of death if hospitalised in low-income countries. Tuberculosis has long been the leading cause of admission and death, in part due to suboptimal diagnostics. Two promising new diagnostic tools ... ...

    Abstract Background People living with HIV (PLHIV) have a high risk of death if hospitalised in low-income countries. Tuberculosis has long been the leading cause of admission and death, in part due to suboptimal diagnostics. Two promising new diagnostic tools are digital chest Xray with computer-aided diagnosis (DCXR-CAD) and urine testing with Fujifilm SILVAMP LAM (FujiLAM). Neither test has been rigorously evaluated among inpatients. Test characteristics may be complementary, with FujiLAM especially sensitive for disseminated tuberculosis and DCXR-CAD especially sensitive for pulmonary tuberculosis, making combined interventions of interest. Design and methods An exploratory unblinded, single site, two-arm cluster randomised controlled trial, with day of admission as the unit of randomisation. A third, smaller, integrated cohort arm (4:4:1 random allocation) contributes to understanding case-mix, but not trial outcomes. Participants are adults living with HIV not currently on TB treatment. The intervention (DCXR-CAD plus urine FujiLAM plus usual care) is compared to usual care alone. The primary outcome is proportion of participants started on tuberculosis treatment by day 56, with secondary outcomes of mortality (time to event) measured to to 56 days from enrolment, proportions with undiagnosed tuberculosis at death or hospital discharge and comparing proportions with enrolment-day tuberculosis treatment initiation. Discussion Both DCXR-CAD and FujiLAM have potential clinical utility and may have complementary diagnostic performance. To our knowledge, this is the first randomised trial to evaluate these tests among hospitalised PLHIV.
    Keywords Medicine ; R ; Science ; Q
    Subject code 310
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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