Stool Culture for Diagnosis of Pulmonary Tuberculosis in Children.

Bacteriological confirmation of Mycobacterium tuberculosis is achieved in the minority of young children with tuberculosis (TB), since specimen collection is resource intensive and respiratory secretions are mostly paucibacillary, leading to limited sensitivity of available diagnostic tests. Although molecular tests are increasingly available globally, mycobacterial culture remains the gold standard for diagnosis and determination of drug susceptibility and is more sensitive than molecular methods for paucibacillary TB. We evaluated stool culture as an alternative to respiratory specimens for the diagnosis of suspected intrathoracic TB in a subgroup of 188 children (median age, 14.4 months; 15.4% HIV infected) enrolled in a TB diagnostic study at two local hospitals in Cape Town, South Africa. One stool culture was compared to overall bacteriological confirmation by stool Xpert and by Xpert and culture of multiple respiratory specimens. After decontamination/digestion with NALC (N-acetyl-l-cysteine)-NaOH (1.25%), concentrated fluorescent smear microscopy, Xpert MTB/RIF, and liquid culture were completed for all specimens. Culture contamination of stool specimens was high at 41.5%. Seven of 90 (7.8%) children initiating TB treatment were stool culture positive for M. tuberculosis Excluding contaminated cultures, the sensitivity of stool culture versus confirmed TB was 6/25 (24.0%; 95% confidence interval [CI] = 9.4 to 45.1%). In addition, stool culture detected TB in 1/93 (1.1%) children with "unconfirmed TB." Testing the same stool by Xpert increased sensitivity to 33.3% (95% CI = 18.0 to 51.8%). In conclusion, stool culture had low sensitivity for M. tuberculosis detection in children with intrathoracic TB. Reducing culture contamination through improved laboratory protocols may enable more reliable estimates of its diagnostic utility.

Optimizing the detection of recent tuberculosis infection in children in a high tuberculosis-HIV burden setting.

RATIONALE: Children who are young, malnourished, and infected with HIV have significant risk of tuberculosis (TB) morbidity and mortality following TB infection. Treatment of TB infection is hindered by poor detection and limited pediatric data. OBJECTIVES: Identify improved testing to detect pediatric TB infection. METHODS: This was a prospective community-based study assessing use of the tuberculin skin test and IFN-γ release assays among children (n = 1,343; 6 mo to <15 yr) in TB-HIV high-burden settings; associations with child characteristics were measured. MEASUREMENTS AND MAIN RESULTS: Contact tracing detects TB in 8% of child contacts within 3 months of exposure. Among children with no documented contact, tuberculin skin test and QuantiFERON-TB Gold In-Tube positivity was greater than T-SPOT.TB. Nearly 8% of children had IFN-γ release assay positive and skin test negative discordance. In a model accounting for confounders, all tests correlate with TB contact, but IFN-γ release assays correlate better than the tuberculin skin test (P = 0.0011). Indeterminate IFN-γ release assay results were not associated with age. Indeterminate QuantiFERON-TB Gold In-Tube results were more frequent in children infected with HIV (4.7%) than uninfected with HIV (1.9%), whereas T-SPOT.TB indeterminates were rare (0.2%) and not affected by HIV status. Conversion and reversion were not associated with HIV status. Among children infected with HIV, tests correlated less with contact as malnutrition worsened. CONCLUSIONS: Where resources allow, use of IFN-γ release assays should be considered in children who are young, recently exposed, and infected with HIV because they may offer advantages compared with the tuberculin skin test for identifying TB infection, and improve targeted, cost-effective delivery of preventive therapy. Affordable tests of infection could dramatically impact global TB control.

Modelling the cost-effectiveness of strategies to prevent tuberculosis in child contacts in a high-burden setting.

BACKGROUND: WHO recommends isoniazid preventive therapy (IPT) for young children in close contact with an infectious tuberculosis (TB) case. No models have examined the cost effectiveness of this recommendation. METHODS: A decision analysis model was developed to estimate health and economic outcomes of five TB infection screening strategies in young household contacts. In the no-testing strategy, children received IPT based on age and reported exposure. Other strategies included testing for infection with a tuberculin skin test (TST), interferon γ release assay (IGRA) or IGRA after TST. Markov modelling included age-specific disease states and probabilities while considering risk of re-infection in a high-burden country. RESULTS: Among the 0-2-year-old cohort, the no-testing strategy was most cost effective. The discounted societal cost of care per life year saved ranged from US$237 (no-testing) to US$538 (IGRA only testing). Among the 3-5-year-old cohort, strategies employing an IGRA after a negative TST were most effective, but were associated with significant incremental cost (incremental cost-effectiveness ratio >US$233 000), depending on the rate of Mycobacterium tuberculosis infection. CONCLUSION: Screening for M tuberculosis infection and provision of IPT in young children is a highly cost-effective intervention. Screening without testing for M tuberculosis infection is the most cost-effective strategy in 0-2-year-old children and the preferred strategy in 3-5-year-old children. Lack of testing capacity should therefore not be a barrier to IPT delivery. These findings highlight the cost effectiveness of contact tracing and IPT delivery in young children exposed to TB in high-burden countries.

Evaluation of tuberculosis diagnostics in children: 1. Proposed clinical case definitions for classification of intrathoracic tuberculosis disease. Consensus from an expert panel.

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.

Childhood tuberculosis: progress requires an advocacy strategy now.

Childhood tuberculosis (TB) is a preventable and curable infectious disease that remains overlooked by public health authorities, health policy makers and TB control programmes. Childhood TB contributes significantly to the burden of disease and represents the failure to control transmission in the community. Furthermore, the pool of infected children constitutes a reservoir of infection for the future burden of TB. It is time to prioritise childhood TB, advocate for addressing the challenges and grasp the opportunities in its prevention and control. Herein, we propose a scientifically informed advocacy agenda developed at the International Childhood TB meeting held in Stockholm, Sweden, from March 17 to 18, 2011, which calls for a renewed effort to improve the situation for children affected by Mycobacterium tuberculosis exposure, infection or disease. The challenges and needs in childhood TB are universal and apply to all settings and must be addressed more effectively by all stakeholders.

No decrease in annual risk of tuberculosis infection in endemic area in Cape Town, South Africa.

OBJECTIVE: To estimate the change in annual risk of tuberculosis infection (ARTI) in two neighbouring urban communities of Cape Town, South Africa with an HIV prevalence of approximately 2%, and to compare ARTI with notification rates and treatment outcomes in the tuberculosis (TB) programme. METHODS: In 1998-1999 and 2005, tuberculin skin test surveys were conducted to measure the prevalence of Mycobacterium tuberculosis infection and to calculate the ARTI. All 6 to 9-year-old children from all primary schools were included in the survey. Notification rates and treatment outcomes were obtained from the TB register. RESULTS: A total of 2067 children participated in the survey from 1998 to 1999 and a total of 1954 in 2005. Based on a tuberculin skin test cut-off point of 10 mm, the ARTI was 3.7% (3.4-4.0%) in the 1998-1999 survey and 4.1% (3.8-4.5%) in 2005. The notification rate for pulmonary TB increased significantly from 646 per 100 000 in 1998 to 784 per 100,000 in 2002. In Ravensmead, there was no significant change in ARTI [first survey: 3.5% (3.1-3.9%), second survey: 3.2% (2.9-3.6%)], but in Uitsig the ARTI increased significantly from 4.1% (3.6-4.6%) to 5.8% (5.2-6.5%). The difference in ARTI between the two areas was associated with differences in reported case rates and the proportion of previously treated cases. CONCLUSION: Tuberculosis transmission remains very high in these two communities and control measures to date have failed. Additional measures to control TB are needed.

Indoor air pollution and tobacco smoke exposure: impact on nasopharyngeal bacterial carriage in mothers and infants in an African birth cohort study.

Indoor air pollution (IAP) or environmental tobacco smoke (ETS) exposure may influence nasopharyngeal carriage of bacterial species and development of lower respiratory tract infection (LRTI). The aim of this study was to longitudinally investigate the impact of antenatal or postnatal IAP/ETS exposure on nasopharyngeal bacteria in mothers and infants. A South African cohort study followed mother-infant pairs from birth through the first year. Nasopharyngeal swabs were taken at birth, 6 and 12 months for bacterial culture. Multivariable and multivariate Poisson regression investigated associations between nasopharyngeal bacterial species and IAP/ETS. IAP exposures (particulate matter, carbon monoxide, nitrogen dioxide, volatile organic compounds) were measured at home visits. ETS exposure was measured through maternal and infant urine cotinine. Infants received the 13-valent pneumococcal and Haemophilus influenzae B conjugate vaccines. There were 881 maternal and 2605 infant nasopharyngeal swabs. Antenatal ETS exposure was associated with Streptococcus pneumoniae carriage in mothers (adjusted risk ratio (aRR) 1.73 (95% CI 1.03-2.92)) while postnatal ETS exposure was associated with carriage in infants (aRR 1.14 (95% CI 1.00-1.30)) Postnatal particulate matter exposure was associated with the nasopharyngeal carriage of H. influenzae (aRR 1.68 (95% CI 1.10- 2.57)) or Moraxella catarrhalis (aRR 1.42 (95% CI 1.03-1.97)) in infants. Early-life environmental exposures are associated with an increased prevalence of specific nasopharyngeal bacteria during infancy, which may predispose to LRTI.

Specimen Pooling as a Diagnostic Strategy for Microbiologic Confirmation in Children with Intrathoracic Tuberculosis.

Three-hundred four young children with suspected pulmonary tuberculosis had a gastric aspirate, induced sputum and nasopharyngeal aspirate collected on each of 2 consecutive weekdays. Specimens collected on the second day were pooled in the laboratory for each child individually. The diagnostic yield by Xpert and culture from pooled specimens was not significantly different to a single gastric aspirate.

Lethal fibrosing mediastinitis in a child possibly due to Mycobacterium tuberculosis.

Fibrosing mediastinitis (FM) is a rare benign disease resulting from an excessive fibro-inflammatory reaction in the mediastinum that can compress and occlude mediastinal structures. There is a granulomatous and a diffuse non-granulomatous form of FM. We present a case of granulomatous FM following possible tuberculosis in a young child who presented with severe compression of the airways, pulmonary artery and the superior vena cava (SVC), unresponsive to treatment, resulting in death. Bronchoscopic findings included concentric narrowing and mucosal hyperaemia of the tracheobronchial airways. This case raises awareness of this rare complication and the limited treatment options available.

HIV-related chronic lung disease in adolescents: are we prepared for the future?

INTRODUCTION: Chronic lung diseases (CLD) are the most chronic disease occurring in adolescents living with human immunodeficiency virus (ALHIV). In ALHIV who received antiretroviral therapy (ART) late in childhood, bronchiectasis, bronchiolitis obliterans and interstitial pneumonitis are common. In adolescents who received ART early in life the spectrum of CLD has changed with asthma and chronic obstructive pulmonary disease being common. Areas covered: The aim of this paper was to review CLD in ALHIV. We conducted a literature review of electronic databases focusing on CLD that were common prior to the introduction of ART (1996-2004), the present situation where ART is widely available (2005 to 2016), and articles which aided us speculating on the impact of HIV-related CLD in adolescents transitioning to adult HIV-clinics. Amongst the approximately 2.1 million adolescents living with HIV, CLD commonly occurs. Awareness of the CLD amongst ALHIV needs to be raised to ensure that disease appropriate treatment is available to these vulnerable adolescents. Expert commentary: As adolescents' transition from pediatric HIV-clinics to adult HIV-clinics the evidence shows that adolescents might not receive optimal care if adult pulmonologists are not aware of the CLD that commonly occur in ALHIV.

Early-life exposure to indoor air pollution or tobacco smoke and lower respiratory tract illness and wheezing in African infants: a longitudinal birth cohort study.

BACKGROUND: Indoor air pollution (IAP) and environmental tobacco smoke (ETS) are associated with lower respiratory tract illness (LRTI) or wheezing in children. However, the effect of the timing of these exposures, specifically antenatal versus postnatal, and of alternate fuel sources such as the increasingly used volatile organic compounds have not been well studied. We longitudinally investigated the effect of antenatal or postnatal IAP and ETS on LRTI or wheezing prevalence and severity in African infants. METHODS: Mother and infant pairs enrolled over a 3-year period in a birth cohort study in two centres in Paarl, South Africa, were followed for the first year of life for LRTI or wheezing illness. We measured exposure to IAP (particulate matter, nitrogen dioxide, sulphur dioxide, carbon monoxide, and volatile organic compounds benzene and toluene) using devices placed in homes, antenatally and postnatally. We measured ETS longitudinally by maternal self-report and by urine cotinine measures. Study staff trained in recognition of LRTI or wheeze documented all episodes, which were categorised according to WHO case definition criteria. We used multivariate logistic and Poisson regressions to explore associations. FINDINGS: Between March 1, 2012, and March 31, 2015, we enrolled 1137 mothers with 1143 livebirths. Of 1065 infants who attended at least one study visit, 524 episodes of LRTI occurred after discharge with a wheezing prevalence of 0·23 (95% CI 0·21-0·26) episodes per child year. Exposures associated with LRTI were antenatal maternal smoking (incidence rate ratio 1·62, 95% CI 1·14-2·30; p=0·004) or particulate matter (1·43, 1·06-1·95; p=0·008). Subanalyses of LRTI requiring hospitalisation (n=137) and supplemental oxygen (n=69) found antenatal toluene significantly increased the risk of LRTI-associated hospitalisation (odds ratio 5·13, 95% CI 1·43-18·36; p=0·012) and need for supplemental oxygen (13·21, 1·96-89·16; p=0·008). Wheezing illness was associated with both antenatal (incidence rate ratio 2·09, 95% CI 1·54-2·84; p<0·0001) and postnatal (1·27, 95% CI 1·03-1·56; p=0·024) maternal smoking. Antenatally, wheezing was associated with maternal passive smoke exposure (1·70, 1·25-2·31; p=0·001) and, postnatally, with any household member smoking (1·55, 1·17 -2·06; p=0·002). INTERPRETATION: Antenatal exposures were the predominant risk factors associated with LRTI or wheezing illness. Toluene was a novel exposure associated with severe LRTI. Urgent and effective interventions focusing on antenatal environmental factors are required, including smoking cessation programmes targeting women of childbearing age pre-conception and pregnant women. FUNDING: Bill & Melinda Gates Foundation, Discovery Foundation, South African Thoracic Society AstraZeneca Respiratory Fellowship, Medical Research Council South Africa, National Research Foundation South Africa, and CIDRI Clinical Fellowship.

Xpert MTB/RIF on Stool Is Useful for the Rapid Diagnosis of Tuberculosis in Young Children With Severe Pulmonary Disease.

BACKGROUND: Tuberculosis (TB) continues to result in high morbidity and mortality in children from resource-limited settings. Diagnostic challenges, including resource-intense sputum collection methods and insensitive diagnostic tests, contribute to diagnostic delay and poor outcomes in children. We evaluated the diagnostic utility of stool Xpert MTB/RIF (Xpert) compared with bacteriologic confirmation (combination of Xpert and culture of respiratory samples). METHODS: In a hospital-based study in Cape Town, South Africa, we enrolled children younger than 13 years of age with suspected pulmonary TB from April 2012 to August 2015. Standard clinical investigations included tuberculin skin test, chest radiograph and HIV testing. Respiratory samples for smear microscopy, Xpert and liquid culture included gastric aspirates, induced sputum, nasopharyngeal aspirates and expectorated sputum. One stool sample per child was collected and tested using Xpert. RESULTS: Of 379 children enrolled (median age, 15.9 months, 13.7% HIV infected), 73 (19.3%) had bacteriologically confirmed TB. The sensitivity and specificity of stool Xpert versus overall bacteriologic confirmation were 31.9% [95% confidence interval (CI): 21.84%-44.50%] and 99.7% (95% CI: 98.2%-100%), respectively. A total of 23/51 (45.1%) children with bacteriologically confirmed TB with severe disease were stool Xpert positive. Cavities on chest radiograph were associated with Xpert stool positivity regardless of age and other relevant factors [odds ratios (OR) 7.05; 95% CI: 2.16-22.98; P = 0.001]. CONCLUSIONS: Stool Xpert can rapidly confirm TB in children who present with radiologic findings suggestive of severe TB. In resource-limited settings where children frequently present with advanced disease, Xpert on stool samples could improve access to rapid diagnostic confirmation and appropriate treatment.

Radiographic signs and symptoms in children treated for tuberculosis: possible implications for symptom-based screening in resource-limited settings.

BACKGROUND: The World Health Organization advises active tracing of children younger than 5 years old in household contact with a sputum smear-positive tuberculosis index case. This study compared radiographic disease manifestations in 2 groups of children treated for tuberculosis in an endemic setting: those who presented with suspicious symptoms; and those actively traced as household contacts of an adult index case. METHODS: We conducted a prospective descriptive study from February 2003 through October 2004 at 5 primary health care clinics in Cape Town South Africa, including all children (younger than 5 years old) treated for tuberculosis (TB). RESULTS: A total of 326 children (younger than 5 years old) received antituberculosis treatment; 190 (58.3%) presented with suspicious symptoms, and 136 (41.7%) were actively traced contacts. Children were categorized as; "not TB" 71 (22%), intrathoracic tuberculosis 230 (70%) and extrathoracic tuberculosis 25 (8%). Significantly more actively traced contacts were categorized as "not TB" (odds ratio, 7.4; 95% confidence interval, 3.8-14.3), or demonstrated elements of the primary complex only on the chest radiograph (odds ratio, 26.2; 95% confidence interval, 8.6-89.2), compared with children who presented with suspicious symptoms. Of all children diagnosed with intrathoracic tuberculosis, 20 of 230 (9%) reported no symptoms, all of whom demonstrated elements of the primary complex only. CONCLUSIONS: The majority of actively traced contacts had minimal disease. Symptom-based screening would have identified all but 9% of children diagnosed with intrathoracic tuberculosis, all of whom demonstrated elements of the primary complex only. Further investigation is required to establish whether symptom-based screening can be justified to improve access to preventive chemotherapy in resource-limited endemic settings.

Tuberculous lymphadenitis as a cause of persistent cervical lymphadenopathy in children from a tuberculosis-endemic area.

BACKGROUND: Cervical lymphadenitis is the most common form of extrapulmonary tuberculosis in children, although its relative contribution as a cause of persistent cervical adenopathy is not well-documented. The aim of this study was to determine the relative contribution of tuberculous lymphadenitis as a cause of persistent cervical adenopathy in a tuberculosis-endemic setting and to document its clinical presentation at the primary health care level. METHODS: A prospective descriptive study was conducted from February 2003 through October 200 at 5 primary health care clinics in Cape Town, South Africa. The study included all children younger than 13 years presenting with persistent cervical adenopathy to the local primary health care clinic. RESULTS: A total of 158 children were evaluated of whom 35 (22.2%) were diagnosed with tuberculous lymphadenitis. Bacteriologic confirmation was achieved in 27 of 35 (77.1%) children; all 35 responded to standard antituberculosis treatment. The majority of those without tuberculous lymphadenitis (105 of 123, 85.4%) had a visible superficial lesion in the area drained by the affected nodes. In children with persistent lymphadenopathy > or =2 x 2 cm, tuberculosis lymphadenitis was diagnosed in 31 of 33 (93.9%); specificity was 98.4%, sensitivity was 88.6% and the positive predictive value was 93.4%. CONCLUSION: Children commonly present with persistent cervical adenopathy to the primary health care clinic. The use of a simple clinical algorithm provided an accurate diagnosis of tuberculous lymphadenitis in the study setting. Fine needle aspirations provided a rapid and definitive diagnosis in the majority of children and will have added diagnostic value in settings where alternative diagnoses are more likely.

Adult-type pulmonary tuberculosis in children 10-14 years of age.

We report 8 children (10-14 years of age) who were diagnosed with tuberculosis at their local primary health care clinic from July to September 2004, after routine sputum testing was extended to all children older than 10 years of age with suspected tuberculosis. This case series emphasizes that older children develop adult-type cavitating disease, which can be diagnosed by sputum smear microscopy, in contrast to younger children for whom smear microscopy has very little diagnostic value.

Home environment and indoor air pollution exposure in an African birth cohort study.

BACKGROUND: Household indoor air pollution (IAP) is a global health problem and a risk factor for childhood respiratory disease; the leading cause of mortality in African children. This study aimed to describe the home environment and measure IAP in the Drakenstein Child Health Study (DCHS), an African birth cohort. METHODS: An antenatal home visit to assess the home environment and measure IAP (particulate matter, sulphur dioxide, nitrogen dioxide, carbon monoxide and volatile organic compounds (VOCs)) was done on pregnant women enrolled to the DCHS, in a low-socioeconomic, peri-urban South African community. Urine cotinine measured maternal tobacco smoking and exposure. Dwellings were categorised according to 6 household dimensions. Univariate and multivariate analysis explored associations between home environment, seasons and IAP levels measured. RESULTS: 633 home visits were completed, with IAP measured in 90% of homes. Almost a third of participants were of the lowest socio-economic status and the majority of homes (65%) lacked 2 or more of the dwelling category dimensions. Most households had electricity (92%), however, fossil fuels were still used for cooking (19%) and heating (15%) in homes. Antenatal maternal smoking prevalence was 31%; 44% had passive smoke exposure. Of IAP measured, benzene (VOC) was significantly above ambient standards with median 5.6 µg/m3 (IQR 2.6-17.1). There were significant associations between the use of fossil fuels for cooking and increased benzene [OR 3.4 (95% CI 2.1-5.4)], carbon monoxide [OR 2.9 (95% CI 1.7-5.0)] and nitrogen dioxide [OR 18.6 (95% CI 3.9-88.9)] levels. A significant seasonal association was found with higher IAP levels in winter. CONCLUSION: In this low-socioeconomic African community, multiple environmental factors and pollutants, with the potential to affect child health, were identified. Measurement of IAP in a resource-limited setting is feasible. Recognising and quantifying these risk factors is important in effecting public health policy changes.

Decompression of enlarged mediastinal lymph nodes due to mycobacterium tuberculosis causing severe airway obstruction in children.

BACKGROUND: Large airway compression by enlarged tuberculosis (TB) lymph nodes results in life-threatening airway obstruction in a small proportion of children. The indications, safety, and efficacy of TB lymph node decompression are inadequately described. This study aims to describe the indications and efficacy of TB lymph node decompression in children with severe airway compression and investigate variables influencing outcome. METHODS: A prospective cohort of children (aged 3 months to 13 years) with life-threatening airway obstruction resulting from TB lymph node compression of the large airways were enrolled. The site and degree of airway obstruction were assessed by bronchoscopy and chest computed tomography scan. RESULTS: Of the 250 children enrolled, 34% (n = 86) required transthoracic lymph node decompression, 29% as an urgent procedure and 71% (n = 63) after failing 1 month of antituberculosis treatment that included glucosteroids. Compression (less than 75%) of the bronchus intermedius (odds ratio 2.28, 95% confidence interval: 1.29 to 4.02) and left main bronchus (odds ratio 3.34, 95% confidence interval: 1.73 to 6.83) were the best predictors for lymph node decompression. Human immunodeficiency virus status, drug resistance, and malnutrition were not associated with decompression. Few complications (self-limiting, 8%) or treatment failures (2%) resulted from the decompression. There were no deaths. CONCLUSIONS: In one third of children with TB, severe airway obstruction caused by enlarged lymph nodes requires decompression. Transthoracic decompression can be safely performed with low complication, failure, and fatality rates.

Potentially Modifiable Factors Associated with Death of Infants and Children with Severe Pneumonia Routinely Managed in District Hospitals in Malawi.

OBJECTIVE: To investigate recognised co-morbidities and clinical management associated with inpatient pneumonia mortality in Malawian district hospitals. METHODS: Prospective cohort study, of patient records, carried out in Malawi between 1st October 2000 and 30th June 2003. The study included all children aged 0-59 months admitted to the paediatric wards in sixteen district hospitals throughout Malawi with severe and very severe pneumonia. We compared individual factors between those that survived (n = 14 076) and those that died (n = 1 633). RESULTS: From logistic regression analysis, predictors of death in hospital, adjusted for age, sex and severity grade included comorbid conditions of meningitis (OR =2.49, 95% CI 1.50-4.15), malnutrition (OR =2.37, 95% CI 1.94-2.88) and severe anaemia (OR =1.41, 95% CI 1.03-1.92). Requiring supplementary oxygen (OR =2.16, 95% CI 1.85-2.51) and intravenous fluids (OR =3.02, 95% CI 2.13-4.28) were associated with death while blood transfusion was no longer significant (OR =1.10, 95% CI 0.77-1.57) when the model included severe anaemia. CONCLUSIONS: This study identified a number of challenges to improve outcome for Malawian infants and children hospitalised with pneumonia. These included improved assessment of co-morbidities and more rigorous application of standard case management.