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.
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.
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.
Children experience high tuberculosis (TB)-related mortality but causes of death among those with presumptive TB are poorly documented. We describe the mortality, likely causes of death, and associated risk factors among vulnerable children admitted with presumptive TB in rural Uganda.
METHODS:
We conducted a prospective study of vulnerable children, defined as <2 years of age, HIV-positive, or severely malnourished, with a clinical suspicion of TB. Children were assessed for TB and followed for 24 weeks. TB classification and likely cause of death were assessed by an expert endpoint review committee, including insight gained from minimally invasive autopsies, when possible.
RESULTS:
Of the 219 children included, 157 (71.7%) were <2 years of age, 72 (32.9%) were HIV-positive, and 184 (84.0%) were severely malnourished. Seventy-one (32.4%) were classified as “likely tuberculosis” (15 confirmed and 56 unconfirmed), and 72 (32.9%) died. The median time to death was 12 days. The most frequent causes of death, ascertained for 59 children (81.9%), including 23 cases with autopsy results, were severe pneumonia excluding confirmed TB (23.7%), hypovolemic shock due to diarrhea (20.3%), cardiac failure (13.6%), severe sepsis (13.6%), and confirmed TB (10.2%). Mortality risk factors were confirmed TB (adjusted hazard ratio [aHR] = 2.84 [95% confidence interval (CI): 1.19–6.77]), being HIV-positive (aHR = 2.45 [95% CI: 1.37–4.38]), and severe clinical state on admission (aHR = 2.45 [95% CI: 1.29–4.66]).
CONCLUSIONS:
Vulnerable children hospitalized with presumptive TB experienced high mortality. A better understanding of the likely causes of death in this group is important to guide empirical management.
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.
Increasing childhood TB case detection requires the deployment of diagnostic services at peripheral healthcare level. Capacity and readiness of healthcare workers (HCWs) are key to the delivery of innovative approaches.
METHODS
In 2019, HCWs from five district hospitals (DHs) and 20 primary healthcare centres (PHCs) in Cambodia, Cameroon, Cote d´Ivoire, Sierra Leone and Uganda completed a self-administered knowledge-attitudes-practices (KAP) questionnaire on childhood TB. We computed knowledge and attitudes as scores and identified HCW characteristics associated with knowledge scores using linear regression.
RESULT
Of 636 eligible HCWs, 497 (78%) participated. Median knowledge scores per country ranged between 7.4 and 12.1 (/18). Median attitude scores ranged between 2.8 and 3.3 (/4). Between 13.3% and 34.4% of HCWs reported diagnosing childhood with (presumptive) TB few times a week. Practising at PHC level, being female, being involved in indirect TB care, having a non-permanent position, having no previous research experience and working in Cambodia, Cameroon, Cote d´Ivoire and Sierra Leone as compared to Uganda were associated with a lower knowledge score.
CONCLUSION
HCWs had overall limited knowledge, favourable attitudes and little practice of childhood TB diagnosis. Increasing HCW awareness, capacity and skills, and improving access to effective diagnosis are urgently needed.
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.