Conference Material > Abstract
Arago M, Mangue M, Cumbi N, Zamudio AG, Loarec A, et al.
MSF Scientific Days International 2021: Innovation. 2021 May 20
WHAT CHALLENGE OR OPPORTUNITY DID YOU TRY TO ADDRESS? WERE EXISTING SOLUTIONS NOT AVAILABLE OR NOT GOOD ENOUGH?
Ototoxicity is an unfortunate side-effect of second-line injectable drugs for drug-resistant tuberculosis (DRTB), including aminoglycosides and peptides. Worldwide, up to 15% of patients on treatment regimens containing these drugs develop a degree of ototoxicity. Patients who experience ototoxicity are generally switched to an oral treatment regimen. Although regular audiological evaluations are recommended for patients receiving these drugs, there is limited access to these services, and few patients with noticeable hearing problems are referred for confirmation and follow-up.
WHY DOES THIS CHALLENGE OR OPPORTUNITY MATTER – WHY SHOULD MSF ADDRESS IT?
Before the introduction of this digital tool, the MSF DRTB project in Mozambique had to refer patients to the Central Hospital in Maputo. This limited the number of patients screened and referred for testing, curtailing the potential to switch treatment early for those showing mild-to-moderate hearing loss.
DESCRIBE YOUR INNOVATION AND WHAT MAKES IT INNOVATIVE
In 2018, the team piloted a way to simplify monitoring of hearing using a clinically approved mobile tablet-based tool that has been found to be comparable with traditional audiometry measurements in children and adults. MSF acquired three kits of CE-marked and FDA-certified iOS-based audiometry kits from SHOEBOX® Audiometry systems. The units were comprised of calibrated headphones and tablet-based software that have acceptable accuracy (±10dB) with 90% sensitivity and specificity. The portable units were deployed in rotation in six health centres over two years; a total of 673 audiometry tests were performed in MSF-supported public health centres in Maputo. Patients were tested at baseline during their first consultation and then monthly while on treatment regimens that included injectable drugs.
WHO WILL BENEFIT (WHOSE LIFE / WORK WILL IT IMPROVE?) AND WERE THEY INVOLVED IN THE DESIGN?
The 2018 Mozambique National TB Committee approved treatment without injectable drugs in patients who had any degree of hearing impairment before the initiation of treatment. Patients screened using the digital tool directly benefitted from switching to oral DRTB treatment if they exhibited any hearing loss, without requiring hospital referral.
WHAT OBJECTIVES DID YOU SET FOR THE PROJECT – WHAT DID YOU WANT TO ACHIEVE AND HOW DID YOU DEFINE AND MEASURE SUCCESS (IMPROVED SERVICE, LOWER COST, BETTER EFFICIENCY, BETTER USER EXPERIENCE, ETC.)?
We describe the implementation and use of a mobile audiometry system for patients with treatment-related ototoxicity in the MSF DRTB project in Mozambique, and consider its potential for easily assessing hearing deterioration in this cohort.
WHAT DATA DID YOU COLLECT TO MEASURE THE INNOVATION AGAINST THESE INDICATORS AND HOW DID YOU COLLECT IT? INCLUDE IF YOU DECIDED TO CHANGE THE INDICATORS AND WHY
Routinely collected data were evaluated.
WERE THERE ANY LIMITATIONS TO THE DATA YOU COLLECTED, HOW YOU COLLECTED IT OR HOW YOU ANALYSED IT, OR WERE THERE ANY UNFORESEEN FACTORS THAT MAY HAVE INTERFERED WITH YOUR RESULTS?
Data were analysed retrospectively from routine records and may not be exhaustive. Separate analysis of baseline and follow-up was not possible.
WHAT RESULTS DID YOU GET?
Of the 673 audiometry tests conducted using the digital tool, 480 (71%) showed normal hearing, 65 (10%) mild hearing loss, 81 (12%) moderate hearing loss, and 47 (7%) severe-to-profound hearing loss.
COMPARING THE RESULTS FROM YOUR DATA ANALYSIS TO YOUR OBJECTIVES, EXPLAIN WHY YOU CONSIDER YOUR INNOVATION A SUCCESS OR FAILURE?
This decentralised approach does not need specialised setup, which may lead to increased screening, proper follow-up, and more potential for early switching of drug regimens.
TO WHAT EXTENT DID THE INNOVATION BENEFIT PEOPLE’S LIVES / WORK?
Decreasing the need for hospital referrals improved time and transport costs for patients.
IS THERE ANYTHING THAT YOU WOULD DO DIFFERENTLY IF YOU WERE TO DO THE WORK AGAIN?:
A cost-benefit analysis to compare the mobile audiometry system to referrals would be beneficial for programmatic decisions.
WHAT ARE THE NEXT STEPS FOR THE INNOVATION ITSELF (SCALE UP, IMPLEMENTATION, FURTHER DEVELOPMENT, DISCONTINUED)?
In December 2019, the project was phased out as there was a protocol change in which injectable drugs were replaced with more potent and fully oral regimens that made monitoring for ototoxicity unnecessary for most patients.
IS THE INNOVATION TRANSFERABLE OR ADAPTABLE TO OTHER SETTINGS OR DOMAINS?
The tools adapted are clinically approved for screening activities for any programmes that deal with hearing loss.
WHAT BROADER IMPLICATIONS ARE THERE FROM THE INNOVATION FOR MSF AND / OR OTHERS (CHANGE IN PRACTICE, CHANGE IN POLICY, CHANGE IN GUIDELINES, PARADIGM SHIFT)?
The project demonstrates the potential to improve follow-up and detect complications early for patients who take ototoxic medications.
WHAT OTHER LEARNINGS FROM YOUR WORK ARE IMPORTANT TO SHARE?
User-friendly and automated audiometry systems that are mobile and do not require audiologists or sound-insulated booths could be extremely useful to various medical projects using potentially ototoxic drugs such as aminoglycosides. They may also be beneficial for environmental projects with noise and toxic pollutions. The high cost of the license could present a limitation necessitating a cost-benefit analysis before contemplating scale-up.
ETHICS
This description and evaluation of an innovation project involved human participants or their data, and has had ethics oversight from Monica Rull, Medical Director, Operational Centre Geneva, MSF.
Ototoxicity is an unfortunate side-effect of second-line injectable drugs for drug-resistant tuberculosis (DRTB), including aminoglycosides and peptides. Worldwide, up to 15% of patients on treatment regimens containing these drugs develop a degree of ototoxicity. Patients who experience ototoxicity are generally switched to an oral treatment regimen. Although regular audiological evaluations are recommended for patients receiving these drugs, there is limited access to these services, and few patients with noticeable hearing problems are referred for confirmation and follow-up.
WHY DOES THIS CHALLENGE OR OPPORTUNITY MATTER – WHY SHOULD MSF ADDRESS IT?
Before the introduction of this digital tool, the MSF DRTB project in Mozambique had to refer patients to the Central Hospital in Maputo. This limited the number of patients screened and referred for testing, curtailing the potential to switch treatment early for those showing mild-to-moderate hearing loss.
DESCRIBE YOUR INNOVATION AND WHAT MAKES IT INNOVATIVE
In 2018, the team piloted a way to simplify monitoring of hearing using a clinically approved mobile tablet-based tool that has been found to be comparable with traditional audiometry measurements in children and adults. MSF acquired three kits of CE-marked and FDA-certified iOS-based audiometry kits from SHOEBOX® Audiometry systems. The units were comprised of calibrated headphones and tablet-based software that have acceptable accuracy (±10dB) with 90% sensitivity and specificity. The portable units were deployed in rotation in six health centres over two years; a total of 673 audiometry tests were performed in MSF-supported public health centres in Maputo. Patients were tested at baseline during their first consultation and then monthly while on treatment regimens that included injectable drugs.
WHO WILL BENEFIT (WHOSE LIFE / WORK WILL IT IMPROVE?) AND WERE THEY INVOLVED IN THE DESIGN?
The 2018 Mozambique National TB Committee approved treatment without injectable drugs in patients who had any degree of hearing impairment before the initiation of treatment. Patients screened using the digital tool directly benefitted from switching to oral DRTB treatment if they exhibited any hearing loss, without requiring hospital referral.
WHAT OBJECTIVES DID YOU SET FOR THE PROJECT – WHAT DID YOU WANT TO ACHIEVE AND HOW DID YOU DEFINE AND MEASURE SUCCESS (IMPROVED SERVICE, LOWER COST, BETTER EFFICIENCY, BETTER USER EXPERIENCE, ETC.)?
We describe the implementation and use of a mobile audiometry system for patients with treatment-related ototoxicity in the MSF DRTB project in Mozambique, and consider its potential for easily assessing hearing deterioration in this cohort.
WHAT DATA DID YOU COLLECT TO MEASURE THE INNOVATION AGAINST THESE INDICATORS AND HOW DID YOU COLLECT IT? INCLUDE IF YOU DECIDED TO CHANGE THE INDICATORS AND WHY
Routinely collected data were evaluated.
WERE THERE ANY LIMITATIONS TO THE DATA YOU COLLECTED, HOW YOU COLLECTED IT OR HOW YOU ANALYSED IT, OR WERE THERE ANY UNFORESEEN FACTORS THAT MAY HAVE INTERFERED WITH YOUR RESULTS?
Data were analysed retrospectively from routine records and may not be exhaustive. Separate analysis of baseline and follow-up was not possible.
WHAT RESULTS DID YOU GET?
Of the 673 audiometry tests conducted using the digital tool, 480 (71%) showed normal hearing, 65 (10%) mild hearing loss, 81 (12%) moderate hearing loss, and 47 (7%) severe-to-profound hearing loss.
COMPARING THE RESULTS FROM YOUR DATA ANALYSIS TO YOUR OBJECTIVES, EXPLAIN WHY YOU CONSIDER YOUR INNOVATION A SUCCESS OR FAILURE?
This decentralised approach does not need specialised setup, which may lead to increased screening, proper follow-up, and more potential for early switching of drug regimens.
TO WHAT EXTENT DID THE INNOVATION BENEFIT PEOPLE’S LIVES / WORK?
Decreasing the need for hospital referrals improved time and transport costs for patients.
IS THERE ANYTHING THAT YOU WOULD DO DIFFERENTLY IF YOU WERE TO DO THE WORK AGAIN?:
A cost-benefit analysis to compare the mobile audiometry system to referrals would be beneficial for programmatic decisions.
WHAT ARE THE NEXT STEPS FOR THE INNOVATION ITSELF (SCALE UP, IMPLEMENTATION, FURTHER DEVELOPMENT, DISCONTINUED)?
In December 2019, the project was phased out as there was a protocol change in which injectable drugs were replaced with more potent and fully oral regimens that made monitoring for ototoxicity unnecessary for most patients.
IS THE INNOVATION TRANSFERABLE OR ADAPTABLE TO OTHER SETTINGS OR DOMAINS?
The tools adapted are clinically approved for screening activities for any programmes that deal with hearing loss.
WHAT BROADER IMPLICATIONS ARE THERE FROM THE INNOVATION FOR MSF AND / OR OTHERS (CHANGE IN PRACTICE, CHANGE IN POLICY, CHANGE IN GUIDELINES, PARADIGM SHIFT)?
The project demonstrates the potential to improve follow-up and detect complications early for patients who take ototoxic medications.
WHAT OTHER LEARNINGS FROM YOUR WORK ARE IMPORTANT TO SHARE?
User-friendly and automated audiometry systems that are mobile and do not require audiologists or sound-insulated booths could be extremely useful to various medical projects using potentially ototoxic drugs such as aminoglycosides. They may also be beneficial for environmental projects with noise and toxic pollutions. The high cost of the license could present a limitation necessitating a cost-benefit analysis before contemplating scale-up.
ETHICS
This description and evaluation of an innovation project involved human participants or their data, and has had ethics oversight from Monica Rull, Medical Director, Operational Centre Geneva, MSF.
Journal Article > ResearchFull Text
Infect Agent Cancer. 2018 January 19; Volume 13 (Issue 1); DOI:10.1186/s13027-018-0177-6
Fardhdiani V, Molfino L, Zamudio AG, Manuel R, Luciano G, et al.
Infect Agent Cancer. 2018 January 19; Volume 13 (Issue 1); DOI:10.1186/s13027-018-0177-6
Kaposi's sarcoma (KS) is a common HIV-associated malignancy associated with disability, pain and poor outcomes. The cornerstone of its treatment is antiretroviral therapy, but advanced disease necessitates the addition of chemotherapy. In high-income settings, this often consists of liposomal anthracyclines, but in Mozambique, the first line includes conventional doxorubicin, bleomycin and vincristine, which is poorly-tolerated. Médecins Sans Frontières supports the Ministry of Health (MOH) in a specialized HIV and KS treatment center at the Centro de Referencia de Alto Maé in Maputo.
Journal Article > ResearchFull Text
AIDS. 2018 November 16; Volume 33 (Issue 2); DOI:10.1097/QAD.0000000000002070
Loarec A, Carnimeo V, Molfino L, Kizito W, Muyindike WR, et al.
AIDS. 2018 November 16; Volume 33 (Issue 2); DOI:10.1097/QAD.0000000000002070
: A multicentric, retrospective case-series analysis (facility-based) in five sites across Kenya, Malawi, Mozambique, and Uganda screened HIV-positive adults for hepatitis C virus (HCV) antibodies using Oraquick rapid testing and viral confirmation (in three sites). Results found substantially lower prevalence than previously reported for these countries compared with previous reports, suggesting that targeted integration of HCV screening in African HIV programs may be more impactful than routine screening.This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0.
Conference Material > Slide Presentation
Ansbro E, Masri S, Prieto-Merino D, Bahous SA, Molfino L, et al.
MSF Scientific Days International 2022. 2022 May 11; DOI:10.57740/mzsh-8t29
Journal Article > ResearchFull Text
Am J Trop Med Hyg. 2020 March 5; Volume 102 (Issue 3); 562-566.; DOI:10.4269/ajtmh.19-0493
Huerga H, Cossa L, Manhiça I, Bastard M, Telnov A, et al.
Am J Trop Med Hyg. 2020 March 5; Volume 102 (Issue 3); 562-566.; DOI:10.4269/ajtmh.19-0493
Point-of-care urine-lipoarabinomannan (LAM) Alere Determine TB-LAM assay has shown utility diagnosing tuberculosis (TB) in HIV-positive, severely immunocompromised, TB-symptomatic patients. We assessed LAM results in severely immunocompromised patients, who had LAM systematically performed at new or follow-up HIV consultations. This was a prospective, observational study on consecutive ambulatory, > 15-year-old HIV-positive patients with CD4 < 100 cells/µL in Mozambique. Clinical assessments and LAM were performed for all and microscopy, Xpert, sputum culture, and chest X-ray for LAM-positive participants. Patients were followed up for 6 months. Of 360 patients, half were ART-naive. Lipoarabinomannan positivity was 11.9% (43/360), higher among symptomatic patients compared with asymptomatic: 18.5% (30/162), and 6.6% (13/198), respectively, P = 0.001. Tuberculosis was bacteriologically confirmed in 6/35 LAM-positive patients (2 of them asymptomatic). Lipoarabinomannan positivity was associated with higher risk of mortality (adjusted odds ratio [aOR]: 4.6, 95% CI: 1.3–15.6, P = 0.015). Systematic urine-LAM allows for rapid TB treatment initiation in severely immunocompromised HIV ambulatory patients and identifies patients at a higher risk of death.
Journal Article > ResearchFull Text
Infect Agent Cancer. 2021 January 7; Volume 16 (Issue 1); DOI:10.1186/s13027-020-00341-4
Coldiron ME, Gutierrez Zamudio AG, Manuel R, Luciano G, Rusch B, et al.
Infect Agent Cancer. 2021 January 7; Volume 16 (Issue 1); DOI:10.1186/s13027-020-00341-4
BACKGROUND
Kaposi’s sarcoma (KS) is a common HIV-associated malignancy frequently associated with poor outcomes. It is the most frequently diagnosed cancer in major cities of Mozambique. Antiretroviral therapy is the cornerstone of KS treatment, but many patients require cytotoxic chemotherapy. The traditional regimen in Mozambique includes conventional doxorubicin, bleomycin and vincristine, which is poorly tolerated. In 2016, pegylated liposomal doxorubicin was introduced at a specialized outpatient center in Maputo, Mozambique.
METHODS
We performed a prospective, single-arm, open-label observational study to demonstrate the feasibility, safety, and outcomes of treatment with pegylated liposomal doxorubicin (PLD) in patients with AIDS-associated Kaposi sarcoma (KS) in a low-resource setting. Chemotherapy-naïve adults with AIDS-associated KS (T1 or T0 not responding to 6 months of antiretroviral therapy) were eligible if they were willing to follow up for 2 years. Patients with Karnofsky scores < 50 or contraindications to PLD were excluded. One hundred eighty-three patients were screened and 116 participants were enrolled. Patients received PLD on three-week cycles until meeting clinical stopping criteria. Follow-up visits monitored HIV status, KS disease, side effects of chemotherapy, mental health (PHQ-9) and quality of life (SF-12). Primary outcome measures included vital status and disease status at 6, 12, and 24 months after enrollment.
RESULTS
At 24 months, 23 participants (20%) had died and 15 (13%) were lost to follow-up. Baseline CD4 < 100 was associated with death (HR 2.7, 95%CI [1.2–6.2], p = 0.016), as was T1S1 disease compared to T1S0 disease (HR 2.7, 95%CI [1.1–6.4], p = 0.023). Ninety-two participants achieved complete or partial remission at any point (overall response rate 80%), including 15 (13%) who achieved complete remission. PLD was well-tolerated, and the most common AEs were neutropenia and anemia. Quality of life improved rapidly after beginning PLD.
DISCUSSION
PLD was safe, well-tolerated and effective as first-line treatment of KS in Mozambique. High mortality was likely due to advanced immunosuppression at presentation, underscoring the importance of earlier screening and referral for KS.
Kaposi’s sarcoma (KS) is a common HIV-associated malignancy frequently associated with poor outcomes. It is the most frequently diagnosed cancer in major cities of Mozambique. Antiretroviral therapy is the cornerstone of KS treatment, but many patients require cytotoxic chemotherapy. The traditional regimen in Mozambique includes conventional doxorubicin, bleomycin and vincristine, which is poorly tolerated. In 2016, pegylated liposomal doxorubicin was introduced at a specialized outpatient center in Maputo, Mozambique.
METHODS
We performed a prospective, single-arm, open-label observational study to demonstrate the feasibility, safety, and outcomes of treatment with pegylated liposomal doxorubicin (PLD) in patients with AIDS-associated Kaposi sarcoma (KS) in a low-resource setting. Chemotherapy-naïve adults with AIDS-associated KS (T1 or T0 not responding to 6 months of antiretroviral therapy) were eligible if they were willing to follow up for 2 years. Patients with Karnofsky scores < 50 or contraindications to PLD were excluded. One hundred eighty-three patients were screened and 116 participants were enrolled. Patients received PLD on three-week cycles until meeting clinical stopping criteria. Follow-up visits monitored HIV status, KS disease, side effects of chemotherapy, mental health (PHQ-9) and quality of life (SF-12). Primary outcome measures included vital status and disease status at 6, 12, and 24 months after enrollment.
RESULTS
At 24 months, 23 participants (20%) had died and 15 (13%) were lost to follow-up. Baseline CD4 < 100 was associated with death (HR 2.7, 95%CI [1.2–6.2], p = 0.016), as was T1S1 disease compared to T1S0 disease (HR 2.7, 95%CI [1.1–6.4], p = 0.023). Ninety-two participants achieved complete or partial remission at any point (overall response rate 80%), including 15 (13%) who achieved complete remission. PLD was well-tolerated, and the most common AEs were neutropenia and anemia. Quality of life improved rapidly after beginning PLD.
DISCUSSION
PLD was safe, well-tolerated and effective as first-line treatment of KS in Mozambique. High mortality was likely due to advanced immunosuppression at presentation, underscoring the importance of earlier screening and referral for KS.
Other > Pre-Print
F1000Research. 2019 February 8; Volume 8; 169.; DOI:10.12688/f1000research.17776.1
Baudin E, Bhatt NB, Rouzioux C, Serafini M, Molfino L, et al.
F1000Research. 2019 February 8; Volume 8; 169.; DOI:10.12688/f1000research.17776.1
BACKGROUND
In the CARINEMO ANRS 12146 clinical trial, HIV-tuberculosis co-infected patients in Mozambique were randomized to nevirapine (NVP) or to efavirenz (EFV)-based antiretroviral therapy to compare these two non-nucleoside reverse transcriptase inhibitors (NNRTIs) in treatment naïve patients.
METHODS
In this sub study, we explored the relationship of NNRTI concentrations with virological escape and the possible emergence of resistance mutations at week 48. The virological escape was defined as an HIV-RNA above 400 copies/m at week 48.
RESULTS
Among the 570 randomized patients, 470 (82%) had an HIV-RNA result at week 48; 54 (12.1%) patients had a viral escape and 35 patients had at least one major resistance mutation detected. Low drug concentration at weeks 12 and 24 (below the 10th percentile) were independently associated with virologic escape at week 48 (adjusted odds ratio [aOR]=2.9; 95% CI: 1.1 -7.2; p=0.0312 and aOR=4.2; 95% CI: 1.8-9.8; p=0.0019, respectively), and independently associated with an increased risk of emergence of resistance mutation (aOR=4.5; 95% CI: 1.8-14.6; p=0.009 at week 12; aOR=5.1; 95% CI: 1.8-14.6 at week 24). Receiver operating characteristic curves analyses indicated a better predictability of the mid-dose concentration and of the HIV-1 RNA values on resistance mutations in contrast to virological escape.
CONCLUSIONS
Very low drug plasma concentrations early after treatment initiation (week 12) were predictive factors of virological escape and the emergence of resistance mutations at week 48, and early monitoring of drug intake may prevent the occurrence of late virological escape and the selection of vial resistance mutations.
In the CARINEMO ANRS 12146 clinical trial, HIV-tuberculosis co-infected patients in Mozambique were randomized to nevirapine (NVP) or to efavirenz (EFV)-based antiretroviral therapy to compare these two non-nucleoside reverse transcriptase inhibitors (NNRTIs) in treatment naïve patients.
METHODS
In this sub study, we explored the relationship of NNRTI concentrations with virological escape and the possible emergence of resistance mutations at week 48. The virological escape was defined as an HIV-RNA above 400 copies/m at week 48.
RESULTS
Among the 570 randomized patients, 470 (82%) had an HIV-RNA result at week 48; 54 (12.1%) patients had a viral escape and 35 patients had at least one major resistance mutation detected. Low drug concentration at weeks 12 and 24 (below the 10th percentile) were independently associated with virologic escape at week 48 (adjusted odds ratio [aOR]=2.9; 95% CI: 1.1 -7.2; p=0.0312 and aOR=4.2; 95% CI: 1.8-9.8; p=0.0019, respectively), and independently associated with an increased risk of emergence of resistance mutation (aOR=4.5; 95% CI: 1.8-14.6; p=0.009 at week 12; aOR=5.1; 95% CI: 1.8-14.6 at week 24). Receiver operating characteristic curves analyses indicated a better predictability of the mid-dose concentration and of the HIV-1 RNA values on resistance mutations in contrast to virological escape.
CONCLUSIONS
Very low drug plasma concentrations early after treatment initiation (week 12) were predictive factors of virological escape and the emergence of resistance mutations at week 48, and early monitoring of drug intake may prevent the occurrence of late virological escape and the selection of vial resistance mutations.
Conference Material > Poster
Antabak NT, Loarec A, Nguyen AP, Eliseo NDM, Molfino L, et al.
MSF Scientific Days UK 2018: Research. 2018 May 4; DOI:10.7490/f1000research.1115424.1
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.
Journal Article > Short ReportFull Text
Clin Infect Dis. 2019 March 11; Volume 69 (Issue 10); 1809-1811.; DOI:10.1093/cid/ciz196
Bastard M, Molfino L, Mutaquiha C, Galindo MA, Zindoga P, et al.
Clin Infect Dis. 2019 March 11; Volume 69 (Issue 10); 1809-1811.; DOI:10.1093/cid/ciz196
Bedaquiline was recommended by WHO as the preferred option in treatment of MDR-TB patients with long regimen. However, no recommendation was given for the short MDR-TB regimen. Data from our small cohort of patients who switched injectable dug to bedaquiline suggest that bedaquiline based short regimen is effective and safe.