Maria Mathisen

RNA viruses in community-acquired childhood pneumonia in semi-urban Nepal; a cross-sectional study

BackgroundPneumonia is among the main causes of illness and death in children <5 years of age. There is a need to better describe the epidemiology of viral community-acquired pneumonia (CAP) in developing countries.MethodsFrom July 2004 to June 2007, we examined nasopharyngeal aspirates (NPA) from 2,230 cases of pneumonia (World Health Organization criteria) in children 2 to 35 months old recruited in a randomized trial of zinc supplementation at a field clinic in Bhaktapur, Nepal. The specimens were examined for respiratory syncytial virus (RSV), influenza virus type A (InfA) and B (InfB), parainfluenza virus types 1, 2 and 3 (PIV1, PIV2, and PIV3), and human metapneumovirus (hMPV) using a multiplex reverse transcriptase polymerase chain reaction (PCR) assay.ResultsWe identified 919 virus isolates in 887 (40.0%) of the 2,219 NPA specimens with a valid PCR result, of which 334 (15.1%) yielded RSV, 164 (7.4%) InfA, 129 (5.8%) PIV3, 98 (4.4%) PIV1, 93 (4.2%) hMPV, 84 (3.8%) InfB, and 17 (0.8%) PIV2. CAP occurred in an epidemic pattern with substantial temporal variation during the three years of study. The largest peaks of pneumonia occurrence coincided with peaks of RSV infection, which occurred in epidemics during the rainy season and in winter. The monthly number of RSV infections was positively correlated with relative humidity (rs= 0.40, P = 0.01), but not with temperature or rainfall. An hMPV epidemic occurred during one of the three winter seasons and the monthly number of hMPV cases was also associated with relative humidity (rs= 0.55, P = 0.0005).ConclusionRespiratory RNA viruses were detected from NPA in 40% of CAP cases in our study. The most commonly isolated viruses were RSV, InfA, and PIV3. RSV infections contributed substantially to the observed CAP epidemics. The occurrence of viral CAP in this community seemed to reflect more or less overlapping micro-epidemics with several respiratory viruses, highlighting the challenges of developing and implementing effective public health control measures.

Acute Lower Respiratory Infection in Childhood and Household Fuel Use in Bhaktapur, Nepal

Background: Globally, solid fuels are used by about 3 billion people for cooking. These fuels have been associated with many health effects, including acute lower respiratory infection (ALRI) in young children. Nepal has a high prevalence of use of biomass for cooking and heating. Objective: This case–control study was conducted among a population in the Bhaktapur municipality, Nepal, to investigate the relationship of cookfuel type to ALRI in young children. Methods: Cases with ALRI and age-matched controls were enrolled from an open cohort of children 2–35 months old, under active monthly surveillance for ALRI. A questionnaire was used to obtain information on family characteristics, including household cooking and heating appliances and fuels. The main analysis was carried out using conditional logistic regression. Population-attributable fractions (PAF) for stove types were calculated. Results: A total of 917 children (452 cases and 465 controls) were recruited into the study. Relative to use of electricity for cooking, ALRI was increased in association with any use of biomass stoves [odds ratio (OR) = 1.93; 95% CI: 1.24, 2.98], kerosene stoves (OR = 1.87; 95% CI: 1.24, 2.83), and gas stoves (OR = 1.62; 95% CI: 1.05, 2.50). Use of wood, kerosene, or coal heating was also associated with ALRI (OR = 1.45; 95% CI: 0.97, 2.14), compared with no heating or electricity or gas heating. PAFs for ALRI were 18.0% (95% CI: 8.1, 26.9%) and 18.7% (95% CI: 8.4%–27.8%), for biomass and kerosene stoves, respectively. Conclusions: The study supports previous reports indicating that use of biomass as a household fuel is a risk factor for ALRI, and provides new evidence that use of kerosene for cooking may also be a risk factor for ALRI in young children.

A randomized controlled trial of the effect of zinc as adjuvant therapy in children 2–35 mo of age with severe or nonsevere pneumonia in Bhaktapur, Nepal

BACKGROUND Pneumonia is a leading cause of illness and death in young children. Interventions to improve case management of pneumonia are needed. OBJECTIVE Our objective was to measure the effect of zinc supplementation in children with pneumonia in a population in which zinc deficiency is common. DESIGN In a double-blind, placebo-controlled clinical trial, children aged 2-35 mo with severe (n = 149) or nonsevere (n = 2479) pneumonia defined according to criteria established by the World Health Organization were randomly assigned to receive zinc (10 mg for children aged 2-11 mo, 20 mg for children aged > or =12 mo) or placebo daily for 14 d as an adjuvant to antibiotics. The primary outcomes were treatment failure, defined as a need for change in antibiotics or hospitalization, and time to recovery from pneumonia. RESULTS One of 5 children did not respond adequately to antibiotic treatment; the odds ratios between zinc and placebo groups for treatment failure were 0.95 (95% CI: 0.78, 1.2) for nonsevere pneumonia and 0.97 (95% CI: 0.42, 2.2) for severe pneumonia. There was no difference in time to recovery between zinc and placebo groups for nonsevere (median: 2 d; hazard ratio: 1.0; 95% CI: 0.96, 1.1) or severe (median: 4 d; hazard ratio: 1.1; 95% CI: 0.79, 1.5) pneumonia. Regurgitation or vomiting < or =15 min after supplementation was observed more frequently among children in the zinc group than among those in the placebo group during the supplementation period (37% compared with 13%; odds ratio: 0.25; 95% CI: 0.20, 0.30). CONCLUSION Adjuvant treatment with zinc neither reduced the risk of treatment failure nor accelerated recovery in episodes of nonsevere or severe pneumonia. This trial was registered at clinicaltrials.gov as NCT00148733.

Zinc Deficiency Is Common among Healthy Women of Reproductive Age in Bhaktapur, Nepal

Zinc deficiency is a major public health problem in many developing countries. However, its prevalence is still unknown in most populations. Women of reproductive age in developing countries are highly vulnerable to nutritional deficiencies, including that of zinc. To estimate the prevalence of zinc deficiency and to identify important dietary sources of zinc, we undertook a cross-sectional survey in 500 nonpregnant Nepalese women and measured their plasma zinc concentrations. We also examined the associations between plasma zinc and dietary intake of zinc or phytate, iron status, plasma concentrations of C-reactive protein, albumin, and hemoglobin. Food intake was estimated by 2 24-h dietary recalls and 1 FFQ for each woman. The plasma zinc concentration was (mean +/- SD) 8.5 +/- 2.4 micromol/L and more than three-quarters of the women were zinc deficient. Dietary zinc intake did not predict plasma zinc concentration, whereas phytate intake was negatively and significantly associated with plasma zinc. The other variables that were associated with plasma zinc were plasma albumin and hemoglobin concentration. Rice contributed 50% to the total estimated daily zinc intake and wheat and meat each contributed 15%. Rice also contributed 68% to the daily intake of phytate. In conclusion, we found that zinc deficiency was common in women of reproductive age and that the foods contributing substantial amounts of zinc also contributed importantly to the intake of phytate.

Respiratory viruses in Nepalese children with and without pneumonia: a case-control study.

Background: The causative role of respiratory viruses detected in upper airway secretions in childhood pneumonia needs further investigation. Objective: To measure the association between infection with respiratory RNA viruses and pneumonia in children. Methods: From March 2006 to July 2007, we conducted a case-control study of 680 pneumonia cases (WHO criteria) and 680 randomly selected, concurrently sampled age-matched controls among children aged 2–35 months in Bhaktapur, Nepal. A nasopharyngeal aspirate from each child was examined for 7 respiratory viruses using reverse transcription polymerase chain reaction. We calculated the matched odds ratios (MORs) for the detection of the individual viruses from a case compared with a control as measures of pathogenicity using conditional logistic regression. Results: At least 1 virus was recovered in 248 (36.5%) cases and 48 (7.1%) controls. The MOR varied from 2.0 to 13.0; the highest associations were observed for parainfluenza virus type 3 (MOR 13.0; 95% confidence interval [CI] 6.0–28.0), respiratory syncytial virus (MOR 10.7; CI 4.6–24.6), and influenza A (MOR 6.3; CI 1.9–21.4). We observed that the association was lower for children age 2–5 months compared with older children for parainfluenza virus type 3 (P value for interaction 0.002). Conclusions: All of the 7 respiratory viruses were associated with pneumonia, but their pathogenicity varied. Parainfluenza type 3, RSV, and influenza A were most strongly associated with pneumonia.

Clinical Presentation and Severity of Viral Community-acquired Pneumonia in Young Nepalese Children

Background: Most deaths from pneumonia in children <5 years of age occur in developing countries, where information about the clinical impact and severity of viral causes of respiratory infections is limited. Methods: From June 29, 2004 to June 30, 2007 we evaluated 2230 cases of pneumonia (World Health Organization criteria) in children aged 2 to 35 months in Bhaktapur, Nepal. A nasopharyngeal aspirate from each case was examined for 7 respiratory viruses using reverse-transcription polymerase chain reaction. We compared illness duration, severity, and treatment failure between cases positive and negative for the individual viruses in multiple regression models. Results: A total of 2219 cases had a valid polymerase chain reaction result and were included in the analyses. Overall, 46.1% of cases were 2 to 11 months of age. Being infected with respiratory syncytial virus (RSV) was associated with lower chest indrawing (odds ratio [OR] 2.17; 95% confidence interval [CI] 1.42–3.30) and, among infants, oxygen saturation <93% (OR: 1.88; CI: 1.32–2.69). Among the 2088 nonsevere pneumonia cases, those positive for RSV had a longer time to recovery (hazard ratio 0.82; CI 0.75–0.90; P < 0.001) and an increased risk of treatment failure (OR: 1.75; CI: 1.34–2.28; P < 0.001) than the RSV negative cases. Conclusions: Being infected with RSV was associated with a more severe clinical presentation of pneumonia, longer illness duration, and increased risk of treatment failure. The severity of RSV infection was age related, infants being more severely affected.

A Randomized Controlled Trial of Zinc as Adjuvant Therapy for Severe Pneumonia in Young Children

BACKGROUND AND OBJECTIVE: Diarrhea and pneumonia are the leading causes of illness and death in children <5 years of age. Zinc supplementation is effective for treatment of acute diarrhea and can prevent pneumonia. In this trial, we measured the efficacy of zinc when given to children hospitalized and treated with antibiotics for severe pneumonia. METHODS: We enrolled 610 children aged 2 to 35 months who presented with severe pneumonia defined by the World Health Organization as cough and/or difficult breathing combined with lower chest indrawing. All children received standard antibiotic treatment and were randomized to receive zinc (10 mg in 2- to 11-month-olds and 20 mg in older children) or placebo daily for up to 14 days. The primary outcome was time to cessation of severe pneumonia. RESULTS: Zinc recipients recovered marginally faster, but this difference was not statistically significant (hazard ratio = 1.10, 95% CI 0.94–1.30). Similarly, the risk of treatment failure was slightly but not significantly lower in those who received zinc (risk ratio = 0.88 95% CI 0.71–1.10). CONCLUSIONS: Adjunct treatment with zinc reduced the time to cessation of severe pneumonia and the risk of treatment failure only marginally, if at all, in hospitalized children.

Two Weeks of Zinc Administration to Nepalese Children with Pneumonia Does Not Reduce the Incidence of Pneumonia or Diarrhea during the Next Six Months

Diarrhea and pneumonia are the 2 main causes of death in children under 5 y of age. Short courses of zinc administration are now recommended for treatment of childhood diarrhea and some studies have also shown its beneficial effect on treatment of pneumonia. The objective of our study was to assess the efficacy of zinc administration (10 mg/d for children 2-11 mo and 20 mg/d for >or= 12 mo of age) for 14 d on preventing diarrheal and respiratory illnesses for 6 mo of follow-up. This was a randomized, double-blind, placebo-controlled trial in children 2-35 mo of age with community-acquired pneumonia. The number of illness episodes and time until the first episode of various illnesses were compared between the 2 study groups. After 14 d of zinc supplementation, plasma zinc was significantly higher in the group receiving zinc. However, this difference was not detectable at 1 and 2.5 mo after the end of zinc administration. Of 2628 enrolled cases, a total of 2599 (99%) were available for assessment after the completion of zinc supplementation. The number of hospital visits and the median number of days until the first episode of pneumonia, diarrhea, and dysentery was similar in the 2 groups. The hazard ratios (95% CI) were 1.02 (0.92, 1.14) for nonsevere pneumonia, 1.11 (0.72, 1.73) for severe pneumonia, 1.07 (0.91, 1.26) for diarrhea, and 0.96 (0.69, 1.34) for dysentery. A short course of zinc supplementation given during an episode of pneumonia did not prevent diarrheal or respiratory illness over the next 6 mo.

RNA viruses in young Nepalese children hospitalized with severe pneumonia.

Background: Pneumonia is among the leading causes of illness and death in children <5 years of age worldwide. There is little information on the viral etiology of severe pneumonia in low-income countries, where the disease burden is particularly high. Methods: We analyzed nasopharyngeal aspirates from 629 children 2 to 35 months of age meeting World Health Organization criteria for severe pneumonia and presenting at Kanti Childrens Hospital, Kathmandu, Nepal, from January 2006 through June 2008. We examined one specimen from each child for 7 respiratory viruses using reverse transcription polymerase chain reaction. Results: We detected one or more respiratory viruses in 188 (30%; confidence interval: 26.4%–33.7%) of the 627 specimens with a valid polymerase chain reaction result, of which 88 (14%) yielded respiratory syncytial virus (RSV), 28 (4.5%) influenza A, 24 (5.8%) parainfluenza virus (PIV) type 3, 23 (3.7%) PIV type 1, 17 (2.7%) influenza B, 9 (1.4%) human metapneumovirus, and 5 (0.8%) PIV type 2. Episodes of severe pneumonia occurred in an epidemic pattern with 2 main annual peaks, the viral infections contributing importantly to these epidemics. The largest peaks of severe pneumonia coincided with peaks of RSV infection, which occurred during the last part of the monsoon season and in winter. Conclusions: RSV was the dominant respiratory viral pathogen detected in young Nepalese children hospitalized with severe pneumonia.

Oral zinc and common childhood infections--An update.

Zinc is an essential micronutrient important for growth and for normal function of the immune system. Many children in developing countries have inadequate zinc nutrition. Routine zinc supplementation reduces the risk of respiratory infections and diarrhea, the two leading causes of morbidity and mortality in young children worldwide. In childhood diarrhea oral zinc also reduces illness duration and risk of persistent episodes. Oral zinc is therefore recommended for the treatment of acute diarrhea in young children. The results from the studies that have measured the therapeutic effect of zinc on acute respiratory infections, however, are conflicting. Moreover, the results of therapeutic zinc for childhood malaria also are so far not promising.This paper gives a brief outline of the current evidence from clinical trials on therapeutic effect of oral zinc on childhood respiratory infections, pneumonia and malaria and also of new evidence of the effect on serious bacterial illness in young infants.