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90 result(s)
Journal Article > ResearchAbstract Only

Initial evaluation of a new cervical screening strategy combining human papillomavirus genotyping and automated visual evaluation: the Human Papillomavirus–Automated Visual Evaluation Consortium

Journal of the National Cancer Institute . 18 March 2025; DOI:10.1093/jnci/djaf054
Befano B, Kalpathy-Cramer J, Egemen D, Inturrisi F, Jeronimo J,  et al.
Journal of the National Cancer Institute . 18 March 2025; DOI:10.1093/jnci/djaf054

The HPV-Automated Visual Evaluation (PAVE) Consortium is validating a cervical screening strategy enabling accurate cervical screening in resource-limited settings. A rapid, low-cost HPV assay permits sensitive HPV testing of self-collected vaginal specimens; HPV-negative women are reassured. Triage of positives combines HPV genotyping (four groups in order of cancer risk) and visual inspection assisted by automated cervical visual evaluation (AVE) that classifies cervical appearance as severe, indeterminate, or normal. Together, the combination predicts which women have precancer, permitting targeted management to those most needing treatment.


We analyzed CIN3+ yield for each PAVE risk level (HPV genotype crossed by AVE classification) from nine clinical sites (Brazil, Cambodia, Dominican Republic, El Salvador, Eswatini, Honduras, Malawi, Nigeria, and Tanzania). Data from 1832 HPV-positive participants confirmed that HPV genotype and AVE classification each strongly and independently predict risk of histologic CIN3+. The combination of these low-cost tests provided excellent risk stratification, warranting pre-implementation demonstration projects.

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Journal Article > ResearchFull Text

Risk stratification of childhood infection using host markers of immune and endothelial activation: A multi-country prospective cohort study in Asia (Spot Sepsis)

medRxiv. 5 February 2025; DOI:10.1101/2025.02.03.25321543
Chandna A, Koshiaris C, Mahajan R, Ahmad RA, Anh DTV,  et al.
medRxiv. 5 February 2025; DOI:10.1101/2025.02.03.25321543

BACKGROUND

Circulating markers of immune and endothelial activation risk stratify infection syndromes agnostic to disease aetiology. However, their utility in children presenting from the community remains unclear.


METHODS

This study recruited children aged 1-59 months presenting with community-acquired acute febrile illnesses to seven hospitals in Bangladesh, Cambodia, Indonesia, Laos, and Viet Nam. Clinical parameters and biomarker concentrations were measured at presentation. The outcome measure was death or receipt of vital organ support within two days of enrolment. Prognostic performance of endothelial (Ang-1, Ang-2, sFlt-1) and immune (CHI3L1, CRP, IP-10, IL-1ra, IL-6, IL-8, IL-10, PCT, sTNFR-1, sTREM-1, suPAR) activation markers, WHO Danger Signs, and two validated severity scores (LqSOFA, SIRS) was compared.


RESULTS

3,423 participants were recruited. 133 met the outcome (weighted prevalence: 0.34%; 95% CI 0.28-0.41). sTREM-1 exhibited highest prognostic accuracy (AUC 0.86; 95% CI 0.82-0.90), outperforming WHO Danger Signs (AUC 0.75; 95% CI 0.70-0.80; p < 0.001), LqSOFA (AUC 0.74; 95% CI 0.70-0.78; p < 0.001), and SIRS (AUC 0.63; 95% CI 0.58-0.68; p < 0.001). Discrimination of immune and endothelial activation markers was particularly strong for children who deteriorated later in the course of their illness. Compared to WHO Danger Signs, an sTREM-1-based triage strategy improved recognition of children at risk of progression to life-threatening infection (sensitivity: 0.80 vs. 0.72), while maintaining comparable specificity (0.81 vs. 0.79).


CONCLUSIONS

Measuring circulating markers of immune and endothelial activation may help earlier recognition of febrile children at risk of poor outcomes in resource-constrained community settings.

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Journal Article > ResearchFull Text

The genetic diversity of Nipah virus across spatial scales

J Infect Dis. 16 December 2024; Volume 230 (Issue 6); e1235-e1244.; DOI:10.1093/infdis/jiae221
Cortes-Azuero O, Lefrancq N, Nikolay B, McKee C, Cappelle J,  et al.
J Infect Dis. 16 December 2024; Volume 230 (Issue 6); e1235-e1244.; DOI:10.1093/infdis/jiae221

BACKGROUND

Nipah virus (NiV), a highly lethal virus in humans, circulates in Pteropus bats throughout South and Southeast Asia. Difficulty in obtaining viral genomes from bats means we have a poor understanding of NiV diversity.


METHODS

We develop phylogenetic approaches applied to the most comprehensive collection of genomes to date (N = 257, 175 from bats, 73 from humans) from 6 countries over 22 years (1999–2020). We divide the 4 major NiV sublineages into 15 genetic clusters. Using Approximate Bayesian Computation fit to a spatial signature of viral diversity, we estimate the presence and the average size of genetic clusters per area.


RESULTS

We find that, within any bat roost, there are an average of 2.4 co-circulating genetic clusters, rising to 5.5 clusters at areas of 1500–2000 km2. We estimate that each genetic cluster occupies an average area of 1.3 million km2 (95% confidence interval [CI], .6–2.3 million km2), with 14 clusters in an area of 100 000 km2 (95% CI, 6–24 km2). In the few sites in Bangladesh and Cambodia where genomic surveillance has been concentrated, we estimate that most clusters have been identified, but only approximately 15% of overall NiV diversity has been uncovered.


CONCLUSIONS

Our findings are consistent with entrenched co-circulation of distinct lineages, even within roosts, coupled with slow migration over larger spatial scales.

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Journal Article > ResearchFull Text

Implementation of digital chest radiography for childhood tuberculosis diagnosis at district hospital level in six high tuberculosis burden and resources limited countries

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.

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Journal Article > ResearchFull Text

Cost-effectiveness and budget impact of decentralising childhood tuberculosis diagnosis in six high tuberculosis incidence countries: a mathematical modelling study

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

Effect of decentralising childhood tuberculosis diagnosis to primary health centre versus district hospital levels on disease detection in children from six high tuberculosis incidence countries: an operational research, pre-post intervention study

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.
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Journal Article > ResearchFull Text

Evaluation of a short training course of chest X-ray interpretation for the diagnosis of paediatric TB

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.
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Journal Article > ResearchFull Text

Natural killer repertoire restoration in TB/HIV co-infected individuals experienced an immune reconstitution syndrome (CAMELIA Trial, ANRS 12153)

Pathogens. 13 October 2023; Volume 12 (Issue 10); 1241.; DOI:10.3390/pathogens12101241
Pean P, Madec Y, Nerrienet E, Borand L, Laureillard D,  et al.
Pathogens. 13 October 2023; Volume 12 (Issue 10); 1241.; DOI:10.3390/pathogens12101241
IRIS is a common complication in HIV-infected patients treated for tuberculosis (TB) and cART. Our aim was to evaluate NK cell reconstitution in HIV-infected patients with TB-IRIS compared to those without IRIS. 147 HIV-infected patients with TB from the CAMELIA trial were enrolled. HIV+TB+ patients were followed for 32 weeks. The NK cell repertoire was assessed in whole blood at different time points. As CAMELIA has two arms (early and late cART initiation), we analysed them separately. At enrolment, individuals had low CD4 cell counts (27 cells/mm3) and high plasma viral loads (5.76 and 5.50 log/mL for IRIS and non-IRIS individuals, respectively). Thirty-seven people developed IRIS (in the early and late arms). In the early and late arms, we observed similar proportions of total NK and NK cell subsets in TB-IRIS and non-IRIS individuals during follow-up, except for the CD56dimCD16pos (both arms) and CD56dimCD16neg (late arm only) subsets, which were higher in TB-IRIS and non-IRIS individuals, respectively, after cART. Regarding the repertoire and markers of NK cells, significant differences (lower expression of NKp30, NKG2A (CD159a), NKG2D (CD314) were observed in TB-IRIS compared to non-IRIS individuals after the start of cART. In the late arm, some changes (increased expression of CD69, NKG2C, CD158i) were observed in TB-IRIS compared to non-IRIS individuals, but only before cART initiation (during TB treatment). KIR expression by NK cells (CD158a and CD158i) was similar in both groups. CD69 expression by NK cells decreased in all groups. Expression of the NCR repertoire (NKp30, NKp44, NKp46) has similar kinetics in TB-IRIS subjects compared to non-IRIS subjects regardless of the arm analysed. NK cell reconstitution appeared to be better in TB-IRIS subjects. Although NK cell reconstitution is impaired in HIV infection after cART, as previously reported, it does not appear to be affected by the development of IRIS in HIV and TB-infected individuals.More
Journal Article > ResearchFull Text

Acceptability of decentralizing childhood tuberculosis diagnosis in low-income countries with high tuberculosis incidence: Experiences and perceptions from health care workers in Sub-Saharan Africa and South-East Asia

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.More
Conference Material > Abstract

Impact of decentralisation of childhood TB diagnosis to district hospitals and primary health centers; Example from Uganda

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.
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