Epidemiological, clinical, and laboratory characteristics of human granulocytic anaplasmosis in North India.

Human granulocytic anaplasmosis (HGA) is an emerging, rickettsial tick-borne disease caused by Anaplasma phagocytophilum. Sero-epidemiological data demonstrate that this pathogen has a worldwide distribution. The diagnosis of HGA requires a high index of clinical suspicion, even in endemic areas. In recent years, HGA has increasingly been reported from Asia and described in China, Japan, and Korea. We serologically and molecularly screened 467 patients with clinical suspicion of Anaplasmosis. The present study describes the epidemiology, clinical, and laboratory details of 6 confirmed and 43 probable cases of human granulocytic anaplasmosis. One of the HGA patients developed secondary invasive opportunistic Aspergillus fumigatus and Acinetobacter baumanii infection during the illness, which resulted in a fatal infection. The HGA patients without severe complications had excellent treatment responses to doxycycline. The emergence of this newly recognized tick-borne zoonotic HGA in North India is a significant concern for public health and is likely underdiagnosed, underreported, and untreated. Hence, it is also essential to establish a well-coordinated system for actively conducting tick surveillance, especially in the forested areas of the country.IMPORTANCEThe results of the present study show the clinical and laboratory evidence of autochthonous cases of Anaplasma phagocytophilum in North India. The results suggest the possibility of underdiagnosis of HGA in this geographical area. One of the HGA patients developed secondary invasive opportunistic Aspergillus fumigatus and Acinetobacter baumanii infection during the illness, which resulted in a fatal infection.

Pediatric Sepsis Phenotypes and Outcome: 5-Year Retrospective Cohort Study in a Single Center in India (2017-2022).

OBJECTIVES: To describe mortality associated with different clinical phenotypes of sepsis in children. DESIGN: Retrospective study. SETTING: PICU of a tertiary care center in India from 2017 to 2022. PATIENTS: Six hundred twelve children (from 2 mo to 17 yr old) with a retrospectively applied diagnosis of sepsis using 2020 guidance. METHODS: The main outcome was mortality associated with sepsis subtypes. Other analyses included assessment of risk factors, requirement for organ support, and PICU resources used by sepsis phenotype. Clinical data were recorded on a predesigned proforma. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Of the 612 children identified, there were 382 (62%) with sepsis but no multiple organ failure (NoMOF), 48 (8%) with thrombocytopenia-associated MOF (TAMOF), 140 (23%) with MOF without thrombocytopenia, and 40 (6.5%) with sequential MOF (SMOF). Mortality was higher in the SMOF (20/40 [50%]), MOF (62/140 [44%]) and TAMOF (20/48 [42%]) groups, compared with NoMOF group (82/382 [21%] [ p < 0.001]). The requirement for organ support and PICU resources was higher in all phenotypes with MOF as compared with those without MOF. On multivariable analysis elevated lactate and having MOF were associated with greater odds of mortality. CONCLUSIONS: In this single-center experience of sepsis in India, we found that sepsis phenotypes having MOF were associated with mortality and the requirement of PICU resources. Prospective studies in different regions of the world will help identify a classification of pediatric sepsis that is more widely applicable.

Multiple Electrolytes Solution Versus Saline as Bolus Fluid for Resuscitation in Pediatric Septic Shock: A Multicenter Randomized Clinical Trial.

OBJECTIVE: To determine if initial fluid resuscitation with balanced crystalloid (e.g., multiple electrolytes solution [MES]) or 0.9% saline adversely affects kidney function in children with septic shock. DESIGN: Parallel-group, blinded multicenter trial. SETTING: PICUs of four tertiary care centers in India from 2017 to 2020. PATIENTS: Children up to 15 years of age with septic shock. METHODS: Children were randomized to receive fluid boluses of either MES (PlasmaLyte A) or 0.9% saline at the time of identification of shock. All children were managed as per standard protocols and monitored until discharge/death. The primary outcome was new and/or progressive acute kidney injury (AKI), at any time within the first 7 days of fluid resuscitation. Key secondary outcomes included hyperchloremia, any adverse event (AE), at 24, 48, and 72 hours, and all-cause ICU mortality. INTERVENTIONS: MES solution ( n = 351) versus 0.9% saline ( n = 357) for bolus fluid resuscitation during the first 7 days. MEASUREMENTS AND MAIN RESULTS: The median age was 5 years (interquartile range, 1.3-9); 302 (43%) were girls. The relative risk (RR) for meeting the criteria for new and/or progressive AKI was 0.62 (95% CI, 0.49-0.80; p < 0.001), favoring the MES (21%) versus the saline (33%) group. The proportions of children with hyperchloremia were lower in the MES versus the saline group at 24, 48, and 72 hours. There was no difference in the ICU mortality (33% in the MES vs 34% in the saline group). There was no difference with regard to infusion-related AEs such as fever, thrombophlebitis, or fluid overload between the groups. CONCLUSIONS: Among children presenting with septic shock, fluid resuscitation with MES (balanced crystalloid) as compared with 0.9% saline resulted in a significantly lower incidence of new and/or progressive AKI during the first 7 days of hospitalization.

Role of high-sensitivity C-reactive protein (hs-CRP) in assessment of asthma control in children.

INTRODUCTION: Data are scarce on hs-CRP as a biomarker for airway inflammation in pediatric asthma. We aimed to examine correlation between hs-CRP and asthma control levels. METHODS: Children with physician-diagnosed asthma, ages 6-15 years, were enrolled. GINA-2016 criteria were used to assess the level of asthma control. The relationships between serum hs-CRP and each of asthma control measures (asthma control criteria, spirometry, impulse oscillometry, eosinophil counts and fractional exhaled nitric oxide (FeNO) were assessed. RESULTS: 150 asthmatic children were enrolled; 52 (35%) had well controlled asthma, 76 (51%), and 22 (14%) children had partly controlled and uncontrolled asthma, respectively. Median (IQR) values of hs-CRP were 0.47 (0.1, 1.67) mg/L in well controlled, 0.30 (0.1, 1.83) mg/L in partly controlled, and 2.74 (0.55, 3.74) mg/L in uncontrolled asthma (p = 0.029). Using receiver operator characteristic (ROC) curve analysis, area under the curve for hs-CRP (mg/L) to discriminate between uncontrolled and (controlled + partly controlled) asthma was 0.67 (95% CI 0.55, 0.80) and a cutoff 1.1 mg/L of serum hs-CRP level had a sensitivity of 68.1% with specificity of 67.97%. In two groups of hs-CRP (<3 mg/L) and hs-CRP (≥3 mg/L), high hs-CRP group had higher proportion of uncontrolled asthmatic children (p = 0.03). CONCLUSION: We observed higher serum hs-CRP values in children with uncontrolled asthma, suggesting its potential role as a biomarker of asthma control.

Impulse oscillometry (IOS) for detection of exercise induced bronchoconstriction in children with asthma ages 6-15 years.

OBJECTIVES: To determine the discriminatory value of various impulse oscillometry (IOS) parameters, and to find the cutoff value of the appropriate parameter for identifying exercise-induced bronchoconstriction (EIB) in children with asthma. METHODS: This cross-sectional study was conducted in India from October 2016 to March 2018 in children with asthma who were 6-15 years of age. One hundred and five children were enrolled and subjected to pre-exercise IOS and spirometry followed by free running treadmill test as an exercise challenge. All children could achieve minute ventilation >17.5-21 times of FEV1 during the exercise challenge test. Then, IOS and spirometry were performed at 10 ± 2, 20 ± 2, and 30 ± 2 min post-exercise challenge. EIB was defined as reduction of FEV1 ≥10% within 30 min of exercise. For purposes of analysis, the children were grouped into two categories: "EIB Present" or "EIB Absent". RESULTS: The prevalence of EIB in our study was 20.95% (n = 22). ΔR5max percentage within 30 min post-exercise (AUC 0.74; 95% CI: 0.64, 0.84) had the best discriminating capacity among all IOS parameters for identifying EIB. A cutoff value of 14.1% increase in R5 within 30 min post-exercise was obtained for detection of EIB (sensitivity-95.45%, specificity-50.6%, PPV-33.87% and NPV-97.67%). CONCLUSIONS: A percentage change in R5 with a cutoff value of 14.1% increase post-exercise had the best discriminatory capacity among all IOS parameters for detection of EIB in children with asthma. However, low positive predictive value (PPV) with high negative predictive value (NPV) made this cutoff value more apt to rule out EIB.

Feasibility of establishing acute respiratory infection treatment units (ATU) for improvement of care of children with acute respiratory infection.

BACKGROUND: Acute respiratory infections (ARI) are the leading cause of morbidity and mortality in children below 5 years of age. METHODS: This multisite prospective observational study was carried out in the Pediatrics' out-patient departments of 5 medical colleges across India with an objective to assess the feasibility of establishing Acute Respiratory Infection Treatment Unit (ATU) in urban medical college hospitals. ATU (staffed with a nurse and a medical officer) was established in the out-patient areas at study sites. Children, aged 2-59 months, with cough and/ breathing difficulty for < 14 days were screened by study nurse in the ATU for pneumonia, severe pneumonia or no pneumonia. Diagnosis was verified by study doctor. Children were managed as per the World Health Organization (WHO) guidelines. The key outcomes were successful establishment of ATUs, antibiotic usage, treatment outcomes. RESULTS: ATUs were successfully established at the 5 study sites. Of 18,159 under-five children screened, 7026 (39%) children were assessed to have ARI. Using the WHO criteria, 938 were diagnosed as pneumonia (13.4%) and of these, 347 (36.9%) had severe pneumonia. Ambulatory home-based management was done in 6341 (90%) children with ARI; of these, 16 (0.25%) required admission because of non-response or deterioration on follow-up. Case-fatality rate in severe pneumonia was 2%. Nearly 12% of children with 'no pneumonia' received antibiotics. CONCLUSIONS: Setting up of ATUs dedicated to management of ARI in children was feasible in urban medical colleges. The observed case fatality, and rate of unnecessary use of antibiotics were lower than that reported in literature.

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.

An open-label non-inferiority randomised control trial comparing nebulised amphotericin B with oral itraconazole in patients with pulmonary aspergilloma.

BACKGROUND: Pulmonary aspergilloma (PA) is a common complication seen in patients with pulmonary tuberculosis sequelae. Antifungal therapy, including oral azoles, is commonly used though only surgical resection offers curative benefit. Local administration of amphotericin B, like intracavitary instillation, has been effective in aspergilloma patients though nebulised amphotericin B (nAB) has never been formally assessed. OBJECTIVE: The aim of this prospective, non-inferior, open-label, randomised control trial is to evaluate the efficacy and safety of nebulised amphotericin B compared to oral itraconazole therapy in the treatment of PA. PATIENTS/METHODS: Diagnosed cases of PA (n=33) were randomised into the control group receiving oral itraconazole (n=18) and intervention group receiving nebulised amphotericin B (n = 15). Response to treatment was assessed both clinically and radiologically at the end 6 months. RESULTS AND CONCLUSION: The number of patients showing overall improvement at the end of 6 months in the control arm(oral itraconazole) vs intervention arm(nebulised amphotericin B) was 65% (95% CI 38.3-85.8) and 67%(95% CI 38.4%-88.2%), respectively, in the intention-to-treat and 79% (95% CI 49.2%-95.3%), and 65% (95% CI 38.4%-88.2%), respectively, in the per-protocol analysis. While there was no statistically significant difference between the intervention and control arm in both the analyses, non-inferiority was shown in the per-protocol but not in the intention-to-treat analysis. No major adverse events were noted in either group; however, a significant proportion of patients receiving nAB reported minor cough (40%), which, however, did not lead to discontinuation of therapy in any patients. Nebulised amphotericin B can be an effective therapeutic option for pulmonary aspergilloma patients.

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.

Role of Serum MRP8/14 in Predicting Response to Methotrexate in Children With Juvenile Idiopathic Arthritis.

OBJECTIVE: Nearly 40% of children with juvenile idiopathic arthritis (JIA) might not respond to first-line disease-modifying antirheumatic drugs (DMARDs) including methotrexate (MTX). Hence, there is a need for a biomarker that can predict MTX response and help in tailoring initial therapy. Our objective was to study the role of serum myeloid-related protein (MRP) 8/14, and other inflammatory cytokines, as predictors of response to MTX among children with JIA. METHODS: We did a longitudinal follow-up study among children diagnosed with JIA at our institute. All MTX-naive children with JIA requiring DMARDs were eligible for this study; those who either took corticosteroids or DMARDs for more than 6 weeks at time of presentation were excluded. The demographic and clinical information was collected using a pretested semistructured questionnaire, and selected biomarkers were collected at baseline and again at 3 months. Response at 3 months was assessed using the American College of Rheumatology (ACR) criteria; responders were children who achieved ACR50, whereas those failing to achieve ACR30 were classified as nonresponders. Multivariate binary logistic regression was done to assess determinants of being a responder. RESULTS: We enrolled 69 children (36 boys) with JIA, of which 48 (69.5%) were responders. The baseline value of serum MRP8/14 was significantly higher in responders (median, 144.34 [interquartile range, 88.54-188.34] ng/mL) compared with the nonresponders (median, 95.34 [interquartile range, 76.54-130.28] ng/mL), p = 0.047. Being a responder was significantly associated with baseline serum MRP8/14 with adjusted odds ratio of 1.01 (95% confidence interval, 1.00-1.02). CONCLUSIONS: The baseline levels of MRP8/14 were significantly raised in children meeting ACR50 at follow-up and suggest a prognostic value in predicting response to MTX.

Comparison of statistical methods for recurrent event analysis using pediatrics asthma data.

When the same type of event is experienced by a subject more than once it is called recurrent event, which possess two important characteristics, namely "within-subject correlation" and "time-varying covariate." As a result, the traditional statistical methods do not work well on recurrent event data. Over the past few decades, many alternatives methods have been proposed for the analysis of recurrent event data. In this article, the six most prominent methods for recurrent event analysis have been compared on pediatric asthma data. Three variance corrected models (viz "Anderson and Gill [AG] model," "Prentice, William, and Peterson-Counting Process [PWP-CP] model," and "Prentice, William, and Peterson-Gap Time [PWP-GT] model") and three corresponding frailty variants (AG-frailty, PWP-CP-frailty, and PWP-GT-frailty) were compared using three mathematical criterion (AIC, BIC, and log-likelihood) and one graphical criteria (Cox-Snell goodness of fit, visual test). All model comparison indices showed the PWP-GT model as the most appropriate model on asthma data over other models. By using PWP-GT model, seven predictors of asthma exacerbation (viz "abdominal pain at previous visit," "Z5 (%) at previous visit," "diagnosis of asthma at previous visit," "calendar month of exacerbation," "history of maternal asthma," "monthly per capita income," and "emotional stress") were identified. The PWP-GT model was identified as the most appropriate model over other models on pediatrics asthma data.

Polyneuropathy in Critically Ill Mechanically Ventilated Children: Experience From a Tertiary Care Hospital in North India.

OBJECTIVES: To determine the prevalence of critical illness polyneuropathy and its risk factors in critically ill children mechanically ventilated for 7 days or more. DESIGN: Observational cohort study. SETTING: PICU of a tertiary care hospital from North India. PATIENTS: Children 1-15 years old admitted in PICU from June 2016 to September 2017, mechanically ventilated for 7 days or more, excluding those with diagnosed neuromuscular disease, stroke, or spinal pathology. INTERVENTION: Demographic details, diagnosis, treatment details, and anthropometry at admission and enrolment were recorded. Nerve conduction studies were performed after enrolment and repeated a week later, if the child was still in PICU. Medical Research Council scoring for muscle strength was performed in survivors. Risk factors including Pediatric Index of Mortality-2 score, sepsis, multiple organ dysfunction, hypoalbuminemia, use of steroids, neuromuscular-blocking agents, and vasopressors were recorded. Samples for the level of micronutrients (copper, zinc, folate, and vitamin B12) were collected at the time of enrolling the child and at the time of discharge. MEASUREMENTS AND MAIN RESULTS: Thirty-two children were enrolled, of whom 29 had features of critical illness polyneuropathy on evaluation at day 8 of mechanical ventilation (prevalence, 90.6% [95% CI, 80.5-100%]). The polyneuropathy was axonal in 26 (81.2%), mixed in one patient (3.1%), and uncharacterized in two (6.2%). Sepsis and multiple organ dysfunction were present in 31 subjects (96.9%). No risk factors for critical illness polyneuropathy could be identified although the study was not sufficiently powered to do so. The difference between serum micronutrient levels (copper, zinc, folate, and vitamin B12) between patients who developed polyneuropathy, and those who did not, was statistically insignificant. CONCLUSIONS: We observed a high prevalence of critical illness polyneuropathy in children in PICU, mechanically ventilated for 7 days or more; almost all of whom had underlying sepsis.

Prevalence and clinical outcome of respiratory viral infections among children with cancer and febrile neutropenia.

Background: The role of respiratory viruses (RV) in children with cancer having febrile neutropenic episodes has not been well studied. The objectives of our study were to investigate the prevalence and clinical outcomes of Respiratory viral infection (RVI). Methods: Children with cancer and febrile neutropenia (FN) having acute respiratory infections (ARI) were considered as cases and febrile neutropenic cancer patients without ARI were considered as controls. A throat swab sample was obtained for the detection of 21-respiratory pathogens. Results: A total of 81 episodes of FN in cases and 37 episodes of FN in controls were included. Prevalence of RVI (at least 1 RV) was seen in 76.5% of cases and 48.6% of controls (p = 0.005). The mixed-respiratory viruses (co-infections of ≥2 viruses) were seen only in cases (26%) (p = 0.00). Rhinovirus (36.8%) and respiratory syncytial virus (13.6%) were the most frequently detected viruses. Median duration of fever before presentation was more in cases with RVI compared to without RVI [2 (1-5) days vs 1 (1-5) day (p = 0.012)]. The median total duration of febrile period was 4 (IQR, 3-6) days in cases with RVI and 3 (IQR, 1-4) days in cases without RVI (p = 0.005). The median duration of antibiotic days were longer in cases with RVI as compared to patients without RVI [9 (IQR, 7-17) days vs 7 (IQR, 6-10) days (p = 0.046)] respectively. Conclusion: There was high prevalence of RVI in children with cancer and FN; more in association with ARI. The RVI were associated with prolonged febrile period and days of antibiotics therapy.

Exhaled breath condensate metabolome clusters for endotype discovery in asthma.

BACKGROUND: Asthma is a complex, heterogeneous disorder with similar presenting symptoms but with varying underlying pathologies. Exhaled breath condensate (EBC) is a relatively unexplored matrix which reflects the signatures of respiratory epithelium, but is difficult to normalize for dilution. METHODS: Here we explored whether internally normalized global NMR spectrum patterns, combined with machine learning, could be useful for diagnostics or endotype discovery. Nuclear magnetic resonance (NMR) spectroscopy of EBC was performed in 89 asthmatic subjects from a prospective cohort and 20 healthy controls. A random forest classifier was built to differentiate between asthmatics and healthy controls. Clustering of the spectra was done using k-means to identify potential endotypes. RESULTS: NMR spectra of the EBC could differentiate between asthmatics and healthy controls with 80% sensitivity and 75% specificity. Unsupervised clustering within the asthma group resulted in three clusters (n = 41,11, and 9). Cluster 1 patients had lower long-term exacerbation scores, when compared with other two clusters. Cluster 3 patients had lower blood eosinophils and higher neutrophils, when compared with other two clusters with a strong family history of asthma. CONCLUSION: Asthma clusters derived from NMR spectra of EBC show important clinical and chemical differences, suggesting this as a useful tool in asthma endotype-discovery.

Circulating genotypes of Pneumocystis jirovecii and its clinical correlation in patients from a single tertiary center in India.

The present study was carried out with the objectives of genotyping Pneumocystis jirovecii at three distinct loci, to identify the single nucleotide polymorphisms (SNPs), and to study its clinical implications in patients with Pneumocystis pneumonia (PCP). Analysis of genetic diversity in P. jirovecii from immunocompromised patients was carried out by genotyping at three distinct loci encoding mitochondrial large subunit rRNA (mtLSU rRNA), cytochrome b (CYB), and superoxide dismutase (SOD) using polymerase chain reaction (PCR) assays followed by direct DNA sequencing. Of the 300 patients enrolled in the present study, 31 (10.33%) were positive for PCP by a specific mtLSU rRNA nested PCR assay, whereas only 15 P. jirovecii could be amplified at the other two loci (SOD and CYB). These positives were further subjected to sequence typing. Important genotypic combinations between four SNPs (mt85, SOD110, SOD215, and CYB838) and clinical outcomes could be observed in the present study, and mt85A, mt85T, and SOD110C/SOD215T were frequently associated with "negative follow-up". These SNPs were also noted to be relatively more prevalent amongst circulating genotypes in our study population. The present study is the first of its kind from the Indian subcontinent and demonstrated that potential SNPs of P. jirovecii may possibly be attributed to the clinical outcome of PCP episodes in terms of severity or fatality in different susceptible populations likely to develop PCP during their course of illness.

Juvenile systemic sclerosis: experience from a tertiary care center from India.

Juvenile systemic sclerosis (JSSc) is a rare disorder with paucity of information on its treatment and longterm  outcome. Herein, we are sharing our experience with this rare entity. Case records of children, diagnosed to have systemic sclerosis attending Pediatric Rheumatology Clinic at All India Institute of Medical Sciences, New Delhi from January 1998 to June 2016 were reviewed. The demographic, clinical, laboratory, treatment and outcome details were recorded. Disease outcome was classified arbitrarily as controlled, partly controlled or non-responsive/progressive based on: (A) ability to perform activities of daily life (ADL) and (B) presence or absence of musculoskeletal symptoms, skin changes (ulceration/progressive digital pitting/gangrene), and visceral organ involvement (dyspahgia, cardiopulmonary symptoms). Controlled: ability to perform ADL and absence of B features for at least 6 months. Partly controlled: inability to perform ADL or any of the B features. Non-responsive/progressive disease: presence of both A and any of B features. Thirty-two children (21, girls) diagnosed as systemic sclerosis for whom follow-up of more than 6 months was available were included for this retrospective analysis. Mean (SD) age at presentation was 112.79 (30.05) months, while the median (IQR) delay in diagnosis was 28.5 (9-47.25) months. Of the 32 children 17 (53.12%) had diffuse systemic sclerosis (dSSc), 5 (15.62%) had limited systemic sclerosis (lSSc) and 10 (31.25%) had sclerosis with overlap syndrome. The common clinical features apart from sclerosis/induration proximal to metacarpophalangeal joint were Raynauds phenomenon (n = 22, 68.7%), skin rash (n = 20, 62%), arthritis or arthralgia (n = 16, 50%), and muscular weakness (n = 10, 31.2%). Among those for whom data regarding investigations were available; ANA was positive in 50% (12/24), whereas Anti Scl70 was positive in one out three cases. Treatment regimen included naproxen, methotrexate, calcium channel blockers with or without steroids. HCQ was added in children with skin rash or in children with partial control. Median (IQR) follow-up period was 19.75 (12-31.75) months. With the above treatment protocol, 19 (59.3%) children achieved disease control on treatment, 8 (26.6%) had partial control while 5 (16.6%) showed no response or progressive disease. Esophageal dysmotility and intertitial lung disease (ILD) were documented in three children each. Complication (cataract and herpes zoster) related to immunosuppressive therapy were observed in two children. There was no mortality during the study period. Juvenile Sclerosis though rare is associated with significant morbidities and lacks a curative treatment but a reasonable quality of life to perform daily activities can be achieved using methotrexate and steroid-based immuosuppressive therapy.

Calcinosis in juvenile dermatomyositis mimicking cold abscess.

We report a case of dystrophic calcification presenting as soft cystic swelling in a patient with juvenile dermatomyositis. A 15-year-old boy with lumbosacral cystic swelling, which was considered a cold abscess clinically, was evaluated for nonresponse to antitubercular therapy. The cystic swelling had liquefied calcium with a well circumscribed calcified wall on imaging, which was subsequently excised.

Induction of resistant mutants of Salmonella enterica serotype Typhi under ciprofloxacin selective pressure.

BACKGROUND & OBJECTIVES: Infection with Salmonella enterica serovar Typhi (hereafter S. Typhi) is an important public health problem in India. There has been an increase in the number of reported clinical failures to ciprofloxacin treatment but the data on possible mechanism of failure are limited. One mechanism that has been widely reported and found associated with ciprofloxacin resistance, is the mutations in target genes in QRDR (quinolone resistance determining region). It is hypothesized that mutations in DNA gyrase or topoisomerase IV result in therapeutic failure under selective pressure of antibiotic while the patient is on treatment. We undertook in vitro sequential selection studies to expose the clinical isolates of S. Typhi to different concentration of ciprofloxacin to study the role of antibiotic selective pressure in the development of mutations in QRDR. METHODS: Total 26 clinical isolates were divided in to two parts: part I included six isolates obtained from three patients with relapse of enteric fever and part II included 20 isolates with different ciprofloxacin MIC levels. For in vitro induction of mutation experiment, five S. Typhi isolates were selected which included three NAS (nalidixic acid sensitive) and 2 NAR (nalidixic acid resistant) S. Typhi. These isolates were grown under increasing concentrations of ciprofloxacin and mutations acquired in QRDR of DNA gyrase (gyrA and gyrB) and topoisomerase IV (parC and parE) were investigated by sequencing. RESULTS: For the isolates included in the part I of the study, it was found that the MIC to ciprofloxacin increased in the isolates obtained during the relapse of enteric fever as compare to the first isolate. All isolates had single mutation in gyrA gene at S83 without additional mutation in the second isolate. In the second part of the study, the nine isolates with varying MICs to ciprofloxacin also had single mutation in gyrA gene at S83 and another six had triple mutations, two mutations in gyrA gene (at S83 and D87) and one mutation in parC gene (at S80). In in vitro induction of mutation experiment, all mutated isolates showed triple mutation (two mutation in gyrA and one in parC gene) while no mutations were found in wild isolates. INTERPRETATION & CONCLUSIONS: Upon exposure to the step-wise increased concentration of ciprofloxacin, isolates become more tolerant to the ciprofloxacin and showed 2-4 fold higher MICs without new mutation after 8 µg/ml. So the accumulation of mutations under continuous ciprofloxacin pressure and tolerance of the mutant isolates led to the clinical failure. These results also suggested that there could be another mechanism responsible for resistance.

Vitamin D levels in Indian children with intrathoracic tuberculosis.

BACKGROUND & OBJECTIVES: Deficiency of vitamin D, an immunomodulator agent, is associated with increased susceptibility to tuberculosis in adults, but only limited studies are available in the paediatric age group, especially regarding association of vitamin D with type and outcome of tuberculosis. We conducted this study to determine the baseline 25-hydroxy vitamin D levels in children suffering from intrathoracic tuberculosis and its association with type and outcome of tuberculosis. METHODS: Children with intrathoracic tuberculosis, diagnosed on the basis of clinico-radiological criteria, were enrolled as part of a randomized controlled trial on micronutrient supplementation in paediatric tuberculosis patients. Levels of 25-hydroxy vitamin D were measured in serum samples collected prior to starting antitubercular therapy by chemiluminescent immunoassay technology. RESULTS: Two hundred sixty six children (mean age of 106.9 ± 43.7 months; 57.1% girls) were enrolled. Chest X-ray was suggestive of primary pulmonary complex, progressive disease and pleural effusion in 81 (30.5%), 149 (56%) and 36 (13.5%) subjects, respectively. Median serum 25-hydroxy vitamin D level was 8 ng/ml (IQR 5, 12). One hundred and eighty six (69.9%) children were vitamin D deficient (serum 25-hydroxy vitamin D <12 ng/ml), 55 (20.7%) were insufficient (12 to <20 ng/ml) and 25 (9.4%) were vitamin D sufficient (≥ 20 ng/ml). Levels of 25-hydroxy vitamin D were similar in all three types of intrathoracic tuberculosis, and in microbiologically confirmed and probable cases. Levels of 25-hydroxy vitamin D did not significantly affect outcome of the disease. Children who were deficient or insufficient were less likely to convert (become smear/culture negative) at two months as compared to those who were 25-hydroxy vitamin D sufficient ( p <0.05). INTERPRETATION & CONCLUSIONS: Majority of Indian children with newly diagnosed intrathoracic tuberculosis were deficient in vitamin D. Type of disease or outcome was not affected by 25-hydroxy vitamin D levels in these children. However, children who did not demonstrate sputum conversion after intensive phase of antitubercular therapy had lower baseline 25-hydroxy vitamin D levels as compared to those who did.