Journal Article > ResearchFull Text
Journal of Clinical Tuberculosis and Other Mycobacterial Diseases. 2022 May 1; Volume 27; 100316.; DOI: 10.1016/j.jctube.2022.100316
Rucker SCM, Lissouba P, Akinyi M, Lubega AV, Stewart RC, et al.
Journal of Clinical Tuberculosis and Other Mycobacterial Diseases. 2022 May 1; Volume 27; 100316.; DOI: 10.1016/j.jctube.2022.100316
BACKGROUND
The novel urine-based FujiLAM test identifies tuberculosis in HIV-positive patients but may be challenging to use at point-of-care (POC).
OBJECTIVES
We assessed the feasibility and acceptability of using the FujiLAM test at the point of care in outpatient settings.
METHODS
We conducted a mixed-methods study in four outpatient settings in Kenya, Mozambique, South Africa, and Uganda between November 2020 and September 2021. The test was performed at POC in existing clinic laboratories and consultation spaces. We performed direct observations in the four health facilities, individual questionnaires, proficiency testing evaluations, and individual interviews among healthcare workers performing the FujiLAM test (healthcare workers), and group discussions with programme managers.
RESULTS
Overall, 18/19 (95%) healthcare workers and 14/14 (100%) managers agreed to participate in the study. Most assessed healthcare workers, including lay health workers (10/11; 91%), met the minimum required theoretical knowledge and practical skill in performing the FujiLAM test. Most healthcare workers (17/18; 94%) found the FujiLAM test overall “Easy/Very easy” to perform. Some challenges were mentioned: many timed steps (5/18; 28%); ensuring correct incubation period (5/18; 28%); test result readability (4/18; 22%); and difficulties with cartridge buttons (3/18; 17%). Half of the healthcare workers regularly performing the test (4/7; 57%) found it “Easy” to integrate into routine activities. Most healthcare workers and managers believed that any healthcare worker could perform the test after adequate training.
CONCLUSIONS
Implementing the FujiLAM test in outpatient POC settings is feasible and acceptable to healthcare workers and managers. This test can be performed in various clinic locations by any healthcare worker. The timed, multi-step test procedure is challenging and may affect the workload in resource-constrained health facilities.
The novel urine-based FujiLAM test identifies tuberculosis in HIV-positive patients but may be challenging to use at point-of-care (POC).
OBJECTIVES
We assessed the feasibility and acceptability of using the FujiLAM test at the point of care in outpatient settings.
METHODS
We conducted a mixed-methods study in four outpatient settings in Kenya, Mozambique, South Africa, and Uganda between November 2020 and September 2021. The test was performed at POC in existing clinic laboratories and consultation spaces. We performed direct observations in the four health facilities, individual questionnaires, proficiency testing evaluations, and individual interviews among healthcare workers performing the FujiLAM test (healthcare workers), and group discussions with programme managers.
RESULTS
Overall, 18/19 (95%) healthcare workers and 14/14 (100%) managers agreed to participate in the study. Most assessed healthcare workers, including lay health workers (10/11; 91%), met the minimum required theoretical knowledge and practical skill in performing the FujiLAM test. Most healthcare workers (17/18; 94%) found the FujiLAM test overall “Easy/Very easy” to perform. Some challenges were mentioned: many timed steps (5/18; 28%); ensuring correct incubation period (5/18; 28%); test result readability (4/18; 22%); and difficulties with cartridge buttons (3/18; 17%). Half of the healthcare workers regularly performing the test (4/7; 57%) found it “Easy” to integrate into routine activities. Most healthcare workers and managers believed that any healthcare worker could perform the test after adequate training.
CONCLUSIONS
Implementing the FujiLAM test in outpatient POC settings is feasible and acceptable to healthcare workers and managers. This test can be performed in various clinic locations by any healthcare worker. The timed, multi-step test procedure is challenging and may affect the workload in resource-constrained health facilities.
Journal Article > ResearchFull Text
Open Forum Infect Dis. 2020 December 23; Volume 8 (Issue 2); ofaa639.; DOI:10.1093/ofid/ofaa639
Huerga H, Rucker SCM, Bastard M, Mpunga J, Amoros Quiles I, et al.
Open Forum Infect Dis. 2020 December 23; Volume 8 (Issue 2); ofaa639.; DOI:10.1093/ofid/ofaa639
BACKGROUND
Diagnosing tuberculosis (TB), the leading cause of death in people with HIV, remains a challenge in resource-limited countries. We assessed TB diagnosis using a strategy that included systematic urine lipoarabinomannan (LAM) testing for all HIV patients hospitalized in the medical wards and 6-month mortality according to the LAM result.
METHODS
This prospective, observational study included adult HIV patients hospitalized in the medical wards of a public district hospital in Malawi regardless of their TB symptoms or CD4 count. Each patient had a clinical examination and Alere Determine TB-LAM, sputum microscopy, sputum GeneXpert MTB/RIF (Xpert), chest X-ray, and CD4 count were systematically requested.
RESULTS
Among 387 inpatients, 54% had a CD4<200 cells/µL, 64% had presumptive TB and 90% had ≥1 TB symptom recorded in the medical file. LAM results were available for 99.0% of the patients, microscopy for 62.8% and Xpert for 60.7%. In total, 26.1% (100/383) had LAM-positive results, 48% (48/100) of which were grades 2-4. Any TB laboratory test result was positive in 30.8% (119/387). Among patients with no Xpert result, 28.5% (43/151) were LAM-positive. Cumulative 6-months mortality was 40.1% (151/377): 50.5% (49/97) in LAM-positives and 36.2% (100/276) in LAM-negatives, p=0.013. In multivariable regression analyses, LAM-positive patients had higher risk of mortality than LAM-negatives (aOR: 2.5, 95%CI: 1.1-5.8, p=0.037).
CONCLUSIONS
In resource-limited hospital medical wards with high TB prevalence, a diagnostic strategy including systematic urine-LAM testing for all HIV patients is an easily implementable strategy that identifies a large proportion of patients with TB at risk of death.
Diagnosing tuberculosis (TB), the leading cause of death in people with HIV, remains a challenge in resource-limited countries. We assessed TB diagnosis using a strategy that included systematic urine lipoarabinomannan (LAM) testing for all HIV patients hospitalized in the medical wards and 6-month mortality according to the LAM result.
METHODS
This prospective, observational study included adult HIV patients hospitalized in the medical wards of a public district hospital in Malawi regardless of their TB symptoms or CD4 count. Each patient had a clinical examination and Alere Determine TB-LAM, sputum microscopy, sputum GeneXpert MTB/RIF (Xpert), chest X-ray, and CD4 count were systematically requested.
RESULTS
Among 387 inpatients, 54% had a CD4<200 cells/µL, 64% had presumptive TB and 90% had ≥1 TB symptom recorded in the medical file. LAM results were available for 99.0% of the patients, microscopy for 62.8% and Xpert for 60.7%. In total, 26.1% (100/383) had LAM-positive results, 48% (48/100) of which were grades 2-4. Any TB laboratory test result was positive in 30.8% (119/387). Among patients with no Xpert result, 28.5% (43/151) were LAM-positive. Cumulative 6-months mortality was 40.1% (151/377): 50.5% (49/97) in LAM-positives and 36.2% (100/276) in LAM-negatives, p=0.013. In multivariable regression analyses, LAM-positive patients had higher risk of mortality than LAM-negatives (aOR: 2.5, 95%CI: 1.1-5.8, p=0.037).
CONCLUSIONS
In resource-limited hospital medical wards with high TB prevalence, a diagnostic strategy including systematic urine-LAM testing for all HIV patients is an easily implementable strategy that identifies a large proportion of patients with TB at risk of death.
Conference Material > Poster
Moreto-Planas L, Mahajan R, Sagrado MJ, Flevaud L, Gallo J, et al.
MSF Scientific Day International 2023. 2023 June 7; DOI:10.57740/0xmg-7p42
Journal Article > ResearchAbstract Only
Eur Respir J. 2021 June 17; Volume 59 (Issue 1); 2101116.; DOI:10.1183/13993003.01116-2021
Orikiriza P, Smith JS, Ssekyanzi B, Nyehangane D, Mugisha IT, et al.
Eur Respir J. 2021 June 17; Volume 59 (Issue 1); 2101116.; DOI:10.1183/13993003.01116-2021
BACKGROUND
Non-sputum-based diagnostic approaches are crucial in children at high risk of disseminated tuberculosis (TB) who cannot expectorate sputum. We evaluated the diagnostic accuracy of stool Xpert MTB/RIF and urine AlereLAM tests in this group of children.
METHODS
Hospitalised children with presumptive TB and either age <2 years, HIV-positive or with severe malnutrition were enrolled in a diagnostic cohort. At enrolment, we attempted to collect two urine, two stool and two respiratory samples. Urine and stool were tested with AlereLAM and Xpert MTB/RIF, respectively. Respiratory samples were tested with Xpert MTB/RIF and mycobacterial culture. Both a microbiological and a composite clinical reference standard were used.
RESULTS
The study analysed 219 children; median age 16.4 months, 72 (32.9%) HIV-positive and 184 (84.4%) severely malnourished. 12 (5.5%) and 58 (28.5%) children had confirmed and unconfirmed TB, respectively. Stool and urine were collected in 219 (100%) and 216 (98.6%) children, respectively. Against the microbiological reference standard, the sensitivity and specificity of stool Xpert MTB/RIF was 50.0% (6/12, 95% CI 21.1–78.9%) and 99.1% (198/200, 95% 96.4–99.9%), while that of urine AlereLAM was 50.0% (6/12, 95% 21.1–78.9%) and 74.6% (147/197, 95% 67.9–80.5%), respectively. Against the composite reference standard, sensitivity was reduced to 11.4% (8/70) for stool and 26.2% (17/68) for urine, with no major difference by age group (<2 and ≥2 years) or HIV status.
CONCLUSIONS
The Xpert MTB/RIF assay has excellent specificity on stool, but sensitivity is suboptimal. Urine AlereLAM is compromised by poor sensitivity and specificity in children.
Non-sputum-based diagnostic approaches are crucial in children at high risk of disseminated tuberculosis (TB) who cannot expectorate sputum. We evaluated the diagnostic accuracy of stool Xpert MTB/RIF and urine AlereLAM tests in this group of children.
METHODS
Hospitalised children with presumptive TB and either age <2 years, HIV-positive or with severe malnutrition were enrolled in a diagnostic cohort. At enrolment, we attempted to collect two urine, two stool and two respiratory samples. Urine and stool were tested with AlereLAM and Xpert MTB/RIF, respectively. Respiratory samples were tested with Xpert MTB/RIF and mycobacterial culture. Both a microbiological and a composite clinical reference standard were used.
RESULTS
The study analysed 219 children; median age 16.4 months, 72 (32.9%) HIV-positive and 184 (84.4%) severely malnourished. 12 (5.5%) and 58 (28.5%) children had confirmed and unconfirmed TB, respectively. Stool and urine were collected in 219 (100%) and 216 (98.6%) children, respectively. Against the microbiological reference standard, the sensitivity and specificity of stool Xpert MTB/RIF was 50.0% (6/12, 95% CI 21.1–78.9%) and 99.1% (198/200, 95% 96.4–99.9%), while that of urine AlereLAM was 50.0% (6/12, 95% 21.1–78.9%) and 74.6% (147/197, 95% 67.9–80.5%), respectively. Against the composite reference standard, sensitivity was reduced to 11.4% (8/70) for stool and 26.2% (17/68) for urine, with no major difference by age group (<2 and ≥2 years) or HIV status.
CONCLUSIONS
The Xpert MTB/RIF assay has excellent specificity on stool, but sensitivity is suboptimal. Urine AlereLAM is compromised by poor sensitivity and specificity in children.
Journal Article > ResearchFull Text
Clin Infect Dis. 2020 January 9; Volume 71 (Issue 8); 1973-1976.; DOI:10.1093/cid/ciaa024
Sossen B, Broger T, Kerkhoff AD, Schutz C, Trollip AP, et al.
Clin Infect Dis. 2020 January 9; Volume 71 (Issue 8); 1973-1976.; DOI:10.1093/cid/ciaa024
Reducing diagnostic delay is key towards decreasing tuberculosis-associated deaths in people living with HIV. In tuberculosis patients with retrospective urine testing, the point-of-care Fujifilm SILVAMP TB LAM (FujiLAM) could have rapidly diagnosed tuberculosis in up to 89% who died. In FujiLAM negative patients, the probability of 12-week survival was 86-97%.
Journal Article > ResearchAbstract Only
J. Infect.. 2022 May 16; Volume S0163-4453 (Issue 22); 00292-4.; DOI:10.1016/j.jinf.2022.05.010
Dhana A, Hamada Y, Kengne AP, Kerkhoff AD, Broger T, et al.
J. Infect.. 2022 May 16; Volume S0163-4453 (Issue 22); 00292-4.; DOI:10.1016/j.jinf.2022.05.010
BACKGROUND
WHO recommends urine lateral-flow lipoarabinomannan (LF-LAM) testing with AlereLAM in HIV-positive inpatients only if screening criteria are met. We assessed the performance of WHO screening criteria and alternative screening tests/strategies to guide LF-LAM testing and compared diagnostic accuracy of the WHO AlereLAM algorithm (WHO screening criteria → AlereLAM) with AlereLAM and FujiLAM (a novel LF-LAM test).
METHODS
We searched MEDLINE, Embase, and Cochrane Library from Jan 1, 2011 to March 1, 2020 for studies among adult/adolescent HIV-positive inpatients regardless of tuberculosis signs and symptoms. The reference standards were 1) AlereLAM or FujiLAM for screening tests/strategies and 2) culture or Xpert for AlereLAM/FujiLAM. We determined proportion of inpatients eligible for AlereLAM using WHO screening criteria; assessed accuracy of WHO criteria and alternative screening tests/strategies to guide LF-LAM testing; compared accuracy of WHO AlereLAM algorithm with AlereLAM/FujiLAM in all; and determined diagnostic yield of AlereLAM, FujiLAM, and Xpert MTB/RIF (Xpert). We estimated pooled proportions with a random-effects model, assessed diagnostic accuracy using random-effects bivariate models, and assessed diagnostic yield descriptively.
FINDINGS
We obtained data from all 5 identified studies (n=3,504). The pooled proportion of inpatients eligible for AlereLAM using WHO criteria was 93% (95%CI 91, 95). Among screening tests/strategies to guide LF-LAM testing, WHO criteria, C-reactive protein (≥5 mg/L), and CD4 count (<200 cells/μL) had high sensitivities but low specificities; cough (≥2 weeks), haemoglobin (<8 g/dL), body mass index (<18.5 kg/m2), lymphadenopathy, and WHO-defined danger signs had higher specificities but suboptimal sensitivities. AlereLAM in all had the same sensitivity (62%) and specificity (88%) as WHO AlereLAM algorithm. Sensitivity of FujiLAM and AlereLAM was 69% and 48%, while specificity was 48% and 96%, respectively. Diagnostic yield of sputum Xpert was 29-41%, AlereLAM was 39-76%, and urine Xpert was 35-62%. In one study, FujiLAM diagnosed 80% of tuberculosis cases (vs 39% for AlereLAM), and sputum Xpert combined with AlereLAM, urine Xpert, or FujiLAM diagnosed 69%, 81%, and 92% of all cases, respectively.
INTERPRETATION
WHO criteria and alternative screening tests/strategies have limited utility in guiding LF-LAM testing, suggesting that AlereLAM testing in all HIV-positive medical inpatients be implemented. Routine FujiLAM may improve tuberculosis diagnosis.
WHO recommends urine lateral-flow lipoarabinomannan (LF-LAM) testing with AlereLAM in HIV-positive inpatients only if screening criteria are met. We assessed the performance of WHO screening criteria and alternative screening tests/strategies to guide LF-LAM testing and compared diagnostic accuracy of the WHO AlereLAM algorithm (WHO screening criteria → AlereLAM) with AlereLAM and FujiLAM (a novel LF-LAM test).
METHODS
We searched MEDLINE, Embase, and Cochrane Library from Jan 1, 2011 to March 1, 2020 for studies among adult/adolescent HIV-positive inpatients regardless of tuberculosis signs and symptoms. The reference standards were 1) AlereLAM or FujiLAM for screening tests/strategies and 2) culture or Xpert for AlereLAM/FujiLAM. We determined proportion of inpatients eligible for AlereLAM using WHO screening criteria; assessed accuracy of WHO criteria and alternative screening tests/strategies to guide LF-LAM testing; compared accuracy of WHO AlereLAM algorithm with AlereLAM/FujiLAM in all; and determined diagnostic yield of AlereLAM, FujiLAM, and Xpert MTB/RIF (Xpert). We estimated pooled proportions with a random-effects model, assessed diagnostic accuracy using random-effects bivariate models, and assessed diagnostic yield descriptively.
FINDINGS
We obtained data from all 5 identified studies (n=3,504). The pooled proportion of inpatients eligible for AlereLAM using WHO criteria was 93% (95%CI 91, 95). Among screening tests/strategies to guide LF-LAM testing, WHO criteria, C-reactive protein (≥5 mg/L), and CD4 count (<200 cells/μL) had high sensitivities but low specificities; cough (≥2 weeks), haemoglobin (<8 g/dL), body mass index (<18.5 kg/m2), lymphadenopathy, and WHO-defined danger signs had higher specificities but suboptimal sensitivities. AlereLAM in all had the same sensitivity (62%) and specificity (88%) as WHO AlereLAM algorithm. Sensitivity of FujiLAM and AlereLAM was 69% and 48%, while specificity was 48% and 96%, respectively. Diagnostic yield of sputum Xpert was 29-41%, AlereLAM was 39-76%, and urine Xpert was 35-62%. In one study, FujiLAM diagnosed 80% of tuberculosis cases (vs 39% for AlereLAM), and sputum Xpert combined with AlereLAM, urine Xpert, or FujiLAM diagnosed 69%, 81%, and 92% of all cases, respectively.
INTERPRETATION
WHO criteria and alternative screening tests/strategies have limited utility in guiding LF-LAM testing, suggesting that AlereLAM testing in all HIV-positive medical inpatients be implemented. Routine FujiLAM may improve tuberculosis diagnosis.