Point-of-care strategies to improve tuberculosis care among severely immunocompromised HIV-infected patients in Ghana

Johanna Åhsberg

doi:10.21996/qs6v-rh74

Point-of-care strategies to improve tuberculosis care among severely immunocompromised HIV-infected patients in Ghana

Johanna Åhsberg

Publikation: Afhandling › Ph.d.-afhandling

176 Downloads (Pure)

Abstract

HIV-associeret TB er forbundet med høj risiko for tidlig død. På grund af den højeforekomst af TB udenfor lungerne, dissemineret TB og sputumfattig lunge-TB er detnødvendigt at supplere rutine diagnostik med ikke-sputumbaseret diagnostik. Med denneafhandling ønskede vi at identificere patientnære strategier, der kan forbedre diagnostik afTB og prognose blandt patienter med fremskreden HIV.

I artikel I så vi på TB-kaskaden før og under COVID-19-pandemien ved tre hospitaler i Ghana. I artikel II evaluerede vi effekten af en pragmatisk Determine LAM-intervention på vigtige trin i TB-kaskaden gennem et stepped-wedge cluster randomized design på tre hospitaler. Endelig gennemførte vi i artikel III et mixed methods studie, hvor vi brugte de vigtigste resultater fra artikel I og II, kvantitativ spørgeskemaundersøgelse og kvalitative interviews af sundhedspersonale for bedre forstå, hvordan Determine LAM-interventionen blev implementeret i hverdagens kliniske praksis. Inklusionskriterierne for at deltagelse var: HIV-positiv, nyindlagt, 18 år eller derover og at opfylde guideline kriterier for LAMtesten. Sundhedspersonalet blev udvalgt til at deltage i studie 3, hvis de var involveret i diagnostik eller behandling af patienter med HIV-associeret TB.

Af 248 patienter i kontrolgruppen (artikel I) havde 99,2% en positiv W4SS, og medianværdien for CD4 T-celletallet var 80,5 eller/mm3. I alt 45,2% fik udført en sputum Xpert test, TB-prævalensen (klinisk og bekræftet af Xpert eller dyrkning) var 18,7%, og 8- ugers dødeligheden var 25,2%. Vi fandt ingen forskel i andelen, der havde adgang til Xpert, havde TB eller døde ved sammenligning af de patienter som var inkluderet henholdsvis før eller under pandemien. I alt 422 patienter blev inkluderet i interventionsstudiet (artikel II) med 174 (41,2%) i interventionsgruppen. Patienterne i interventionsgruppen var oftere indlagt under pandemien, var ældre, færre var i behandling for HIV og flere havde kendt nyresygdom i sammenligning med
kontrolgruppen. Sundhedspersonalet brugte hyppigt LAM-testen, men mindre end halvdelen af LAM-positive patienter (19/41) blev startet i TB-behandling. Signifikant flere patienter (34,1 % vs. 18,7 %) blev diagnosticeret med TB (klinisk og bekræftet af Xpert,
dyrkning eller Determine LAM) efter kortere tid (median 0 dage vs. median 2 dage). Patienterne i interventionsgruppen blev opstartet i TB behandling hyppigere (aHR 2,19, 95%CI1,60-3,00) sammenlignet med kontrolgruppen. Mixed methods studiet (artikel III) viste, at manglende sputumproduktion og logistik omkring prøvehåndtering var vigtige barrierer til rutine diagnostik af TB. Determine LAM testen bemyndigede sundhedspersonale i behandling af svært immunsvækkede patienter med TB. Mistillid til
positive resultater var relateret til bekymringer om falsk-positive resultater og andre differentialdiagnoser end TB forud for gennemførelse af testen.

Samlet fandt vi at en høj andel af patienter med HIV ikke fik udført rutine undersøgelser for TB under indlæggelse, og en uacceptabel høj dødelighed. Determine LAM-interventionen var gennemførlig og kunne overkomme mange udfordringer i håndtering af TB. For at forbedre prognosen blandt alvorligt syge patienter indlagt med HIV, understreger denne afhandling vigtigheden i at opskalere brugen af Determine LAM testen sideløbende med brug af Xpert til undersøgelse for TB.

Originalsprog	Engelsk
Bevilgende institution	Syddansk Universitet
Vejledere/rådgivere	Johansen, Isik Somuncu, Hovedvejleder Bjerrum, Stephanie, Bivejleder Lartey, Margaret, Bivejleder, Ekstern person Andersen, Åse Bengård, Bivejleder Kenu, Ernest, Bivejleder, Ekstern person
Dato for forsvar	24. aug. 2023
Udgiver	Syddansk Universitet. Det Sundhedsvidenskabelige Fakultet
DOI	https://doi.org/10.21996/qs6v-rh74
Status	Udgivet - 10. jul. 2023

Dokumenter og links

10.21996/qs6v-rh74

PhD_Thesis_Johanna_ÅhsbergForlagets udgivne version, 22,1 MB

3 Tidsskriftartikel

Point-of-Care Urine Lipoarabinomannan Testing to Guide Tuberculosis Treatment among Severely Ill Inpatients with Human Immunodeficiency Virus in Real-World Practice: a multi-center stepped wedge cluster-randomized trial from Ghana
Åhsberg, J., Puplampu, P., Kwashie, A., Commey, J. O., Ganu, V. J., Omari, M. A., Adusi-Poku, Y., Andersen, Å. B., Kenu, E., Lartey, M., Johansen, I. S. & Bjerrum, S., 15. okt. 2023, I: Clinical Infectious Diseases. 77, 8, s. 1185-1193
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
The in-hospital tuberculosis diagnostic cascade and early clinical outcomes among people living with HIV before and during the COVID-19 pandemic - a prospective multisite cohort study from Ghana
Åhsberg, J., Bjerrum, S., Ganu, V. J., Kwashie, A., Commey, J. O., Adusi-Poku, Y., Puplampu, P., Andersen, Å. B., Kenu, E., Lartey, M. & Johansen, I. S., mar. 2023, I: International Journal of Infectious Diseases. 128, s. 290-300
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

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Use of the urine Determine LAM test in the context of tuberculosis diagnosis among inpatients with HIV in Ghana: a mixed methods study
Åhsberg, J., Tersbøl, B. P., Puplampu, P., Kwashie, A., Commey, J. O., Adusi-Poku, Y., Moseholm, E., Andersen, Å. B., Kenu, E., Lartey, M., Johansen, I. S. & Bjerrum, S., 2023, I: Frontiers in Public Health. 11, 15 s., 1271763.
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

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173 Downloads (Pure)

Citationsformater

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title = "Point-of-care strategies to improve tuberculosis care among severely immunocompromised HIV-infected patients in Ghana",

abstract = "HIV-associated TB is associated with late presentation to care and high risk of early mortality. Due to high prevalence of EPTB, disseminated TB, and sputum scarce PTB, non-sputum based TB investigations need to complement routinely used sputum based TB tests. With this thesis we aimed to identify POC strategies that can improve TB case detection and clinical outcomes among patients with advanced HIV.In Paper I, we assessed the in-hospital TB diagnostic care cascade before and during the COVID-19 pandemic at three hospitals in Ghana. In Paper II, we evaluated a pragmatic Determine LAM intervention impact on key steps along the TB care cascade using a stepped-wedge cluster-randomized design at the three hospitals. In paper III, we conducted a mixed methods study using key results from Paper I and II, HCW quantitative surveys and qualitative interviews to better understand how the Determine LAM intervention was received and worked in a real-world context. Study eligibility criteria for patients were being HIV-positive, newly admitted, being 18 years or above and eligible to the Determine LAM test. HCW were purposively sampled if involved in HIV-associated TB care. Of 248 patients in the SOC population (Paper I), 99.2% had a positive W4SS and the median CD4 T cell count was 80.5 cells/mm3. In all 45.2% accessed a sputum Xpert, the TB prevalence (clinical and confirmed by Xpert or culture) was 18.7% and the 8 weeks all-cause mortality was 25.2%. We found no difference in proportion accessing Xpert, having TB or in mortality across the prepandemic and the pandemic period. In total 422 patients were enrolled in the Determine LAM intervention study (Paper II) with 174 (41.2%) in the intervention group. Patients in the intervention group were enrolled during the pandemic, were older of age, had lower ART coverage, and more kidney disease compared with the SOC group. HCW used the Determine LAM test frequently, but less than half of LAM positive patients (19/41) were initiated on TB treatment. Significantly more patients were diagnosed with TB (34.1% vs 18.7%) (clinical and confirmed by Xpert, culture or Determine LAM) after a shorter time (median 0 days vs median 2 days). With Determine LAM, patients were 2 times more likely to initiate TB treatment (aHR 2.19, 95%CI1.60-3.00) in the intervention group compared with the SOC group, but the intervention did not reduce time to TB treatment that remained short at 3 days in both groups. The mixed methods study (Paper III) found that sputum availability and sample logistics were important barriers to accessing TB testing. Determine LAM empowered HCW especially in the management of severely immunosuppressed patients with EPTB, and reluctance in LAM guided TB treatment was related to concerns of false positive results and low pre-test TB suspicion. The gap in access to routine TB testing among PWH inpatients was large and the early mortality was unacceptably high. However, the Determine LAM intervention was feasible and closed several gaps in the TB diagnostic care cascade. To improve the poor outcomes among severely ill PWH on medical admission this thesis stress the scale-up of Determine LAM and the use of extrapulmonary samples for Xpert. ",

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doi = "10.21996/qs6v-rh74",

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publisher = "Syddansk Universitet. Det Sundhedsvidenskabelige Fakultet",

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N2 - HIV-associated TB is associated with late presentation to care and high risk of early mortality. Due to high prevalence of EPTB, disseminated TB, and sputum scarce PTB, non-sputum based TB investigations need to complement routinely used sputum based TB tests. With this thesis we aimed to identify POC strategies that can improve TB case detection and clinical outcomes among patients with advanced HIV.In Paper I, we assessed the in-hospital TB diagnostic care cascade before and during the COVID-19 pandemic at three hospitals in Ghana. In Paper II, we evaluated a pragmatic Determine LAM intervention impact on key steps along the TB care cascade using a stepped-wedge cluster-randomized design at the three hospitals. In paper III, we conducted a mixed methods study using key results from Paper I and II, HCW quantitative surveys and qualitative interviews to better understand how the Determine LAM intervention was received and worked in a real-world context. Study eligibility criteria for patients were being HIV-positive, newly admitted, being 18 years or above and eligible to the Determine LAM test. HCW were purposively sampled if involved in HIV-associated TB care. Of 248 patients in the SOC population (Paper I), 99.2% had a positive W4SS and the median CD4 T cell count was 80.5 cells/mm3. In all 45.2% accessed a sputum Xpert, the TB prevalence (clinical and confirmed by Xpert or culture) was 18.7% and the 8 weeks all-cause mortality was 25.2%. We found no difference in proportion accessing Xpert, having TB or in mortality across the prepandemic and the pandemic period. In total 422 patients were enrolled in the Determine LAM intervention study (Paper II) with 174 (41.2%) in the intervention group. Patients in the intervention group were enrolled during the pandemic, were older of age, had lower ART coverage, and more kidney disease compared with the SOC group. HCW used the Determine LAM test frequently, but less than half of LAM positive patients (19/41) were initiated on TB treatment. Significantly more patients were diagnosed with TB (34.1% vs 18.7%) (clinical and confirmed by Xpert, culture or Determine LAM) after a shorter time (median 0 days vs median 2 days). With Determine LAM, patients were 2 times more likely to initiate TB treatment (aHR 2.19, 95%CI1.60-3.00) in the intervention group compared with the SOC group, but the intervention did not reduce time to TB treatment that remained short at 3 days in both groups. The mixed methods study (Paper III) found that sputum availability and sample logistics were important barriers to accessing TB testing. Determine LAM empowered HCW especially in the management of severely immunosuppressed patients with EPTB, and reluctance in LAM guided TB treatment was related to concerns of false positive results and low pre-test TB suspicion. The gap in access to routine TB testing among PWH inpatients was large and the early mortality was unacceptably high. However, the Determine LAM intervention was feasible and closed several gaps in the TB diagnostic care cascade. To improve the poor outcomes among severely ill PWH on medical admission this thesis stress the scale-up of Determine LAM and the use of extrapulmonary samples for Xpert.

AB - HIV-associated TB is associated with late presentation to care and high risk of early mortality. Due to high prevalence of EPTB, disseminated TB, and sputum scarce PTB, non-sputum based TB investigations need to complement routinely used sputum based TB tests. With this thesis we aimed to identify POC strategies that can improve TB case detection and clinical outcomes among patients with advanced HIV.In Paper I, we assessed the in-hospital TB diagnostic care cascade before and during the COVID-19 pandemic at three hospitals in Ghana. In Paper II, we evaluated a pragmatic Determine LAM intervention impact on key steps along the TB care cascade using a stepped-wedge cluster-randomized design at the three hospitals. In paper III, we conducted a mixed methods study using key results from Paper I and II, HCW quantitative surveys and qualitative interviews to better understand how the Determine LAM intervention was received and worked in a real-world context. Study eligibility criteria for patients were being HIV-positive, newly admitted, being 18 years or above and eligible to the Determine LAM test. HCW were purposively sampled if involved in HIV-associated TB care. Of 248 patients in the SOC population (Paper I), 99.2% had a positive W4SS and the median CD4 T cell count was 80.5 cells/mm3. In all 45.2% accessed a sputum Xpert, the TB prevalence (clinical and confirmed by Xpert or culture) was 18.7% and the 8 weeks all-cause mortality was 25.2%. We found no difference in proportion accessing Xpert, having TB or in mortality across the prepandemic and the pandemic period. In total 422 patients were enrolled in the Determine LAM intervention study (Paper II) with 174 (41.2%) in the intervention group. Patients in the intervention group were enrolled during the pandemic, were older of age, had lower ART coverage, and more kidney disease compared with the SOC group. HCW used the Determine LAM test frequently, but less than half of LAM positive patients (19/41) were initiated on TB treatment. Significantly more patients were diagnosed with TB (34.1% vs 18.7%) (clinical and confirmed by Xpert, culture or Determine LAM) after a shorter time (median 0 days vs median 2 days). With Determine LAM, patients were 2 times more likely to initiate TB treatment (aHR 2.19, 95%CI1.60-3.00) in the intervention group compared with the SOC group, but the intervention did not reduce time to TB treatment that remained short at 3 days in both groups. The mixed methods study (Paper III) found that sputum availability and sample logistics were important barriers to accessing TB testing. Determine LAM empowered HCW especially in the management of severely immunosuppressed patients with EPTB, and reluctance in LAM guided TB treatment was related to concerns of false positive results and low pre-test TB suspicion. The gap in access to routine TB testing among PWH inpatients was large and the early mortality was unacceptably high. However, the Determine LAM intervention was feasible and closed several gaps in the TB diagnostic care cascade. To improve the poor outcomes among severely ill PWH on medical admission this thesis stress the scale-up of Determine LAM and the use of extrapulmonary samples for Xpert.

U2 - 10.21996/qs6v-rh74

DO - 10.21996/qs6v-rh74

M3 - Ph.D. thesis

PB - Syddansk Universitet. Det Sundhedsvidenskabelige Fakultet

ER -

Point-of-care strategies to improve tuberculosis care among severely immunocompromised HIV-infected patients in Ghana

Abstract

Dokumenter og links

Fingeraftryk

Relaterede publikationer

Point-of-Care Urine Lipoarabinomannan Testing to Guide Tuberculosis Treatment among Severely Ill Inpatients with Human Immunodeficiency Virus in Real-World Practice: a multi-center stepped wedge cluster-randomized trial from Ghana

The in-hospital tuberculosis diagnostic cascade and early clinical outcomes among people living with HIV before and during the COVID-19 pandemic - a prospective multisite cohort study from Ghana

Use of the urine Determine LAM test in the context of tuberculosis diagnosis among inpatients with HIV in Ghana: a mixed methods study

Citationsformater