Paediatrics (RCH) - Research Publications

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    A Prospective Evaluation of the Symptom-Based Screening Approach to the Management of Children Who Are Contacts of Tuberculosis Cases
    Triasih, R ; Robertson, CF ; Duke, T ; Graham, SM (OXFORD UNIV PRESS INC, 2015-01-01)
    BACKGROUND: Child tuberculosis contact screening and management can enhance case finding and prevent tuberculosis disease. It is universally recommended but rarely implemented in tuberculosis-endemic settings. The World Health Organization (WHO)-recommended symptom-based screening approach could improve implementation but has not been prospectively evaluated. METHODS: We conducted a cohort study of children who were close contacts of pulmonary tuberculosis patients in Indonesia from August 2010 to December 2012. We performed clinical assessment, tuberculin skin test, and chest radiography in all eligible children irrespective of symptoms at baseline. Mycobacterial culture and Xpert MTB/RIF assay were performed on sputum from children with persistent symptoms of suspected tuberculosis. Children were managed according to WHO guidelines and were prospectively followed for 12 months. RESULTS: A total of 269 child contacts of 140 index cases were evaluated. At baseline, 21 (8%) children had tuberculosis diagnosed clinically; an additional 102 (38%) had evidence of infection without disease. Of children with any tuberculosis-related symptoms at baseline, 21% had tuberculosis diagnosed compared with none of the asymptomatic children (P < .001). After 12 months of follow-up, none of the 99 eligible young child contacts (<5 years) who received isoniazid preventive therapy (IPT) had developed disease compared with 4 of 149 (2.6%) asymptomatic older children who did not receive IPT. CONCLUSIONS: Symptom-based screening is an effective and simple approach to child tuberculosis contact management that can be implemented at the primary healthcare level.
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    Bubble continuous positive airway pressure for children with severe pneumonia and hypoxaemia in Bangladesh: an open, randomised controlled trial
    Chisti, MJ ; Salam, MA ; Smith, JH ; Ahmed, T ; Pietroni, MAC ; Shahunja, KM ; Shahid, ASMSB ; Faruque, ASG ; Ashraf, H ; Bardhan, PK ; Sharifuzzaman, ; Graham, SM ; Duke, T (ELSEVIER SCIENCE INC, 2015-09-12)
    BACKGROUND: In developing countries, mortality in children with very severe pneumonia is high, even with the provision of appropriate antibiotics, standard oxygen therapy, and other supportive care. We assessed whether oxygen therapy delivered by bubble continuous positive airway pressure (CPAP) improved outcomes compared with standard low-flow and high-flow oxygen therapies. METHODS: This open, randomised, controlled trial took place in Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh. We randomly assigned children younger than 5 years with severe pneumonia and hypoxaemia to receive oxygen therapy by either bubble CPAP (5 L/min starting at a CPAP level of 5 cm H2O), standard low-flow nasal cannula (2 L/min), or high-flow nasal cannula (2 L/kg per min up to the maximum of 12 L/min). Randomisation was done with use of the permuted block methods (block size of 15 patients) and Fisher and Yates tables of random permutations. The primary outcome was treatment failure (ie, clinical failure, intubation and mechanical ventilation, death, or termination of hospital stay against medical advice) after more than 1 h of treatment. Primary and safety analyses were by intention to treat. We did two interim analyses and stopped the trial after the second interim analysis on Aug 3, 2013, as directed by the data safety and monitoring board. This trial is registered at ClinicalTrials.gov, number NCT01396759. FINDINGS: Between Aug 4, 2011, and July 17, 2013, 225 eligible children were recruited. We randomly allocated 79 (35%) children to receive oxygen therapy by bubble CPAP, 67 (30%) to low-flow oxygen therapy, and 79 (35%) to high-flow oxygen therapy. Treatment failed for 31 (14%) children, of whom five (6%) had received bubble CPAP, 16 (24%) had received low-flow oxygen therapy, and ten (13%) had received high-flow oxygen therapy. Significantly fewer children in the bubble CPAP group had treatment failure than in the low-flow oxygen therapy group (relative risk [RR] 0·27, 99·7% CI 0·07-0·99; p=0·0026). No difference in treatment failure was noted between patients in the bubble CPAP and those in the high-flow oxygen therapy group (RR 0·50, 99·7% 0·11-2·29; p=0·175). 23 (10%) children died. Three (4%) children died in the bubble CPAP group, ten (15%) children died in the low-flow oxygen therapy group, and ten (13%) children died in the high-flow oxygen therapy group. Children who received oxygen by bubble CPAP had significantly lower rates of death than the children who received oxygen by low-flow oxygen therapy (RR 0·25, 95% CI 0·07-0·89; p=0·022). INTERPRETATION: Oxygen therapy delivered by bubble CPAP improved outcomes in Bangladeshi children with very severe pneumonia and hypoxaemia compared with standard low-flow oxygen therapy. Use of bubble CPAP oxygen therapy could have a large effect in hospitals in developing countries where the only respiratory support for severe childhood pneumonia and hypoxaemia is low-flow oxygen therapy. The trial was stopped early because of higher mortality in the low-flow oxygen group than in the bubble CPAP group, and we acknowledge that the early cessation of the trial reduces the certainty of the findings. Further research is needed to test the feasibility of scaling up bubble CPAP in district hospitals and to improve bubble CPAP delivery technology. FUNDING: International Centre for Diarrhoeal Disease Research, Bangladesh, and Centre for International Child Health, University of Melbourne.
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    A mixed-methods evaluation of adherence to preventive treatment among child tuberculosis contacts in Indonesia
    Triasih, R ; Padmawati, RS ; Duke, T ; Robertson, C ; Sawyer, SM ; Graham, SM (INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D), 2016-08)
    BACKGROUND: Tuberculosis (TB) can be prevented using isoniazid preventive therapy (IPT) among child contacts. However, the benefits of IPT depend on adherence to at least 6 months of daily treatment. A greater understanding of the barriers to and facilitators of adherence to IPT in resource-poor settings is required to optimise the benefits. METHODS: We prospectively evaluated adherence to IPT and its associated factors among child contacts (age 0-5 years) eligible for IPT. We undertook in-depth interviews with care givers and a focus group discussion with health care workers, which were thematically analysed to explore barriers to and facilitators of adherence from the perspective of both care givers and health workers. RESULTS: Of 99 eligible children, 49 (49.5%) did not complete 6 months of IPT. Children whose care giver collected their IPT medications from primary health centres were more likely to have incomplete adherence than those who collected them from hospitals (aOR 2.9, 95%CI 1.1-7.8). Thematic analyses revealed major barriers to and facilitators of adherence: regimen-related, care giver-related and health care-related factors, social support and access. Many of these factors are readily modifiable. CONCLUSION: Providing information about IPT and improving accessibility for care givers to receive IPT at the primary health care facility should be priorities to facilitate implementation.
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    A Prospective Study of the Prevalence of Tuberculosis and Bacteraemia in Bangladeshi Children with Severe Malnutrition and Pneumonia Including an Evaluation of Xpert MTB/RIF Assay
    Chisti, MJ ; Graham, SM ; Duke, T ; Ahmed, T ; Ashraf, H ; Faruque, ASG ; La Vincente, S ; Banu, S ; Raqib, R ; Salam, MA ; Nicol, MP (PUBLIC LIBRARY SCIENCE, 2014-04-02)
    BACKGROUND: Severe malnutrition is a risk factor for pneumonia due to a wide range of pathogens but aetiological data are limited and the role of Mycobacterium tuberculosis is uncertain. METHODS: We prospectively investigated severely malnourished young children (<5 years) with radiological pneumonia admitted over a 15-month period. Investigations included blood culture, sputa for microscopy and mycobacterial culture. Xpert MTB/RIF assay was introduced during the study. Study children were followed for 12 weeks following their discharge from the hospital. RESULTS: 405 eligible children were enrolled, with a median age of 10 months. Bacterial pathogens were isolated from blood culture in 18 (4.4%) children, of which 72% were Gram negatives. Tuberculosis was confirmed microbiologically in 7% (27/396) of children that provided sputum - 10 by culture, 21 by Xpert MTB/RIF assay, and 4 by both tests. The diagnostic yield from induced sputum was 6% compared to 3.5% from gastric aspirate. Sixty (16%) additional children had tuberculosis diagnosed clinically that was not microbiologically confirmed. Most confirmed tuberculosis cases did not have a positive contact history or positive tuberculin test. The sensitivity and specificity of Xpert MTB/RIF assay compared to culture was 67% (95% CI: 24-94) and 92% (95% CI: 87-95) respectively. Overall case-fatality rate was 17% and half of the deaths occurred in home following discharge from the hospital. CONCLUSION AND SIGNIFICANCE: TB was common in severely malnourished Bangladeshi children with pneumonia. X-pert MTB/RIF assay provided higher case detection rate compared to sputum microscopy and culture. The high mortality among the study children underscores the need for further research aimed at improved case detection and management for better outcomes.
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    An evaluation of chest X-ray in the context of community-based screening of child tuberculosis contacts
    Triasih, R ; Robertson, C ; de Campo, J ; Duke, T ; Choridah, L ; Graham, SM (INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D), 2015-12)
    BACKGROUND: There are no published data on the critical review of chest X-ray (CXR) findings of children in the context of community-based contact screening. OBJECTIVES: To describe the quality, findings and inter-observer agreement of CXRs in child TB contacts in Indonesia. METHODS: We performed antero-posterior (AP) and lateral CXR in children who had had close contact with a pulmonary TB case. The CXRs were interpreted independently by four reviewers. RESULTS: A total of 530 CXRs of 265 children were reviewed. Most (63%) of the children were asymptomatic at the time of CXR. Only 60% of the CXRs were reported as moderate to good quality by all reviewers, and inter-observer agreement on quality was slight to moderate (weighted κ = 0.16-0.35) for AP view. The majority of the CXRs were reported as normal (range 65-77%), with fair to moderate inter-observer agreement (κ = 0.25-0.46). Hilar lymphadenopathy (6-16%) was the most common CXR abnormality reported with poor inter-observer agreement (κ = -0.03 to 0.25). CONCLUSION: The CXRs of child TB contacts investigated in the community were characterised by low quality, low agreement and low yield. Our findings support guidelines that CXR is not routinely indicated in asymptomatic child TB contacts in this setting.
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    Post-Discharge Mortality in Children with Severe Malnutrition and Pneumonia in Bangladesh
    Chisti, MJ ; Graham, SM ; Duke, T ; Ahmed, T ; Faruque, ASG ; Ashraf, H ; Bardhan, PK ; Shahid, ASMSB ; Shahunja, KM ; Salam, MA ; Esposito, S (PUBLIC LIBRARY SCIENCE, 2014-09-16)
    BACKGROUND: Post-discharge mortality among children with severe illness in resource-limited settings is under-recognized and there are limited data. We evaluated post-discharge mortality in a recently reported cohort of children with severe malnutrition and pneumonia, and identified characteristics associated with an increased risk of death. METHODS: Young children (<5 years of age) with severe malnutrition (WHO criteria) and radiographic pneumonia on admission to Dhaka Hospital of icddr,b over a 15-month period were managed according to standard protocols. Those discharged were followed-up and survival status at 12 weeks post-discharge was determined. Verbal autopsy was requested from families of those that died. RESULTS: Of 405 children hospitalized with severe malnutrition and pneumonia, 369 (median age, 10 months) were discharged alive with a follow-up plan. Of these, 32 (8.7%) died in the community within 3 months of discharge: median 22 (IQR 9-35) days from discharge to death. Most deaths were reportedly associated with acute onset of new respiratory or gastrointestinal symptoms. Those that died following discharge were significantly younger (median 6 [IQR 3,12] months) and more severely malnourished, on admission and on discharge, than those that survived. Bivariate analysis found that severe wasting on admission (OR 3.64, 95% CI 1.66-7.97) and age <12 months (OR 2.54, 95% CI 1.1-8.8) were significantly associated with post-discharge death. Of those that died in the community, none had attended a scheduled follow-up and care-seeking from a traditional healer was more common (p<0.001) compared to those who survived. CONCLUSION AND SIGNIFICANCE: Post-discharge mortality was common in Bangladeshi children following inpatient care for severe malnutrition and pneumonia. The underlying contributing factors require a better understanding to inform the potential of interventions that could improve survival.
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    Risk of infection and disease with Mycobacterium tuberculosis among children identified through prospective community-based contact screening in Indonesia
    Triasih, R ; Robertson, C ; Duke, T ; Graham, SM (WILEY, 2015-06)
    OBJECTIVE: To identify characteristics of the child contact, index case or environment that are associated with infection or tuberculosis in child contacts in an urban community in Indonesia. METHOD: Children who were close contacts of an index case with pulmonary tuberculosis were screened for infection and disease in Yogyakarta, Indonesia from August 2010 to December 2012. Data of the index case and child were collected prospectively, and all child contacts had clinical assessment, tuberculin skin test (TST) and chest X-ray performed. Those with clinically suspected tuberculosis also had sputum examined by Xpert MTB/RIF and culture. Child contacts were managed according to national guidelines, followed for 12 months and had a final classification of either tuberculosis 'disease', latent tuberculous infection (LTBI) or 'exposed only'. RESULTS: About 269 children of 141 index cases were investigated. Final classification was tuberculosis in 25 (9%) and LTBI in 121 (45%). The risk of infection was significantly greater if the source case was female (AOR 1.7; 95% CI: 1.0-2.8), had sputum smear-positive tuberculosis (AOR 3.0; 95% CI 1.5-6.0) or slept in the same room (AOR 1.7, 95% CI 1.0-2.9). A positive TST was independently associated with a diagnosis of tuberculosis (AOR 7.3; 95% CI 2.4-22). CONCLUSION: This study highlights the high risk and the risk factors associated with tuberculosis and LTBI among child contacts in Indonesia.