Paradoxical Reaction to Tuberculosis Therapy among HIV-Negative Children: A Systematic Review and Meta-Analysis.

Tuberculosis treatment is sometimes associated with clinical deterioration, referred to as paradoxical reaction (PR), especially in those with HIV coinfection. However, the burden and characteristics of PR in children without HIV coinfection are unclear. We undertook a systematic review to estimate the burden and clinical characteristics of PR in HIV-negative children. We searched PubMed, Embase, Web of Science, CINAHL, Scopus, Cochrane Library, ProQuest, and OpenGrey for studies reporting PR in HIV-negative children (<18 years old). We included observational studies including case series with at least five cases. Data on incidence/prevalence, clinical features, risk factors, management strategies, and outcome of PR were extracted. Risk of bias in the included studies was assessed using the NIH's quality assessment and Joanna Briggs Institute critical appraisal tools. We pooled the prevalence data using random effects meta-analysis. We identified 1,673 studies, of which 10 were eligible for inclusion. They described PR in 133 HIV-negative children. The pooled prevalence was 8.8% (95% CI: 2.9%, 14.6%). Owing to heterogeneity among studies, risk factors for the development of PR could not be identified. Limited data suggested that children developing PR were younger and had neurological or lymph node tuberculosis more often. Most children were treated with corticosteroids, but data were insufficient to identify the optimal management strategy. The review showed that PR affects nearly 1 in 12 HIV-negative children receiving tuberculosis treatment. The paucity of studies emphasizes the need for surveillance/studies to better characterize clinical features, risk factors, appropriate management strategies, and outcome.

Multidrug-resistant tuberculosis in children: A practical update on epidemiology, diagnosis, treatment and prevention.

Pediatric multidrug-resistant tuberculosis (MDR-TB) remains a significant global problem, and there are numerous barriers preventing children with MDR-TB from being identified, confirmed with microbiologic tests, and treated with a safe, practical, and effective regimen. However, several recent advances in diagnostics and treatment regimens have the promise to improve outcomes for children with MDR-TB. We introduce this review with two cases that exemplify both the challenges in management of MDR-TB in children, but also the potential to achieve a positive outcome. More than 30,000 cases of MDR-TB per year are believed to occur in children but less than 5% are confirmed microbiologically, contributing to poorer outcomes and excess mortality. Rapid molecular-based testing that provides information on rifampin susceptibility is increasingly globally available and recommended for all children suspected of TB disease--but remains limited by challenges obtaining appropriate samples and the paucibacillary nature of most pediatric TB. More complex assays allowing better characterization of drug-resistant isolates are emerging. For children diagnosed with MDR-TB, treatment regimens have traditionally been long and utilize multiple drugs associated with significant side effects, particularly injectable agents. Several new or repurposed drugs including bedaquiline, delamanid, clofazimine and linezolid now allow most treatment regimens to be shorter and all-oral. Yet data to support short, all-oral, novel regimens for young children containing pretomanid remain insufficient at present, and there is a compelling need to conduct pediatric trials of promising therapeutics and MDR-TB treatment regimens.

Indian Tick Typhus Presenting as Gangrene: a Case Report.

Rickettsial infections are an important cause of acute febrile illness in developing countries. They can rarely present with cutaneous manifestations such as gangrene. Here we report a 12-year-old boy who presented with acute undifferentiated fever, multiorgan dysfunction, and gangrene of bilateral toes and ear lobes. The diagnosis was made by serologic testing of paired sera and clinical recovery occurred with doxycycline.

Clinical Spectrum and Microbial Etiology of Bone and Joint Infections in Children: A Retrospective Analysis from South India.

Acute infections of bone and joints are medical emergencies. Early diagnosis and treatment are essential for limb salvage and prevention of deformities. Data from developing countries are essential to develop region-specific treatment guidelines including choice of empiric antibiotics. We reviewed electronic medical records of children (≤ 12 years old) admitted to the pediatrics or orthopedics department of a tertiary care hospital in South India from 2013 to 2017 with a diagnosis of septic arthritis and/or osteomyelitis. Clinical, microbiological, and follow-up data were collected and analyzed. The median (interquartile range, IQR) age of the children (N = 207) was 48 (7.5-105) months. Acute infections were more common in infants, whereas chronic cases were common in children > 5 years of age. Staphylococcus aureus (71%) was the most common organism identified. Gram-negative organisms were more frequently isolated in infants compared with older children. Blood and/or wound culture positivity was 78% (N = 161) overall and 78% (N = 31) in chronic cases. The median (IQR) duration of antibiotics was 7 (5-8) weeks. Sequelae and readmissions occurred in 47% (N = 81) of the 172 patients followed for a year. Culture positivity rates especially of wound were high even after receiving antibiotics.

Emerging pediatric visceral leishmaniasis in Kashmir valley: A report of three cases.

Visceral leishmaniasis is the most severe form of leishmaniasis. There has been an increase in number of cases in the sub-Himalayan regions of India in the past few years. Here we present three pediatric cases diagnosed with visceral leishmaniasis from the region.

Pertussis in India: Past, Present, and Future.

While vaccines have markedly reduced the incidence of pertussis, a resurgence has occurred in many countries. Until recently, pertussis has not been recognized as an important public health challenge in India due to its successful infant immunization program. However, India still accounts for a large proportion of the world's cases, and increasing reports of pertussis in other countries and in neonates have regenerated interest in pertussis among Indian authorities. The Global Pertussis Initiative (GPI) Annual Meeting was held virtually in October 2020, in part, to gain a better understanding of the epidemiology and disease burden of pertussis and to explore opportunities to improve its prevention in India. There was a consensus that pertussis cases are being underestimated in India due to multiple factors, such as a reliance on passive surveillance and diagnostic challenges. India offers both whole-cell pertussis and acellular pertussis vaccines, but vaccine coverage is inconsistent across regions due to differences in vaccine availability, access to health care, and regional administrative challenges. This report summarizes the outcomes and considers the key clinical implications of this meeting. The GPI agreed that active surveillance of pertussis in India would be optimal and recommended several studies, including serosurveillance among women of reproductive age to assess the prevalence of recent pertussis infection and to enable policy changes that will enhance the rational use of acellular and whole-cell vaccines. It also recommended engagement with nongovernmental organizations in order to encourage pregnancy immunization in the public sector. To achieve effective control of pertussis in the future, the GPI recognizes there are opportunities to characterize the burden of pertussis in India appropriately and increase vaccination coverage in multiple age groups.

Clinical, Microbiological Profile and Treatment Outcomes of Infants with BCG Adenitis: A Retrospective Study.

BACKGROUND: Bacille Calmette-Guérin (BCG) adenitis is an uncommon complication following BCG vaccination. In rare cases, infants can develop other complications. Controversy exists regarding the diagnosis and management of these cases. Not much information is available in literature regarding their microbiological and immunological characteristics. METHODS: Electronic medical records of children presenting to the Pediatric Infectious Diseases clinic in a tertiary care hospital from January 2011-December 2020 with a diagnosis of BCG adenitis were retrospectively reviewed. Their clinical, microbiological, treatment and follow-up data were noted and analyzed. FINDINGS: During the study period, 40 infants presented with a probable diagnosis of BCG adenitis with or without disseminated BCG. Median age at symptom onset was 4(2.5-5.9) months. Nine infants had disseminated disease at presentation. Fifteen infants were suspected to have underlying immune deficiency of whom 12 had proven defects in immune function. On multivariable logistic regression analysis, presence of disseminated disease was the only factor predictive of underlying immunodeficiency. Isoniazid monoresistance was seen in seven cases (32%) of the 22 samples sent for TB cultures. CONCLUSIONS: Though BCG adenitis runs a benign course, it could rarely be the first manifestation of an underlying immune defect. There is sizable isoniazid monoresistance, hence sending tissue samples for microbiologic evaluation is necessary to guide anti-tubercular therapy.

Folate Deficiency: A Possible Association with Congenital Heart Defects.

Congenital heart defects continue to remain a major cause of serious morbidity and mortality, especially in the developing world. This study was planned to get some insight into the role of modifiable nutritional elements in structural CHD etiology. This cross-sectional, observational study was conducted at a hospital in Northern India from January 2017 to December 2017. Infants < 6 mo with structural CHD as cases and those without structural heart disease were enrolled as controls. Blood samples were collected from mother-child pairs and tested for serum folate, vitamin B12, and homocysteine. It was found that 46.7% infant-mother pairs, out of 45 in the cases group had folate deficiency, whereas in the control group, only 20% had folate deficiency, which was statistically significant (p = 0.013). Baby (0-6 mo) with congenital heart defects (CHD) and their mothers are more likely to have low folate levels compared to those not having CHD.

Clinicolaboratory Profile, Treatment, Intensive Care Needs, and Outcome of Pediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2: A Systematic Review and Meta-analysis.

This study was aimed to summarize the current data on clinicolaboratory features, treatment, intensive care needs, and outcome of pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2; PIMS-TS) or multisystem inflammatory syndrome in children (MIS-C). Articles published in PubMed, Web of Science, Scopus, Google Scholar, and novel coronavirus disease 2019 (COVID-19) research database of World Health Organization (WHO), Centers for Disease Control and Prevention (CDC) database, and Cochrane COVID-19 study register between December 1, 2019 and July 10, 2020. Observational studies involving patients <21 years with PIMS-TS or MIS-C were reported the clinicolaboratory features, treatment, intensive care needs, and outcome. The search identified 422 citations and finally 18 studies with 833 participants that were included in this study, and pooled estimate was calculated for parameters of interest utilizing random effect model. The median age was 9 (range: 8-11) years. Fever, gastrointestinal symptoms, rash, conjunctival injection, and respiratory symptoms were common clinical features. Majority (84%) had positive SARS-CoV-2 antibody test and only one-third had positive reverse transcript polymerase chain reaction (RT-PCR). The most common laboratory abnormalities noted were elevated C-reactive protein (CRP), D-dimer, procalcitonin, brain natriuretic peptide (BNP), fibrinogen, ferritin, troponin, interleukin 6 (IL-6), lymphopenia, hypoalbuminemia, and thrombocytopenia. Cardiovascular complications included shock (65%), myocardial dysfunction (61%), myocarditis (65%), and coronary artery abnormalities (39%). Three-fourths of children required admission to pediatric intensive care unit (PICU) where they received vasoactive medications (61%) and mechanical ventilation (25%). Treatment strategies used included intravenous immunoglobulin (IVIg; 82%), steroids (54%), antiplatelet drugs (64%), and anticoagulation (51%). Mortality for patients with PIMS-TS or MIS-C was low ( n = 13). In this systematic review, we highlight key clinical features, laboratory findings, therapeutic strategies, intensive care needs, and observed outcomes for patients with PIMS-TS or MIS-C. Commonly observed clinical manifestations include fever, gastrointestinal symptoms, mucocutaneous findings, cardiac dysfunction, shock, and evidence of hyperinflammation. The majority of children required PICU admission, received immunomodulatory treatment, and had good outcome with low mortality.

Infant Dengue a 10-Year Experience from a Tertiary Center in South India.

Dengue remains a major problem in the tropics. Several Asian countries have reported an increasing trend in the proportion of infants with dengue fever. However, most studies are limited to case reports or small case series from isolated outbreaks. We planned this study to look at clinico-laboratory profile, outcome, and predictors of severity in a large cohort of infants over a decade. Electronic medical records of infants admitted at a tertiary center of South India, with laboratory confirmed dengue infection between 2009 and 2019 were reviewed. Diagnosis was based on detection of NS-1 antigen and/or immunoglobulin M antibody against DENV(dengue virus) or positive DENV RNA polymerase chain reaction in infants presenting with acute febrile illness and clinical features consistent with dengue. Of 395 children with dengue admitted during study period, 99 (25%) were infants. A cyclical incidence pattern was noted, with higher cases in alternate years. Fever (99%) was most common, followed by gastrointestinal symptoms (vomiting, diarrhea-28%) and upper respiratory symptoms (cough, coryza-22%). Fifty-three infants had severe dengue, and 39 had shock. Fourteen children had multiorgan dysfunction syndrome, and 13 died. Infants with severe dengue were older than those with nonsevere disease, had lower serum albumin and greater frequency of severe thrombocytopenia, and had coagulopathy. On multivariable analysis, low serum albumin predicted development of severe dengue [P = 0.003, odds ratio 12.4 (95% confidence interval: 2.42-63.7)]. Dengue in infants may be challenging to recognize because of its undifferentiated presentation, with gastrointestinal and upper respiratory symptoms that are similar to other viral illness. Severe dengue is common in this sample, and lower serum albumin at presentation was predictive of severe disease.

Acute respiratory distress syndrome in paediatric scrub typhus.

Acute respiratory distress syndrome is a life-threatening complication of scrub typhus; we sought to describe its mortality and associated factors, namely eschar, hepatomegaly and severe thrombocytopenia, in a retrospective study in India of 65 children.

Congenital Rubella: A Salient Cause of Congenital Heart Defects in Infants.

BACKGROUND: Structural congenital heart defects (CHD) take a huge toll of congenital defects in children in India. Limited information is available regarding modifiable risk factors for its causation. This study was planned with an aim to determine the prevalence of congenital rubella infection in Indian infants with structural CHD's. METHODOLOGY: This cross-sectional, observational study was conducted at a tertiary care hospital in Northern India over 1 year period (1 July 2016 to 30 June 2017). Infants <6 months with structural CHD were enrolled after taking informed consent from their mothers. Blood samples were collected from mother-child binomials and tested for rubella IgM and IgG antibodies. RESULTS: A total of 80 infants (M : F = 56 : 24), having mean age 69.4 (±56.5) days; were enrolled. In these infants, prevalence of congenital rubella infection (either infant's IgM rubella positive or infant's IgG rubella titers higher than mother's) was 8.75% (7/80). A total of 12.5% of studied mothers were seronegative for rubella IgG antibodies. Statistically significant association was found between the occurrence of congenital rubella and cataract (p = 0.0039), splenomegaly (p = 0.007) and microcephaly (p = 0.0084) in infants having structural CHD. CONCLUSIONS: Congenital rubella syndrome still remains an important modifiable cause for structural CHD in India. Sincere efforts for rubella elimination via further strengthening current vaccination strategy would help in decreasing burden of structural CHD in India.