Factors Predicting Blood Culture Positivity in Children With Enteric Fever.

BACKGROUND: Blood culture, despite low sensitivity, is the gold standard for enteric fever diagnosis. Understanding predictors of blood culture positivity may help design strategies to optimize enteric fever diagnosis. METHODS: A cohort of 6760 children aged 0.5-15 years was followed for 3 years for enteric fever with blood cultures in an automated system, for fevers >3 days. Factors affecting test positivity in fevers and participant-level predictors for culture refusals were analyzed using regression models. RESULTS: Overall, 6097 suspected typhoid/paratyphoid fever (STF) episodes were reported, of which 5703 (93.5%) STFs had sampling for blood cultures, with 394 (6.5%) refusals. Salmonella enterica serovar Typhi/Paratyphi positivity was culture-confirmed in 3.8% (218/5703) of STF episodes. Older children (odds ratio [OR], 1.96 [95% CI, 1.39-2.77]), larger blood volume inoculated (OR, 2.82 [95% CI, 1.71-4.66]), higher temperatures during fever (OR, 3.77 [95% CI, 2.89-4.91]), and fevers diagnosed as suspected typhoid or acute undifferentiated fever (OR, 6.06 [95% CI, 3.11-11.78]) had a higher probability of culture positivity. Antibiotics before culture did not decrease culture positivity. Blood culture refusals were higher for children from wealthier households or with milder illness. CONCLUSIONS: Performing blood cultures in older children with fever, especially those fevers with toxic presentation and increasing blood volume for inoculation are strategies to improve enteric fever detection in surveillance settings.

Subsultus Tendinum in a Child with Typhoid Fever.

A 5-year-old male child with blood culture confirmed typhoid fever presented with twitching over the left scapular region. Contrast computerized tomography and electroencephalogram were normal. Following treatment with azithromycin and clonazepam, the twitching subsided. Subsultus tendinum, a rare neurological complication of typhoid fever, resolves spontaneously with treatment.

Genotype distribution of Group A rotavirus from southern India, 2005-2016.

Diarrheal disease due to Group A rotaviruses remain a leading cause of mortality and morbidity in the less developed parts of the world. India has started a phased roll out of rotavirus vaccine in the national immunization program. This analysis summarizes the rotavirus genotype strain distribution pre-vaccine introduction in Vellore, India from December 2005 to June 2016. Rotavirus was responsible for 32% of all diarrheal admission to the hospital. G2P[4] was the predominant strain in the initial years and was gradually replaced by G1P[8]. The emergence of G9P[4] replacing G9P[8], and the detection of G12 strains over several years were documented. There was no clear seasonality of disease. These data form the baseline to monitor genotype distribution post-vaccine introduction in Tamil Nadu.

The Duration of Intestinal Immunity After an Inactivated Poliovirus Vaccine Booster Dose in Children Immunized With Oral Vaccine: A Randomized Controlled Trial.

Background: In 2014, 2 studies showed that inactivated poliovirus vaccine (IPV) boosts intestinal immunity in children previously immunized with oral poliovirus vaccine (OPV). As a result, IPV was introduced in mass campaigns to help achieve polio eradication. Methods: We conducted an open-label, randomized, controlled trial to assess the duration of the boost in intestinal immunity following a dose of IPV given to OPV-immunized children. Nine hundred healthy children in Vellore, India, aged 1-4 years were randomized (1:1:1) to receive IPV at 5 months (arm A), at enrollment (arm B), or no vaccine (arm C). The primary outcome was poliovirus shedding in stool 7 days after bivalent OPV challenge at 11 months. Results: For children in arms A, B, and C, 284 (94.7%), 297 (99.0%), and 296 (98.7%), respectively, were eligible for primary per-protocol analysis. Poliovirus shedding 7 days after challenge was less prevalent in arms A and B compared with C (24.6%, 25.6%, and 36.4%, respectively; risk ratio 0.68 [95% confidence interval: 0.53-0.87] for A versus C, and 0.70 [0.55-0.90] for B versus C). Conclusions: Protection against poliovirus remained elevated 6 and 11 months after an IPV boost, although at a lower level than reported at 1 month. Clinical Trials Registration: CTRI/2014/09/004979.

Multi-center surveillance of rotavirus diarrhea in hospitalized children <5 years of age in India, 2009-2012.

Diarrheal disease due to Group A rotaviruses continues to be an important cause of morbidity in the developing world and India contributes significantly to the disease burden. Surveillance carried out between July 2009 and June 2012 at two medical centers in south India and one center in north India estimated 39% of all diarrheal admissions to be due to rotavirus. The most prevalent genotype isolated was G1P[8](33%) followed by G2P[4](17%). G9P[4] has also emerged as a significant cause of rotavirus diarrhea. No seasonal variation was noticed from the centers in south India, whereas we observed increased rotavirus diarrhea in the center in north India during March and April.

A novel mutation c.1048A>T at codon 350(Lys>Stop) in PROC gene causing neonatal purpura fulminans.

Purpura fulminans in the neonatal period due to severe congenital protein C deficiency (protein C activity <1 IU/dl) is a rare autosomal recessive disorder. If untreated, it is fatal. Early identification of such patients may be lifesaving. Acquired deficiency of protein C caused by increased consumption as overt disseminated intravascular coagulation (DIC) and severe infection creates a diagnostic dilemma. Mutation analysis plays a critical role in confirming the diagnosis of the disease and offering prenatal diagnosis. In this report, we describe a newborn who presented with purpura fulminans and DIC, molecular analysis showed a novel c.1048A>T transversion in a homozygous state at codon 350 (Lys>Stop) of protein C (PROC) gene. Prenatal diagnosis in subsequent pregnancy was done which revealed the affected fetus had the same mutation in homozygous form.

Rotavirus shedding in symptomatic and asymptomatic children using reverse transcription-quantitative PCR.

Reverse transcription-real-time polymerase chain reaction (RT-qPCR) for the VP6 gene was used to study group A rotavirus shedding in children with symptomatic and asymptomatic rotavirus infection. Sequential stool samples (n = 345) from 10 children with rotavirus associated diarrhea and from five children (n = 161) with asymptomatic rotavirus infection were collected over a period of 2 months. A RT-qPCR assay on the samples using a rotavirus VP6 plasmid standard demonstrated high reproducibility, with an inter-assay coefficient of variation (CV) of 1.40-2.97% and an intra-assay CV of 0.03-3.03%. The median duration of shedding was longer in children with diarrhea compared to asymptomatic children (24 days vs. 18 days; P = 0.066). The median quantitation cycle (C(q)) at presentation in symptomatic children was 17.21 compared to 30.98 in asymptomatic children (P = 0.086). The temporal pattern in symptomatic children consisted of a high initial viral shedding coinciding with the duration of diarrhea, followed by a rapid fall, and then a small increase in secondary shedding 21 days later. Compared to children with rotavirus diarrhea, those with asymptomatic infection shed lower quantities of virus throughout the observation period. No difference was noted between the G and P genotypes of samples collected at onset of infection and during the shedding period. Shedding was intermittent in a subset of children in both groups. RT-qPCR is a useful method to characterize shedding patterns.

Diversity of circulating rotavirus strains in children hospitalized with diarrhea in India, 2005-2009.

BACKGROUND: India accounts for 22% of the 453,000 global rotavirus deaths among children <5 years annually. The Indian Rotavirus Strain Surveillance Network provides clinicians and public health partners with valuable rotavirus disease surveillance data. Our analysis offers policy-makers an update on rotavirus disease burden with emphasis on regional shifts in rotavirus strain epidemiology in India. METHODS: Children <5 years requiring hospitalization for acute gastroenteritis were selected from 10 representative hospitals in 7 cities throughout India between November 2005 through June 2009. We used a modified World Health Organization protocol for rotavirus surveillance; stool specimens were collected and tested for rotavirus using enzyme immunoassay and reverse-transcription polymerase chain reaction. RESULTS: A total of 7285 stool specimens collected were tested for rotavirus, among which 2899 (40%) were positive for rotavirus. Among the 2899 rotavirus detections, a G-type could not be determined for 662 (23%) and more than one G type was detected in 240 (8%). Of 1997 (69%) patients with only one G-type, the common types were G1 (25%), G2 (21%), G9 (13%), and G12 (10%). The proportion of rotavirus infections attributed to G12 infections rose from 8% to 39% in the Northern region and from 8% to 24% in the Western region. CONCLUSIONS: This study highlights the large, ongoing burden of rotavirus disease in India, as well as interesting regional shifts in rotavirus strain epidemiology, including an increasing detection of G12 rotavirus strains in some regions. While broad heterotypic protection from rotavirus vaccination is expected based on pre- and post-licensure data from other settings, effectiveness assessments and rotavirus strain monitoring after vaccine introduction will be important.

Isolated pulmonary Langerhans cell histiocytosis.

Isolated pulmonary involvement in Langerhans Cell Histiocytosis (LCH) is rare in childhood. The authors report a 6-y- old boy presenting with recurrent pneumothorax, whose CT thorax showed diffuse pulmonary cystic lucencies bilaterally. Biopsy of the lesions confirmed pulmonary LCH with Cd1a and S 100 positivity.

Estimation of the burden of pandemic(H1N1)2009 in developing countries: experience from a tertiary care center in South India.

BACKGROUND: The burden of the pandemic (H1N1) 2009 influenza might be underestimated if detection of the virus is mandated to diagnose infection. Using an alternate approach, we propose that a much higher pandemic burden was experienced in our institution. METHODOLOGY/PRINCIPAL FINDINGS: Consecutive patients (n = 2588) presenting to our hospital with influenza like illness (ILI) or severe acute respiratory infection (SARI) during a 1-year period (May 2009-April 2010) were prospectively recruited and tested for influenza A by real-time RT-PCR. Analysis of weekly trends showed an 11-fold increase in patients presenting with ILI/SARI during the peak pandemic period when compared with the pre-pandemic period and a significant (P<0.001) increase in SARI admissions during the pandemic period (30 ± 15.9 admissions/week) when compared with pre-pandemic (7 ± 2.5) and post-pandemic periods (5 ± 3.8). However, Influenza A was detected in less than one-third of patients with ILI/SARI [699 (27.0%)]; a majority of these (557/699, 79.7%) were Pandemic (H1N1)2009 virus [A/H1N1/09]. An A/H1N1/09 positive test was correlated with shorter symptom duration prior to presentation (p = 0.03). More ILI cases tested positive for A/H1N1/09 when compared with SARI (27.4% vs. 14.6%, P = 0.037). When the entire study population was considered, A/H1N1/09 positivity was associated with lower risk of hospitalization (p<0.0001) and ICU admission (p = 0.013) suggesting mild self-limiting illness in a majority. CONCLUSION/SIGNIFICANCE: Analysis of weekly trends of ILI/SARI suggest a higher burden of the pandemic attributable to A/H1N1/09 than estimates assessed by a positive PCR test alone. The study highlights methodological consideration in the estimation of burden of pandemic influenza in developing countries using hospital-based data that may help assess the impact of future outbreaks of respiratory illnesses.

Novel STXBP2 mutation causing familial hemophagocytic lymphohistiocytosis.

Familial Hemophagocytic Lymphohistiocytosis (FHL) is a rare autosomal recessive disorder. Diagnosis is established in presence of genetic mutation or positive family history in one of the siblings. Common genetic mutations associated with FHL are mutations in gene PRF1 (also known as FHL 2), UNC13D (FHL 3) and STX11 (FHL 4). Recently mutation in STXBP2 encoding syntaxin binding protein 2 (Munc 18 -2) has been found to be associated with FHL type 5. Here we describe the first reported Indian patient with homozygous mutation in STX BP2 gene (c1697 G > A resulting in amino acid change p.G566D) causing FHL 5.

Severity of rotavirus gastroenteritis in Indian children requiring hospitalization.

INTRODUCTION: The burden of rotavirus gastroenteritis is greatest in India and other developing countries. With the availability of two licensed vaccines and a number of additional vaccines in various stages of development and trial, analysis of detailed clinical information is essential for the development of a uniform method of severity assessment. METHODS: Diarrhoeal stool samples from 1001 children <5 years of age hospitalized with gastroenteritis were screened for rotavirus using a commercial enzyme immunoassay. Positive samples were confirmed by genotyping using hemi nested multiplex RT-PCR. Detailed clinical data was collected for gastroenteritis assessment for 934 children and extraintestinal presentations were analyzed in 470 children. Severity scoring was carried out for all children using the Vesikari score and in a subset by Clark's scoring system. RESULTS: Rotavirus was detected in 35.4% of samples tested between December 2005 and November 2008. Clark's and Vesikari scores showed moderate correlation but varied greatly in the categorization of severe disease. Using Clark's scoring, only 1.6% were categorized as presenting with severe disease in comparison to 66.1% by the Vesikari score. Association of extraintestinal symptoms with rotavirus gastroenteritis was not documented in this study. CONCLUSION: The assessment of disease severity using two common severity scoring systems highlights the difference in the categorization of "severe" disease. This underscores the need for a robust scoring system which is needed for vaccine trial and in post-licensure surveillance, because vaccine efficacy is estimated for protection against severe rotavirus gastroenteritis.

Validation of the children's depression rating scale- revised for adolescents in primary-care pediatric use in India.

BACKGROUND: Adolescent depression needs to be identified and treated in the primary care settings. There is no clinician-rated measure validated in India for identifying depression among adolescents. AIM: We studied the diagnostic accuracy, reliability, and validity of Children's Depression Rating Scale - Revised (CDRS-R) for primary care pediatrics. SETTING AND DESIGN: Prospective study in three schools in Southern India. MATERIALS AND METHODS: Adolescents recruited were administered the CDRS-R by a pediatrician and clinical psychologist along with Beck Depression Inventory (BDI) for convergent validity. Impact of Event Scale (IES) for divergent validity and the ICD-10 clinical diagnosis of depressive disorders using modified Kiddie-SADS-Present and Lifetime Version (K-SADS-PL) interview as reference standard were administered by a psychiatrist independently. Appropriate statistical analyses for diagnostic accuracy, reliability, and validity were done. RESULTS: A cut-off score of 30 (sensitivity = 83%, specificity = 84%; AUC in ROC = 87%) in CDRS-R is suggested for diagnosing depression. The inter-rater reliability (r = 0.73) and test-retest reliability (r = 0.98) was good. In addition to the adequate face and content validity, CDRS-R had good internal consistency (α = 0.76), high convergent (r = 0.71; P = 0.001), and divergent validity (r = 0.28; P = 0.20). There was moderate concordance with the reference standard of ICD-10 diagnosis (45.5%) in identifying depression and CDRS-R discriminated 80% of the other psychiatric morbidity. The six-factor structure explained 60.6% of variance. CONCLUSION: The CDRS-R showed strong psychometric properties and is now available for use in the primary-care pediatric practice in India.

Costing of severe pneumonia in hospitalized infants and children aged 2-36 months, at a secondary and tertiary level hospital of a not-for-profit organization.

OBJECTIVES: To determine health care provider cost and household cost of the treatment of severe pneumonia in infants and young children admitted to secondary and tertiary level health care facilities. METHODS: The study was done in a private, not-for-profit medical college hospital, in Vellore, India, in mid-2008. Children aged 2-36 months admitted with severe pneumonia with no underlying chronic disease were included in the study. The relatives were interviewed daily on matters relating to patients' view point of the costs. These were direct medical costs, direct non-medical costs which comprised travel, accommodation and special food during the period of illness, and indirect costs of productivity loss for family members. Patient specific resource consumption and related charges were recorded from charts, nursing records, pharmacy lists and hospital bills, and the providers view point of the costs was estimated. Unit cost estimates for bed days, treatment and investigation inputs were calculated. RESULTS: Total cost to health care provider for one episode of hospitalized childhood pneumonia treated at secondary level was US$ 83.89 (INR 3524) and US$ 146.59 (INR 6158) at tertiary level. At both levels the greatest single cost was the hospital stay itself, comprising 74% and 56% of the total cost, respectively. Diagnostic investigations were a large expense and supportive treatment with nebulization and oxygen therapy added to the costs. Mean household expenditure on secondary level was US$ 41.35 (INR 1737) and at tertiary level was US$ 134.62 (INR 5655), the largest single expense being medicines in the former and the hospitalization in the latter. (one US$=INR 42.1 at time of study) CONCLUSIONS: A considerable cost difference exists between secondary and tertiary level treatment. Admission at lowest possible treatment level for appropriate patients could decrease the costs borne by the provider and the patient.

Prolonged neurologic course of familial hemophagocytic lymphohistiocytosis.

Familial hemophagocytic lymphohistiocytosis is a very unusual cause for demyelination and the clinician would do well to be aware of the condition, especially when children present with atypical findings on magnetic resonance imaging associated with fever, pancytopenia, and hepatosplenomegaly. This is a rare autosomal recessive, multisystem inflammatory disorder characterized by widespread organ infiltration by macrophages and activated lymphocytes. It is usually diagnosed in the first 2 years of life and is rapidly fatal if untreated. Reported here is the case of a 12-year-old boy, from a poor family, with a 6-year history of visual loss and fever for 5 months, and transient hemiparesis with hepatosplenomegaly and pancytopenia. Cranial magnetic resonance imaging showed multiple areas of hyperintense signal, predominantly involving white matter. The boy also had elevated triglycerides and ferritin, with low fibrinogen level. Bone marrow aspiration revealed hemophagocytosis. He was diagnosed as having familial hemophagocytic lymphohistiocytosis and treated with the HLH 2004 protocol. A sibling also had evidence of hemophagocytosis. Remission was achieved, but his parents could not afford the cost of hematopoietic stem cell transplantation. He relapsed after 8 months and later died.

Acute pancreatitis as the initial presentation in pediatric systemic lupus erythematosus.

It is exceptionally rare for acute pancreatitis to be the presenting manifestation of childhood systemic lupus erythematosus. We report a 14-year-old girl who presented with a history of fever, generalized rash, arthralgia and abdominal pain. Her serum amylase was 1472U/L and lipase 3316 U/L suggestive of acute pancreatitis. Other investigations revealed pancytopenia, low complement, high 24-hour urinary protein and elevated ANA and dsDNA. She was treated with IV methylprednisone, followed by oral steroids.

The psychometric properties of Beck Depression Inventory for adolescent depression in a primary-care paediatric setting in India.

BACKGROUND: There is increasing interest in identifying adolescents with depression in primary care settings by paediatricians in India. This article studied the diagnostic accuracy, reliability and validity of Beck Depression Inventory (BDI) while used by paediatricians in a primary care setting in India. METHODS: 181 adolescents attending 3 schools were administered a back translated Tamil version of BDI by a paediatrician to evaluate its psychometric properties along with Children's Depression Rating Scale (CDRS-R) for convergent validity. Clinical diagnosis of depressive disorders, for reference standard, was based on ICD-10 interview by an independent psychiatrist who also administered the Impact of Event Scale (IES) for divergent validity. Appropriate analyses for validity and diagnostic accuracy both at the item and scale levels were conducted. RESULTS: A cut-off score of >or= 5 (Sn = 90.9%, Sp = 17.6 %) for screening and cut-off score of >or= 22 (Sn = 27.3%, Sp = 90%) for diagnostic utility is suggested. The 4 week test - retest reliability was good (r = 0.82). In addition to the adequate face and content validity, BDI has very good internal consistency (alpha = 0.96), high convergent validity with CDRS-R (r = 0.72; P = 0.001), and high discriminant validity with IES (r = 0.26; P = 0.23). There was a moderate concordance rate with the reference standard (54.5%) in identifying depression among the adolescents. Factor analysis replicated the 2-factor structure explaining 30.5 % of variance. CONCLUSION: The BDI proved to be a psychometrically sound measure for use by paediatricians in a primary care setting in India. The possibility of screening for depressive disorders through the use of BDI may be helpful in identifying probable cases of the disorder among adolescents.

Infectious etiology modifies the treatment effect of zinc in severe pneumonia.

BACKGROUND: Zinc is undergoing evaluation as an inexpensive therapeutic adjuvant for severe pediatric pneumonia. OBJECTIVE: We explored the effect of etiology on the treatment effect of zinc in young children hospitalized for severe pneumonia. DESIGN: We analyzed data from a randomized, double-blind, placebo-controlled clinical trial conducted at the Christian Medical College Hospital, a teaching hospital in Tamilnadu, India. Children aged 2-23 mo (n = 299) were randomly assigned to receive a 10-mg tablet of zinc sulfate or placebo twice a day during hospitalization. The primary outcomes were length of hospitalization and time to resolution of severe pneumonia stratified by etiologic classification on the basis of serum C-reactive protein (CRP) concentrations at admission. RESULTS: CRP concentrations were available for 295 (98.7%) of the enrolled cases. Of these 295 cases, 223 (75.6%) were classified as suspected nonbacterial pneumonias (CRP concentrations 40 mg/L), the median length of hospitalization was approximately 20 h longer in the zinc-supplemented group than in the placebo group (87.3 and 68.3 h, respectively; HR: 0.56; 95% CI: 0.34, 0.93; P = 0.025). The treatment effect was not modified in the suspected nonbacterial cases of pneumonia. CONCLUSIONS: Our results suggest that the treatment effect of zinc for severe pediatric pneumonia may be modified by bacterial infection. Further studies are required to develop appropriate recommendations for the use of zinc in the treatment of severe pneumonia. This trial was registered at clinicaltrials.gov as NCT00198666.

Human caliciviruses in symptomatic and asymptomatic infections in children in Vellore, South India.

Pediatric gastroenteritis is a major cause of childhood morbidity and mortality worldwide, especially in developing countries. It has been increasingly recognised that human caliciviruses (HuCV), comprising noroviruses (NoV), and sapoviruses (SaV), are important in both outbreak and non-outbreak settings. This study aimed to characterise caliciviruses detected in the faeces of hospitalized children and children in the community in India. This study examined 350 faecal samples from children presenting to the hospital with acute gastroenteritis and 673 samples collected from children in the community, 500 from children with diarrhea, and 173 samples from children without diarrhea. Strain characterisation was performed by reverse transcription-polymerase chain reaction (RT-PCR) and partial sequencing of the gene encoding the RNA-dependent RNA polymerase (RdRp) and/or a region spanning the open reading frames (ORFs) 1 and 2 (ORF1/ORF2) junction. A total of 68 of 350 specimens (19.4%) from hospitalized children were positive, and SaV and NoV accounted for 5.1 and 15.1% of the infections, respectively. Mixed infections of HuCVs with other enteric pathogens were seen in 9.4% of the total children tested. Sixty-eight out of 673 (10.1%) samples collected from children in the community were positive for caliciviruses, and SaV and NoV accounted for 3.4 and 6.6% of the infections. In the community cohort 55/500 (11%) and 13/173 (7.5%) were from symptomatic and asymptomatic children, respectively, and SaVs accounted for 17/500 (3.4%) and NoVs for 38/500 (7.6%) of the symptomatic infections. This is the first report of genotyping of circulating caliciviruses in both hospital and community in India and has increased the evidence for the role of these viruses in pediatric gastroenteritis in India.

Prevalence of anaemia among adolescent girls in the urban slums of Vellore, south India.

A community-based, cross-sectional study was conducted to determine the prevalence of anaemia among unmarried, adolescent south Indian girls in an urban slum setting. A total of 100 apparently healthy girls between the ages of 11 and 18 years were recruited. Their socioeconomic, dietary and anthropometric information was collected, and blood haemoglobin (Hb) was estimated. The prevalence of anaemia (Hb < 12 g%) was 29%. Most had mild anaemia; severe anaemia was not seen. Two-thirds of those with anaemia had low serum ferritin (<12 microg/L). Significant associations were observed between anaemia and low socioeconomic status, religion and reporting infrequent/non-consumption of meat (heme iron). Only meat consumption was related to haemoglobin by multiple regression analysis. Anaemia is a common problem among adolescent girls in this setting, though severe anaemia is rare. There is a need to improve their haemoglobin status through dietary modification along with preventive supplementation and nutrition education.