Journal Article > ResearchFull Text
PLOS Med. 2019 April 30; Volume 16 (Issue 4); DOI:10.1371/journal.pmed.1002792
Huerga H, Rucker SCM, Cossa L, Bastard M, Amoros I, et al.
PLOS Med. 2019 April 30; Volume 16 (Issue 4); DOI:10.1371/journal.pmed.1002792
BACKGROUND:
Current guidelines recommend the use of the lateral flow urine lipoarabinomannan assay (LAM) in HIV-positive, ambulatory patients with signs and symptoms of tuberculosis (TB) only if they are seriously ill or have CD4 count ≤ 100 cells/μl. We assessed the diagnostic yield of including LAM in TB diagnostic algorithms in HIV-positive, ambulatory patients with CD4 < 200 cells/μl, as well as the risk of mortality in LAM-positive patients who were not diagnosed using other diagnostic tools and not treated for TB.
METHODS AND FINDINGS:
We conducted a prospective observational study including HIV-positive adult patients with signs and symptoms of TB and CD4 < 200 cells/μl attending 6 health facilities in Malawi and Mozambique. Patients were included consecutively from 18 September 2015 to 27 October 2016 in Malawi and from 3 December 2014 to 22 August 2016 in Mozambique. All patients had a clinical exam and LAM, chest X-ray, sputum microscopy, and Xpert MTB/RIF assay (Xpert) requested. Culture in sputum was done for a subset of patients. The diagnostic yield was defined as the proportion of patients with a positive assay result among those with laboratory-confirmed TB. For the 456 patients included in the study, the median age was 36 years (IQR 31-43) and the median CD4 count was 50 cells/μl (IQR 21-108). Forty-five percent (205/456) of the patients had laboratory-confirmed TB. The diagnostic yields of LAM, microscopy, and Xpert were 82.4% (169/205), 33.7% (69/205), and 40.0% (84/205), respectively. In total, 50.2% (103/205) of the patients with laboratory-confirmed TB were diagnosed only through LAM. Overall, the use of LAM in diagnostic algorithms increased the yield of algorithms with microscopy and with Xpert by 38.0% (78/205) and 34.6% (71/205), respectively, and, specifically among patients with CD4 100-199 cells/μl, by 27.5% (14/51) and 29.4% (15/51), respectively. LAM-positive patients not diagnosed through other tools and not treated for TB had a significantly higher risk of mortality than LAM-positive patients who received treatment (adjusted risk ratio 2.57, 95% CI 1.27-5.19, p = 0.009). Although the TB diagnostic conditions in the study sites were similar to those in other resource-limited settings, the added value of LAM may depend on the availability of microscopy or Xpert results.
CONCLUSIONS:
LAM has diagnostic value for identifying TB in HIV-positive patients with signs and symptoms of TB and advanced immunodeficiency, including those with a CD4 count of 100-199 cells/μl. In this study, the use of LAM enabled the diagnosis of TB in half of the patients with confirmed TB disease; without LAM, these patients would have been missed. The rapid identification and treatment of TB enabled by LAM may decrease overall mortality risk for these patients.
Current guidelines recommend the use of the lateral flow urine lipoarabinomannan assay (LAM) in HIV-positive, ambulatory patients with signs and symptoms of tuberculosis (TB) only if they are seriously ill or have CD4 count ≤ 100 cells/μl. We assessed the diagnostic yield of including LAM in TB diagnostic algorithms in HIV-positive, ambulatory patients with CD4 < 200 cells/μl, as well as the risk of mortality in LAM-positive patients who were not diagnosed using other diagnostic tools and not treated for TB.
METHODS AND FINDINGS:
We conducted a prospective observational study including HIV-positive adult patients with signs and symptoms of TB and CD4 < 200 cells/μl attending 6 health facilities in Malawi and Mozambique. Patients were included consecutively from 18 September 2015 to 27 October 2016 in Malawi and from 3 December 2014 to 22 August 2016 in Mozambique. All patients had a clinical exam and LAM, chest X-ray, sputum microscopy, and Xpert MTB/RIF assay (Xpert) requested. Culture in sputum was done for a subset of patients. The diagnostic yield was defined as the proportion of patients with a positive assay result among those with laboratory-confirmed TB. For the 456 patients included in the study, the median age was 36 years (IQR 31-43) and the median CD4 count was 50 cells/μl (IQR 21-108). Forty-five percent (205/456) of the patients had laboratory-confirmed TB. The diagnostic yields of LAM, microscopy, and Xpert were 82.4% (169/205), 33.7% (69/205), and 40.0% (84/205), respectively. In total, 50.2% (103/205) of the patients with laboratory-confirmed TB were diagnosed only through LAM. Overall, the use of LAM in diagnostic algorithms increased the yield of algorithms with microscopy and with Xpert by 38.0% (78/205) and 34.6% (71/205), respectively, and, specifically among patients with CD4 100-199 cells/μl, by 27.5% (14/51) and 29.4% (15/51), respectively. LAM-positive patients not diagnosed through other tools and not treated for TB had a significantly higher risk of mortality than LAM-positive patients who received treatment (adjusted risk ratio 2.57, 95% CI 1.27-5.19, p = 0.009). Although the TB diagnostic conditions in the study sites were similar to those in other resource-limited settings, the added value of LAM may depend on the availability of microscopy or Xpert results.
CONCLUSIONS:
LAM has diagnostic value for identifying TB in HIV-positive patients with signs and symptoms of TB and advanced immunodeficiency, including those with a CD4 count of 100-199 cells/μl. In this study, the use of LAM enabled the diagnosis of TB in half of the patients with confirmed TB disease; without LAM, these patients would have been missed. The rapid identification and treatment of TB enabled by LAM may decrease overall mortality risk for these patients.
Conference Material > Abstract
Haider A, Goossens S, Desforges C, Chilinda G, Osman H, et al.
International Papillomavirus 2024. 2024 November 12
INTRODUCTION
MSF is providing cervical cancer screening in Blantyre and Chiradzulu districts in Southern Malawi in the catchment area of 10 health centres. Improved screening strategies under diverse recruitment models are introduced to increase HPV screening coverage at health centres and with outreach activities.
METHODS
Under PAVE study, self-collected vaginal swabs are tested by an isothermal amplification PCR assay followed byvisual inspection, imaging, and histological assessment for HPV +ve women. Women living <5km from health centers are recruited opportunistically during routine visits. After HPV test, they are advised either to wait onsite (test-and-wait model) or called back in two days’ time (test-and-call model) for triage and treatment visit.Women living>10km from health centers are offered HPV test, triage, and treatment in community settings by outreach teams (mobile-clinic model). A fourth model for women living 5-10km from a health center with HPV testing in their communities followed by a triage and treatment visit at respective health centers (mobile-lab model) is not yet implemented.
RESULTS
As of April 2024, over 2000 women have undergone HPV screening across all active sites. Key insights from the experience are focused at: i)streamlining patient flow during opportunistic recruitment at health centers,ii)improving HPV results communication, iii)effectively tracing women back for triage and treatment visits using phone and community based tracing, iv)ensuring provision of stable internet for effective and real time data collection and synchronization, v)reducing gaps in logistics and quality assurances at HPV lab particularly in mobile lab setup, vi)ensuring real-time quality histopathology review of cervical biopsies for case management,and vii)continuous monitoring of patients and data flow to ensure quality of screening, compliance, and effective case management.
CONCLUSIONS
Diverse HPV-based screening strategies are key to achieve good screening coverage, and subsequently reducethe cervical cancer morbidity and mortality in southern Malawi.
Conference Material > Poster
Haider A, Goossens S, Desforges C, Chilinda G, Osman H, et al.
International Papillomavirus 2024. 2024 November 12
Journal Article > ResearchFull Text
J Acquir Immune Defic Syndr. 2020 January 1; Volume 83; DOI:10.1097/QAI.0000000000002206
Huerga H, Rucker SCM, Bastard M, Dimba A, Kamba C, et al.
J Acquir Immune Defic Syndr. 2020 January 1; Volume 83; DOI:10.1097/QAI.0000000000002206
Background: Current eligibility criteria for urine lateral-flow-lipoarabinomannan assay (LF-LAM) in ambulatory, HIV-positive patients rely on the CD4 count. We investigated the diagnostic yield of LF-LAM and the 6-month mortality in ambulatory, TB symptomatic, HIV-positive patients regardless of their CD4 count.
Methods: We conducted a prospective, observational study that included all ambulatory, >15-year-old, TB symptomatic (cough, weight loss, fever, or night sweats) HIV-positive patients presenting at 4 health facilities in Malawi. Patients received a clinical examination and were requested urine LF-LAM, sputum microscopy and Xpert MTB/RIF. TB was defined as bacteriologically confirmed if Xpert was positive.
Results: Of 485 patients included, 171 (35.3%) had a CD4<200 and 32 (7.2%) were seriously ill. Median CD4 count was 341 cells/µL (IQR: 129-256). LAM was positive in 24.9% patients with CD4<200 (50% LAM Grades 2-4) and 12.5% with CD4≥200 (12.8% LAM Grades 2-4). Xpert was positive in 14.1% (44/312). Among Xpert-positive patients, LAM-positivity was: 56.7% (CD4<200) and 42.9% (CD4≥200), p=0.393. Of the patients without an Xpert result, 13.4% (23/172) were LAM-positive (i.e. potentially missed patients). Overall mortality was 9.2% (44/478). More pronounced LAM-positive patients had higher mortality than LAM-negative (Grades 2-4: 36.0%; Grade 1: 9.1%; Negative: 7.4%; p<0.001). LAM-positive patients with CD4<200 cells/µL had higher risk of mortality than LAM-negatives (aHR:3.2, 95CI:1.4-7.2, p=0.006), particularly those with LAM Grades 2-4 (aHR:4.9, 95CI:1.8-13.3, p=0.002).
Conclusions: Urine-LAM testing can be useful for TB diagnosis in HIV-positive TB-symptomatic patients with no CD4 cell count. LAM grade can identify patients at higher risk of death in this situation.
Methods: We conducted a prospective, observational study that included all ambulatory, >15-year-old, TB symptomatic (cough, weight loss, fever, or night sweats) HIV-positive patients presenting at 4 health facilities in Malawi. Patients received a clinical examination and were requested urine LF-LAM, sputum microscopy and Xpert MTB/RIF. TB was defined as bacteriologically confirmed if Xpert was positive.
Results: Of 485 patients included, 171 (35.3%) had a CD4<200 and 32 (7.2%) were seriously ill. Median CD4 count was 341 cells/µL (IQR: 129-256). LAM was positive in 24.9% patients with CD4<200 (50% LAM Grades 2-4) and 12.5% with CD4≥200 (12.8% LAM Grades 2-4). Xpert was positive in 14.1% (44/312). Among Xpert-positive patients, LAM-positivity was: 56.7% (CD4<200) and 42.9% (CD4≥200), p=0.393. Of the patients without an Xpert result, 13.4% (23/172) were LAM-positive (i.e. potentially missed patients). Overall mortality was 9.2% (44/478). More pronounced LAM-positive patients had higher mortality than LAM-negative (Grades 2-4: 36.0%; Grade 1: 9.1%; Negative: 7.4%; p<0.001). LAM-positive patients with CD4<200 cells/µL had higher risk of mortality than LAM-negatives (aHR:3.2, 95CI:1.4-7.2, p=0.006), particularly those with LAM Grades 2-4 (aHR:4.9, 95CI:1.8-13.3, p=0.002).
Conclusions: Urine-LAM testing can be useful for TB diagnosis in HIV-positive TB-symptomatic patients with no CD4 cell count. LAM grade can identify patients at higher risk of death in this situation.
Journal Article > ResearchFull Text
Glob Health Action. 2019 October 15
Cossa L, Harrison RE, Mpunga J, Lobo S, Kisaka Kimupelenge P, et al.
Glob Health Action. 2019 October 15
Background: Determine TB-LAM is a urine-based point-of-care assay for diagnosis of tuberculosis (TB).
Objective: To assess the feasibility of using LAM to diagnose TB in adult HIV-positive patients in resource-limited settings.
Methods: We performed a multi-centric mixed-methods cross-sectional descriptive study in the Democratic Republic of Congo, Malawi, and Mozambique. We used the study and program monitoring tools to estimate user workload, turn-around time (TAT), and proportion of patients with LAM and sputum-based results. We conducted semi-structured interviews to assess the user acceptability of the LAM.
Results: The duration of the LAM testing activity per patient was 27 min (IQR 26-29); staff continued with other duties whilst waiting for the result. More patients had a LAM versus a sputum-based result: 168/213 (78.9%) vs 77/213 (36.1%), p < 0.001 in DRC; 691/695 (99.4%) vs 429/695 (61.7%), p < 0.001 in Malawi; and 646/647 (99.8%) vs 262/647 (40.5%), p < 0.001 in Mozambique. The median TAT in minutes when LAM was performed in the consultation room was 75 (IQR 45-188) in DRC, 29 (IQR 27-39) in Malawi, and 36 (IQR 35-41) in Mozambique. In comparison, the overall median TAT for sputum-based tests (smear or GeneXpert) was 2 (IQR 1-3) days. The median time to the first anti-TB drug dose for LAM-positive patients was 155 (IQR 90-504) minutes in DRC and 90 (IQR 60-117) minutes in Mozambique. The overall inter-reader agreement for the interpretation of the LAM result as positive or negative was 98.9%, kappa 0.97 (95%CI 0.96-0.99). Overall, LAM users found the test easy to perform. Major concerns were use of the reading card and the prior requirement of CD4 results before LAM testing.
Conclusion: It is feasible to implement the LAM test in low resource settings. The short TAT permitted same day initiation of TB treatment for LAM-positive patients.
Objective: To assess the feasibility of using LAM to diagnose TB in adult HIV-positive patients in resource-limited settings.
Methods: We performed a multi-centric mixed-methods cross-sectional descriptive study in the Democratic Republic of Congo, Malawi, and Mozambique. We used the study and program monitoring tools to estimate user workload, turn-around time (TAT), and proportion of patients with LAM and sputum-based results. We conducted semi-structured interviews to assess the user acceptability of the LAM.
Results: The duration of the LAM testing activity per patient was 27 min (IQR 26-29); staff continued with other duties whilst waiting for the result. More patients had a LAM versus a sputum-based result: 168/213 (78.9%) vs 77/213 (36.1%), p < 0.001 in DRC; 691/695 (99.4%) vs 429/695 (61.7%), p < 0.001 in Malawi; and 646/647 (99.8%) vs 262/647 (40.5%), p < 0.001 in Mozambique. The median TAT in minutes when LAM was performed in the consultation room was 75 (IQR 45-188) in DRC, 29 (IQR 27-39) in Malawi, and 36 (IQR 35-41) in Mozambique. In comparison, the overall median TAT for sputum-based tests (smear or GeneXpert) was 2 (IQR 1-3) days. The median time to the first anti-TB drug dose for LAM-positive patients was 155 (IQR 90-504) minutes in DRC and 90 (IQR 60-117) minutes in Mozambique. The overall inter-reader agreement for the interpretation of the LAM result as positive or negative was 98.9%, kappa 0.97 (95%CI 0.96-0.99). Overall, LAM users found the test easy to perform. Major concerns were use of the reading card and the prior requirement of CD4 results before LAM testing.
Conclusion: It is feasible to implement the LAM test in low resource settings. The short TAT permitted same day initiation of TB treatment for LAM-positive patients.
Journal Article > ResearchFull Text
J Int AIDS Soc. 2019 August 1; Volume 22 (Issue 8); DOI:10.1002/jia2.25387
Nicholas S, Poulet E, Wolters L, Wapling J, Rakesh A, et al.
J Int AIDS Soc. 2019 August 1; Volume 22 (Issue 8); DOI:10.1002/jia2.25387
INTRODUCTION:
Routinely monitoring the HIV viral load (VL) of people living with HIV (PLHIV) on anti-retroviral therapy (ART) facilitates intensive adherence counselling and faster ART regimen switch when treatment failure is indicated. Yet standard VL-testing in centralized laboratories can be time-intensive and logistically difficult in low-resource settings. This paper evaluates the outcomes of the first four years of routine VL-monitoring using Point-of-Care technology, implemented by Médecins Sans Frontières (MSF) in rural clinics in Malawi.
METHODS:
We conducted a retrospective cohort analysis of patients eligible for routine VL- testing between 2013 and 2017 in four decentralized ART-clinics and the district hospital in Chiradzulu, Malawi. We assessed VL-testing coverage and the treatment failure cascade (from suspected failure (first VL>1000 copies/mL) to VL suppression post regimen switch). We used descriptive statistics and multivariate logistic regression to assess factors associated with suspected failure.
RESULTS AND DISCUSSION:
Among 21,400 eligible patients, VL-testing coverage was 85% and VL suppression was found in 89% of those tested. In the decentralized clinics, 88% of test results were reviewed on the same day as blood collection, whereas in the district hospital the median turnaround-time for results was 85 days. Among first-line ART patients with suspected failure (N = 1544), 30% suppressed (VL<1000 copies/mL), 35% were treatment failures (confirmed by subsequent VL-testing) and 35% had incomplete VL follow-up. Among treatment failures, 80% (N = 540) were switched to a second-line regimen, with a higher switching rate in the decentralized clinics than in the district hospital (86% vs. 67%, p < 0.01) and a shorter median time-to-switch (6.8 months vs. 9.7 months, p < 0.01). Similarly, the post-switch VL-testing rate was markedly higher in the decentralized clinics (61% vs. 26%, p < 0.01). Overall, 79% of patients with a post-switch VL-test were suppressed.
CONCLUSIONS:
Viral load testing at the point-of-care in Chiradzulu, Malawi achieved high coverage and good drug regimen switch rates among those identified as treatment failures. In decentralized clinics, same-day test results and shorter time-to-switch illustrated the game-changing potential of POC-based VL-testing. Nevertheless, gaps were identified along all steps of the failure cascade. Regular staff training, continuous monitoring and creating demand are essential to the success of routine VL-testing.
Routinely monitoring the HIV viral load (VL) of people living with HIV (PLHIV) on anti-retroviral therapy (ART) facilitates intensive adherence counselling and faster ART regimen switch when treatment failure is indicated. Yet standard VL-testing in centralized laboratories can be time-intensive and logistically difficult in low-resource settings. This paper evaluates the outcomes of the first four years of routine VL-monitoring using Point-of-Care technology, implemented by Médecins Sans Frontières (MSF) in rural clinics in Malawi.
METHODS:
We conducted a retrospective cohort analysis of patients eligible for routine VL- testing between 2013 and 2017 in four decentralized ART-clinics and the district hospital in Chiradzulu, Malawi. We assessed VL-testing coverage and the treatment failure cascade (from suspected failure (first VL>1000 copies/mL) to VL suppression post regimen switch). We used descriptive statistics and multivariate logistic regression to assess factors associated with suspected failure.
RESULTS AND DISCUSSION:
Among 21,400 eligible patients, VL-testing coverage was 85% and VL suppression was found in 89% of those tested. In the decentralized clinics, 88% of test results were reviewed on the same day as blood collection, whereas in the district hospital the median turnaround-time for results was 85 days. Among first-line ART patients with suspected failure (N = 1544), 30% suppressed (VL<1000 copies/mL), 35% were treatment failures (confirmed by subsequent VL-testing) and 35% had incomplete VL follow-up. Among treatment failures, 80% (N = 540) were switched to a second-line regimen, with a higher switching rate in the decentralized clinics than in the district hospital (86% vs. 67%, p < 0.01) and a shorter median time-to-switch (6.8 months vs. 9.7 months, p < 0.01). Similarly, the post-switch VL-testing rate was markedly higher in the decentralized clinics (61% vs. 26%, p < 0.01). Overall, 79% of patients with a post-switch VL-test were suppressed.
CONCLUSIONS:
Viral load testing at the point-of-care in Chiradzulu, Malawi achieved high coverage and good drug regimen switch rates among those identified as treatment failures. In decentralized clinics, same-day test results and shorter time-to-switch illustrated the game-changing potential of POC-based VL-testing. Nevertheless, gaps were identified along all steps of the failure cascade. Regular staff training, continuous monitoring and creating demand are essential to the success of routine VL-testing.