Biofilm Producing Methicillin-Resistant Staphylococcus aureus (MRSA) Infections in Humans: Clinical Implications and Management.

Since its initial description in the 1960s, methicillin-resistant Staphylococcus aureus (MRSA) has developed multiple mechanisms for antimicrobial resistance and evading the immune system, including biofilm production. MRSA is now a widespread pathogen, causing a spectrum of infections ranging from superficial skin issues to severe conditions like osteoarticular infections and endocarditis, leading to high morbidity and mortality. Biofilm production is a key aspect of MRSA's ability to invade, spread, and resist antimicrobial treatments. Environmental factors, such as suboptimal antibiotics, pH, temperature, and tissue oxygen levels, enhance biofilm formation. Biofilms are intricate bacterial structures with dense organisms embedded in polysaccharides, promoting their resilience. The process involves stages of attachment, expansion, maturation, and eventually disassembly or dispersion. MRSA's biofilm formation has a complex molecular foundation, involving genes like icaADBC, fnbA, fnbB, clfA, clfB, atl, agr, sarA, sarZ, sigB, sarX, psm, icaR, and srtA. Recognizing pivotal genes for biofilm formation has led to potential therapeutic strategies targeting elemental and enzymatic properties to combat MRSA biofilms. This review provides a practical approach for healthcare practitioners, addressing biofilm pathogenesis, disease spectrum, and management guidelines, including advances in treatment. Effective management involves appropriate antimicrobial therapy, surgical interventions, foreign body removal, and robust infection control practices to curtail spread within healthcare environments.

Turning the Gaze from Survive to Thrive for Children in India: Learnings from Two Case Studies.

Despite significant efforts and progress made in newborn care programs in India, implementation gaps persist across the continuum of care. The present case studies of two districts in Himachal Pradesh revealed that pathways of care were often fragmented with inconsistent linkages between facility and community due to poor documentation, lack of tiered referral, health system weaknesses, low utilization of primary level institutions, and inadequate post-natal home visits by Accredited Social Health Activists (ASHAs). Involvement of healthcare providers (HCPs) and frontline health workers (FHWs) was low and uneven in generating awareness across the districts with limited participation in supporting care in the community. Ensuring functionality of health centers and first-level care facilities; strengthening referral systems; adequate/trained human resources; strengthening routine health management systems, discharge processes and community-based care with adequate integration with facilities are necessary in closing access gaps.

Diagnostic accuracy of urine based lipoarabinomannan point of care tuberculosis diagnostic test in HIV negative children: a systematic review and meta-analysis.

Tuberculosis is predicted to be a major undocumented cause of mortality in children. This systematic review with meta-analysis assessed the diagnostic accuracy of Lipoarabinomannan antigen testing (FujiLAM) in urine in HIV-negative children with TB-like signs and symptoms. PubMed, EMBASE, Scopus, Cochrane database and Google Scholar search engine were searched to identify relevant studies from earliest records to June 2022 without any language restriction. Three studies were finalized, patients were recruited from Africa and Haiti. Among microbiologically confirmed pediatric TB patients, pooled sensitivity and specificity of FujiLAM (with 95% CI) was 52% (35%-69%) and 90% (85%-93%) respectively. In both clinical (unconfirmed) and microbiological confirmed TB cases, sensitivity reduced to 24% (16%-34%) while specificity was 91%(80%-97%). We concluded that due to ease in obtaining urine sample, FujiLAM can be used as point-of-care TB test in HIV negative children, however more data from different population is needed.

Is perinatal asphyxia associated with an increase in serum bilirubin in neonates? A case-control study.

Objective: Perinatal asphyxia affects different organs of body depending upon the severity of hypoxemia and ischemia. This study was carried out to evaluate severity of hyperbilirubinemia in relation to severity of asphyxia. Study Design: A case-control study. Methodology: Asphyxiated newborns with Apgar score ≤7 at 1 min. and categorized as severe birth asphyxia according to the WHO classification of diseases (ICD10) were matched with controls without birth asphyxia. All babies were examined twice daily for dermal icterus until start of phototherapy. Babies with congenital heart disease, sepsis, cephalohematoma, blood group incompatibility were excluded. Arterial blood gas analysis was done along with serial TSB measurement as per standard guidelines. Results: 50 cases and 50 matched controls were enrolled. The average birth weight and gestation in cases was 2427 ± 30.05 g and 35.9 ± 2.5 weeks and among control it was 2633 ± 378.62 g and 37.76 ± 0.116 weeks. Among cases, onset of jaundice was 56.64 ± 20.43 h compared to 63.36 ± 23 h in control group. In the cases, the average pH was 7.31 ± 0.06, CO2 was 41.52 ± 84, O2 was 94.98 ± 14.83, and HCO3 was 18.56 ± 2.04. The rise and peak of serum bilirubin differed between the case and control groups; in the cases, the peak occurred at the 22nd h of life, then plateaued from the 40th to the 78th hour of life, and ultimately fell at the 96th hour of life. In comparison, the rise and peak of serum bilirubin occurred comparatively late in the control group. The rise and peak in the control group occurred at the 80th and 96th h of life, respectively. The multiple linear regression analysis showed CRP, Apgar at 5 min. below 7 and male gender significantly affects the rise of serum bilirubin (P < 0.05). Conclusion: The peak serum bilirubin in asphyxiated newborns occurs earlier, and plateau for longer duration compared to normal newborns. Low Apgar at 5 min. has significant correlation to earlier rise of bilirubin.

Smart and connected devices in point-of-care molecular diagnostics: what role can they play in the response to COVID-19?

INTRODUCTION: Coronavirus disease-2019 (COVID-19) has been a huge public health challenge that has led to significant morbidity and mortality across the globe. Given the high prevalence and continued circulation of SARS-CoV-2 infection globally, accurate and rapid point-of-care testing is critical. AREAS COVERED: Knowledge of role of digital technology including smart and connected devices in rapid diagnosis of COVID-19 is an evolving area of scientific investigation. This review discusses the importance of rapid at-home point-of-care testing, highlighting the possible role of smart and connected device-based molecular diagnostics for COVID-19. EXPERT OPINION: Accurate and rapid diagnostic modalities have the potential to improve accessibility and efficiency of diagnosis of symptomatic and asymptomatic patients and could be instrumental in timely implementation of appropriate therapeutic interventions as well as public health measures to mitigate spread of infection. With emerging challenges like newer viral variants, global vaccine shortages and vaccine hesitancy, accurate diagnostic testing with the ability to rapidly identify infection remains critical. Digital technologies are likely to become important tools in future of healthcare and technological advancements may play a crucial role in response to COVID-19 with the goal of ultimately overcoming this pandemic.

Burden of disease and survival rate amongst hospitalized newborns in Himalayan region in North India.

Objective: To describe the patient population, priority diseases, and outcomes in neonates admitted to neonatal unit in the Himalayan region of North India. Study Design: The retrospective study was conducted at a University teaching hospital in Himachal Pradesh, and captured anonymized data on all admissions in newborn unit over 6-year period. Results: Total 12449 newborns were admitted, 4669 were outborn, M:F of 1.35:1 and 81% of them were discharged successfully. Overall admissions surged by 76 percent in six years, preterm admissions increased by 41%. During the same period delivery load grew by 24.7%. Majority 64.9% were full-term; 50.4% (6279/12449) of neonates were low birthweight (LBW; <2.5 kg) and 3.8% were Extreme LBW (ELBW; <1.0 kg). Among intramural, out of 20.2% preterm, 1.8% were <28 week; compared to 1.5% <28 week and 14.1% preterm in extramural. The intrauterine growth restriction rate was 17.6% for intramural and 19.3% for extramural, respectively. The most common morbidities were prematurity (40.2% & 27%), jaundice (32.6% & 27.5%), RDS and respiratory problems (19.2% & 9.8%), sepsis (11.3% & 23.5%), and perinatal asphyxia (6.2% and 7.5%) among inborn and outborn respectively. Total 798 (6.4%) newborns died, 10.5% of all deaths happened within 24 hours; mortality was very high amongst ELBW (110/205, 53.7%) and very preterm infants <28 weeks (81/135,60%). Only 993 inborn and 18 outborn received antenatal corticosteroids, with only 383 inborn and 4 outborn receiving four doses of Dexamethasone. Low gestational age, LBW, less of antenatal corticosteroids, outborns, male sex, and congenital deformity were all found to have a significant association with death (P < 0.001). Conclusion: Preterm accounts for a considerable majority of our total admissions. Greater efforts and investment in better prenatal care, infrastructure, therapeutic facilities, manpower, and periodic training and review of staff nurses are all urgently needed to address the extremely high burden of illnesses and mortality among hospitalized newborns; otherwise, lowering the NMR will remain an unattainable goal.

Pediatric Scrub Typhus Manifesting with Multisystem Inflammatory Syndrome: A New Cause for Confusion or Concern-A Case Series.

The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has discovered a new disease called multisystem inflammatory syndrome in children (MIS-C). In developing nations, pediatricians must be mindful of the similarities between MIS-C and other tropical fevers such as scrub typhus. Not only should such patients be kept on high alert to rule out tropical diseases and receive appropriate treatment, such as steroids or immunomodulatory medications, but this is also concerning because, if rickettsial or bacterial infection is not detected through cultures and serology, steroid, or immunomodulatory treatment alone can be fatal. How to cite this article: Bhardwaj P, Sood M, Singh R. Pediatric Scrub Typhus Manifesting with Multisystem Inflammatory Syndrome: A New Cause for Confusion or Concern-A Case Series. Indian J Crit Care Med 2022;26(6):723-727.

Growth Faltering Among Discharged Babies from Inpatient Newborn Care Facilities: Learnings from Two Districts of Himachal Pradesh.

OBJECTIVE: To determine the burden of early growth faltering and understand the care practices for small and sick babies discharged from newborn units in the district. STUDY DESIGN: Observational and follow-up study. PARTICIPANTS: 512 babies discharged from two Special Newborn Care Units (SNCUs) and four Newborn Stabilization Units (NBSUs) in two districts of Himachal Pradesh. METHODS: Anthropometric assessments, interview of mothers and Accredited Social Health Activists (ASHAs) conducted between August, 2018 and March, 2019. Change in weight-for-age z-score (DWAZ) of <-0.67SD between birth and assessment was used to define growth faltering. OUTCOMES: Proportion of growth faltering (or catch-down growth) in small and sick babies discharged from SNCUs and NBSUs, and infant care practices. RESULTS: Growth faltering was observed in a significant proportion of both term (30%) and preterm (52.6%) babies between 1 to 4 months of age. Among babies with growth faltering (n=180), 73.9% received a home visit by ASHA, and only 36.7% received a follow-up visit at a facility. There were 71.3% mothers counselled at discharge (mostly informed about breast feeding). Most (96.7%) mothers did not perceive inadequate weight gain in their babies post-discharge. During home visits, ASHAs weighed 61.6% of the infants with growth faltering. Amongst infants who had growth faltering, only 49.6% of mothers had been provided information about their infant's growth and 57.1% mothers had received breastfeeding counselling. CONCLUSION: Small and sick newborn infants (both term and preterm babies) discharged from special care newborn units are at increased risk of early growth faltering. Follow-up care provided to these infants is inadequate. There is a need to strengthen both facility-based and home-based follow up of small and sick newborn infants discharged from newborn care facilities.

Effect of a quality improvement package on reducing newborn mortality from 26 to 14 in a Himalayan North Indian State.

Background: In India, newborn mortality remains high due to a number of factors, including poor quality of care at health facilities. The experience of executing complete neonatal care quality improvement (QI) package at selected hospitals in Himachal Pradesh and reduction in newborn mortality rate (NMR) is described in this study. Objective: The short-term objective was the participants' retention of knowledge and skills, and the achievement of uniform QI objectives following training and after a minimum of 6 months. Overall reduction in NMR was long-term objective. Methods: Newborn care QI package was implemented according to India Newborn Action Plan over a period of 48 months from 2013 to 2016, through infrastructure, trainings, and supportive supervision. Results: Total 13 health facilities were upgraded; 350 staff nurses and medical officers were trained. The mean posttraining knowledge score was 75% compared to 29% in the pretraining test, and 63% 1 year later. The competencies of health workers in the care of high-risk babies and 12 QI targets had improved, resulting in a 46% reduction in neonatal mortality in the state across all gestations and weights based on sample registration survey. Conclusion: Implementation of a bundle of evidence-based practices in low-resource setting for health system strengthening for intrapartum and neonatal care was linked to changed care behaviors among health-care providers, and reduction in NMR.

"Authors' Reply: Emerging Evidence on Multisystem Inflammatory Syndrome in Children Associated with SARS-CoV-2 Infection".

With increased patients of severe acute respiratory syndrome coronavirus 2 infection, more children with multisystem inflammatory syndrome (MIS-C) are being reported worldwide. Our focus is to share the new evidence-based findings and experiences during the early stage of the pandemic with the researchers on a larger platform . We hope this review will help to frame appropriate strategies and guidelines for management of MIS-C.

Emerging Evidence on Multisystem Inflammatory Syndrome in Children Associated with SARS-CoV-2 Infection: a Systematic Review with Meta-analysis.

With the increased spread of severe acute respiratory syndrome coronavirus 2 infection, more patients with multisystem inflammatory syndrome in children (MIS-C) are being reported worldwide. This systematic review with meta-analysis aims to analyse the clinical features, proposed pathogenesis and current treatment options for effective management of children with this novel entity. Electronic databases (Medline, Google Scholar, WHO, CDC, UK National Health Service, LitCovid, and other databases with unpublished pre-prints) were extensively searched, and all articles on MIS-C published from January 1, 2020, to October 10, 2020, were retrieved. English language studies were included. This systematic review analysed 17 studies with 992 MIS-C patients from low-income and middle-income countries (LMICs) and developed countries (France, the UK, Italy, Spain, Chile and the US CDC data). Fever (95%) was the most common clinical manifestation followed by gastrointestinal (78%), cardiovascular (75.5%), and respiratory system (55.3%) involvement. Laboratory or epidemiologic evidence of inflammation and SARS-CoV-2 infection was present. Though the exact pathogenesis remains elusive, virus-induced post-infective immune dysregulation appears to play a predominant role. Features resembling Kawasaki disease, toxic shock syndrome or macrophage activation syndrome were present; 49% had shock; 32% had myocarditis; 18% had coronary vessel abnormalities and 9% had congestive cardiac failure. Sixty-three percent of the patients were admitted in paediatric intensive care unit (PICU); 63% received intravenous immunoglobulin, 58% received corticosteroids and 19% received alternate agents like tocilizumab; there were 22 (2.2%) deaths. Only 9/144 children in LMICs received tocilizumab that was significantly less than children in developed countries (p < 0.0001). This systematic review delineates and summarises recently published data on MIS-C from LMICs and developed countries. Although most needed PICU admission and received treatment with IVIG and steroids, most of the patients survived. Significantly fewer patients in developing countries received tocilizumab therapy than those in developed countries. It is crucial for clinician to recognise MIS-C, to differentiate it from other defined inflammatory conditions and initiate early treatment. Further studies are needed for long-term prognosis, especially relating to cardiac complications of MIS-C. Supplementary Information: The online version of this article (10.1007/s42399-020-00690-6) contains supplementary material, which is available to authorized users.

Management of possible serious bacterial infection in young infants closer to home when referral is not feasible: Lessons from implementation research in Himachal Pradesh, India.

BACKGROUND: Government of India and the World Health Organization have guidelines for outpatient management of young infants 0-59 days with signs of Possible Serious Bacterial Infection (PSBI), when referral is not feasible. Implementation research was conducted to identify facilitators and barriers to operationalizing these guidelines. METHODS: Himachal Pradesh government implemented the guidelines in program settings supported by Centre for Health Research and Development, Society for Applied Studies. The strategy included community sensitization, skill enhancement of Accredited Social Health Activists (ASHA), Auxiliary Nurse Midwives (ANMs) and Medical Officers (MOs) to identify PSBI and treat when referral was not feasible. The research team collected information on facilitators and barriers. A technical support unit provided training and oversight. FINDINGS: Among 1997 live births from June 2017 to January 2019, we identified 160 cases of PSBI in young infants resulting in a coverage of 80%, assuming an incidence of 10%. Of these,29(18.1%) had signs of critical illness (CI), 92 (57.5%) had clinical severe infection (CSI), 5 (3.1%)had severe pneumonia (only fast breathing in young infants 0-6 days), while 34 (21%) had pneumonia (only fast breathing in young infants 7-59 days). Hospital referral was accepted by 48/160 (30%), whereas 112/160 (70%) were treated with the simplified treatment regimens at primary level facilities. Of the 29 infants with CI, 18 (62%) accepted referral; 26 (90%) recovered while 3 (10%) who had accepted referral, died. Of the 92 infants who had CSI, 86 (93%) recovered, 65 (71%) received simplified treatment and one infant who had accepted referral, died. All the five infants who had severe pneumonia, recovered; 3 (60%) had received simplified treatment. Of the 34 pneumonia cases, 33 received simplified treatment of which 5 (15%) failed treatment; two out of these 5 died. Overall, 6/160 infants died (case-fatality-rate 3.4%); 2 in the simplified treatment (case-fatality-rate 1.8%) and 4 in the hospital group (case-fatality-rate 8.3%). Delayed identification and care-seeking by families and health system weaknesses like manpower gaps and interrupted supplies were challenges in implementation. CONCLUSIONS: Implementation of the guidelines in program settings is possible and acceptable. Scaling up would require creating community awareness, early identification and appropriate care-seeking, strengthening ASHA home-visitation program, building skills and confidence of MOs and ANMs, uninterrupted supplies and a dependable referral system.

A Systematic Review of Multisystem Inflammatory Syndrome in Children Associated With SARS-CoV-2 Infection.

BACKGROUND: Recently, severe manifestations associated with coronavirus disease 2019 (COVID-19) called multisystem inflammatory syndrome in children (MIS-C) have been recognized. Analysis of studies for this novel syndrome is needed for a better understanding of effective management among affected children. METHODS: An extensive search strategy was conducted by combining the terms multisystem inflammatory syndrome in children and coronavirus infection or using the term multisystem inflammatory syndrome in children in bibliographic electronic databases (PubMed, EMBASE, and CINAHL) and in preprint servers (BioRxiv.org and MedRxiv.org) following the Preferred Reporting Items for Systematic Reviews and Metaanalyses guidelines to retrieve all articles published from January 1, 2020, to July 31, 2020. Observational cross-sectional, cohort, case series, and case reports were included. RESULTS: A total of 328 articles were identified. Sixteen studies with 655 participants (3 months-20 years of age) were included in the final analysis. Most of the children in reported studies presented with fever, gastrointestinal symptoms, and Kawasaki Disease-like symptoms. Sixty-eight percent of the patients required critical care; 40% needed inotropes; 34% received anticoagulation; and 15% required mechanical ventilation. More than two-thirds of the patients received intravenous immunoglobulin and 49% received corticosteroids. Remdesivir and convalescent plasma were the least commonly utilized therapies. Left ventricular dysfunction was reported in 32% of patients. Among patients presenting with KD-like symptoms, 23% developed coronary abnormalities and 26% had circulatory shock. The majority recovered; 11 (1.7%) children died. CONCLUSIONS: This systematic review delineates and summarizes clinical features, management, and outcomes of MIS-C associated with SARS-CoV-2 infection. Although most children required intensive care and immunomodulatory therapies, favorable outcomes were reported in the majority with low-mortality rates.

Documentation of vaccine wastage in two different geographic contexts under the universal immunization program in India.

BACKGROUND: Government of India is introducing new and relatively costly vaccines under immunization program. Monitoring of vaccine wastage is needed to guide the program implementation and forecasting. Under pilot introduction of rotavirus vaccine in two districts both 5- and 10-doses vials were used, which was considered as an opportunity for documenting the wastage. The wastage rates for other routine vaccines were also documented. METHODS: A survey conducted in two districts (Kangra, Himachal Pradesh and Pune, Maharashtra) covered 49 vaccine stores, 34 sub-centres and 34 outreach sessions collected vaccine receipt, distribution and usage data for two complete years 2016 and 2017. RESULTS: The overall wastage rates for almost all vaccines were higher in Kangra district (BCG 37.1%, DPT 32.1%, Measles 32.2%, OPV 50.8%, TT 34.1% and pentavalent 18.4%) than Pune district (BCG 35.1%, DPT 25.4%, Measles 21.7%, OPV 14.3%, TT 23.1% and pentavalent 13.2%). Wastage for pneumococcal conjugate and measles-rubella vaccines in Kangra district were 27 and 40.5%, respectively. With transition from 5- to 10-doses vials for rotavirus vaccine, wastage at stores levels increased in both Kangra (29 to 33.2%) and Pune (17.8 to 25.7%) districts. With transition from intramuscular to intradermal fractional inactivated polio vaccine, the wastage increased from 36.1 to 54.8% in Kangra and 18.4 to 26.9% in Pune district. CONCLUSIONS: The observed vaccine wastage rates for several vaccines were relatively higher than program assumption for forecasting. The observed variations in the vaccine wastage indicates need for state or region based documentation and monitoring in India for appropriate programmatic action.

Neuromuscular adaptations with flexible fixed functional appliance--a 2-year follow-up study.

AIM: To evaluate long-term neuromuscular adaptation with the flexible fixed functional appliance. PATIENTS AND METHODS: Electromyography (EMG) was performed on 15 young, growing females with Class II Division 1 malocclusion treated with a flexible fixed functional appliance. Bilateral EMG activity from the anterior temporalis and masseter muscles was monitored longitudinally to determine changes in posture, swallowing, and maximum voluntary clenching during a 24-month observation period. RESULTS: There was a significant decrease in EMG activity during saliva swallowing (p < 0.05) and maximum clenching (p < 0.05 at 3 months and p < 0.01 at 1 month after treatment); this persisted for up to 1 month but gradually returned to pre-appliance levels near the end of 6 months. It remained stable from then on until the end of the observation period (24 months). CONCLUSION: The anterior temporalis and masseter muscles clearly responded to appliance therapy. The neuromuscular adaptation documented after 6 months of treatment remained stable over a 24-month observation period.

Teething: myths and facts.

From grandmothers to medical professionals, everyone seems to have a list of symptoms they believe are linked to teething. During this time period of an infant's life, passive immunity due to maternal antibodies wanes and exposure to a wide variety of childhood illnesses occurs. Parental false beliefs associated with teething may interfere with the prompt diagnosis and management of a range of serious illnesses. Strong parental beliefs which are not borne out by evidence will unlikely change until professionals (most of whom are also parents) change theirs. Therefore, there is a need to know the facts and the false beliefs attributed to teething. Medical professionals need to be educated about teething to provide reasonable explanations to concerned caregivers. This article examines the signs and symptoms frequently attributed to teething and their possible alternative causes. The contemporary principles of the management of teething are discussed, including supportive care.