Joseph L. Mathew

Prevalence and risk factors for transmission of infection among children in household contact with adults having pulmonary tuberculosis

Aims: To study the prevalence of tuberculosis infection among children in household contact with adults having pulmonary tuberculosis, and identify the possible risk factors. Methods: Children under the age of 5 years who were in household contact with 200 consecutive adults with pulmonary tuberculosis underwent tuberculin skin testing. Transverse induration of greater than 10 mm was defined as positive tuberculin test suggestive of tubercular infection. Infected children underwent chest radiography and analysis of gastric lavage fluid or induced sputum for detection of acid fast bacilli. Results: Tuberculin test was positive in 95 of 281 contacts (33.8%), of which 65 were contacts of sputum positive patients, while 30 were contacts of sputum negative patients. Nine of these children were diagnosed as having tuberculosis based on clinical features and/or recovery of acid fast bacilli; seven were in contact with sputum positive adults. The important risk factors for transmission of infection were younger age, severe malnutrition, absence of BCG vaccination, contact with an adult who was sputum positive, and exposure to environmental tobacco smoke. Conclusion: The prevalence of tuberculosis infection and clinical disease among children in household contact with adult patients is higher than in the general population, and risk is significantly increased by contact with sputum positive adults.

Inequity in childhood immunization in India: A systematic review

BackgroundDespite a reduction in disease burden of vaccine-preventable diseases through childhood immunization, considerable progress needs to be made in terms of ensuring efficiency and equity of vaccination coverage.ObjectiveTo conduct a systematic review to identify and explore factors associated with inequities in routine vaccination of children in India.MethodsPublications reporting vaccination inequity were retrieved through a systematic search of Medline, and websites of the WHO, UNICEF and demographic health surveys in India. No restrictions were applied in terms of study designs. The primary outcome measure was ‘complete vaccination/immunization’ defined as per the standard WHO definition.ResultsThere were three nation-wide data sets viz. the three National Family Health Surveys (NFHS), a research study conducted by the Indian Council of Medical Research (ICMR) and a UNICEF coverage evaluation survey. In addition, several publications representing different population groups or geographic regions were available. A small number of publications were re-analyses of data from the NFHS series. There is considerable inequity in vaccination coverage in different states. Within states, traditionally poor performing states have greater inequities, although there are significant inequities even within better performing states. There are significant inequities in childhood vaccination based on various factors related to individual (gender, birth order), family (area of residence, wealth, parental education), demography (religion, caste), and the society (access to health-care, community literacy level) characteristics. Girls fare uniformly worse than boys and higher birth order infants have lower vaccination coverage. Urban infants have higher coverage than rural infants and those living in urban slums. There is an almost direct relationship between household wealth and vaccination rates. The vaccination rates are lower among infants with mothers having no or low literacy, and families with insufficient empowerment of women. Paternal literacy has an inconsistent positive relationship with infant vaccination. There is a relationship between religion and caste and childhood vaccination. Access to health services and other infrastructure, is associated with better vaccination coverage of infants. The precise impact of specific risk factors operating singly or in combination cannot be calculated from this systematic review.ConclusionThis systematic review identifies and explores factors associated with inequity in childhood immunization in India; and provides information for urgent action to redress the imbalances.

Randomized controlled trial of intrapleural streptokinase in empyema thoracis in children

Aim: To compare intrapleural streptokinase and placebo in paediatric empyema. Methods: Children with empyema greater than stage 5 received intrapleural streptokinase (n= 19) or normal saline (n= 21) along with intercostal drainage. Clinical and serial sonographic outcomes were compared. Results: Although there was no difference in clinical and sonographic outcome, none of the children with stage 7 empyema (multi‐loculated empyema) who received streptokinase developed pleural thickening 30 d later.

Promoting appropriate management of diarrhea: A systematic review of literature for advocacy and action: UNICEF-PHFI series on newborn and child health, India

BackgroundScaling up of evidence-based management and prevention of childhood diarrhea is a public health priority in India, and necessitates robust literature review, for advocacy and action.ObjectiveTo identify, synthesize and summarize current evidence to guide scaling up of management of diarrhea among under-five children in India, and identify existing knowledge gaps.MethodsA set of questions pertaining to the management (prevention, treatment, and control) of childhood diarrhea was identified through a consultative process. A modified systematic review process developed a priori was used to identify, synthesize and summarize, research evidence and operational information, pertaining to the problem in India. Areas with limited or no evidence were identified as knowledge gaps.ResultsChildhood diarrhea is a significant public health problem in India; the point (two-weeks) prevalence is 9–20%. Diarrhea accounts for 14% of the total deaths in under-five children in India. Infants aged 6–24 months are at the highest risk of diarrhea. There is a lack of robust nation-wide data on etiology; rotavirus and diarrheogenic E.coli are the most common organisms identified. The current National Guidelines are sufficient for case-management of childhood diarrhea. Exclusive breastfeeding, handwashing and point-of-use water treatment are effective strategies for prevention of all-cause diarrhea; rotavirus vaccines are efficacious to prevent rotavirus specific diarrhea. ORS and zinc are the mainstay of management during an episode of childhood diarrhea but have low coverage in India due to policy and programmatic barriers, whereas indiscriminate use of antibiotics and other drugs is common. Zinc therapy given during diarrhea can be upscaled through existing infrastructure is introducing the training component and information, education and communication activities.ConclusionThis systematic review summarizes current evidence on childhood diarrhea and provides evidence to inform child health programs in India.

Etiology of community acquired pneumonia among children in India: prospective, cohort study.

Background Childhood community acquired pneumonia (CAP) is a significant problem in developing countries, and confirmation of microbial etiology is important for individual, as well as public health. However, there is paucity of data from a large cohort, examining multiple biological specimens for diverse pathogens (bacteria and viruses). The Community Acquired Pneumonia Etiology Study (CAPES) was designed to address this knowledge gap. Methods We enrolled children with CAP (based on WHO IMCI criteria of tachypnea with cough or breathing difficulty) over 24 consecutive months, and recorded presenting symptoms, risk factors, clinical signs, and chest radiography. We performed blood and nasopharyngeal aspirate (NPA) bacterial cultures, and serology (Mycoplasma pneumoniae, Chlamydophila pneumoniae). We also performed multiplex PCR for 25 bacterial/viral species in a subgroup representing 20% of the cohort. Children requiring endotracheal intubation underwent culture and PCR of bronchoalveolar lavage (BAL) specimens. Findings We enrolled 2345 children. NPA and blood cultures yielded bacteria in only 322 (13.7%) and 49 (2.1%) children respectively. In NPA, Streptococcus pneumoniae (79.1%) predominated, followed by Haemophilus influenzae (9.6%) and Staphylococcus aureus (6.8%). In blood, S. aureus (30.6%) dominated, followed by S. pneumoniae (20.4%) and Klebsiella pneumoniae (12.2%). M. pneumoniae and C. pneumoniae serology were positive in 4.3% and 1.1% respectively. Multiplex PCR in 428 NPA specimens identified organisms in 422 (98.6%); of these 352 (82.2%) had multiple organisms and only 70 (16.4%) had a single organism viz. S. pneumoniae: 35 (50%), Cytomegalovirus (CMV): 13 (18.6%), Respiratory Syncytial Virus (RSV): 9 (12.9%), other viruses: 6 (8.7%), S. aureus: 5 (7.1%), and H. influenzae: 2 (2.9%). BAL PCR (n = 30) identified single pathogens in 10 (S. pneumoniae–3, CMV–3, S. aureus–2, H. influenzae–2) and multiple pathogens in 18 children. There were 108 (4.6%) deaths. The pattern of pathogens identified did not correlate with pneumonia severity or mortality. Conclusions The majority of children with CAP have multiple pathogens (bacteria and viruses). S. pneumoniae and S. aureus predominate in NPA and blood respectively. CMV and RSV were the dominant respiratory viruses in NPA and BAL. The presence of multiple pathogens, especially organisms associated with nasopharyngeal carriage, precludes confirmation of a causal relationship in most cases.

Treatment with 400 μg of inhaled budesonide vs 200 μg of inhaled budesonide and oral montelukast in children with moderate persistent asthma: randomized controlled trial

Background Montelukast is reported to be beneficial in asthma as add-on therapy to inhaled corticosteroids and may reduce the need for the latter. Objective To evaluate whether a combination of oral montelukast and 200 μg of inhaled budesonide has comparable efficacy to 400 μg of inhaled budesonide alone in children with moderate persistent asthma. Methods In this prospective, blinded, hospital-based randomized controlled trial, 71 children with moderate persistent asthma were randomized to receive either montelukast, 5-mg chewable tablet, with 200 μg of inhaled budesonide or only 400 μg of inhaled budesonide daily for 12 weeks. Baseline and serial measurements of forced expiratory volume in 1 second, peak expiratory flow rate, and Asthma Symptom Score were performed; the frequency and severity of exacerbations were also recorded. Results Measurements of forced expiratory volume in 1 second, peak expiratory flow rate, and Asthma Symptom Score showed no significant differences between the 2 groups at baseline, during the serial follow-up visits, and at the end of the study. However, children who received montelukast had a greater frequency of exacerbations vs those who did not (33.3% vs 9.1%; P Conclusion The overall control of asthma with 5 mg of oral montelukast and 200 μg of inhaled budesonide is inferior to that with 400 μg of inhaled budesonide in children with moderate persistent asthma.

The diagnostic criteria for allergic bronchopulmonary aspergillosis in children with poorly controlled asthma need to be re‐evaluated

The aim of this study was to examine the association between allergic bronchopulmonary aspergillosis (ABPA) and poorly controlled asthma in children and appraise the diagnostic criteria.

Evaluation of quality of life in indian children with bronchial asthma using a disease-specific and locally appropriate questionnaire.

Aim: To evaluate quality of life (QOL) in Indian children with bronchial asthma. Methods: A disease‐specific, locally appropriate QOL questionnaire was administered in asthmatic children and compared with FEV1, FVC, PEFR and asthma symptom score, on three occasions. Results: QOL score had strong negative correlation with symptom score and weaker positive correlation with pulmonary function tests.

Assessment of Cytokine and Chemokine Signatures as Potential Biomarkers of Childhood Community-acquired Pneumonia Severity: A Nested Cohort Study in India

Background: Pediatric community-acquired pneumonia (CAP) is a leading cause of childhood mortality in developing countries. In resource-poor settings, pneumonia diagnosis is commonly made clinically, based on World Health Organization guidelines, where breathing difficulty or cough and age-adjusted tachypnea suffice to establish diagnosis. Also, the severity of CAP is generally based on clinical features and existing biomarkers do not reliably correlate to either clinical severity or outcome. Here, we asked whether systemic immune and inflammatory mediators could act as biomarkers predicting CAP severity or outcome. Methods: Serum from a subset of a CAP cohort (n = 196), enrolled in India, classified according to World Health Organization criteria as having pneumonia or severe pneumonia, was used for simultaneous measurement of 21 systemic cytokines and chemokines. Results: We found significantly higher IL-6, IL-8, IL-13, IFN-&ggr; and lower CCL22 concentrations in patients with severe compared with mild CAP (P values: 0.019, 0.036, 0.006, 0.016 and 0.003, respectively). Based on higher MIP-1&agr;, IL-8, IL-17 or lower CCL22 response pattern at the time of enrolment, children with fatal outcome showed markedly different pattern of inflammatory response compared with children classified with the same disease severity, but with nonfatal outcome (P values: 0.043, 0.017, 0.008 and 0.020, respectively). Conclusions: Our results suggest a relation between an elevated mixed cytokine response and CAP severity on one hand, and a bias toward uncontrolled neutrophilic inflammation in subjects with fatal outcome on the other. Collectively our findings contribute to increased knowledge on new biomarkers that can potentially predict severity and outcome of childhood CAP in the future.

Fatal Disseminated Aspergillus penicillioides Infection in a 3-Month-Old Infant with Suspected Cystic Fibrosis: Autopsy Case Report with Review of Literature.

Patients with cystic fibrosis (CF) often are colonized by Aspergillus species in their respiratory tract, but invasive aspergillosis is a rare complication. We describe the autopsy findings of an infant with cystic fibrosis who had fatal disseminated aspergillosis. The causative agent was identified as A. penicillioides by molecular technique. To our knowledge, this is the first report of disseminated aspergillosis caused by A. penicillioides in any type of patient. The literature on invasive aspergillosis in patients with cystic fibrosis also is reviewed.