Journal Article > ResearchFull Text
J Trop Med. 3 November 2024; Online ahead of print; DOI:10.1111/tmi.14053
Melingui BF, Basant J, Taguebue Jv, Massom DM, Leroy Terquem E, et al.
J Trop Med. 3 November 2024; Online ahead of print; DOI:10.1111/tmi.14053
OBJECTIVES
Chest x‐ray (CXR) plays an important role in childhood tuberculosis (TB) diagnosis, but access to quality CXR remains a major challenge in resource‐limited settings. Digital CXR (d‐CXR) can solve some image quality issues and facilitate their transfer for quality control. We assess the implementation of introducing d‐CXR in 12 district hospitals (DHs) in 2021–2022 across Cambodia, Cameroon, Ivory Coast, Mozambique, Sierra Leone and Uganda as part of the TB‐speed decentralisation study on childhood TB diagnosis.
METHODS
For digitisation of CXR, digital radiography (DR) plates were setup on existing analogue radiography devices. d‐CXR were transferred to an international server at Bordeaux University and downloaded by sites' clinicians for interpretation. We assessed the uptake and performance of CXR services and health care workers' (HCW) perceptions of d‐CXR implementation. We used a convergent mixed method approach utilising process data, individual interviews with 113 HCWs involved in performing or interpreting d‐CXRs and site support supervision reports.
RESULTS
Of 3104 children with presumptive TB, 1642 (52.9%) had at least one d‐CXR, including 1505, 136 and 1 children with one, two and three d‐CXRs, respectively, resulting in a total of 1780 d‐CXR. Of them, 1773 (99.6%) were of good quality and 1772/1773 (99.9%) were interpreted by sites' clinicians. One hundred and sixty‐four children had no d‐CXR performed despite attending the radiography department: 126, 37 and 1 with one, two and three attempts, respectively. d‐CXRs were not performed in 21.6% (44/203) due to connectivity problem between the DR plate captor and the computer. HCW reported good perceptions of d‐CXR and of the DR plates provided. The main challenge was the upload to and download from the server of d‐CXRs due to limited internet access.
CONCLUSION
d‐CXR using DR plates was feasible at DH level and provided good quality images but required overcoming operational challenges.
Journal Article > ResearchFull Text
E Clinical Medicine. 21 March 2024; Volume 70; 102528.; DOI:10.1016/j.eclinm.2024.102528
d’Elbée M, Harker M, Mafirakureva N, Nanfuka M, Nguyet MHTN, et al.
E Clinical Medicine. 21 March 2024; Volume 70; 102528.; DOI:10.1016/j.eclinm.2024.102528
Journal Article > ResearchFull Text
ACG Case Rep J. 21 March 2024; Volume 70; 102527.; DOI:10.1016/j.eclinm.2024.102527
Wobudeya E, Nanfuka M, Ton Nu Nguyet MH, Taguebue JV, Moh R, et al.
ACG Case Rep J. 21 March 2024; Volume 70; 102527.; DOI:10.1016/j.eclinm.2024.102527
BACKGROUND
Childhood tuberculosis (TB) remains underdiagnosed largely because of limited awareness and poor access to all or any of specimen collection, molecular testing, clinical evaluation, and chest radiography at low levels of care. Decentralising childhood TB diagnostics to district hospitals (DH) and primary health centres (PHC) could improve case detection.
METHODS
We conducted an operational research study using a pre-post intervention cross-sectional study design in 12 DHs and 47 PHCs of 12 districts across Cambodia, Cameroon, Côte d'Ivoire, Mozambique, Sierra Leone and Uganda. The intervention included 1) a comprehensive diagnosis package at patient-level with tuberculosis screening for all sick children and young adolescents <15 years, and clinical evaluation, Xpert Ultra-testing on respiratory and stool samples, and chest radiography for children with presumptive TB, and 2) two decentralisation approaches (PHC-focused or DH-focused) to which districts were randomly allocated at country level. We collected aggregated and individual data. We compared the proportion of tuberculosis detection in children and young adolescents <15 years pre-intervention (01 August 2018-30 November 2019) versus during intervention (07 March 2020-30 September 2021), overall and by decentralisation approach. This study is registered with ClinicalTrials.gov, NCT04038632.
FINDINGS
TB was diagnosed in 217/255,512 (0.08%) children and young adolescent <15 years attending care pre-intervention versus 411/179,581 (0.23%) during intervention, (OR: 3.59 [95% CI 1.99-6.46], p-value<0.0001; p-value = 0.055 after correcting for over-dispersion). In DH-focused districts, TB diagnosis was 80/122,570 (0.07%) versus 302/86,186 (0.35%) (OR: 4.07 [1.86-8.90]; p-value = 0.0005; p-value = 0.12 after correcting for over-dispersion); and 137/132,942 (0.10%) versus 109/93,395 (0.11%) in PHC-focused districts, respectively (OR: 2.92 [1.25-6.81; p-value = 0.013; p-value = 0.26 after correcting for over-dispersion).
INTERPRETATION
Decentralising and strengthening childhood TB diagnosis at lower levels of care increases tuberculosis case detection but the difference was not statistically significant.
Childhood tuberculosis (TB) remains underdiagnosed largely because of limited awareness and poor access to all or any of specimen collection, molecular testing, clinical evaluation, and chest radiography at low levels of care. Decentralising childhood TB diagnostics to district hospitals (DH) and primary health centres (PHC) could improve case detection.
METHODS
We conducted an operational research study using a pre-post intervention cross-sectional study design in 12 DHs and 47 PHCs of 12 districts across Cambodia, Cameroon, Côte d'Ivoire, Mozambique, Sierra Leone and Uganda. The intervention included 1) a comprehensive diagnosis package at patient-level with tuberculosis screening for all sick children and young adolescents <15 years, and clinical evaluation, Xpert Ultra-testing on respiratory and stool samples, and chest radiography for children with presumptive TB, and 2) two decentralisation approaches (PHC-focused or DH-focused) to which districts were randomly allocated at country level. We collected aggregated and individual data. We compared the proportion of tuberculosis detection in children and young adolescents <15 years pre-intervention (01 August 2018-30 November 2019) versus during intervention (07 March 2020-30 September 2021), overall and by decentralisation approach. This study is registered with ClinicalTrials.gov, NCT04038632.
FINDINGS
TB was diagnosed in 217/255,512 (0.08%) children and young adolescent <15 years attending care pre-intervention versus 411/179,581 (0.23%) during intervention, (OR: 3.59 [95% CI 1.99-6.46], p-value<0.0001; p-value = 0.055 after correcting for over-dispersion). In DH-focused districts, TB diagnosis was 80/122,570 (0.07%) versus 302/86,186 (0.35%) (OR: 4.07 [1.86-8.90]; p-value = 0.0005; p-value = 0.12 after correcting for over-dispersion); and 137/132,942 (0.10%) versus 109/93,395 (0.11%) in PHC-focused districts, respectively (OR: 2.92 [1.25-6.81; p-value = 0.013; p-value = 0.26 after correcting for over-dispersion).
INTERPRETATION
Decentralising and strengthening childhood TB diagnosis at lower levels of care increases tuberculosis case detection but the difference was not statistically significant.
Journal Article > ResearchFull Text
J Acquir Immune Defic Syndr; JAIDS. 1 March 2024; Online ahead of print; DOI:10.1097/QAI.0000000000003404
Ben Farhat J, TiendrebeogoMD T, Malateste K, Poda A, Minga A, et al.
J Acquir Immune Defic Syndr; JAIDS. 1 March 2024; Online ahead of print; DOI:10.1097/QAI.0000000000003404
Français
OBJECTIVES
Efforts to control the COVID-19 pandemic have potentially compromised the availability and/or quality of HIV services. We aimed to assess the pandemic’s impact on ART initiation and HIV viral load (VL) monitoring in three West African countries.
METHODS
We used routinely collected data from five clinics contributing to the IeDEA collaboration in Burkina Faso, Côte d'Ivoire and Nigeria. We included ART-naïve adults living with HIV (ALWH) initiating ART from 01/01/2018. We conducted regression discontinuity analysis to estimate changes in the number of ART initiations and VL measures per week, before and during the pandemic period in each country.
RESULTS
In clinics in Burkina Faso and Côte d’Ivoire, ART initiations per week remained constant throughout the studied periods (-0.24 points (p) of ART initiations/week 95%CI -5.5, 5.9, -0.9 p 95%CI -8.5,8.6, respectively), whereas in Nigeria’s clinic, they decreased significantly (-6.3 p, 95% CI -10.8, -1.7) after the beginning of the pandemic. The volume of VL tests performed decreased significantly in all three countries (-17.0 p 95%CI -25.3, -8.6 in Burkina Faso, -118.4 p 95%CI -171.1, -65.8 in Côte d’Ivoire and -169.1p 95%CI-282.6, -55.6 in Nigeria).
CONCLUSIONS
Access to ART was maintained for newly diagnosed ALWH despite pandemic-related physical/social distancing measures. However, VL monitoring was severely disrupted and did not return to pre-pandemic levels approximately one year after the beginning of the pandemic. While HIV services in West Africa appear rather resilient, the impact of disruptions in VL monitoring on virological and clinical outcomes should continue to be monitored.
Efforts to control the COVID-19 pandemic have potentially compromised the availability and/or quality of HIV services. We aimed to assess the pandemic’s impact on ART initiation and HIV viral load (VL) monitoring in three West African countries.
METHODS
We used routinely collected data from five clinics contributing to the IeDEA collaboration in Burkina Faso, Côte d'Ivoire and Nigeria. We included ART-naïve adults living with HIV (ALWH) initiating ART from 01/01/2018. We conducted regression discontinuity analysis to estimate changes in the number of ART initiations and VL measures per week, before and during the pandemic period in each country.
RESULTS
In clinics in Burkina Faso and Côte d’Ivoire, ART initiations per week remained constant throughout the studied periods (-0.24 points (p) of ART initiations/week 95%CI -5.5, 5.9, -0.9 p 95%CI -8.5,8.6, respectively), whereas in Nigeria’s clinic, they decreased significantly (-6.3 p, 95% CI -10.8, -1.7) after the beginning of the pandemic. The volume of VL tests performed decreased significantly in all three countries (-17.0 p 95%CI -25.3, -8.6 in Burkina Faso, -118.4 p 95%CI -171.1, -65.8 in Côte d’Ivoire and -169.1p 95%CI-282.6, -55.6 in Nigeria).
CONCLUSIONS
Access to ART was maintained for newly diagnosed ALWH despite pandemic-related physical/social distancing measures. However, VL monitoring was severely disrupted and did not return to pre-pandemic levels approximately one year after the beginning of the pandemic. While HIV services in West Africa appear rather resilient, the impact of disruptions in VL monitoring on virological and clinical outcomes should continue to be monitored.
Journal Article > ResearchFull Text
IJTLD OPEN. 1 February 2024; Volume 1 (Issue 2); 76-82.; DOI:10.5588/ijtldopen.23.0484
Melingui BF, Leroy-Terquem E, Palmer M, Taguebue JV, Wachinou AP, et al.
IJTLD OPEN. 1 February 2024; Volume 1 (Issue 2); 76-82.; DOI:10.5588/ijtldopen.23.0484
BACKGROUND
Chest X-ray (CXR) interpretation is challenging for the diagnosis of paediatric TB. We assessed the performance of a three half-day CXR training module for healthcare workers (HCWs) at low healthcare levels in six high TB incidence countries.
METHODS
Within the TB-Speed Decentralization Study, we developed a three half-day training course to identify normal CXR, CXR of good quality and identify six TB-suggestive features. We performed a pre–post training assessment on a pre-defined set of 20 CXR readings. We compared the proportion of correctly interpreted CXRs and the median reading score before and after the training using the McNemar test and a linear mixed model.
RESULTS
Of 191 HCWs, 43 (23%) were physicians, 103 (54%) nurses, 18 (9.4%) radiology technicians and 12 (6.3%) other professionals. Of 2,840 CXRs with both assessment, respectively 1,843 (64.9%) and 2,277 (80.2%) were correctly interpreted during pre-training and post-training (P < 0.001). The median reading score improved significantly from 13/20 to 16/20 after the training, after adjusting by country, facility and profession (adjusted β = 3.31, 95% CI 2.44–4.47).
CONCLUSION
Despite some limitations of the course assessment that did not include abnormal non-TB suggestive CXR, study findings suggest that a short CXR training course could improve HCWs’ interpretation skills in diagnosing paediatric TB.
Chest X-ray (CXR) interpretation is challenging for the diagnosis of paediatric TB. We assessed the performance of a three half-day CXR training module for healthcare workers (HCWs) at low healthcare levels in six high TB incidence countries.
METHODS
Within the TB-Speed Decentralization Study, we developed a three half-day training course to identify normal CXR, CXR of good quality and identify six TB-suggestive features. We performed a pre–post training assessment on a pre-defined set of 20 CXR readings. We compared the proportion of correctly interpreted CXRs and the median reading score before and after the training using the McNemar test and a linear mixed model.
RESULTS
Of 191 HCWs, 43 (23%) were physicians, 103 (54%) nurses, 18 (9.4%) radiology technicians and 12 (6.3%) other professionals. Of 2,840 CXRs with both assessment, respectively 1,843 (64.9%) and 2,277 (80.2%) were correctly interpreted during pre-training and post-training (P < 0.001). The median reading score improved significantly from 13/20 to 16/20 after the training, after adjusting by country, facility and profession (adjusted β = 3.31, 95% CI 2.44–4.47).
CONCLUSION
Despite some limitations of the course assessment that did not include abnormal non-TB suggestive CXR, study findings suggest that a short CXR training course could improve HCWs’ interpretation skills in diagnosing paediatric TB.
Journal Article > ResearchFull Text
PLOS Glob Public Health. 11 October 2023; Volume 3 (Issue 10); e0001525.; DOI:10.1371/journal.pgph.0001525
Joshi B, De Lima YV, Massom DM, Kaing S, Banga MF, et al.
PLOS Glob Public Health. 11 October 2023; Volume 3 (Issue 10); e0001525.; DOI:10.1371/journal.pgph.0001525
Decentralizing childhood tuberculosis services, including diagnosis, is now recommended by the WHO and could contribute to increasing tuberculosis detection in high burden countries. However, implementing microbiological tests and clinical evaluation could be challenging for health care workers (HCWs) in Primary Health Centers (PHCs) and even District Hospitals (DHs). We sought to assess the acceptability of decentralizing a comprehensive childhood tuberculosis diagnosis package from HCWs’ perspective. We conducted implementation research nested within the TB-Speed Decentralization study. HCWs from two health districts of Cambodia, Cameroon, Côte d’Ivoire, Mozambique, Sierra Leone, and Uganda implemented systematic screening, nasopharyngeal aspirates (NPA) and stool sample collection with molecular testing, clinical evaluation and chest X-ray (CXR) interpretation. We investigated their experiences and perceptions in delivering the diagnostic package components in 2020–21 using individual semi-structured interviews. We conducted thematic analysis, supported by the Theoretical Framework of Acceptability. HCWs (n = 130, 55% female, median age 36 years, 53% nurses, 72% PHC-based) perceived that systematic screening, although increasing workload, was beneficial as it improved childhood tuberculosis awareness. Most HCWs shared satisfaction and confidence in performing NPA, despite procedure duration, need to involve parents/colleagues and discomfort for children. HCWs shared positive attitudes towards stool sample-collection but were frustrated by delayed stool collection associated with cultural practices, transport and distance challenges. Molecular testing, conducted by nurses or laboratory technicians, was perceived as providing quality results, contributing to diagnosis. Clinical evaluation and diagnosis raised self-efficacy issues and need for continuous training and clinical mentoring. HCWs valued CXR, however complained that technical and logistical problems limited access to digital reports. Referral from PHC to DH was experienced as burdensome. HCWs at DH and PHC-levels perceived and experienced decentralized childhood tuberculosis diagnosis as acceptable. Implementation however could be hampered by feasibility issues, and calls for innovative referral mechanisms for patients, samples and CXR.
Conference Material > Abstract
Natukunda N
Epicentre Scientific Day Paris 2023. 8 June 2023
BACKGROUND
Childhood tuberculosis is underdiagnosed at low-level healthcare settings because of poor access to specimen collection, rapid molecular testing, clinical evaluation and chest radiography. Decentralizing childhood tuberculosis diagnosis at district hospital (DH) and primary health centre (PHC) levels could improve case detection.
METHODS
TB-Speed decentralisation is an operational research using a pre-post intervention cross-sectional design in 12 DHs and 47 PHCs of 12 districts in Cambodia, Cameroon, Côte d’Ivoire, Mozambique, Sierra Leone and Uganda. The intervention included a comprehensive childhood tuberculosis diagnosis package consisting of systematic tuberculosis screening for all under-15-year-old sick children, clinical evaluation, Xpert Ultra-testing on one nasopharyngeal aspirate (NPA) and stool samples, and chest radiography for children with presumptive tuberculosis, using either PHC-focused or DH-focused decentralization approaches. We collected aggregated and individual data for children whose parents consented. We present the comparison of the proportion of tuberculosis case detected pre-intervention from August 2018 to Nov 2019 versus post-intervention from March 2020 to September 2021, overall and by decentralization approach, and the uptake and acceptability of the diagnostic package in Uganda.
FINDINGS
In Uganda, 52233 and 46035 children attended care pre-intervention versus post-intervention respectively. 26/52233 (0.05%) and 42/46035 (0.09%) children were diagnosed with tuberculosis pre-intervention and post-intervention respectively, p-value=0.114. In DH-focused district, it was 10/24208 (0.04%) and 23/17914 (0.1%) pre-intervention and post-intervention respectively, and 16/28025 (0.06%) and 19/28121 (0.1%) for PHC-districts, respectively. The uptake of TB screening was 43104/46035 (93.6%) overall, among the 732 enrolled children 724/ and 532 had a valid Ultra result using NPA and stool, respectively. Health care workers overall experienced decentralized childhood TB diagnostic as acceptable, with NPA and stool sample collection feasible both at DH and PHC.
CONCLUSION
Decentralizing innovative childhood tuberculosis diagnosis can increase tuberculosis case detection with limited impact when using the PHC decentralization approach.
KEY MESSAGE
Although decentralizing childhood TB diagnosis is acceptable, overcoming feasibility issues may improve the effective implementation and scale-up of such interventions at low levels of care.
This abstract is not to be quoted for publication.
Childhood tuberculosis is underdiagnosed at low-level healthcare settings because of poor access to specimen collection, rapid molecular testing, clinical evaluation and chest radiography. Decentralizing childhood tuberculosis diagnosis at district hospital (DH) and primary health centre (PHC) levels could improve case detection.
METHODS
TB-Speed decentralisation is an operational research using a pre-post intervention cross-sectional design in 12 DHs and 47 PHCs of 12 districts in Cambodia, Cameroon, Côte d’Ivoire, Mozambique, Sierra Leone and Uganda. The intervention included a comprehensive childhood tuberculosis diagnosis package consisting of systematic tuberculosis screening for all under-15-year-old sick children, clinical evaluation, Xpert Ultra-testing on one nasopharyngeal aspirate (NPA) and stool samples, and chest radiography for children with presumptive tuberculosis, using either PHC-focused or DH-focused decentralization approaches. We collected aggregated and individual data for children whose parents consented. We present the comparison of the proportion of tuberculosis case detected pre-intervention from August 2018 to Nov 2019 versus post-intervention from March 2020 to September 2021, overall and by decentralization approach, and the uptake and acceptability of the diagnostic package in Uganda.
FINDINGS
In Uganda, 52233 and 46035 children attended care pre-intervention versus post-intervention respectively. 26/52233 (0.05%) and 42/46035 (0.09%) children were diagnosed with tuberculosis pre-intervention and post-intervention respectively, p-value=0.114. In DH-focused district, it was 10/24208 (0.04%) and 23/17914 (0.1%) pre-intervention and post-intervention respectively, and 16/28025 (0.06%) and 19/28121 (0.1%) for PHC-districts, respectively. The uptake of TB screening was 43104/46035 (93.6%) overall, among the 732 enrolled children 724/ and 532 had a valid Ultra result using NPA and stool, respectively. Health care workers overall experienced decentralized childhood TB diagnostic as acceptable, with NPA and stool sample collection feasible both at DH and PHC.
CONCLUSION
Decentralizing innovative childhood tuberculosis diagnosis can increase tuberculosis case detection with limited impact when using the PHC decentralization approach.
KEY MESSAGE
Although decentralizing childhood TB diagnosis is acceptable, overcoming feasibility issues may improve the effective implementation and scale-up of such interventions at low levels of care.
This abstract is not to be quoted for publication.
Conference Material > Video
Natukunda N
Epicentre Scientific Day Paris 2023. 8 June 2023
English
Français
Journal Article > ResearchFull Text
PLOS Glob Public Health. 8 June 2023; Volume 3 (Issue 6); e0001457.; DOI:10.1371/journal.pgph.0001457
Simons E, Nikolay B, Ouedraogo P, Pasquier E, Tiemeni C, et al.
PLOS Glob Public Health. 8 June 2023; Volume 3 (Issue 6); e0001457.; DOI:10.1371/journal.pgph.0001457
Although seroprevalence studies have demonstrated the wide circulation of SARS-COV-2 in African countries, the impact on population health in these settings is still poorly understood. Using representative samples of the general population, we evaluated retrospective mortality and seroprevalence of anti-SARS-CoV-2 antibodies in Lubumbashi and Abidjan. The studies included retrospective mortality surveys and nested anti-SARS-CoV-2 antibody prevalence surveys. In Lubumbashi the study took place during April-May 2021 and in Abidjan the survey was implemented in two phases: July-August 2021 and October-November 2021. Crude mortality rates were stratified between pre-pandemic and pandemic periods and further investigated by age group and COVID waves. Anti-SARS-CoV-2 seroprevalence was quantified by rapid diagnostic testing (RDT) and laboratory-based testing (ELISA in Lubumbashi and ECLIA in Abidjan). In Lubumbashi, the crude mortality rate (CMR) increased from 0.08 deaths per 10 000 persons per day (pre-pandemic) to 0.20 deaths per 10 000 persons per day (pandemic period). Increases were particularly pronounced among <5 years old. In Abidjan, no overall increase was observed during the pandemic period (pre-pandemic: 0.05 deaths per 10 000 persons per day; pandemic: 0.07 deaths per 10 000 persons per day). However, an increase was observed during the third wave (0.11 deaths per 10 000 persons per day). The estimated seroprevalence in Lubumbashi was 15.7% (RDT) and 43.2% (laboratory-based). In Abidjan, the estimated seroprevalence was 17.4% (RDT) and 72.9% (laboratory-based) during the first phase of the survey and 38.8% (RDT) and 82.2% (laboratory-based) during the second phase of the survey. Although circulation of SARS-CoV-2 seems to have been extensive in both settings, the public health impact varied. The increases, particularly among the youngest age group, suggest indirect impacts of COVID and the pandemic on population health. The seroprevalence results confirmed substantial underdetection of cases through the national surveillance systems.
Journal Article > ResearchFull Text
Lancet Infect Dis. 1 March 2023; Volume 23 (Issue 3); 341-351.; DOI:10.1016/S1473-3099(22)00668-5
Marcy O, Wobudeya E, Font H, Vessière A, Chabala C, et al.
Lancet Infect Dis. 1 March 2023; Volume 23 (Issue 3); 341-351.; DOI:10.1016/S1473-3099(22)00668-5
BACKGROUND
Tuberculosis diagnosis might be delayed or missed in children with severe pneumonia because this diagnosis is usually only considered in cases of prolonged symptoms or antibiotic failure. Systematic tuberculosis detection at hospital admission could increase case detection and reduce mortality.
METHODS
We did a stepped-wedge cluster-randomised trial in 16 hospitals from six countries (Cambodia, Cameroon, Côte d'Ivoire, Mozambique, Uganda, and Zambia) with high incidence of tuberculosis. Children younger than 5 years with WHO-defined severe pneumonia received either the standard of care (control group) or standard of care plus Xpert MTB/RIF Ultra (Xpert Ultra; Cepheid, Sunnyvale, CA, USA) on nasopharyngeal aspirate and stool samples (intervention group). Clusters (hospitals) were progressively switched from control to intervention at 5-week intervals, using a computer-generated random sequence, stratified on incidence rate of tuberculosis at country level, and masked to teams until 5 weeks before switch. We assessed the effect of the intervention on primary (12-week all-cause mortality) and secondary (including tuberculosis diagnosis) outcomes, using generalised linear mixed models. The primary analysis was by intention to treat. We described outcomes in children with severe acute malnutrition in a post hoc analysis. This study is registered with ClinicalTrials.gov (NCT03831906) and the Pan African Clinical Trial Registry (PACTR202101615120643).
FINDINGS
From March 21, 2019, to March 30, 2021, we enrolled 1401 children in the control group and 1169 children in the intervention group. In the intervention group, 1140 (97·5%) children had nasopharyngeal aspirates and 942 (80·6%) had their stool collected; 24 (2·1%) had positive Xpert Ultra. At 12 weeks, 110 (7·9%) children in the control group and 91 (7·8%) children in the intervention group had died (adjusted odds ratio [OR] 0·986, 95% CI 0·597-1·630, p=0·957), and 74 (5·3%) children in the control group and 88 (7·5%) children in the intervention group had tuberculosis diagnosed (adjusted OR 1·238, 95% CI 0·696-2·202, p=0·467). In children with severe acute malnutrition, 57 (23·8%) of 240 children in the control group and 53 (17·8%) of 297 children in the intervention group died, and 36 (15·0%) of 240 children in the control group and 56 (18·9%) of 297 children in the intervention group were diagnosed with tuberculosis. The main adverse events associated with nasopharyngeal aspirates were samples with blood in 312 (27·3%) of 1147 children with nasopharyngeal aspirates attempted, dyspnoea or SpO2 less than 95% in 134 (11·4%) of children, and transient respiratory distress or SpO2 less than 90% in 59 (5·2%) children. There was no serious adverse event related to nasopharyngeal aspirates reported during the trial.
INTERPRETATION
Systematic molecular tuberculosis detection at hospital admission did not reduce mortality in children with severe pneumonia. High treatment and microbiological confirmation rates support more systematic use of Xpert Ultra in this group, notably in children with severe acute malnutrition.
Tuberculosis diagnosis might be delayed or missed in children with severe pneumonia because this diagnosis is usually only considered in cases of prolonged symptoms or antibiotic failure. Systematic tuberculosis detection at hospital admission could increase case detection and reduce mortality.
METHODS
We did a stepped-wedge cluster-randomised trial in 16 hospitals from six countries (Cambodia, Cameroon, Côte d'Ivoire, Mozambique, Uganda, and Zambia) with high incidence of tuberculosis. Children younger than 5 years with WHO-defined severe pneumonia received either the standard of care (control group) or standard of care plus Xpert MTB/RIF Ultra (Xpert Ultra; Cepheid, Sunnyvale, CA, USA) on nasopharyngeal aspirate and stool samples (intervention group). Clusters (hospitals) were progressively switched from control to intervention at 5-week intervals, using a computer-generated random sequence, stratified on incidence rate of tuberculosis at country level, and masked to teams until 5 weeks before switch. We assessed the effect of the intervention on primary (12-week all-cause mortality) and secondary (including tuberculosis diagnosis) outcomes, using generalised linear mixed models. The primary analysis was by intention to treat. We described outcomes in children with severe acute malnutrition in a post hoc analysis. This study is registered with ClinicalTrials.gov (NCT03831906) and the Pan African Clinical Trial Registry (PACTR202101615120643).
FINDINGS
From March 21, 2019, to March 30, 2021, we enrolled 1401 children in the control group and 1169 children in the intervention group. In the intervention group, 1140 (97·5%) children had nasopharyngeal aspirates and 942 (80·6%) had their stool collected; 24 (2·1%) had positive Xpert Ultra. At 12 weeks, 110 (7·9%) children in the control group and 91 (7·8%) children in the intervention group had died (adjusted odds ratio [OR] 0·986, 95% CI 0·597-1·630, p=0·957), and 74 (5·3%) children in the control group and 88 (7·5%) children in the intervention group had tuberculosis diagnosed (adjusted OR 1·238, 95% CI 0·696-2·202, p=0·467). In children with severe acute malnutrition, 57 (23·8%) of 240 children in the control group and 53 (17·8%) of 297 children in the intervention group died, and 36 (15·0%) of 240 children in the control group and 56 (18·9%) of 297 children in the intervention group were diagnosed with tuberculosis. The main adverse events associated with nasopharyngeal aspirates were samples with blood in 312 (27·3%) of 1147 children with nasopharyngeal aspirates attempted, dyspnoea or SpO2 less than 95% in 134 (11·4%) of children, and transient respiratory distress or SpO2 less than 90% in 59 (5·2%) children. There was no serious adverse event related to nasopharyngeal aspirates reported during the trial.
INTERPRETATION
Systematic molecular tuberculosis detection at hospital admission did not reduce mortality in children with severe pneumonia. High treatment and microbiological confirmation rates support more systematic use of Xpert Ultra in this group, notably in children with severe acute malnutrition.