Episodes Of Acute Lower Respiratory Infection Research Articles

Quantifying the RSV immunity debt following COVID-19: a public health matter

Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection in children younger than 5 years. In 2019, a meta-analysis estimated that RSV was associated with 33 million acute lower respiratory infection episodes and 3·6 million hospitalisations for acute lower respiratory infection annually.1 In England alone, an average of 33 561 annual RSV-associated hospitalisations were observed between 2007 and 2012.2 Before the COVID-19 pandemic, RSV was highly seasonal in temperate countries like England.

Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in children younger than 5 years in 2019: a systematic analysis

SummaryBackgroundRespiratory syncytial virus (RSV) is the most common cause of acute lower respiratory infection in young children. We previously estimated that in 2015, 33·1 million episodes of RSV-associated acute lower respiratory infection occurred in children aged 0–60 months, resulting in a total of 118 200 deaths worldwide. Since then, several community surveillance studies have been done to obtain a more precise estimation of RSV associated community deaths. We aimed to update RSV-associated acute lower respiratory infection morbidity and mortality at global, regional, and national levels in children aged 0–60 months for 2019, with focus on overall mortality and narrower infant age groups that are targeted by RSV prophylactics in development.MethodsIn this systematic analysis, we expanded our global RSV disease burden dataset by obtaining new data from an updated search for papers published between Jan 1, 2017, and Dec 31, 2020, from MEDLINE, Embase, Global Health, CINAHL, Web of Science, LILACS, OpenGrey, CNKI, Wanfang, and ChongqingVIP. We also included unpublished data from RSV GEN collaborators. Eligible studies reported data for children aged 0–60 months with RSV as primary infection with acute lower respiratory infection in community settings, or acute lower respiratory infection necessitating hospital admission; reported data for at least 12 consecutive months, except for in-hospital case fatality ratio (CFR) or for where RSV seasonality is well-defined; and reported incidence rate, hospital admission rate, RSV positive proportion in acute lower respiratory infection hospital admission, or in-hospital CFR. Studies were excluded if case definition was not clearly defined or not consistently applied, RSV infection was not laboratory confirmed or based on serology alone, or if the report included fewer than 50 cases of acute lower respiratory infection. We applied a generalised linear mixed-effects model (GLMM) to estimate RSV-associated acute lower respiratory infection incidence, hospital admission, and in-hospital mortality both globally and regionally (by country development status and by World Bank Income Classification) in 2019. We estimated country-level RSV-associated acute lower respiratory infection incidence through a risk-factor based model. We developed new models (through GLMM) that incorporated the latest RSV community mortality data for estimating overall RSV mortality. This review was registered in PROSPERO (CRD42021252400).FindingsIn addition to 317 studies included in our previous review, we identified and included 113 new eligible studies and unpublished data from 51 studies, for a total of 481 studies. We estimated that globally in 2019, there were 33·0 million RSV-associated acute lower respiratory infection episodes (uncertainty range [UR] 25·4–44·6 million), 3·6 million RSV-associated acute lower respiratory infection hospital admissions (2·9–4·6 million), 26 300 RSV-associated acute lower respiratory infection in-hospital deaths (15 100–49 100), and 101 400 RSV-attributable overall deaths (84 500–125 200) in children aged 0–60 months. In infants aged 0–6 months, we estimated that there were 6·6 million RSV-associated acute lower respiratory infection episodes (4·6–9·7 million), 1·4 million RSV-associated acute lower respiratory infection hospital admissions (1·0–2·0 million), 13 300 RSV-associated acute lower respiratory infection inhospital deaths (6800–28 100), and 45700 RSV-attributable overall deaths (38 400–55 900). 2·0% of deaths in children aged 0–60 months (UR 1·6–2·4) and 3·6% of deaths in children aged 28 days to 6 months (3·0–4·4) were attributable to RSV. More than 95% of RSV-associated acute lower respiratory infection episodes and more than 97% of RSV-attributable deaths across all age bands were in low-income and middle-income countries (LMICs).InterpretationRSV contributes substantially to morbidity and mortality burden globally in children aged 0–60 months, especially during the first 6 months of life and in LMICs. We highlight the striking overall mortality burden of RSV disease worldwide, with one in every 50 deaths in children aged 0–60 months and one in every 28 deaths in children aged 28 days to 6 months attributable to RSV. For every RSV-associated acute lower respiratory infection in-hospital death, we estimate approximately three more deaths attributable to RSV in the community. RSV passive immunisation programmes targeting protection during the first 6 months of life could have a substantial effect on reducing RSV disease burden, although more data are needed to understand the implications of the potential age-shifts in peak RSV burden to older age when these are implemented.FundingEU Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe (RESCEU).

Acute lower respiratory infections in Indigenous infants in Australia's Northern Territory across three eras of pneumococcal conjugate vaccine use (2006–15): a population-based cohort study

The burden of acute lower respiratory infection (ALRI) in Indigenous children of Australia's Northern Territory is among the highest globally. No published data exists on the effect of pneumococcal conjugate vaccine (PCV) introduction on ALRIs in this population beyond 2005. The aim of this study was to describe the rates of ALRI admissions to hospital in Indigenous infants in the Northern Territory from 2006 to 2015, across three periods of different PCV use. We hypothesised that broader valency PCVs would be more effective against hospitalisations for pneumonia. We did a retrospective population-based cohort study of Indigenous infants born in the Northern Territory followed up until age 12 months. Data were from administrative hospital and perinatal datasets. International classification of diseases codes (tenth revision, Australian modification; ICD-10AM) were used to identify respiratory hospitalisations of interest: all-cause ALRI, all-cause pneumonia, bacterial pneumonia, viral pneumonia, influenza-like illness (ILI), respiratory syncytial virus ALRI (RSV-ALRI), and pneumococcal ALRI. Incidence rates were compared between PCV eras (7-valent PCV [PCV7], 2006-09; 10-valent PCV [PCV10], 2009-11; and 13-valent PCV [PCV13], 2011-15) using interrupted time trend analysis and negative binomial regression. For children born between Jan 1, 2006, and Dec 31, 2015, 4138 ALRI episodes (31% of all hospitalisations) occurred among 2888 (20%) of the 14 594 infants. The overall ALRI hospitalisation rate was 29·7 episodes per 100 child-years. Prominent risk factors associated with ALRI hospitalisation were living in a remote community or the Central desert region, being born preterm or with low birthweight. ALRI rates were lowest in the PCV13 era, in association with a significant reduction in bacterial pneumonia hospitalisations in the PCV13 era compared with the PCV10 (incidence rate ratio 0·68, 95% CI 0·57-0·81) and PCV7 (0·70, 0·60-0·81) eras. In contrast, RSV-ALRI rates were 4·9 episodes per 100 child-years in each era. A 30% reduction in bacterial-coded pneumonia hospitalisations in the Northern Territory during the era of PCV13 immunisation supports its ongoing use in the region. Despite the reduction, one in five Indigenous infants born in the region continue to be hospitalised with an ALRI in their first year of life. Future gains require multifaceted environmental and biomedical approaches. National Health and Medical Research Council of Australia.

Bacteria and viruses in the nasopharynx immediately prior to onset of acute lower respiratory infections in Indigenous Australian children

Acute lower respiratory infection (ALRI) is a major cause of hospitalization for Indigenous children in remote regions of Australia. The associated microbiology remains unclear. Our aim was to determine whether the microbes present in the nasopharynx before an ALRI were associated with its onset. A retrospective case-control/crossover study among Indigenous children aged up to 2 years. ALRI cases identified by medical note review were eligible where nasopharyngeal swabs were available: (1) 0–21 days before ALRI onset (case); (2) 90–180 days before ALRI onset (same child controls); and (3) from time and age-matched children without ALRI (different child controls). PCR assays determined the presence and/or load of selected respiratory pathogens. Among 104 children (182 recorded ALRI episodes), 120 case-same child control and 170 case-different child control swab pairs were identified. Human adenoviruses (HAdV) were more prevalent in cases compared to same child controls (18 vs 7%; OR = 3.08, 95% CI 1.22–7.76, p = 0.017), but this association was not significant in cases versus different child controls (15 vs 10%; OR = 1.93, 95% CI 0.97–3.87 (p = 0.063). No other microbes were more prevalent in cases compared to controls. Streptococcus pneumoniae (74%), Haemophilus influenzae (75%) and Moraxella catarrhalis (88%) were commonly identified across all swabs. In a pediatric population with a high detection rate of nasopharyngeal microbes, HAdV was the only pathogen detected in the period before illness presentation that was significantly associated with ALRI onset. Detection of other potential ALRI pathogens was similar between cases and controls.Electronic supplementary materialThe online version of this article (10.1007/s10096-018-3314-7) contains supplementary material, which is available to authorized users.

Vitamin-D deficiency predicts infections in young north Indian children: A secondary data analysis.

BackgroundRecent studies have demonstrated a relationship between poor vitamin D status and respiratory infections and diarrhea among young children. Acute lower respiratory infections (ALRI) and diarrhea are among the two most important causes of death in under-5 children. In this paper, we examined the extent to which vitamin-D deficiency (<10 ng/ml) predicts ALRI, clinical pneumonia and diarrhea among 6 to 30 months old children.MethodsWe used data from a randomized controlled trial (RCT) of daily folic acid and/or vitamin B12 supplementation for six months in 6 to 30 months old children conducted in Delhi, India. Generalized estimating equations (GEE) were used to examine the associations between vitamin-D deficiency and episodes of ALRI, clinical pneumonia and diarrhea.ResultsOf the 960 subjects who had vitamin-D concentrations measured, 331(34.5%) were vitamin-D deficient. We found, after controlling for relevant potential confounders (age, sex, breastfeeding status, wasting, stunting, underweight, anemia status and season), that the risk of ALRI was significantly higher among vitamin-D deficient (OR 1.26; 95% CI: 1.03 to 1.55) compared to vitamin-D-replete children in the six months follow-up period. Vitamin-D status was not associated with episodes of diarrhea or clinical pneumonia.ConclusionVitamin-D deficiency is common in young children in New Delhi and is associated with a higher risk of ALRI. The role of vitamin D in Indian children needs to be elucidated in further studies.

Zinc Supplementation Reduces Recurrent Acute Lower Respiratory Infection (ALRI)

Introduction: Pneumonia is a frequent and serious human illness. In Bangladesh, Acute Lower Respiratory Infection (ALRI) is a major cause of death among young children. Childhood mortality can be reduced by 50% with detection and early treatment of illness with antibiotics and immunization. Zinc plays an important role in the optimal function of the immune system by reducing the risk, severity and duration of infectious diseases. Zinc supplementation improves health and cell mediated immunity. Objectives: This study is aimed at documenting effect of zinc supplementation in preschool children on reducing ALRI. Methods: This was a double blind random control trial interventional study among180 child, conducted at Comilla CMH, from January 2010 to December 2011. The children aged 6-60 months were selected randomly for comparison of effect of Zinc and Vitamin B-Complex on ALRI. Results: In the study population, male to female ratio was 1.05:1. Baseline average age was 32 months and weight for height was 92% Of NCHS mean. It was found that 89% children completed immunization as per EPI schedule, the rest 11% were partially immunized. Twenty nine percent children had family history of Atopy. This study showed 15 episodes of ALRI in Zinc group in the control B-Complex group (1.09episodes/child/year) during the six months follow-up. There was no association of ALRI with sex. The male female ratio in this respect was 1.07:1. In this study there was statistically significant and clinically important (67%) reduction of episodes of ALRI in oral Zinc supplement group. Conclusion: This finding strongly suggests that oral supplement of Zinc reduces episodes of ALRI in children. DOI: http://dx.doi.org/10.3329/jafmc.v9i1.18736 Journal of Armed Forces Medical College Bangladesh Vol.9(1) 2013: 84-89

Does comorbidity increase the risk of mortality among children under 3 years of age?

ObjectivesDiarrhoea and pneumonia remain leading causes of morbidity and mortality in children under 5 years of age. Little data is available to quantify the burden of comorbidity and the relationship...

An evaluation of the emerging vaccines against influenza in children

BackgroundInfluenza is an under-appreciated cause of acute lower respiratory infections (ALRI) in children. It is estimated to cause approximately 20 million new episodes of ALRI in children annually, 97% of these occurring in developing countries. It is also estimated to result in 28000 to 112000 deaths annually in young children. Apart from hospitalisations and deaths, influenza has significant economic consequences. The current egg-based inactivated influenza vaccines have several limitations: annual vaccination, high production costs, and cannot respond adequately to meet the demand during pandemics.MethodsWe used a modified CHNRI methodology for setting priorities in health research investments. This was done in two stages. In Stage I, we systematically reviewed the literature related to emerging cross-protective vaccines against influenza relevant to several criteria of interest: answerability; cost of development, production and implementation; efficacy and effectiveness; deliverability, affordability and sustainability; maximum potential impact on disease burden reduction; acceptability to the end users and health workers; and effect on equity. In Stage II, we conducted an expert opinion exercise by inviting 20 experts (leading basic scientists, international public health researchers, international policy makers and representatives of pharmaceutical companies). They answered questions from the CHNRI framework and their “collective optimism” towards each criterion was documented on a scale from 0 to 100%.ResultsThe experts expressed very high level of optimism for deliverability, impact on equity, and acceptability to health workers and end users. However, they expressed concerns over the criteria of answerability, low development cost, low product cost, low implementation cost, affordability and, to a lesser extent sustainability. In addition they felt that the vaccine would have higher efficacy and impact on disease burden reduction on overall influenza-associated disease rather than specifically influenza-associated pneumonia.ConclusionAlthough the landscape of emerging influenza vaccines shows several promising candidates, it is unlikely that the advancements in the newer vaccine technologies will be able to progress through to large scale production in the near future. The combined effects of continued investments in researching new vaccines and improvements of available vaccines will hopefully shorten the time needed to the development of an effective seasonal and pandemic influenza vaccine suitable for large scale production.

Mass Distribution of Azithromycin for Trachoma Control Is Associated With Short-term Reduction in Risk of Acute Lower Respiratory Infection in Young Children

We evaluated the effect of a single mass distribution of azithromycin for trachoma on the risk of acute lower respiratory infection (ALRI) during a 6-month period among young children living in 8 communities in rural Tanzania. In 8 communities, a cohort of randomly selected children (n = 1036) was followed for incidence of ALRI episodes. Mass treatment for trachoma using a single dose of oral azithromycin was provided in 4 of the 8 communities where trachoma prevalence was .10%. All children were followed with biweekly surveillance at home for 6 months. Incidence of ALRI episodes was calculated for 0 to 1 month, 1 to 3 months, and 3 to 6 months posttreatment and in comparable time points in the nontreated villages. In the multivariate analysis, living in a MDA village was associated with a 38% (rate ratio 5 0.62, 95% confidence interval [CI] = 0.43-0.91) decreased risk of ALRI in the 0- to 1-month follow-up period as compared with those in the untreated communities after adjusting for covariates and clustering. There were no significant differences in ALRI incidence by exposure status in the 1- to 3-month (rate ratio = 0.91, 95% CI = 0.69-1.20) and in the 3- to 6-month (rate ratio = 1.00, 95% CI = 0.76-1.30) follow-up periods. Mass distribution of a single dose of oral azithromycin for trachoma is associated with a significant short-term reduction in ALRI morbidity among young children.

An evaluation of the emerging interventions against Respiratory Syncytial Virus (RSV)-associated acute lower respiratory infections in children

BackgroundRespiratory Syncytial Virus (RSV) is the leading cause of acute lower respiratory infections (ALRI) in children. It is estimated to cause approximately 33.8 million new episodes of ALRI in children annually, 96% of these occurring in developing countries. It is also estimated to result in about 53,000 to 199,000 deaths annually in young children. Currently there are several vaccine and immunoprophylaxis candidates against RSV in the developmental phase targeting active and passive immunization.MethodsWe used a modified CHNRI methodology for setting priorities in health research investments. This was done in two stages. In Stage I, we systematically reviewed the literature related to emerging vaccines against RSV relevant to 12 criteria of interest. In Stage II, we conducted an expert opinion exercise by inviting 20 experts (leading basic scientists, international public health researchers, international policy makers and representatives of pharmaceutical companies). The policy makers and industry representatives accepted our invitation on the condition of anonymity, due to the sensitive nature of their involvement in such exercises. They answered questions from the CHNRI framework and their “collective optimism” towards each criterion was documented on a scale from 0 to 100%.ResultsIn the case of candidate vaccines for active immunization of infants against RSV, the experts expressed very low levels of optimism for low product cost, affordability and low cost of development; moderate levels of optimism regarding the criteria of answerability, likelihood of efficacy, deliverability, sustainability and acceptance to end users for the interventions; and high levels of optimism regarding impact on equity and acceptance to health workers. While considering the candidate vaccines targeting pregnant women, the panel expressed low levels of optimism for low product cost, affordability, answerability and low development cost; moderate levels of optimism for likelihood of efficacy, deliverability, sustainability and impact on equity; high levels of optimism regarding acceptance to end users and health workers. The group also evaluated immunoprophylaxis against RSV using monoclonal antibodies and expressed no optimism towards low product cost; very low levels of optimism regarding deliverability, affordability, sustainability, low implementation cost and impact on equity; moderate levels of optimism against the criteria of answerability, likelihood of efficacy, acceptance to end-users and health workers; and high levels of optimism regarding low development cost. They felt that either of these vaccines would have a high impact on reducing burden of childhood ALRI due to RSV and reduce the overall childhood ALRI burden by a maximum of about 10%.ConclusionAlthough monoclonal antibodies have proven to be effective in providing protection to high-risk infants, their introduction in resource poor settings might be limited by high cost associated with them. Candidate vaccines for active immunization of infants against RSV hold greatest promise. Introduction of a low cost vaccine against RSV would reduce the inequitable distribution of burden due to childhood ALRI and will most likely have a high impact on morbidity and mortality due to severe ALRI.

Human respiratory syncytial virus in children hospitalized for acute lower respiratory infection

To evaluate the prevalence and seasonality of human respiratory syncytial virus (HRSV) in children aged 0 to 6 years, hospitalized with acute lower respiratory infection (ALRI) in São José do Rio Preto, SP, Brazil, and the association between age, diagnosis, and HRSV. Between May 2004 and September 2005, we studied 290 consecutive episodes of community-acquired ALRI in children aged 0 to 6 years admitted to the Hospital de Base of São José do Rio Preto. In order to detect HRSV, nasopharyngeal secretion samples were collected and RT-PCR molecular analysis was performed. The HRSV prevalence was 29.3% for the cases of hospitalized patients with ALRI. ALRI was common in infants (median age = 13.5 months). HRSV was more frequent in cases of bronchiolitis (64%) and during the first year of life (35%). Episodes of HRSV infection occurred between fall and spring, showing higher frequency in 2004 than in 2005. Clinical and radiological criteria were not sufficient to establish the diagnosis of infection with HRSV. Antibiotic therapy was used in 78.8% of episodes of HRSV. There was a high prevalence of HRSV in children aged 0 to 6 years who were hospitalized for ALRI, predominantly in younger patients or those with bronchiolitis. The circulation of the virus varied in the two years studied. Our results suggest the need for laboratory diagnosis of HRSV in the clinical practice.

Effectiveness of zinc supplementation plus oral rehydration salts for diarrhoea in infants aged less than 6months in Haryana state, India.

To determine if educating caregivers in providing zinc supplements to infants < 6months old with acute diarrhoea is effective in treating diarrhoea and preventing acute lower respiratory infections (ALRIs), and whether it leads to a decrease in the use of oral rehydration salts (ORS). In this retrospective subgroup analysis of infants aged < 6months, six clusters were randomly assigned to intervention or control sites. Care providers were trained to give zinc and ORS to children with acute diarrhoea at intervention sites, and only ORS at control sites. Surveys were conducted at 3 and 6months to assess outcomes. Differences between intervention and control sites in episodes of diarrhoea and ALRI in the preceding 24 hours or 14 days and of hospitalizations in the preceding 3months were analysed by logistic regression. Compared with control sites, intervention sites had lower rates of acute diarrhoea in the preceding 14 days at 3months (odds ratio, OR: 0.60; 95% confidence interval, CI: 0.43-0.84) and 6months (OR: 0.72; 95% CI: 0.54-0.94); lower rates of acute diarrhoea in the preceding 24 hours at 3months (0.66; 95% CI: 0.50-0.87) and of ALRI in the preceding 24 hours at 6months (OR: 0.59; 95% CI: 0.37-0.93); and lower rates of hospitalization at 6months for all causes (OR: 0.40; 95% CI: 0.34-0.49), diarrhoea (OR: 0.34; 0.18-0.63) and pasli chalna or pneumonia (OR: 0.36; 95% CI: 0.24-0.55). Educating caregivers in zinc supplementation and providing zinc to infants < 6months old can reduce diarrhoea and ALRI. More studies are needed to confirm these findings as these data are from a subgroup analysis.

Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis

SummaryBackgroundThe global burden of disease attributable to respiratory syncytial virus (RSV) remains unknown. We aimed to estimate the global incidence of and mortality from episodes of acute lower respiratory infection (ALRI) due to RSV in children younger than 5 years in 2005.MethodsWe estimated the incidence of RSV-associated ALRI in children younger than 5 years, stratified by age, using data from a systematic review of studies published between January, 1995, and June, 2009, and ten unpublished population-based studies. We estimated possible boundaries for RSV-associated ALRI mortality by combining case fatality ratios with incidence estimates from hospital-based reports from published and unpublished studies and identifying studies with population-based data for RSV seasonality and monthly ALRI mortality.FindingsIn 2005, an estimated 33·8 (95% CI 19·3–46·2) million new episodes of RSV-associated ALRI occurred worldwide in children younger than 5 years (22% of ALRI episodes), with at least 3·4 (2·8–4·3) million episodes representing severe RSV-associated ALRI necessitating hospital admission. We estimated that 66 000–199 000 children younger than 5 years died from RSV-associated ALRI in 2005, with 99% of these deaths occurring in developing countries. Incidence and mortality can vary substantially from year to year in any one setting.InterpretationGlobally, RSV is the most common cause of childhood ALRI and a major cause of admission to hospital as a result of severe ALRI. Mortality data suggest that RSV is an important cause of death in childhood from ALRI, after pneumococcal pneumonia and Haemophilus influenzae type b. The development of novel prevention and treatment strategies should be accelerated as a priority.FundingWHO; Bill & Melinda Gates Foundation.

Acute lower respiratory infections in childhood: opportunities for reducing the global burden through nutritional interventions.

Inadequate nutrition and acute lower respiratory infection (ALRI) are overlapping and interrelated health problems affecting children in developing countries. Based on a critical review of randomized trials of the effect of nutritional interventions on ALRI morbidity and mortality, we concluded that: (1) zinc supplementation in zinc-deficient populations prevents about one-quarter of episodes of ALRI, which may translate into a modest reduction in ALRI mortality; (2) breastfeeding promotion reduces ALRI morbidity; (3) iron supplementation alone does not reduce ALRI incidence; and (4) vitamin A supplementation beyond the neonatal period does not reduce ALRI incidence or mortality. There was insufficient evidence regarding other potentially beneficial nutritional interventions. For strategies with a strong theoretical rationale and probable operational feasibility, rigorous trials with active clinical case-finding and adequate sample sizes should be undertaken. At present, a reduction in the burden of ALRI can be expected from the continued promotion of breastfeeding and scale-up of zinc supplementation or fortification strategies in target populations.

Zinc and vitamin A supplementation in Indigenous Australian children hospitalised with lower respiratory tract infection: a randomised controlled trial

To evaluate the efficacy of supplementation with zinc and vitamin A in Indigenous children hospitalised with acute lower respiratory infection (ALRI). Randomised controlled, 2-by-2 factorial trial of supplementation with zinc and vitamin A. 187 Indigenous children aged < 11 years hospitalised with 215 ALRI episodes at Alice Springs Hospital (April 2001 to July 2002). Vitamin A was administered on Days 1 and 5 of admission at a dose of 50 000 IU (infants under 12 months), or 100 000 IU; and zinc sulfate was administered daily for 5 days at a daily dose of 20 mg (infants under 12 months) or 40 mg. Time to clinical recovery from fever and tachypnoea, duration of hospitalisation, and readmission for ALRI within 120 days. There was no clinical benefit of supplementation with vitamin A, zinc or the two combined, with no significant difference between zinc and no-zinc, vitamin A and no-vitamin A or zinc + vitamin A and placebo groups in time to resolution of fever or tachypnoea, or duration of hospitalisation. Instead, we found increased morbidity; children given zinc had increased risk of readmission for ALRI within 120 days (relative risk, 2.4; 95% CI, 1.003-6.1). This study does not support the use of vitamin A or zinc supplementation in the management of ALRI requiring hospitalisation in Indigenous children living in remote areas. Even in populations with high rates of ALRI and poor living conditions, vitamin A and zinc therapy may not be useful. The effect of supplementation may depend on the prevalence of deficiency of these micronutrients in the population.