Role of procalcitonin in diagnosis of community acquired pneumonia in Children.

BACKGROUND: The role of serum Procalcitonin (PCT) in adults in diagnosis of Community acquired pneumonia (CAP) is well established, however, role in pediatric CAP remains controversial. OBJECTIVES: The objective of this study was to investigate the utility of serum procalcitonin in differentiating bacterial community-acquired lower respiratory tract infection from non-bacterial respiratory infection in children; radiologically confirmed pneumonia was used as the reference. In addition, we assessed the utility of adding the PCT assay to the clinical criteria for diagnosis of pneumonia. STUDY DESIGN: Subanalysis of a larger prospective,multicentriccohort study. PARTICIPANTS: Children, 2 months to 59 months of age, attending paediatric OPD of 5 urban tertiary care hospitals, suffering from acute respiratory infection (ARI). INTERVENTION: Detailed clinical history and examination findings of enrolled children were recorded on predesigned case record form. Samples for PCT were obtained at admission and were measured centrally at the end of the study except for one site using VIDAS® B.R.A.H.M.S PCT kit (Biomerieux SA, France). OUTCOMES: Sensitivity and specificity of procalcitonin for diagnosis of radiologically confirmed pneumonia. RESULTS: Serum Procalcitonin was measured in 370 patients; median (IQR) age of these children being 12 (7, 22) months, 235 (63.5%) were boys. The median (IQR) serum procalcitonin concentration was 0.1(0.05, 0.4) ng/mL.Sensitivity and specificity of raised PCT (> 0.5 ng/mL) for pneumonia as per any CXR abnormalities were 29.7% and87.5%,(P < 0.001) respectively. Raised PCT was also significantly associated with consolidation (34.5%,79.2%,P < 0.02)and pleural effusion(54.6%,79%,P < 001). Adding PCT to the existing clinical criteria of WHO did not improve the sensitivity for diagnosis of pneumonia. PCT was significantly higher in children with severe pneumonia. CONCLUSION: Positive PCT (> 0.5 ng/mL) is significantly associated with radiographic pneumonia but not with pneumonia based on WHO criteria.However, it can act as a surrogate marker for severe pneumonia.

Chikungunya-specific IgG and neutralizing antibody responses in natural infection of Chikungunya virus in children from India.

Chikungunya virus (CHIKV) infection is endemic in many different countries. CHIKV outbreaks are emerging in new areas and re-emerging in previously exposed geographical regions, thus making it a significant public health concern. CHIKV infections are often clinically inapparent, especially in children, which poses a challenge to testing and evaluating any vaccine. During CHIKV infection, CHIKV-specific antibodies are produced, and some of these antibodies can neutralize viruses released from infected cells before they can enter uninfected cells. In this study, we evaluated IgG binding and neutralizing antibody responses in paired serum samples from CHIKV-infected children and those with other febrile illness, using a recombinant truncated E2 protein and whole CHIKV particles as test antigens. Antibody detection using the truncated E2 protein showed a significant overlap between CHIKV-infected subjects and those with other febrile illnesses. This overlap was greater when binding antibody titers were determined using fixed CHIKV particles as the test antigen. Acute- and convalescent-phase sera collected from children after CHIKV infection showed significant differences in their neutralizing capacity. The neutralizing and binding antibody response showed a significant positive correlation. We detected IgG antibodies in most cases during the acute phase of infection. This was observed at two different geographical locations, one of which is not considered highly endemic. Conventional wisdom would suggest this to be a marker of re-infection (secondary infection). However, dissenting opinions have been voiced in other viral diseases (such as Ebola) where studies have detected IgG in acute illness. In the absence of any significant body of work documenting secondary CHIKV infections, we believe further work is needed to understand the early IgG response that we observed.

Clinical Profile and Risk Factors for Severe Disease in 402 Children Hospitalized with SARS-CoV-2 from India: Collaborative Indian Pediatric COVID Study Group.

INTRODUCTION: There is a lack of large multicentric studies in children with COVID-19 from developing countries. We aimed to describe the clinical profile and risk factors for severe disease in children hospitalized with COVID-19 from India. METHODS: In this multicentric retrospective study, we retrieved data related to demographic details, clinical features, including the severity of disease, laboratory investigations and outcome. RESULTS: We included 402 children with a median (IQR) age of 7 (2-11) years. Fever was the most common symptom, present in 38.2% of children. About 44% had underlying comorbidity. The majority were asymptomatic (144, 35.8%) or mildly symptomatic (219, 54.5%). There were 39 (9.7%) moderate-severe cases and 13 (3.2%) deaths. The laboratory abnormalities included lymphopenia 25.4%, thrombocytopenia 22.1%, transaminitis 26.4%, low total serum protein 34.7%, low serum albumin 37.9% and low alkaline phosphatase 40%. Out of those who were tested, raised inflammatory markers were ferritin 58.9% (56/95), c-reactive protein 33.3% (41/123), procalcitonin 53.5% (46/86) and interleukin-6 (IL-6) 76%. The presence of fever, rash, vomiting, underlying comorbidity, increased total leucocyte count, thrombocytopenia, high urea, low total serum protein and raised c-reactive protein was factors associated with moderate to severe disease. CONCLUSION: Fever was the commonest symptom. We identified additional laboratory abnormalities, namely lymphopenia, low total serum protein and albumin and low alkaline phosphatase. The majority of the children were asymptomatic or mildly symptomatic. We found high urea and low total serum protein as risk factors for moderate to severe disease for the first time.

Pulmonary Function Tests in Childhood Asthma: Which indices are Better for Assessment of Severity?

OBJECTIVE: To study pulmonary function tests in childhood asthma and to determine which indices are better for assessment of severity. METHODS: This was a hospital-based, cross-sectional study. All consecutive children aged between 5 and 15 y with mild and severe persistent asthma were enrolled. Children in whom diagnosis of asthma was doubtful and those with chronic lung disease or suppurative lung disease were excluded. Diagnosis and classification was based on GINA guidelines. Age-/sex-matched controls who did not have history of wheezing any time in the past were selected. Detailed spirometry was performed on all children enrolled using RMS HELIOS 401. RESULTS: A total of 144 children were enrolled in the study (48 children in each group, i.e., control, mild and severe). Mean age of the study population was 9.06 ± 2.604 y with M:F ratio of 1.9:1. Mean percent of predicted values of FEV1, FVC, FEV1/FVC, FEF25-75, and PEFR in the control group was 94.83, 92.63, 103.25, 73.90, and 93.60; in the mild group was 90.58, 83.52, 111.10, 76.50, and 92.00; and in the severe group 57.56, 62.83, 92.85, 40.15, and 62.12, respectively. Values of all the indices decreased with increase in severity. FEV1 (95% CI: 0.884 to 0.971) having the highest correlation coefficient (-0.652) with respect to severity of asthma and FEV1/FVC having the least (-0.202). FEF25-75 (95% CI: 0.652 to 0.803) having a higher area under the curve, was a better spirometric parameter in predicting mild asthma. CONCLUSION: FEV1 was better index for assessing severity of asthma and FEF25-75 better in predicting mild asthma.

Status of Vitamin B12, Zinc, Copper, Selenium, Manganese, Molybdenum and Cobalt in Severe Acute Malnutrition.

OBJECTIVES: To define the vitamin B12 levels and other micronutrients status in severe acute malnutrition (SAM) children. METHODS: This was a prospective hospital based cross-sectional study. INCLUSION CRITERIA: Children with severe acute malnutrition as per WHO criteria. EXCLUSION CRITERIA: (i) Pernicious anemia (ii) Autoimmune gastritis (iii) SAM children on exclusive vitamin B12 supplementation. All enrolled children underwent a detailed clinical history, general physical examination with more emphasis on clinical features of vitamin B12 and other micronutrients deficiencies. Three ml of venous blood was collected to estimate vitamin B12 and other micronutrients. Primary outcome was percentage of deficiency of serum vitamin B12, zinc, copper, selenium, manganese, molybdenum and cobalt in SAM children. RESULTS: Fifty children were included in the study. The mean age of children was 15.60±12.90 mo with male to female ratio 0.85:1. The common clinical presentation in order of frequency were upper respiratory infection (URI) symptoms 35 (70%), hepatomegaly 24 (48%), Hyperpigmentation 17 (34%), angular cheilitis 14 (28%), tremors 11 (22%), edema 07 (14%), and hypotonia 05 (10%). Anemia was found in 44 (88%) children. Prevalence of vitamin B12 deficiency was 34%. Other micronutrient deficiencies observed were cobalt 24 (100%), copper 05 (12%), zinc 04 (9.5%), and molybdenum 03 (12.5%). No statistical significance was found between clinical symptoms and levels of vitamin B12 with different age and sex. CONCLUSIONS: Prevalence of low vitamin B12 and cobalt were more common than other micronutrients.

Role of Clinical Criteria and Oxygen Saturation Monitoring in Diagnosis of Childhood Pneumonia in Children Aged 2 to 59 Months.

BACKGROUND: Current WHO algorithm has retained the signs and symptoms used in the older version for classifying severity of childhood pneumonia. OBJECTIVE: To study the role of clinical features (including that of current WHO criteria), and oxygen saturation (SpO2) in the diagnosis of childhood pneumonia. STUDY DESIGN: Multicenter prospective cohort study. PARTICIPANTS: Children, 2 to 59 months of age, suffering from acute respiratory infection (ARI). OUTCOME MEASURES: Sensitivity, specificity, and likelihood ratios were calculated for clinical features, and SpO2. RESULTS: Of a total 7026 children with ARI enrolled, 13.4% had pneumonia (37% of them had severe pneumonia), according to WHO criteria. Based on any abnormality on chest x ray (CXR), 46% had pneumonia. The sensitivity and specificity of the existing WHO criteria for diagnosis of pneumonia was 56.5% and 66.2%, respectively, when compared against abnormalities in CXR. Cough and fever, each had sensitivity of >80%. Audible wheeze and breathing difficulty, each had a specificity of >80%. Sensitivity and specificity of tachypnoea were 58.7% and 63.3%, respectively. None of the clinical features alone had a sensitivity and specificity of >80%. Addition of SpO2 of <92% to chest indrawing alone or WHO criteria increased the likelihood of diagnosis of pneumonia. CONCLUSIONS: Current WHO criteria based on rapid respiratory rate and/or chest indrawing has modest sensitivity and specificity, considering CXR abnormalities as gold standard for diagnosis of pneumonia. Addition of SpO2 of <92% to chest indrawing alone or WHO criteria increases the probability of pneumonia diagnosis, and is important in the management of a child with pneumonia.

Risk of Hospitalization in Under-five Children With Community-Acquired Pneumonia: A Multicentric Prospective Cohort Study.

OBJECTIVE: To evaluate factors associated with risk of hospitalization in children with community-acquired pneumonia (CAP). DESIGN: Prospective cohort study. SETTING: Multi-site hospital based study. INTERVENTION: A separate acute respiratory tract infection (ARI) treatment unit (ATU) was established. The revised WHO case definition for ARI was used across all the study sites to ensure uniformity in management of ARI patients (2-59 months). Clinical history, examination findings and investigations of enrolled patients were recorded on a predesigned case record form. Children were followed up at 1 week (± 1 day). MAIN OUTCOME MEASURE: Risk factors for hospitalization among pneumonia patients. RESULTS: A total of 7026 children with the diagnosis of ARI were enrolled. Pneumonia was diagnosed in 938 (13.4%) patients (median (IQR) age: 15 (8, 25) months; 63.5% boys). Hospitalization was needed in 56.8% of pneumonia patients. On multi-variate analysis, factors associated with risk of hospitalization were: Oxygen saturation on pulse oximetry (SpO2) <92% in room air (OR 7.04; 95% CI 1.6, 30.8, P=0.01), procalcitonin level >0.5 ng/mL (OR: 7.5, 95% CI: 1.0, 57.7, P=0.05), and lower weight for height z-score (OR 0.8; 95% CI: 0.6, 0.9, P=0.02). CONCLUSION: Present study found SpO2 <92% at room air, serum procalcitonin level >0.5 ng/mL and lower weight for height z-score to be predictors for risk of hospitalization in under-five children presenting with community acquired pneumonia. These factors can be utilized to assess a child with CAP regarding the need of hospitalization.

Antibody response patterns in chikungunya febrile phase predict protection versus progression to chronic arthritis.

Chikungunya virus (CHIKV) infection causes acute febrile illness in humans, and some of these individuals develop a debilitating chronic arthritis that can persist for months to years for reasons that remain poorly understood. In this study from India, we characterized antibody response patterns in febrile chikungunya patients and further assessed the association of these initial febrile-phase antibody response patterns with protection versus progression to developing chronic arthritis. We found 5 distinct patterns of the antibody responses in the febrile phase: no CHIKV binding or neutralizing (NT) antibodies but PCR positive, IgM alone with no NT activity, IgM alone with NT activity, IgM and IgG without NT activity, and IgM and IgG with NT activity. A 20-month follow-up showed that appearance of NT activity regardless of antibody isotype or appearance of IgG regardless of NT activity during the initial febrile phase was associated with a robust protection against developing chronic arthritis in the future. These findings, while providing potentially novel insights on correlates of protective immunity against chikungunya-induced chronic arthritis, suggest that qualitative differences in the antibody response patterns that have evolved during the febrile phase can serve as biomarkers that allow prediction of protection or progression to chronic arthritis in the future.

The Utility of CSF Xpert MTB/RIF in Diagnosis of Tubercular Meningitis in Children.

OBJECTIVE: To determine the utility of CSF Xpert MTB/RIF (GeneXpert) in diagnosis of tubercular meningitis in children in the age group of 2 mo to 12 y. METHODS: This hospital based prospective observational study was conducted at Department of Pediatrics, Karnataka Institute of Medical Sciences (KIMS), Hubli from December 2015 through November 2016. All children with clinically suspected tuberculous meningitis (TBM) were included in the study. These children underwent a detailed history taking, clinical examination, blood investigations, lumbar puncture and CT brain. Cerebrospinal fluid (CSF) samples were sent for CSF GeneXpert examination. Statistical analysis was done using IBM SPSS Statistics Version 20. RESULTS: A total of 28 children were enrolled in the study. Six (21.4%), 4 (14.3%) and 18 (64.3%) cases were definite, probable and possible TBM cases respectively. Most common age group affected was <5 y (83.33%) with median age 2.5 y (IQR 4.875). Male:female ratio was 1.5:1. CSF GeneXpert was tested positive in 6 cases (21.4%). The sensitivity of the test against the clinical scoring (>/=10) was 46.15% (95% CI, 19.22-74.87) and specificity was 100% (95% CI, 78.20-100). There was a significant association between CSF GeneXpert and Mantoux test (P = 0.002), CSF cell type >50% lymphocytes (P = 0.005) and CSF protein >100 mg/dl (P = 0.025) along with CT hydrocephalus (P = 0.021), granuloma (P = 0.009) and basal exudates (P = 0.025). None of the cases were tested smear positive for acid-fast bacilli (AFB). CONCLUSIONS: CSF GeneXpert is superior to smear for AFB in TBM.

Prediction of Neonatal Hyperbilirubinemia Using 1st Day Serum Bilirubin Levels.

The study was conducted on Full term neonates with birth weight > 2.5 kg born in KIMS, Hubballi with an objective to determine the first day Total Serum Bilirubin (TSB) value so as to predict subsequent development of significant hyperbilirubinemia in term neonates. All enrolled neonates were sampled for TSB and blood group on Day 1 at 20 ± 4 h and then followed up clinically by Kramer's rule and when the clinical jaundice by Kramer's rule was >10 mg/dl, TSB levels were repeated. A total of 180 newborns were enrolled for the study and 165 babies completed the study. Out of these, 17(10.3%) babies had significant hyperbilirubinemia by day 5 of life. Using Receiver Operating Characteristic (ROC) Curve, a cut off TSB value of 6.15 mg/dl was determined with sensitivity of 82.4%, specificity of 81.8%, positive predictive value of 32.8%, negative predictive value 97.6%. In term neonates, the first day total bilirubin level at 20 ± 4 h of life <6.15 predicts the low risk of subsequent significant hyperbilirubinemia with high probability.

Virus load and clinical features during the acute phase of Chikungunya infection in children.

BACKGROUND: Chikungunya virus (CHIKV) infection is a long known mosquito-borne disease that is associated with severe morbidity, characterized by fever, headache, rashes, joint pain, and myalgia. It is believed that virus load has relation with severity of clinical features. OBJECTIVES: We performed this study to assess the relationship between virus load and clinical features in children during the acute phase of CHIKV infection, in order to draw insights for better-informed treatment. STUDY DESIGN: Between June 1, 2009, and May 31, 2010, 338 patients with fever and susceptive to CHIKV during first 4 days of illness were prospectively enrolled from Karnataka Institute of Medical Sciences, Hubli in our hospital based cross sectional observational study. Sybr green quantitative reverse transcription polymerase chain reaction was performed to estimate the virus load. RESULTS: Quantitative RT-PCR was positive for CHIKV in 54 patients. The median copy number of CHIKV was 1.3x 108 copies/ml (1.7x105-9.9x109 copies/ml). Among the observed clinical features, a statistically significant difference in log mean virus load was found between patients with and without myalgia (log mean 7.50 vs 8.34, P = 0.01). CONCLUSION: Patients with myalgia had lower virus load and those without myalgia had a higher virus load.

Food Allergy in Children: An Overview.

The estimated prevalence of food allergy amongst children in the west is around 6-8% but there is paucity of data in the Indian population. There is a complex interplay of environmental influences and genetic factors in the immuno-pathogenesis and manifestations of food allergy. A reliable thorough clinical history, combined with positive skin prick tests or food-specific IgE, is essential for a more precise diagnosis of food allergy. Currently there is no cure for food allergy. The management of food allergy usually includes strict avoidance, patient education and provision of emergency medication (adrenaline-autoinjectors). Emerging therapies based on evolving research are focused on a more active approach to management which includes early introduction of potentially allergenic foods, anticipatory testing and desensitisation to food allergens. Lack of food labelling policy and non availability of adrenaline auto-injectors is a huge limiting factor for effective management of food allergy among children in India. The present review focuses on IgE mediated food allergy.