The Great Masquerade: Varying Manifestations of Lysinuric Protein Intolerance.

Lysinuric protein intolerance (LPI) is an inborn metabolic error caused by cationic amino acid transport defects. The disease has a significant degree of phenotypic variation, with no confirmed genotype-phenotype correlation. Because it presents with symptoms similar to far more common diseases, the diagnosis is often missed, resulting in increased morbidity and mortality. This case series describes three examples of LPI with pulmonary, neurological, and immunological manifestations, emphasising the importance of keeping this disorder on the differential list. Appropriate metabolic and genetic testing is important in providing the correct diagnosis and timely care in such cases.

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.

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.

Tuberculosis Preventive Treatment.

Some individuals exposed to Mycobacterium tuberculosis develop a latent infection and remain at a lifelong risk of developing tuberculosis (TB) disease, a state called as TB infection (TBI). TB preventive treatment (TPT) aims to treat TBI and prevent progression to active TB in an exposed or infected person. Currently, it is not possible to confirm TBI microbiologically, but can be identified indirectly by means of immune-based tests [Tuberculin skin test (TST), interferon-gamma release assays (IGRAs)]. It is crucial to rule out active TB before initiating TPT. TPT regimens have evolved with time. The most widely used regimen is 6 mo of daily Isoniazid (INH) (6H). Another regime in pipeline for persons >2 y, but not yet widely available, is 3HP (3 mo of weekly Isoniazid and Rifapentine). TPT to contacts of drug resistant TB (DR-TB) patients needs to be tailored depending on the resistance pattern in the index case, and relies on a bacteriological confirmation of the same. Individuals receiving TPT should be closely monitored for emergence of any signs or symptoms suggestive of active TB disease while on TPT.

Comparison of Protocol-Based Continuous and Intermittent Tube Feeding in Mechanically Ventilated Critically Ill Children - An Open Label Randomized Controlled Trial.

OBJECTIVES: To compare the time taken to reach the target calories and proteins by protocol based "continuous tube feeding (CTF)" and "intermittent tube feeding (ITF)" in critically ill children. METHODS: This trial was conducted in the Pediatric Intensive Care Unit (PICU) of a tertiary care institute. Eligible children were randomized to receive CTF or ITF. Target calories were defined as 70% of calorie amount as per the WHO formula and target protein was defined as 1.5 g/kg as per the American Society of Parenteral and Enteral Nutrition (ASPEN) criteria. The primary outcome was time taken to reach target calories, the secondary outcomes were time taken to reach target protein, incidence of feed intolerance, PICU mortality, duration of ventilation, and outcome on 28th day. RESULTS: Fifty-eight children were randomized; 29 in each group. The baseline characters were comparable. The median (IQR) times for reaching target calories were 1.7 (1.4, 2.5) d and 1.8 (1.4, 4.4) d in the CTF and ITF groups, respectively [Hazards ratio (HR) 0.89 (95% CI 0.5, 1.5); p = 0.69]. For the target protein intake, the median times were comparable in the 2 groups [HR 0.82 (95% CI 0.4-1.5); p = 0.55]. The other outcomes were not significantly different between the groups. CONCLUSIONS: The authors did not observe any difference in the time taken to reach target calories and protein between the two different modes of delivery of enteral nutrition.

Short-term exposure to air pollution and emergency room visits for acute respiratory symptoms among adults.

OBJECTIVE: To examine the short-term effect of ambient air pollution on daily acute respiratory emergency room visits among adults.METHODS: A time-series study (June 2017-February 2019) was carried out among adults (≥18 years) visiting a multi-specialty hospital in Delhi. We evaluated the association between the daily levels of particulate matter (PM) <2.5 µm in diameter (PM2.5) and PM <10 µm in diameter (PM10), ozone (O3), nitrogen dioxide (NO2), carbon monoxide (CO) and sulphur dioxide and daily count of emergency room (ER) visits for acute respiratory symptoms. Generalised additive model (GAM) was used with the Poisson link function to analyse the associations for 0-1 to 0-7 lag days.RESULTS: A total of 69,400 ER visits were recorded, of which 2,669 were by adults due to acute respiratory symptoms. At 0-7 lag days, an increment of 1 standard deviation in NO2 and PM2.5 concentration was associated with a percentage increase in acute respiratory ER visits of respectively 53.0% (95% CI 30.84-78.97) and 19.5% (95% CI 4.53-36.65). During 0-7 lag days, a positive trend was observed at higher concentrations of CO (>1.86-3.28 mg/m³), while a negative significant association was observed at low concentrations of CO (<1.171 mg/m³).CONCLUSION: Short-term exposure to ambient NO2 and PM2.5 was associated with acute respiratory emergency visits of adults at lag 0-7 days.

Clinical standards for drug-susceptible TB in children and adolescents.

BACKGROUND: These clinical standards aim to provide guidance for diagnosis, treatment, and management of drug-susceptible TB in children and adolescents.METHODS: Fifty-two global experts in paediatric TB participated in a Delphi consensus process. After eight rounds of revisions, 51/52 (98%) participants endorsed the final document.RESULTS: Eight standards were identified: Standard 1, Age and developmental stage are critical considerations in the assessment and management of TB; Standard 2, Children and adolescents with symptoms and signs of TB disease should undergo prompt evaluation, and diagnosis and treatment initiation should not depend on microbiological confirmation; Standard 3, Treatment initiation is particularly urgent in children and adolescents with presumptive TB meningitis and disseminated (miliary) TB; Standard 4, Children and adolescents should be treated with an appropriate weight-based regimen; Standard 5, Treating TB infection (TBI) is important to prevent disease; Standard 6, Children and adolescents should receive home-based/community-based treatment support whenever possible; Standard 7, Children, adolescents, and their families should be provided age-appropriate support to optimise engagement in care and clinical outcomes; and Standard 8, Case reporting and contact tracing should be conducted for each child and adolescent.CONCLUSION: These consensus-based clinical standards, which should be adapted to local contexts, will improve the care of children and adolescents affected by TB.

Pulmonary Tuberculosis in Severely Malnourished Children Admitted to Nutrition Rehabilitation Centers: A Multicenter Study.

OBJECTIVES: To identify prevalence of pulmonary tuberculosis (TB) in severely malnourished children admitted to nutritional rehabilitation centers. METHODS: A multicenter cross-sectional study involving 41 nutrition rehabilitation centres (NRCs) across India was carried out to document prevalence of pulmonary tuberculosis in acute severe malnourished children admitted in NRCs. After training of the NRC staff to follow algorithm provided by national tuberculosis elimination program, children admitted to NRCs were screened for pulmonary tuberculosis. RESULTS: A total of 4356 children were enrolled across all the sites. Gastric aspirate for Cartridge based nucleic acid amplification test (CBNAAT), tuberculin skin test (TST) and X-ray film of chest were done in more than 99% of enrolled subjects. A total of 189 children (4.3%) had pulmonary tuberculosis. Eighty-seven (1.99%) were microbiologically confirmed by positive CBNAAT. On multivariate analysis, only significant association was with history of contact with TB patient in family. CONCLUSIONS: The present results suggest that a significant proportion (>4%) of children admitted in NRCs suffer from pulmonary tuberculosis. It is feasible to improve diagnosis of tuberculosis as a whole and microbiologically confirmed TB.

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.

Respiratory Syncytial Virus Infection: An Update.

Respiratory syncytial virus (RSV) is a highly contagious respiratory virus that can cause mild to severe illness in children. It is the leading cause of lower respiratory tract infections (LRTI) in children under the age of one year, and it can also affect older children and adults, especially those with underlying medical conditions. In the post-COVID period, there seems to be an increase in the incidence, possibly due to 'immunity debt'. Symptoms of RSV infection in children may include fever, runny nose, and cough. In severe cases, it can lead to bronchiolitis (inflammation of the small airways in the lungs) or pneumonia (infection of the lungs). Most children with RSV infection recover within a week or two, but some may require hospitalization, especially those who are premature or have underlying medical conditions. As there is no specific treatment for RSV infection, supportive care is the mainstay of management. In severe cases, oxygen therapy or mechanical ventilation may be necessary. High flow nasal cannula seems to be beneficial. There have been promising advances in development of RSV vaccines; few trials in adults and pregnant women have reported encouraging results. The US FDA has approved two RSV vaccines for use in older adults (GSK's Arexvy and Pfizer's ABRYSVO).

Pediatric Pulmonology Training in India: Current Status and Future Directions.

Respiratory illnesses are common causes of morbidity and mortality in children. Postgraduates in Pediatrics spent significant time in learning to manage respiratory disorders. Improved survival of preterm neonates, improved diagnosis and survival of chronic respiratory problems, and advances in diagnosis and therapeutics have increased the need for specialists trained in managing these patients. Training programs in Pediatric Pulmonology are evolving over the past few decades. In India, super-specialty training in Pediatric Pulmonology has grown over the past few years. There is a need to modify the training structure used in industrialized countries due to differences in patient population, priorities, and limited available resources and expertise. Formal training courses have been started in a limited number of institutions. There is a large gap between the need for a trained workforce and the available specialists in the limited number of institutions. The Indian Academy of Pediatrics National Respiratory Chapter (IAPNRC) has initiated a fellowship program to bridge the gap. Comprehensive training involving academic and hands-on training may go a long way to improve the care of children with acute and chronic respiratory problems. For sustainable development of the super specialty, there is a need to work towards creating Pediatric Pulmonology service departments in various institutions that may be responsible for comprehensive training and research activities to answer common research questions.

Survival of Persons Living With HIV/AIDS: A Multicentric Study From India.

BACKGROUND: It has been more than 17 years since the introduction of free ART in India. At this point, it would be prudent to look at the factors associated with the survival of persons living with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) (PLHA) who are already enrolled in the ART program. METHODS: PLHAs enrolled from antiretroviral therapy (ART) centers located in three different cities in India - Delhi, Pune and Kolkata, and were followed up at six monthly intervals monitoring the WHO stage, CD4 counts, complete blood counts, and liver and kidney function tests, for a duration of three years. RESULTS AND DISCUSSION: The incidence of mortality among HIV/AIDS patients on ART was 5.0 per 1000 patient-years (21/1410, 1.4%). Age at initiation of ART, being above 35 years, was the only significant predictor of mortality (log-rank p = 0.018). Multivariable analysis showed a significant association of an unfavourable outcome (defined as mortality or development of opportunistic infection during follow-up) with male gender (adjusted odds ratio (AOR) = 5.26, p = <0.01) and being unmarried at ART initiation (AOR = 1.39, p = 0.005). CONCLUSION: The survival of PLHA with good adherence to ART is independent of the WHO stage or CD4 counts at the initiation of ART. Initiation of ART after 35 years of age was a significant predictor of mortality.

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.

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.

Monkeypox: A Review.

Monkeypox is caused by a pox virus closely related to smallpox virus and spreads from animals to humans, and humans to humans following close contact. Prior smallpox vaccination gives partial protection against monkeypox. The steady increase in monkeypox cases in Africa over the past few decades were ignored by the global scientific community till this year, when more than 16,000 cases have been reported from nonendemic countries. Monkeypox has recently been labelled as a public health emergency of international concern by the WHO. While most of the current cases are in men who have sex with men, there is the larger threat of the disease spilling into the general population. The disease is characterized by a short febrile illness with lymphadenopathy followed by a rash which spreads centrifugally and passes through phases of macules, papules, vesicles, and pustules. Recovery occurs in most patients within 2-4 wk. Complications are more likely in children, pregnant women, and the immunocompromised. Specific diagnosis is by detection of viral DNA by PCR. Treatment is largely symptomatic. Tecorivimat is a promising antiviral drug. Vaccination with the currently available smallpox vaccines is recommended for high-risk groups, health care workers, and close contacts. Control of the monkeypox outbreak needs a multipronged effort comprising enhanced surveillance, quick diagnosis, isolation of affected people, ring immunization, and adoption of "one health" approach.

Mycoplasma pneumoniae among Hospitalized Patients with Acute Respiratory Tract Infections in an Indian Tertiary Care Hospital: an Underreported Health Problem.

The epidemiology of Mycoplasma pneumoniae (Mp) is poorly understood in India. The present study was conducted to identify the prevalence of Mp in a large set of patients with acute respiratory tract infections (ARI) in an Indian tertiary hospital. During 2015-2020, we tested throat swab specimens from patients with the clinical diagnosis of ARI (n = 1,098) by a real-time PCR and compared the demographic, clinical, laboratory, and outcome data of Mp-positive and Mp-negative patients. During the study period, 5% (55/1,098) of the tested samples were positive for Mp by PCR. School-aged children and young adults represented 36% (20/55) of the cases and 47.3% (26/55) of the cases were registered during the summer and monsoon. Among the Mp-positive patients, 61.8% (34/55) had underlying conditions; the most common were malignancy (n = 12; 21.8%) and hypertension (n = 6; 10.9%). Fever (98.2% versus 84.9%; P = 0.006), and pharyngitis (27.3% versus 16.3%; P = 0.034) were significantly common in the Mp-positive group than Mp-negative group. Among the Mp-positive group, 20% (11/55) of patients were admitted to an intensive care unit and a total of 7/55 (12.7%) patients received ventilatory support. The mortality in the Mp-positive cohort was 13.3%. The study provides baseline data regarding Mp prevalence and clinical characteristics. The application of molecular assays for diagnosing this pathogen among hospitalized patients with ARI could reduce inappropriate empirical antibiotic treatment and improve patient outcomes. Further large-scale studies are required to avoid the underdiagnosis of Mp infections in India and such studies should address some research gaps, such as macrolide resistance and molecular typing. IMPORTANCE M. pneumoniae (Mp) is a significant pathogen causing atypical pneumonia but by far these infections are underreported clinical entities in India. In the present study, we report the prevalence of Mp and describe the demographic and baseline clinical data of Mp-positive cases in an Indian tertiary care hospital. Our study may improve the clinician's awareness of this important agent of respiratory infection therefore timely and accurate diagnostic tools can be applied for patient management decisions and outcomes.

Initial Immunomodulation and Outcome of Children with Multisystem Inflammatory Syndrome Related to COVID-19: A Multisite Study from India.

OBJECTIVE: To determine the outcomes in children with MIS-C receiving different immunomodulatory treatment. METHODS: In this multicentric, retrospective cohort study, data regarding treatment and outcomes of children meeting the WHO case definition for MIS-C, were collected. The primary composite outcome was the requirement of vasoactive/inotropic support on day 2 or beyond or need of mechanical ventilation on day 2 or beyond after initiation of immunomodulatory treatment or death during hospitalization in the treatment groups. Logistic regression and propensity score matching analyses were used to compare the outcomes in different treatment arms based on the initial immunomodulation, i.e., IVIG alone, IVIG plus steroids, and steroids alone. RESULTS: The data of 368 children (diagnosed between April 2020 and June 2021) meeting the WHO case definition for MIS-C, were analyzed. Of the 368 subjects, 28 received IVIG alone, 82 received steroids alone, 237 received IVIG and steroids, and 21 did not receive any immunomodulation. One hundred fifty-six (42.39%) children had the primary outcome. On logistic regression analysis, the treatment group was not associated with the primary outcome; only the children with shock at diagnosis had higher odds for the occurrence of the outcome [OR (95% CI): 11.4 (5.19-25.0), p < 0.001]. On propensity score matching analysis, the primary outcome was comparable in steroid (n = 45), and IVIG plus steroid (n = 84) groups (p = 0.515). CONCLUSION: While no significant difference was observed in the frequency of occurrence of the primary outcome in different treatment groups, data from adequately powered RCTs are required for definitive recommendations.