ABSTRACT
A girl in the early adolescent age group presented with multisystem manifestations in the form of periodic fever, recurrent abdominal pain, hypertension, seizure, skin lesions over the chest and gangrene over the left ring and middle fingertips. Her condition had remained undiagnosed for 11 years. On evaluation, she had features of polyarteritis nodosa (PAN) (multiple aneurysms, symmetric sensorimotor peripheral neuropathy, superficial ulcers, digital necrosis, myalgia, hypertension and proteinuria). As childhood PAN is a phenocopy of adenosine deaminase 2 with a different management strategy, whole-exome sequencing was performed, which revealed a pathogenic variant in ADA2 gene. The child was treated with TNF alpha inhibitors and showed improvement in the Paediatric Vasculitis Activity Score. The paper highlights the gratifying consequences of correct diagnosis with disease-specific therapy that ended the diagnostic odyssey, providing relief to the patient from debilitating symptoms and to the family from the financial burden of continued out-of-pocket health expenditure.
Subject(s)
Adenosine Deaminase , Polyarteritis Nodosa , Humans , Polyarteritis Nodosa/diagnosis , Polyarteritis Nodosa/drug therapy , Adenosine Deaminase/deficiency , Adenosine Deaminase/genetics , Female , Diagnosis, Differential , Adolescent , Exome Sequencing , Hereditary Autoinflammatory Diseases/diagnosis , Hereditary Autoinflammatory Diseases/genetics , Hereditary Autoinflammatory Diseases/drug therapy , Tumor Necrosis Factor Inhibitors/therapeutic use , Child , Intercellular Signaling Peptides and ProteinsABSTRACT
CONTEXT: Numerous pathogens (bacteria, viruses, or fungi) can cause childhood pneumonia. The clinical presentations of viral and bacterial pneumonia can be similar. Though viruses are a more common cause as compared to bacteria, antibiotics remain the first line of treatment for pneumonia. AIMS: This study was planned to describe the pulmonary histopathological patterns in cases of pediatric pneumonia (age <12 years) at autopsy and aimed to identify the probable etiology and correlate with clinical presentations. MATERIAL AND METHODS: This is a single-center 3-year retrospective descriptive autopsy study. Relevant clinical data was correlated with the postmortem findings. The cases were assigned to one of the following categories based on probable etiology: viral, bacterial, mixed, or others. RESULTS: There were 89 cases with a postmortem diagnosis of pneumonia among 262 autopsied children (34%). Most patients had histological patterns that suggested viral and bacterial etiology in 46 (51.7%) and 27 (30.3%), respectively. A total of 35 out of 46 patients received antibiotics. Twelve cases had mixed viral and bacterial patterns. Antibiotics were also given in the remaining four children (4.5%) with a similar clinical presentation, where a diagnosis of tuberculosis (03 cases) and invasive aspergillosis (01) was made at autopsy. CONCLUSION: Neither clinical features nor investigations reliably differentiate between viral and bacterial pneumonia. Autopsy has an important role in providing insights into the pathogenesis of pneumonia and suggests inappropriate antibiotic exposure. No prior Indian studies have been performed to compare the clinical and postmortem findings of pneumonia in children.
ABSTRACT
Major Histocompatibility Complex (MHC) Class II deficiency is a rare autosomal recessive primary immunodeficiency caused by mutations in regulatory genes of MHC Class II proteins. Clinical manifestations include respiratory/gastrointestinal infections, failure-to-thrive, septicemia and early death. A 9-mo-old-girl presented with repeated episodes of pneumonia requiring hospitalization and ventilator support since the last 5 mo. Examination revealed absent tonsils, sparse scalp-hair, seborrhea and firm hepato-splenomegaly. Radiograph showed absence of thymic shadow with diffuse pulmonary infiltrates. CT scan showed multiple bilateral ground glass pulmonary opacities with patchy consolidation. Primary immunodeficiency disorder was suspected in view of repeated pulmonary infections, failure to thrive and suggestive family history. Lymphocyte subset assay revealed lymphocytopenia and HLA typing showed absence of HLA-DR expression on B cells suggestive of MHC Class II deficiency. Targeted gene panel detected a homozygous mutation in the RFX-5 gene (RFX5: c.848_849del:p.R283Tfs*6;Homozygous). Though this patient succumbed, parents have been counseled regarding need for prenatal diagnosis.
ABSTRACT
Students with specific learning disabilities (SpLD) need timely remedial education and provisions to continue their education within the main-stream. The Government of India has enacted the Rights of Persons with Disabilities (RPwD) Act, 2016, and legitimized SpLD as a disability, nationally. This Act mandates screening of every school student for SpLD on completion of eight years of age, setting up of resource rooms for imparting remedial education in all schools, and provisions in examinations for all afflicted students. This Act authorizes that students with SpLD get benefit of reservations in higher education seats and government jobs. To ensure that this Act is implemented effectively, all stakeholders in the field of education and health will have to collaborate to set up sufficient number of assessment clinics, create sufficient number of special educators, and develop validated screening and assessment tools for diagnosing SpLD in all the regional languages of our country.
Subject(s)
Disabled Persons , Learning Disabilities , Educational Status , Humans , India/epidemiology , Learning Disabilities/diagnosis , Learning Disabilities/epidemiology , Schools , StudentsABSTRACT
Diagnosis of rare disorders requires heightened clinical acumen. When such disorders present with atypical or novel features, it adds to the diagnostic challenge. A 9-month-old female infant who had received a diagnosis of neonatal hepatitis due to cytomegalovirus infection at 2 months of age presented to our institute with developmental delay, fever, vomiting, feeding difficulty, breathlessness and features of elevated intracranial pressure due to hydrocephalus. Key examination findings with cholestatic jaundice as an early manifestation led to suspicion of type 4 Farber disease. Observation of hydrocephalus, hypertension, bilateral pinguecula and Erlenmeyer flask deformity of the femur were unusual findings for Farber disease. The child had few features (pinguecula, Erlenmeyer flask deformity and hydrocephalus) overlapping with Gaucher disease. Alternatively, prosaposin deficiency (Farber disease type 7) was another differential diagnosis. Diagnosis of Farber disease was confirmed by detection of foamy macrophages on skin biopsy and two homozygous missense variants in ASAH1 gene.
Subject(s)
Farber Lipogranulomatosis , Gaucher Disease , Child , Female , Femur , Gaucher Disease/complications , Gaucher Disease/diagnosis , Gaucher Disease/genetics , Humans , Infant , Infant, Newborn , Mutation, Missense , SkinABSTRACT
This retrospective study analyzed the level of concordance between clinical and autopsy diagnosis of pneumonia over a 3-year period. Utilizing the Goldman classification, the concordance rate was found to be 37.5%. Major discrepancies (Class I and II) were found in 25% cases, and minor discrepancies (Class III and IV) in 37.5% cases.
Subject(s)
Pneumonia , Autopsy , Cause of Death , Child , Diagnostic Errors , Humans , Pneumonia/diagnosis , Retrospective StudiesABSTRACT
Myxedema coma due to severe/long standing hypothyroidism is a known fatal endocrine emergency but is rare in children and unreported in pediatric Down syndrome. It mimics other conditions in the emergency room, making the diagnosis challenging. We present a 10-year-old-male child with global developmental delay and Down syndrome phenotype, admitted for altered sensorium subsequent to a febrile illness. The presence of myxedematous changes on clinical examination, on a background of altered sensorium and hypothermia, led to suspicion of myxedema coma, confirmed by laboratory testing. Due to nonavailability of triiodothyronine (T3), thyroxine (T4) was administered through nasogastric tube after an endocrine consult. Despite initial recovery in terms of improved consciousness, the child ultimately succumbed to refractory shock and terminal ventricular tachycardia. Our case highlights the need to consider myxedema coma as a differential diagnosis for altered mental status in the emergency room and use of screening tools for effective selection of patients.
ABSTRACT
Leukocyte adhesion deficiency (LAD) syndrome is a group of inborn errors of immunity characterized by a defect in the cascade of the activation and adhesion leading to the failure of leukocyte to migrate to the site of tissue injury. Three different types of LAD have been described. The most common subtype is LAD type 1 (LAD1) caused due to defects in the ITGß2 gene. LAD type 2 (LAD2) is caused by mutations in the SLC35C1 gene leading to a generalized loss of expression of fucosylated glycans on the cell surface and LAD type 3 (LAD3) is caused by mutations in the FERMT3 gene resulting in platelet function defects along with immunodeficiency. There is a paucity of data available from India on LAD syndromes. The present study is a retrospective analysis of patients with LAD collated from 28 different centers across India. For LAD1, the diagnosis was based on clinical features and flow cytometric expression of CD18 on peripheral blood leukocytes and molecular confirmation by Sanger sequencing. For patients with LAD3 diagnosis was largely based on clinical manifestations and identification of the pathogenic mutation in the FERMT3 gene by next-generation Sequencing. Of the total 132 cases diagnosed with LAD, 127 were LAD1 and 5 were LAD3. The majority of our patients (83%) had CD18 expression less than 2% on neutrophils (LAD1°) and presented within the first three months of life with omphalitis, skin and soft tissue infections, delayed umbilical cord detachment, otitis media, and sepsis. The patients with CD18 expression of more than 30% (LAD1+) presented later in life with skin ulcers being the commonest manifestation. Bleeding manifestations were common in patients with LAD3. Persistent neutrophilic leukocytosis was the characteristic finding in all patients. 35 novel mutations were detected in the ITGß2 gene, and 4 novel mutations were detected in the FERMT3 gene. The study thus presents one of the largest cohorts of patients from India with LAD, focusing on clinical features, immunological characteristics, and molecular spectrum.
Subject(s)
Cell Adhesion/genetics , Leukocyte-Adhesion Deficiency Syndrome/genetics , Leukocytes/pathology , Adolescent , CD18 Antigens/genetics , Child , Child, Preschool , Cohort Studies , Female , Humans , India , Infant , Infant, Newborn , Leukocyte-Adhesion Deficiency Syndrome/pathology , Leukocytosis/genetics , Leukocytosis/pathology , Male , Membrane Proteins/genetics , Mutation/genetics , Neutrophils/pathologySubject(s)
Acute Kidney Injury/microbiology , Candida/isolation & purification , Candidiasis/mortality , Candidiasis/pathology , Respiratory Distress Syndrome, Newborn/microbiology , Acute Kidney Injury/mortality , Humans , Infant , Kidney/microbiology , Male , Respiratory Distress Syndrome, Newborn/mortalityABSTRACT
BACKGROUND: Neurodevelopmental disorders (NDDs) compromise the development and attainment of full social and economic potential at individual, family, community, and country levels. Paucity of data on NDDs slows down policy and programmatic action in most developing countries despite perceived high burden. METHODS AND FINDINGS: We assessed 3,964 children (with almost equal number of boys and girls distributed in 2-<6 and 6-9 year age categories) identified from five geographically diverse populations in India using cluster sampling technique (probability proportionate to population size). These were from the North-Central, i.e., Palwal (N = 998; all rural, 16.4% non-Hindu, 25.3% from scheduled caste/tribe [SC-ST] [these are considered underserved communities who are eligible for affirmative action]); North, i.e., Kangra (N = 997; 91.6% rural, 3.7% non-Hindu, 25.3% SC-ST); East, i.e., Dhenkanal (N = 981; 89.8% rural, 1.2% non-Hindu, 38.0% SC-ST); South, i.e., Hyderabad (N = 495; all urban, 25.7% non-Hindu, 27.3% SC-ST) and West, i.e., North Goa (N = 493; 68.0% rural, 11.4% non-Hindu, 18.5% SC-ST). All children were assessed for vision impairment (VI), epilepsy (Epi), neuromotor impairments including cerebral palsy (NMI-CP), hearing impairment (HI), speech and language disorders, autism spectrum disorders (ASDs), and intellectual disability (ID). Furthermore, 6-9-year-old children were also assessed for attention deficit hyperactivity disorder (ADHD) and learning disorders (LDs). We standardized sample characteristics as per Census of India 2011 to arrive at district level and all-sites-pooled estimates. Site-specific prevalence of any of seven NDDs in 2-<6 year olds ranged from 2.9% (95% CI 1.6-5.5) to 18.7% (95% CI 14.7-23.6), and for any of nine NDDs in the 6-9-year-old children, from 6.5% (95% CI 4.6-9.1) to 18.5% (95% CI 15.3-22.3). Two or more NDDs were present in 0.4% (95% CI 0.1-1.7) to 4.3% (95% CI 2.2-8.2) in the younger age category and 0.7% (95% CI 0.2-2.0) to 5.3% (95% CI 3.3-8.2) in the older age category. All-site-pooled estimates for NDDs were 9.2% (95% CI 7.5-11.2) and 13.6% (95% CI 11.3-16.2) in children of 2-<6 and 6-9 year age categories, respectively, without significant difference according to gender, rural/urban residence, or religion; almost one-fifth of these children had more than one NDD. The pooled estimates for prevalence increased by up to three percentage points when these were adjusted for national rates of stunting or low birth weight (LBW). HI, ID, speech and language disorders, Epi, and LDs were the common NDDs across sites. Upon risk modelling, noninstitutional delivery, history of perinatal asphyxia, neonatal illness, postnatal neurological/brain infections, stunting, LBW/prematurity, and older age category (6-9 year) were significantly associated with NDDs. The study sample was underrepresentative of stunting and LBW and had a 15.6% refusal. These factors could be contributing to underestimation of the true NDD burden in our population. CONCLUSIONS: The study identifies NDDs in children aged 2-9 years as a significant public health burden for India. HI was higher than and ASD prevalence comparable to the published global literature. Most risk factors of NDDs were modifiable and amenable to public health interventions.
Subject(s)
Neurodevelopmental Disorders/epidemiology , Age Distribution , Child , Child Behavior , Child Development , Child, Preschool , Cross-Sectional Studies , Female , Health Surveys , Humans , India/epidemiology , Male , Neurodevelopmental Disorders/diagnosis , Neurodevelopmental Disorders/physiopathology , Neurodevelopmental Disorders/psychology , Prevalence , Risk Assessment , Risk FactorsABSTRACT
Attention-deficit/hyperactivity disorder (ADHD) is associated with significant impairments in social, educational, and occupational functioning, as well as specific strengths. Currently, there is no internationally accepted standard to assess the functioning of individuals with ADHD. WHO's International Classification of Functioning, Disability and Health-child and youth version (ICF) can serve as a conceptual basis for such a standard. The objective of this study is to develop a comprehensive, a common brief, and three age-appropriate brief ICF Core Sets for ADHD. Using a standardised methodology, four international preparatory studies generated 132 second-level ICF candidate categories that served as the basis for developing ADHD Core Sets. Using these categories and following an iterative consensus process, 20 ADHD experts from nine professional disciplines and representing all six WHO regions selected the most relevant categories to constitute the ADHD Core Sets. The consensus process resulted in 72 second-level ICF categories forming the comprehensive ICF Core Set-these represented 8 body functions, 35 activities and participation, and 29 environmental categories. A Common Brief Core Set that included 38 categories was also defined. Age-specific brief Core Sets included a 47 category preschool version for 0-5 years old, a 55 category school-age version for 6-16 years old, and a 52 category version for older adolescents and adults 17 years old and above. The ICF Core Sets for ADHD mark a milestone toward an internationally standardised functional assessment of ADHD across the lifespan, and across educational, administrative, clinical, and research settings.
Subject(s)
Attention Deficit Disorder with Hyperactivity/diagnosis , International Classification of Functioning, Disability and Health/standards , Adolescent , Adult , Attention Deficit Disorder with Hyperactivity/pathology , Child , Child, Preschool , Consensus , Female , Humans , Infant , Infant, Newborn , MaleABSTRACT
This is the fourth and final study designed to develop International Classification of Functioning, Disability and Health (ICF, and children and youth version, ICF-CY) core sets for attention-deficit hyperactivity disorder (ADHD). To investigate aspects of functioning and environment of individuals with ADHD as documented by the ICF-CY in clinical practice settings. An international cross-sectional multi-centre study was applied, involving nine units from eight countries: Denmark, Germany, India, Italy, Portugal, Saudi Arabia, Sweden and Taiwan. Clinicians and clinical researchers rated the functioning level of 112 children, adolescents and adults with ADHD using the extended ICF-CY checklist version 2.1a. The ratings were based on a variety of information sources, such as medical records, medical history, clinical observations, clinical questionnaires, psychometric tests and structured interviews with participants and family members. In total, 113 ICF-CY categories were identified, of which 50 were related to the activities and participation, 33 to environmental factors and 30 to body functions. The clinical study also yielded strengths related to ADHD, which included temperament and personality functions and recreation and leisure. The study findings endorse the complex nature of ADHD, as evidenced by the many functional and contextual domains impacted in ADHD. ICF-CY based tools can serve as foundation for capturing various functional profiles and environmental facilitators and barriers. The international nature of the ICF-CY makes it possible to develop user-friendly tools that can be applied globally and in multiple settings, ranging from clinical services and policy-making to education and research.
Subject(s)
Attention Deficit Disorder with Hyperactivity/diagnosis , International Classification of Functioning, Disability and Health/standards , Psychometrics/methods , Quality of Life/psychology , Adolescent , Adult , Child , Cross-Sectional Studies , Disability Evaluation , Female , Humans , Male , Surveys and Questionnaires , Young AdultABSTRACT
Background: Lack of access to rabies immunoglobulin (RIG) contributes to high rabies mortality. A recombinant human monoclonal antibody (SII RMAb) was tested in a postexposure prophylaxis (PEP) regimen in comparison with a human RIG (HRIG)-containing PEP regimen. Methods: This was a phase 2/3, randomized, single-blind, noninferiority study conducted in 200 participants with World Health Organization category III suspected rabies exposures. Participants received either SII RMAb or HRIG (1:1 ratio) in wounds and, if required, intramuscularly on day 0, along with 5 doses of rabies vaccine intramuscualarly on days 0, 3, 7, 14 and 28. The primary endpoint was the ratio of the day 14 geometric mean concentration (GMC) of rabies virus neutralizing activity (RVNA) as measured by rapid fluorescent focus inhibition test for SII RMAb recipients relative to HRIG recipients. Results: One hundred ninety-nine participants received SII RMAb (n = 101) or HRIG (n = 98) and at least 1 dose of vaccine. The day 14 GMC ratio of RVNA for the SII RMAb group relative to the HRIG group was 4.23 (96.9018% confidence interval [CI], 2.59-6.94) with a GMC of of 24.90 IU/mL (95% CI, 18.94-32.74) for SII RMAb recipients and 5.88 IU/mL (95% CI, 4.11-8.41) for HRIG recipients. The majority of local injection site and systemic adverse reactions reported from both groups were mild to moderate in severity. Conclusions: A PEP regimen containing SII RMAb was safe and demonstrated noninferiority to HRIG PEP in RVNA production. The novel monoclonal potentially offers a safe and potent alternative for the passive component of PEP and could significantly improve the management of bites from suspected rabid animals. Clincical Trials Registration: CTRI/2012/05/002709.
Subject(s)
Antibodies, Monoclonal/administration & dosage , Antibodies, Neutralizing/blood , Antibodies, Viral/administration & dosage , Post-Exposure Prophylaxis/methods , Rabies/prevention & control , Adult , Antibodies, Viral/blood , Bites and Stings/virology , Female , Humans , Injections, Intramuscular , Male , Middle Aged , Rabies Vaccines/administration & dosage , Rabies virus , Single-Blind MethodABSTRACT
This is the third in a series of four cross-cultural empirical studies designed to develop International Classification of Functioning, Disability and Health (ICF, and Children and Youth version, ICF(-CY) Core Sets for Attention-Deficit Hyperactivity Disorder (ADHD). To explore the perspectives of individuals diagnosed with ADHD, self-advocates, immediate family members and professional caregivers on relevant areas of impairment and functional abilities typical for ADHD across the lifespan as operationalized by the ICF(-CY). A qualitative study using focus group discussions or semi-structured interviews of 76 participants, divided into 16 stakeholder groups. Participants from five countries (Brazil, India, Saudi Arabia, South Africa and Sweden) were included. A deductive qualitative content analysis was conducted to extract meaningful functioning and disability concepts from verbatim material. Extracted concepts were then linked to ICF(-CY) categories by independent researchers using a standardized linking procedure. In total, 82 ICF(-CY) categories were identified, of which 32 were related to activities and participation, 25 to environmental factors, 23 to body functions and 2 to body structures. Participants also provided opinions on experienced positive sides to ADHD. A high level of energy and drive, creativity, hyper-focus, agreeableness, empathy, and willingness to assist others were the most consistently reported strengths associated with ADHD. Stakeholder perspectives highlighted the need to appraise ADHD in a broader context, extending beyond diagnostic criteria into many areas of ability and disability as well as environmental facilitators and barriers. This qualitative study, along with three other studies (comprehensive scoping review, expert survey and clinical study), will provide the scientific basis to define ICF(-CY) Core Sets for ADHD, from which assessment tools can be derived for use in clinical and research setting, as well as in health care administration.
Subject(s)
Attention Deficit Disorder with Hyperactivity/psychology , International Classification of Functioning, Disability and Health/standards , Quality of Life/psychology , Adolescent , Attention Deficit Disorder with Hyperactivity/diagnosis , Attention Deficit Disorder with Hyperactivity/pathology , Child , Cross-Cultural Comparison , Female , Humans , Male , Qualitative Research , World Health OrganizationABSTRACT
BACKGROUND: Invasive pneumococcal disease continues to be a major cause of morbidity and mortality among children younger than 5 years of age in India. We aimed to provide nationally representative data for the pattern of disease due to Streptococcus pneumoniae, trends in the serotype of invasive pneumococci, and invasive pneumococci antimicrobial resistance patterns, in India. METHODS: In this prospective hospital-based and retrospective laboratory-based surveillance study, we prospectively enrolled children aged younger than 5 years with suspected or proven invasive pneumococcal disease from 18 hospitals or institutional centres and retrospectively included laboratory-confirmed pneumococcal isolates from ten sentinel laboratories, together representing 11 states in India. Eligibility criteria were fever higher than 38°C without localising symptoms, clinical presentation of suspected meningitis or pneumonia, and evidence of radiographic pneumonia. We cultured blood and other normally sterile body fluids, reconfirmed and serotyped pneumococcal isolates, and established antimicrobial susceptibility using standard study protocols. FINDINGS: Between Jan 1, 2011, and June 30, 2015, we enrolled 4377 patients. Among 361 (8%) patients with culture-proven pneumococcal disease, all clinical data were known for 226 (63%); among these patients, 132 (58%) presented with pneumonia, 78 (35%) presented with meningitis, and 16 (7%) had other clinical conditions. 131 (3%) died overall and 29 (8%) patients with invasive pneumococcal disease died. Serotypes 14 (52 [14%] of 361), 1 (49 [14%]), 5 (37 [10%]), and 19F (33 [9%]) were the most common. Penicillin non-susceptibility occurred in isolates from 29 (8%) patients, co-trimoxazole resistance occurred in 239 (66%), erythromycin resistance occurred in 132 (37%), and chloramphenicol resistance occurred in 33 (9%). We found multidrug resistance in 33 (9%) of 361 patients. INTERPRETATION: The proportion of positive blood cultures, number of isolates, geographical representation, and data generated over the 4·5 years of the study are representative of data for most of India. Continued surveillance is warranted as the decision to introduce protein conjugated vaccine in India is made. FUNDING: GlaxoSmithKline India.