Journal Article > ResearchSubscription Only
Pediatrics. 2023 March 23; Online ahead of print; DOI:10.1542/peds.2022-057912
Bonnet MMB, Nordholm AC, Ssekyanzi B, Byamukama O, Orikiriza P, et al.
Pediatrics. 2023 March 23; Online ahead of print; DOI:10.1542/peds.2022-057912
BACKGROUND AND OBJECTIVES:
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.
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.
Journal Article > Short ReportFull Text
Lancet Global Health. 2024 July 1; Volume 12 (Issue 7); e1184-e1191.; DOI:10.1016/S2214-109X(24)00148-7
Broger T, Marx FM, Theron G, Marais BJ, Nicol MP, et al.
Lancet Global Health. 2024 July 1; Volume 12 (Issue 7); e1184-e1191.; DOI:10.1016/S2214-109X(24)00148-7
Journal Article > ResearchAbstract Only
Eur Respir J. 2021 June 17; Volume 59 (Issue 1); 2101116.; DOI:10.1183/13993003.01116-2021
Orikiriza P, Smith JS, Ssekyanzi B, Nyehangane D, Mugisha IT, et al.
Eur Respir J. 2021 June 17; Volume 59 (Issue 1); 2101116.; DOI:10.1183/13993003.01116-2021
BACKGROUND
Non-sputum-based diagnostic approaches are crucial in children at high risk of disseminated tuberculosis (TB) who cannot expectorate sputum. We evaluated the diagnostic accuracy of stool Xpert MTB/RIF and urine AlereLAM tests in this group of children.
METHODS
Hospitalised children with presumptive TB and either age <2 years, HIV-positive or with severe malnutrition were enrolled in a diagnostic cohort. At enrolment, we attempted to collect two urine, two stool and two respiratory samples. Urine and stool were tested with AlereLAM and Xpert MTB/RIF, respectively. Respiratory samples were tested with Xpert MTB/RIF and mycobacterial culture. Both a microbiological and a composite clinical reference standard were used.
RESULTS
The study analysed 219 children; median age 16.4 months, 72 (32.9%) HIV-positive and 184 (84.4%) severely malnourished. 12 (5.5%) and 58 (28.5%) children had confirmed and unconfirmed TB, respectively. Stool and urine were collected in 219 (100%) and 216 (98.6%) children, respectively. Against the microbiological reference standard, the sensitivity and specificity of stool Xpert MTB/RIF was 50.0% (6/12, 95% CI 21.1–78.9%) and 99.1% (198/200, 95% 96.4–99.9%), while that of urine AlereLAM was 50.0% (6/12, 95% 21.1–78.9%) and 74.6% (147/197, 95% 67.9–80.5%), respectively. Against the composite reference standard, sensitivity was reduced to 11.4% (8/70) for stool and 26.2% (17/68) for urine, with no major difference by age group (<2 and ≥2 years) or HIV status.
CONCLUSIONS
The Xpert MTB/RIF assay has excellent specificity on stool, but sensitivity is suboptimal. Urine AlereLAM is compromised by poor sensitivity and specificity in children.
Non-sputum-based diagnostic approaches are crucial in children at high risk of disseminated tuberculosis (TB) who cannot expectorate sputum. We evaluated the diagnostic accuracy of stool Xpert MTB/RIF and urine AlereLAM tests in this group of children.
METHODS
Hospitalised children with presumptive TB and either age <2 years, HIV-positive or with severe malnutrition were enrolled in a diagnostic cohort. At enrolment, we attempted to collect two urine, two stool and two respiratory samples. Urine and stool were tested with AlereLAM and Xpert MTB/RIF, respectively. Respiratory samples were tested with Xpert MTB/RIF and mycobacterial culture. Both a microbiological and a composite clinical reference standard were used.
RESULTS
The study analysed 219 children; median age 16.4 months, 72 (32.9%) HIV-positive and 184 (84.4%) severely malnourished. 12 (5.5%) and 58 (28.5%) children had confirmed and unconfirmed TB, respectively. Stool and urine were collected in 219 (100%) and 216 (98.6%) children, respectively. Against the microbiological reference standard, the sensitivity and specificity of stool Xpert MTB/RIF was 50.0% (6/12, 95% CI 21.1–78.9%) and 99.1% (198/200, 95% 96.4–99.9%), while that of urine AlereLAM was 50.0% (6/12, 95% 21.1–78.9%) and 74.6% (147/197, 95% 67.9–80.5%), respectively. Against the composite reference standard, sensitivity was reduced to 11.4% (8/70) for stool and 26.2% (17/68) for urine, with no major difference by age group (<2 and ≥2 years) or HIV status.
CONCLUSIONS
The Xpert MTB/RIF assay has excellent specificity on stool, but sensitivity is suboptimal. Urine AlereLAM is compromised by poor sensitivity and specificity in children.
Journal Article > CommentaryFull Text
J Adolesc Health. 2023 March 1; Volume 72 (Issue 3); 323-331.; DOI:10.1016/j.jadohealth.2022.10.036
Chiang SS, Waterous PM, Atieno VF, Bernays S, Bondarenko Y, et al.
J Adolesc Health. 2023 March 1; Volume 72 (Issue 3); 323-331.; DOI:10.1016/j.jadohealth.2022.10.036
Journal Article > CommentaryFull Text
Lancet Child Adolesc Health. 2020 December 1; Volume 4 (Issue 12); 855-857.; DOI:10.1016/S2352-4642(20)30273-X
Nash M, Perrin C, Seddon JA, Furin J, Hauser J, et al.
Lancet Child Adolesc Health. 2020 December 1; Volume 4 (Issue 12); 855-857.; DOI:10.1016/S2352-4642(20)30273-X
Journal Article > ResearchFull Text
Int J Tuberc Lung Dis. 2023 December 1; Volume 27 (Issue 12); 885-898.; DOI:10.5588/ijtld.23.0341
du Cros PAK, Greig J, Cross GB, Cousins C, Berry C, et al.
Int J Tuberc Lung Dis. 2023 December 1; Volume 27 (Issue 12); 885-898.; DOI:10.5588/ijtld.23.0341
English
Français
BACKGROUND
The value, speed of completion and robustness of the evidence generated by TB treatment trials could be improved by implementing standards for best practice.
METHODS
A global panel of experts participated in a Delphi process, using a 7-point Likert scale to score and revise draft standards until consensus was reached.
RESULTS
Eleven standards were defined: Standard 1, high quality data on TB regimens are essential to inform clinical and programmatic management; Standard 2, the research questions addressed by TB trials should be relevant to affected communities, who should be included in all trial stages; Standard 3, trials should make every effort to be as inclusive as possible; Standard 4, the most efficient trial designs should be considered to improve the evidence base as quickly and cost effectively as possible, without compromising quality; Standard 5, trial governance should be in line with accepted good clinical practice; Standard 6, trials should investigate and report strategies that promote optimal engagement in care; Standard 7, where possible, TB trials should include pharmacokinetic and pharmacodynamic components; Standard 8, outcomes should include frequency of disease recurrence and post-treatment sequelae; Standard 9, TB trials should aim to harmonise key outcomes and data structures across studies; Standard 10, TB trials should include biobanking; Standard 11, treatment trials should invest in capacity strengthening of local trial and TB programme staff.
CONCLUSION
These standards should improve the efficiency and effectiveness of evidence generation, as well as the translation of research into policy and practice.
The value, speed of completion and robustness of the evidence generated by TB treatment trials could be improved by implementing standards for best practice.
METHODS
A global panel of experts participated in a Delphi process, using a 7-point Likert scale to score and revise draft standards until consensus was reached.
RESULTS
Eleven standards were defined: Standard 1, high quality data on TB regimens are essential to inform clinical and programmatic management; Standard 2, the research questions addressed by TB trials should be relevant to affected communities, who should be included in all trial stages; Standard 3, trials should make every effort to be as inclusive as possible; Standard 4, the most efficient trial designs should be considered to improve the evidence base as quickly and cost effectively as possible, without compromising quality; Standard 5, trial governance should be in line with accepted good clinical practice; Standard 6, trials should investigate and report strategies that promote optimal engagement in care; Standard 7, where possible, TB trials should include pharmacokinetic and pharmacodynamic components; Standard 8, outcomes should include frequency of disease recurrence and post-treatment sequelae; Standard 9, TB trials should aim to harmonise key outcomes and data structures across studies; Standard 10, TB trials should include biobanking; Standard 11, treatment trials should invest in capacity strengthening of local trial and TB programme staff.
CONCLUSION
These standards should improve the efficiency and effectiveness of evidence generation, as well as the translation of research into policy and practice.
Journal Article > Short ReportFull Text
Public Health Action. 2014 June 21; Volume 4 (Issue 1); DOI:10.5588/pha.13.0071
Harries AD, Marais BJ, Kool B, Ram S, Kumar AMV, et al.
Public Health Action. 2014 June 21; Volume 4 (Issue 1); DOI:10.5588/pha.13.0071
Journal Article > ReviewFull Text
Lancet Infect Dis. 2013 March 24; Volume 13 (Issue 5); DOI:10.1016/S1473-3099(13)70030-6
Abubakar I, Zignol M, Falzon D, Raviglione M, Ditui L, et al.
Lancet Infect Dis. 2013 March 24; Volume 13 (Issue 5); DOI:10.1016/S1473-3099(13)70030-6
Journal Article > ReviewFull Text
Public Health Action. 2014 June 21; Volume 4; DOI:10.5588/pha.13.0091
Bissel K, Viney K, Brostom R, Gounder S, Khogali MA, et al.
Public Health Action. 2014 June 21; Volume 4; DOI:10.5588/pha.13.0091
Operational research (OR) in public health aims to investigate strategies, interventions, tools or knowledge that can enhance the quality, coverage, effectiveness or performance of health systems. Attention has recently been drawn to the lack of OR capacity in public health programmes throughout the Pacific Islands, despite considerable investment in implementation. This lack of ongoing and critical reflection may prevent health programme staff from understanding why programme objectives are not being fully achieved, and hinder long-term gains in public health. The International Union Against Tuberculosis and Lung Disease (The Union) has been collaborating with Pacific agencies to conduct OR courses based on the training model developed by The Union and Médecins Sans Frontières Brussels-Luxembourg in 2009. The first of these commenced in 2011 in collaboration with the Fiji National University, the Fiji Ministry of Health, the World Health Organization and other partners. The Union and the Secretariat of the Pacific Community organised a second course for participants from other Pacific Island countries and territories in 2012, and an additional course for Fijian participants commenced in 2013. Twelve participants enrolled in each of the three courses. Of the two courses completed by end 2013, 18 of 24 participants completed their OR and submitted papers by the course deadline, and 17 papers have been published to date. This article describes the context, process and outputs of the Pacific courses, as well as innovations, adaptations and challenges.
Journal Article > ReviewAbstract
Expert Rev Anti Infect Ther. 2015 March 5
Brigden G, Furin J, van Gulik C, Marais BJ
Expert Rev Anti Infect Ther. 2015 March 5
Children were often the forgotten victims of the global tuberculosis (TB) epidemic, neglected by traditional TB services as well as maternal and child health initiatives. Luckily this is changing with a greater focus on children and the issues regarding their optimal management. A common misconception is that children with TB are always difficult to diagnose and treat. New diagnostic tools are urgently needed, but most children with TB in high-burden settings can be diagnosed with available approaches and treatment outcomes are generally excellent. Increased TB awareness, appropriate training of health care workers and inclusion in integrated management of childhood illness strategies will improve the access and quality of care that children receive. This review highlights what needs to be done to ensure that no child unnecessarily dies from TB and provides a brief overview of new advances in the field.