Background Globally, children under 15 years represent approximately 12% of new tuberculosis cases, but 16% of the estimated 1.4 million deaths. This higher share of mortality highlights the urgent need to develop strategies to improve case detection in this age group and identify children without tuberculosis disease who should be considered for tuberculosis preventive treatment. One such strategy is systematic screening for tuberculosis in high‐risk groups. Objectives To estimate the sensitivity and specificity of the presence of one or more tuberculosis symptoms, or symptom combinations; chest radiography (CXR); Xpert MTB/RIF; Xpert Ultra; and combinations of these as screening tests for detecting active pulmonary childhood tuberculosis in the following groups. – Tuberculosis contacts, including household contacts, school contacts, and other close contacts of a person with infectious tuberculosis. – Children living with HIV. – Children with pneumonia. – Other risk groups (e.g. children with a history of previous tuberculosis, malnourished children). – Children in the general population in high tuberculosis burden settings. Search methods We searched six databases, including the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase, on 14 February 2020 without language restrictions and contacted researchers in the field. Selection criteria Cross‐sectional and cohort studies where at least 75% of children were aged under 15 years. Studies were eligible if conducted for screening rather than diagnosing tuberculosis. Reference standards were microbiological (MRS) and composite reference standard (CRS), which may incorporate symptoms and CXR. Data collection and analysis Two review authors independently extracted data and assessed study quality using QUADAS‐2. We consolidated symptom screens across included studies into groups that used similar combinations of symptoms as follows: one or more of cough, fever, or poor weight gain and one or more of cough, fever, or decreased playfulness. For combination of symptoms, a positive screen was the presence of one or more than one symptom. We used a bivariate model to estimate pooled sensitivity and specificity with 95% confidence intervals (CIs) and performed analyses separately by reference standard. We assessed certainty of evidence using GRADE. Main results Nineteen studies assessed the following screens: one symptom (15 studies, 10,097 participants); combinations of symptoms (12 studies, 29,889 participants); CXR (10 studies, 7146 participants); and Xpert MTB/RIF (2 studies, 787 participants). Several studies assessed more than one screening test. No studies assessed Xpert Ultra. For 16 studies (84%), risk of bias for the reference standard domain was unclear owing to concern about incorporation bias. Across other quality domains, risk of bias was generally low. Symptom screen (verified by CRS) One or more of cough, fever, or poor weight gain in tuberculosis contacts (4 studies, tuberculosis prevalence 2% to 13%): pooled sensitivity was 89% (95% CI 52% to 98%; 113 participants; low‐certainty evidence) and pooled specificity was 69% (95% CI 51% to 83%; 2582 participants; low‐certainty evidence). Of 1000 children where 50 have pulmonary tuberculosis, 339 would be screen‐positive, of whom 294 (87%) would not have pulmonary tuberculosis (false positives); 661 would be screen‐negative, of whom five (1%) would have pulmonary tuberculosis (false negatives). One or more of cough, fever, or decreased playfulness in children aged under five years, inpatient or outpatient (3 studies, tuberculosis prevalence 3% to 13%): sensitivity ranged from 64% to 76% (106 participants; moderate‐certainty evidence) and specificity from 37% to 77% (2339 participants; low‐certainty evidence). Of 1000 children where 50 have pulmonary tuberculosis, 251 to 636 would be screen‐positive, of whom 219 to 598 (87% to 94%) would not have pulmonary tuberculosis; 364 to 749 would be screen‐negative, of whom 12 to 18 (2% to 3%) would have pulmonary tuberculosis. One or more of cough, fever, poor weight gain, or tuberculosis close contact (World Health Organization four‐symptom screen) in children living with HIV, outpatient (2 studies, tuberculosis prevalence 3% and 8%): pooled sensitivity was 61% (95% CI 58% to 64%; 1219 screens; moderate‐certainty evidence) and pooled specificity was 94% (95% CI 86% to 98%; 201,916 screens; low‐certainty evidence). Of 1000 symptom screens where 50 of the screens are on children with pulmonary tuberculosis, 88 would be screen‐positive, of which 57 (65%) would be on children who do not have pulmonary tuberculosis; 912 would be screen‐negative, of which 19 (2%) would be on children who have pulmonary tuberculosis. CXR (verified by CRS) CXR with any abnormality in tuberculosis contacts (8 studies, tuberculosis prevalence 2% to 25%): pooled sensitivity was 87% (95% CI 75% to 93%; 232 participants; low‐certainty evidence) and pooled specificity was 99% (95% CI 68% to 100%; 3281 participants; low‐certainty evidence). Of 1000 children, where 50 have pulmonary tuberculosis, 63 would be screen‐positive, of whom 19 (30%) would not have pulmonary tuberculosis; 937 would be screen‐negative, of whom 6 (1%) would have pulmonary tuberculosis. Xpert MTB/RIF (verified by MRS) Xpert MTB/RIF, inpatient or outpatient (2 studies, tuberculosis prevalence 1% and 4%): sensitivity was 43% and 100% (16 participants; very low‐certainty evidence) and specificity was 99% and 100% (771 participants; moderate‐certainty evidence). Of 1000 children, where 50 have pulmonary tuberculosis, 31 to 69 would be Xpert MTB/RIF‐positive, of whom 9 to 19 (28% to 29%) would not have pulmonary tuberculosis; 969 to 931 would be Xpert MTB/RIF‐negative, of whom 0 to 28 (0% to 3%) would have tuberculosis. Studies often assessed more symptoms than those included in the index test and symptom definitions varied. These differences complicated data aggregation and may have influenced accuracy estimates. Both symptoms and CXR formed part of the CRS (incorporation bias), which may have led to overestimation of sensitivity and specificity. Authors' conclusions We found that in children who are tuberculosis contacts or living with HIV, screening tests using symptoms or CXR may be useful, but our review is limited by design issues with the index test and incorporation bias in the reference standard. For Xpert MTB/RIF, we found insufficient evidence regarding screening accuracy. Prospective evaluations of screening tests for tuberculosis in children will help clarify their use. In the meantime, screening strategies need to be pragmatic to address the persistent gaps in prevention and case detection that exist in resource‐limited settings.

Improving childhood vaccination coverage and timeliness is a key health policy objective in many developing countries such as Uganda. Of the many factors known to influence uptake of childhood immunizations in under resourced settings, parents’ understanding and perception of childhood immunizations has largely been overlooked. The aims of this study were to survey mothers’ knowledge and attitudes towards childhood immunizations and then determine if these variables correlate with the timely vaccination coverage of their children. From September to December 2013, we conducted a cross-sectional survey of 1,000 parous women in rural Sheema district in southwest Uganda. The survey collected socio-demographic data and knowledge and attitudes towards childhood immunizations. For the women with at least one child between the age of one month and five years who also had a vaccination card available for the child (N = 302), the vaccination status of this child was assessed. 88% of these children received age-appropriate, on-time immunizations. 93.5% of the women were able to state that childhood immunizations protect children from diseases. The women not able to point this out were significantly more likely to have an under-vaccinated child (PR 1.354: 95% CI 1.018–1.802). When asked why vaccination rates may be low in their community, the two most common responses were “fearful of side effects” and “ignorance/disinterest/laziness” (44% each). The factors influencing caregivers’ demand for childhood immunizations vary widely between, and also within, developing countries. Research that elucidates local knowledge and attitudes, like this study, allows for decisions and policy pertaining to vaccination programs to be more effective at improving child vaccination rates.

The management of childhood tuberculosis (TB) is hampered by the low sensitivity and limited accessibility of microbiological testing. Optimizing clinical approaches is therefore critical to close the persistent gaps in TB case detection and prevention necessary to realize the child mortality targets of the End TB Strategy. In this review, we provide practical guidance summarizing the evidence and guidelines describing the use of symptoms and signs in decision making for children being evaluated for either TB preventive treatment (TPT) or TB disease treatment in high-TB incidence settings. Among at-risk children being evaluated for TPT, a symptom screen may be used to differentiate children who require further investigation for TB disease before receiving TPT. For symptomatic children being investigated for TB disease, an algorithmic approach can inform which children should receive TB treatment, even in the absence of imaging or microbiological confirmation. Though clinical approaches have limitations in accuracy, they are readily available and can provide valuable guidance for decision making in resource-limited settings to increase treatment access. We discuss the trade-offs in using them to make TB treatment decisions.

With growing attention globally to the childhood tuberculosis epidemic after decades of neglect, and with the burden of severe acute malnutrition (SAM) remaining unacceptably high worldwide, the co...

Background: Severe acute malnutrition (SAM) is a major cause of childhood mortality in resource-limited settings. The relationship between clinical factors and adherence to the ‘WHO 10 Steps’ and mortality in children with SAM is not fully understood. Methods: Data from an ongoing prospective observational cohort study assessing admission characteristics, management patterns and clinical outcome in children aged 6–36 months admitted to a tertiary hospital in Malawi from September 2018 to September 2019 were analysed. Data clerks independently collected data from patients’ charts. Demographics, clinical and nutritional status, identification of SAM and adherence to the ‘WHO 10 Steps’ were summarised. Their relationship to in-hospital mortality was assessed using multivariable logistic regression. Results: Of the 6752 patients admitted, 9.7% had SAM. Mortality was significantly higher in those with SAM (10.1% vs 3.8%, p < 0.001). Compared with independent assessment anthropometrics, clinicians appropriately documented SAM on admission in 39.5%. The following factors were independently associated with mortality: kwashiorkor [adjusted odds ratio (aOR) 5.14, 95% confidence interval (CI) 1.27–20.78], shock (aOR 18.54, 95% CI 3.87–88.90), HIV-positive (aOR 5.32, 95% CI 1.76–16.09), SAM documented on admission (aOR 2.41, 95% CI 1.11–5.22), documentation of blood glucose within 24 hrs (aOR 3.97, 95% CI 1.90–8.33) and IV fluids given without documented shock (aOR 3.13, 95% CI 1.16–8.44). Conclusion: HIV infection remains an important predictor of mortality in children with SAM. IV fluids should be avoided in those without shock. Early identification of SAM by the clinical team represents a focus of future quality improvement interventions at this facility.

There has been much recent progress on control of the tuberculosis (TB) and human immunodeficiency virus (HIV) epidemics globally. However, advances in children have lagged behind, and TB-HIV coinfection continues to be a major driver of pediatric mortality in many settings. This review highlights recent research findings in the areas of prevention, diagnosis, and treatment of HIV-associated childhood TB. Key areas for future research are defined. Current prevention efforts such as vaccination, TB symptom screening, and TB preventive treatment are demonstrated as beneficial but need to be optimized for children living with HIV (CLHIV). Diagnosis of HIV-associated TB in children remains a major challenge, depending heavily on clinicians’ ability to judge an array of signs, symptoms, and imaging findings, but there are a growing number of promising diagnostic tools with improved accuracy and feasibility. Treatment of TB-HIV coinfection has also seen recent progress with more evidence demonstrating the safety and effectiveness of shorter regimens for treatment of TB infection and disease and improved understanding of interactions between antiretrovirals and TB medications. However, several evidence gaps on drug-drug interactions persist, especially for young children and those with drug-resistant TB. Accelerated efforts are needed in these areas to build upon current progress and reduce the burden of TB on CLHIV.