Development of treatment-decision algorithms for children evaluated for pulmonary tuberculosis: an individual participant data meta-analysis.

Background: Many children with pulmonary tuberculosis remain undiagnosed and untreated with related high morbidity and mortality. Recent advances in childhood tuberculosis algorithm development have incorporated prediction modelling, but studies so far have been small and localised, with limited generalisability. We aimed to evaluate the performance of currently used diagnostic algorithms and to use prediction modelling to develop evidence-based algorithms to assist in tuberculosis treatment decision making for children presenting to primary health-care centres. Methods: For this meta-analysis, we identified individual participant data from a WHO public call for data on the management of tuberculosis in children and adolescents and referral from childhood tuberculosis experts. We included studies that prospectively recruited consecutive participants younger than 10 years attending health-care centres in countries with a high tuberculosis incidence for clinical evaluation of pulmonary tuberculosis. We collated individual participant data including clinical, bacteriological, and radiological information and a standardised reference classification of pulmonary tuberculosis. Using this dataset, we first retrospectively evaluated the performance of several existing treatment-decision algorithms. We then used the data to develop two multivariable prediction models that included features used in clinical evaluation of pulmonary tuberculosis-one with chest x-ray features and one without-and we investigated each model's generalisability using internal-external cross-validation. The parameter coefficient estimates of the two models were scaled into two scoring systems to classify tuberculosis with a prespecified sensitivity target. The two scoring systems were used to develop two pragmatic, treatment-decision algorithms for use in primary health-care settings. Findings: Of 4718 children from 13 studies from 12 countries, 1811 (38·4%) were classified as having pulmonary tuberculosis: 541 (29·9%) bacteriologically confirmed and 1270 (70·1%) unconfirmed. Existing treatment-decision algorithms had highly variable diagnostic performance. The scoring system derived from the prediction model that included clinical features and features from chest x-ray had a combined sensitivity of 0·86 [95% CI 0·68-0·94] and specificity of 0·37 [0·15-0·66] against a composite reference standard. The scoring system derived from the model that included only clinical features had a combined sensitivity of 0·84 [95% CI 0·66-0·93] and specificity of 0·30 [0·13-0·56] against a composite reference standard. The scoring system from each model was placed after triage steps, including assessment of illness acuity and risk of poor tuberculosis-related outcomes, to develop treatment-decision algorithms. Interpretation: We adopted an evidence-based approach to develop pragmatic algorithms to guide tuberculosis treatment decisions in children, irrespective of the resources locally available. This approach will empower health workers in primary health-care settings with high tuberculosis incidence and limited resources to initiate tuberculosis treatment in children to improve access to care and reduce tuberculosis-related mortality. These algorithms have been included in the operational handbook accompanying the latest WHO guidelines on the management of tuberculosis in children and adolescents. Future prospective evaluation of algorithms, including those developed in this work, is necessary to investigate clinical performance. Funding: WHO, US National Institutes of Health

Designing freshwater protected areas (FPAs) for indiscriminate fisheries

Freshwater protected areas (FPAs) are increasingly important for biodiversity conservation, given the intensive use of these systems for water, energy and food production. However, the fisheries benefits of FPAs are not well understood, particularly for indiscriminate fisheries typical of tropical systems. Here we report the results of a model that tests the fisheries effects of no-take protected areas in conditions unique to indiscriminate riverine/floodplain systems. The model has a generalized form applicable to a wide range of systems. We report the results of the general model, as well as those from a specialized form parameterized for the Tonle Sap lake, Cambodia. Both the general and Tonle Sap versions of the model show that FPAs can pay important fisheries benefits, especially where it is difficult to control fishing mortality through gear restrictions or other means. The harvest and profit benefit response curves have similar shapes, with additional FPAs paying high dividends at less than approximately 50% FPA coverage, and then truncating and declining thereafter. In the specific setting of the Tonle Sap of Cambodia, FPAs would pay a large increase in harvest because current FPA coverage is low. It may be counterintuitive to community fisheries managers in Cambodia that the best way to increase harvest is to restrict fishing, but at very high levels of fishing effort, reducing effort or area fished will improve both harvest and profit. In Cambodia, it may make sense to maximize harvest rather than profit because fishers living in poverty need to maximize protein offtake, but the benefits of FPAs remain. Similar considerations may apply in many freshwater and indiscriminate fisheries

Designing freshwater protected areas (FPAs) for indiscriminate fisheries

Freshwater protected areas (FPAs) are increasingly important for biodiversity conservation, given the intensive use of these systems for water, energy and food production. However, the fisheries benefits of FPAs are not well understood, particularly for indiscriminate fisheries typical of tropical systems. Here we report the results of a model that tests the fisheries effects of no-take protected areas in conditions unique to indiscriminate riverine/floodplain systems. The model has a generalized form applicable to a wide range of systems. We report the results of the general model, as well as those from a specialized form parameterized for the Tonle Sap lake, Cambodia. Both the general and Tonle Sap versions of the model show that FPAs can pay important fisheries benefits, especially where it is difficult to control fishing mortality through gear restrictions or other means. The harvest and profit benefit response curves have similar shapes, with additional FPAs paying high dividends at less than approximately 50% FPA coverage, and then truncating and declining thereafter. In the specific setting of the Tonle Sap of Cambodia, FPAs would pay a large increase in harvest because current FPA coverage is low. It may be counterintuitive to community fisheries managers in Cambodia that the best way to increase harvest is to restrict fishing, but at very high levels of fishing effort, reducing effort or area fished will improve both harvest and profit. In Cambodia, it may make sense to maximize harvest rather than profit because fishers living in poverty need to maximize protein offtake, but the benefits of FPAs remain. Similar considerations may apply in many freshwater and indiscriminate fisheries

A report from the Cambodia Training Event for Awareness of Melioidosis (C-TEAM), October 2017

Melioidosis is an endemic infection in Cambodia, a lower middle income SE Asian country. Despite more laboratories isolating and identifying Burkholderia pseudomallei in recent years, the infection remains under-recognised and under-diagnosed, particularly in the adult population. Lack of knowledge about the disease and lack of utilization of microbiology laboratories contributes to this, along with laboratory capacity issues. Treatment costs often hamper optimal management. In response to these issues, a national one-health training event was held in October 2017 to raise awareness of the disease amongst clinical, laboratory, and public health professionals. The meeting format, findings, and outcomes are described her

Early versus deferred antiretroviral therapy for children older than 1 year infected with HIV (PREDICT) : a multicentre, randomised, open-label trial

Background The optimum time to start antiretroviral therapy for children diagnosed with HIV infection after 1 year of age is unknown. We assessed whether antiretroviral therapy could be deferred until CD4 percentages declined to less than 15% without affecting AIDS-free survival. Methods In our multicentre, randomised, open-label trial at nine research sites in Thailand and Cambodia, we enrolled children aged 1-12 years who were infected with HIV and had CD4 percentages of 15-24%. Participants were randomly assigned (1:1) by a minimisation scheme to start antiretroviral therapy at study entry (early treatment group) or antiretroviral therapy to start when CD4 percentages declined to less than 15% (deferred treatment group). The primary endpoint was AIDS-free survival (based on US Centers for Disease Control and Prevention category C events) at week 144, assessed with the Kaplan-Meier analysis and the log-rank approach. This study is registered with ClinicalTrials.gov, number NCT00234091. Findings Between March 28,2006, and Sept 10,2008, we enrolled 300 Thai and Cambodian children infected with HIV, with a median age of 6.4 years (IQR 3.9-8.4). 150 children were randomly allocated early antiretroviral therapy (one participant was excluded from analyses after withdrawing before week 0) and 150 children were randomly allocated deferred antiretroviral therapy. Median baseline CD4 percentage was 19% (16-22%). 69 children (46%) in the deferred treatment group started antiretroviral therapy during the study. AIDS-free survival at week 144 in the deferred treatment group was 98.7% (95% CI 94.7-99.7; 148 of 150 patients) compared with 97.9% (93.7-99.3; 146 of 149 patients) in the early treatment group (p=0.6). Interpretation AIDS-free survival in both treatment groups was high. This low event rate meant that our study was underpowered to detect differences between treatment start times and thus additional follow-up of study participants or future studies are needed to answer this clinical question