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We describe a case of congenital tuberculosis in an extremely premature baby, with rapid molecular detection of a pre-extensively drug-resistant (XDR) pattern of drug resistance. The baby was treated successfully with a regimen including bedaquline and delamanid, drugs not previously described in the treatment of congenital tuberculosis (TB). [ABSTRACT FROM AUTHOR]

Background Pneumonia is the leading cause of antibiotic use and hospitalization in Vietnam. There is a need for better prediction of unlikely bacterial pneumonia and adverse pneumonia outcome in order to guide hospital admission and improve rational antibiotic use. Methods All children under 5 admitted with pneumonia (per clinician assessment) to the Da Nang Hospital for Women and Children were prospectively enrolled. Children were classified as having likely or unlikely bacterial pneumonia and followed for outcome assessment. A Bayesian model averaging approach was used to identify predictors of unlikely bacterial pneumonia and adverse pneumonia outcome, which guided the development of a pragmatic management algorithm. Results Of 3817 patients assessed, 2199 (57.6%) met World Health Organization (WHO) pneumonia criteria. In total, 1594 (41.7%) children were classified as having unlikely and 129 (3.4%) as having likely bacterial pneumonia. The remainder (2399; 62.9%) were considered to have disease of uncertain etiology. Factors predictive of unlikely bacterial pneumonia were no fever, no consolidation on chest radiograph, and absolute neutrophil count <5 × 109/L at presentation, which had a negative predictive value (NPV) for likely bacterial pneumonia of 99.0%. Among those who met WHO pneumonia criteria, 8.6% (189/2199) experienced an adverse outcome. Not having any WHO danger sign or consolidation on chest radiograph had an NPV of 96.8% for adverse pneumonia outcome. Conclusions An algorithm that screens for predictors of likely bacterial pneumonia and adverse pneumonia outcome could reduce unnecessary antibiotic use and hospital admission, but its clinical utility requires validation in a prospective study. [ABSTRACT FROM AUTHOR]

Consensus case definitions for childhood tuberculosis have been proposed by an international expert panel, aiming to standardize the reporting of cases in research focusing on the diagnosis of intrathoracic tuberculosis in children. These definitions are intended for tuberculosis diagnostic evaluation studies of symptomatic children with clinical suspicion of intrathoracic tuberculosis, and were not intended to predefine inclusion criteria into such studies. Feedback from researchers suggested that further clarification was required and that these case definitions could be further improved. Particular concerns were the perceived complexity and overlap of some case definitions, as well as the potential exclusion of children with acute onset of symptoms or less severe disease. The updated case definitions proposed here incorporate a number of key changes that aim to reduce complexity and improve research performance, while maintaining the original focus on symptomatic children suspected of having intrathoracic tuberculosis. The changes proposed should enhance harmonized classification for intrathoracic tuberculosis disease in children across studies, resulting in greater comparability and the much-needed ability to pool study results. [ABSTRACT FROM AUTHOR]

Tuberculosis contact screening is universally recommended but rarely implemented in tuberculosis-endemic resource-limited settings. The World Health Organization symptom-based screening approach is a simple and effective method that can be implemented at the primary healthcare level.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. [ABSTRACT FROM PUBLISHER]

The accelerated reductions in global TB incidence required to achieve the End TB Strategy goal will result in reductions in the burden of childhood TB. Contact screening and preventive therapy have emerged as important components of TB burden reduction, and family-centered approaches could be an effective route in delivering these activities. Lack of accurate diagnostics for children remains a critical barrier and a need remains for better collaborative and supportive links between the child health and TB control sectors. Irrespective of whether the ambitious targets can be achieved, the unprecedented opportunities provided by the End TB Strategy must be embraced. [ABSTRACT FROM AUTHOR]

Background. Nontyphoidal salmonellae (NTS) have become the most common cause of bacteremia in tropical Africa, particularly among susceptible children and HIV-infected adults. Methods. We describe 4956 episodes of NTS bacteremia (2439 episodes in adults and 2517 episodes in children) that occurred in Blantyre, Malawi, during the 7-year period 1998-2004. Results. A total of 75% of the cases of NTS bacteremia were due to Salmonella enterica serovar Typhimurium, and 21% were due to S. enterica serovar Enteritidis. Epidemic increases in the incidence of NTS bacteremia were seen sequentially, occurring first among cases caused by S. Enteritidis and then among cases caused by S. Typhimurium. Increased incidence of bacteremia was temporally associated with the acquisition of multidrug resistance to ampicillin, cotrimoxazole, and chloramphenicol by each serovar and occurred while the incidence of infection due to other common bloodstream pathogens remained constant. These epidemics were observed among adults and children. A seasonal pattern was also seen, with increased incidence during and after the rainy season. The median age of the patients was 32 years among adults and 22 months among children. Acquisition of multidrug-resistant infection was not associated with an increased case-fatality rate among children (22%), and the case-fatality rate among adults showed a significant trend toward decreasing (from 29% to 20%). Conclusions. These data have important implications for the treatment of severe febrile illness in adults and children in tropical Africa. Further understanding of the molecular basis of these epidemics of multidrug-resistant NTS infection, including ongoing whole-genome sequencing of multidrug-resistant isolates, will yield important tools for the study of NTS pathogenesis, transmission, epidemiology, and prevention. [ABSTRACT FROM AUTHOR]

Background. Previous prospective studies of bacteremia in African children with severe malaria have mainly included children with cerebral malaria, and no study has examined the impact of human immunodeficiency virus (HIV) infection. We examined the prevalence and etiology of bacteremia and the impact of HIV infection on bacteremia in Malawian children with severe malaria, as well as the impact of bacteremia and HIV infection on outcome. Methods. From 1996 until 2005, blood for culture was obtained on admission from all children admitted with severe malaria during the rainy season to the Paediatric Research Ward at the Queen Elizabeth Central Hospital in Blantyre, Malawi. HIV testing was performed prospectively from 2001 to 2005 and retrospectively for those admitted from 1996 to 2000. Multivariate regression analysis examined independent risk factors for bacteremia and death. Results. Sixty-four (4.6%) of 1388 children with severe malaria had bacteremia; nontyphoidal Salmonellae (NTS) accounted for 58% of all bacteremias. The prevalence of any bacteremia and of NTS bacteremia was highest in children with severe malarial anemia (11.7% and 7.6%), compared with the prevalence in children with cerebral malaria and severe anemia (4.7% and 3.8%) and in those with cerebral malaria alone (3.0% and 0.9%). HIV infection status was determined in 1119 patients. HIV prevalence was 16% (and was highest in those with severe malaria anemia, at 20.4%), but HIV infection was not significantly associated with bacteremia. Neither bacteremia nor HIV infection was associated with death. Conclusions. Antibiotics are not routinely indicated for children with severe malaria in this region, in which HIV is endemic. However, antibiotic therapy should be to treat NTS infection if bacteremia is suspected in children with severe malarial anemia. [ABSTRACT FROM AUTHOR]

Background. Human immunodeficiency virus (HIV) infection and malaria coexist in much of Africa. Previous studies differ in their findings on the interactions between the 2 infections. Methods. Adults living with HIV infection in Blantyre, Malawi, were enrolled in a longitudinal observational study from September 2002 to August 2004. Malaria blood smears were obtained monthly and for any illness suggestive of malaria. Complete evaluations of all illness episodes were conducted, regardless of malaria smear results. Results. The incidence of clinical malaria episodes was higher in participants with CD4 cell counts <200 cells/ mm³ than in those with CD4 cell counts >500 cells/mm³. The trend was preserved when increasingly specific definitions of malaria disease were used. The prevalence of malaria infection was not associated with CD4 cell count. In per-visit analysis, lower CD4 cell counts were associated with higher incidences of pneumonia, sepsis, and tuberculosis but not of malaria. Severe malaria was rare, with only 3 cases in 591 person-years of observation. Parasite density and CD4 cell count were independent risk factors for fever. Conclusions. Profoundly immunosuppressed adults with HIV infection require more-frequent treatment for uncomplicated malaria, but malaria infection and disease are less strongly associated with HIV-associated immunosuppression than are other opportunistic infections. Where malaria is common, the high incidence of fever found among immunosuppressed adults may lead to misclassification of illness episodes as malaria. [ABSTRACT FROM AUTHOR]

Over one million children world-wide are living with HIV infection and respiratory disease is the commonest cause of morbidity and mortality in these children. The initial presentation of respiratory infection is usually in infancy or early childhood. There is enormous potential to prevent childhood HIV infection that is being realised in industrialised countries but not yet elsewhere. Increasingly, therefore, the burden of HIV disease is in children living in or from non-industrialised countries. This review describes and contrasts the pattern of respiratory infection from both regions. This pattern has changed with the implementation of PCP prophylaxis and the availability of potent antiretroviral therapy for children in resource-rich countries, such as the UK. More data are required from resource-poor regions such as tropical Africa, but it is clear that the major differences reflect greater background risk for respiratory infection and very limited management options rather than specific aetiology. [ABSTRACT FROM PUBLISHER]

The author reflects on a study by researcher S.R.C. Howie and colleagues published within the current issue, conducted on lung aspirate specimens from children with severe pneumonia in The Gambia. The results have revealed the effectiveness of molecular techniques over bacterial culture in detecting bacterial DNA in bacterial pneumonia. Topics include a lung aspiration study of Malawian children, comparison between bacterial culture and molecular techniques, and epidemiology of pneumonia.

The article focuses on screening of children who are in close contact of tuberculosis patients. It states that screening of children helps to identify children who are at risk like HIV-infected children. It presents a study conducted in Uganda which reveals that children exposed to tuberculosis patients had tuberculosis. It highlights that the use of chest radiography and tuberculin testing for screening is difficult due to limited resources.

A letter to the editor is presented in response to the article "Perspectives in implementing childhood tuberculosis research case definitions in a low-income, high burden setting" by LL Holm and colleagues in 2012 issue.

There is a critical need for improved diagnosis of tuberculosis in children, particularly in young children with intrathoracic disease as this represents the most common type of tuberculosis in children and the greatest diagnostic challenge. There is also a need for standardized clinical case definitions for the evaluation of diagnostics in prospective clinical research studies that include children in whom tuberculosis is suspected but not confirmed by culture of Mycobacterium tuberculosis. A panel representing a wide range of expertise and child tuberculosis research experience aimed to develop standardized clinical research case definitions for intrathoracic tuberculosis in children to enable harmonized evaluation of new tuberculosis diagnostic technologies in pediatric populations. Draft definitions and statements were proposed and circulated widely for feedback. An expert panel then considered each of the proposed definitions and statements relating to clinical definitions. Formal group consensus rules were established and consensus was reached for each statement. The definitions presented in this article are intended for use in clinical research to evaluate diagnostic assays and not for individual patient diagnosis or treatment decisions. A complementary article addresses methodological issues to consider for research of diagnostics in children with suspected tuberculosis. [ABSTRACT FROM PUBLISHER]

Confirming the diagnosis of childhood tuberculosis is a major challenge. However, research on childhood tuberculosis as it relates to better diagnostics is often neglected because of technical difficulties, such as the slow growth in culture, the difficulty of obtaining specimens, and the diverse and relatively nonspecific clinical presentation of tuberculosis in this age group. Researchers often use individually designed criteria for enrollment, diagnostic classifications, and reference standards, thereby hindering the interpretation and comparability of their findings. The development of standardized research approaches and definitions is therefore needed to strengthen the evaluation of new diagnostics for detection and confirmation of tuberculosis in children.In this article we present consensus statements on methodological issues for conducting research of Tuberculosis diagnostics among children, with a focus on intrathoracic tuberculosis. The statements are complementary to a clinical research case definition presented in an accompanying publication and suggest a phased approach to diagnostics evaluation; entry criteria for enrollment; methods for classification of disease certainty, including the rational use of culture within the case definition; age categories and comorbidities for reporting results; and the need to use standard operating procedures. Special consideration is given to the performance of microbiological culture in children and we also recommend for alternative methodological approaches to report findings in a standardized manner to overcome these limitations are made. This consensus statement is an important step toward ensuring greater rigor and comparability of pediatric tuberculosis diagnostic research, with the aim of realizing the full potential of better tests for children. [ABSTRACT FROM PUBLISHER]