Perceptions regarding child care and perinatal depression during COVID-19 pandemic - A cross-sectional community-based survey from Uttar Pradesh.

Background: High levels of stress among pregnant women have been reported during the coronavirus disease 2019 (COVID-19) pandemic because of various infection-related and lockdown measures. Concerns about safe delivery, breastfeeding, and child care may increase the risk of depression in vulnerable women during the perinatal period. Aim: To study the perceptions regarding child care and prevalence of perinatal depression during the COVID-19 pandemic. Materials and Methods: A cross-sectional community-based survey was conducted among 750 lactating mothers post delivery between September 2020 and February 2021 in 51 districts of Uttar Pradesh. A convenient purposive sampling technique was used. A semi-structured questionnaire was used to collect the socio-demographic details and perceptions regarding child care during the COVID-19 pandemic. Assessment of depression symptoms was performed with the help of patient health questionnaire 9 (PHQ-9). Results: A total of 440 participants were suffering from some form of depression symptoms; the majority had mild depression. Depression was found to be higher among homemakers and young mothers (age <25 years). Depression was found in more than 40% of the respondents who felt fear of COVID infection during breast feeding and hospital stay. Similarly, more than 50% of the respondents who feared unavailability of timely health services and social ignorance had depression. More than 60% of the mothers who did not have any knowledge about safe breast-feeding and child care practices had some form of depression, and the results were statistically significant. Conclusions: Perinatal depression is highly prevalent during the ongoing pandemic. Hence, regular screening, psychoeducation, awareness regarding safe breast feeding, and child care practices are recommended.

The 2022 outbreak and the pathobiology of the coxsackie virus [hand foot and mouth disease] in India.

Outbreaks of HFMD in children aged <5 years have been reported worldwide and the major causative agents are Coxsackievirus (CV) A16, enterovirus (EV)-A71 and recently CVA6. In India, HFMD is a disease that is not commonly reported. The purpose of the study was to identify the enterovirus type(s) associated with large outbreak of Hand, foot, and mouth disease during COVID-19 pandemic in 2022. Four hundred and twenty five clinical samples from 196-suspected cases were collected from different parts of the country. This finding indicated the emergence of CVA6 in HFMD along with CVA16, soon after the gradual easing of non-pharmaceutical interventions during-pandemic COVID-19 and the relevance of continued surveillance of circulating enterovirus types in the post-COVID pandemic era.

Extent of disability among paediatric Japanese encephalitis survivors and predictors of poor outcome: a retrospective cohort study in North India.

OBJECTIVE: To determine the Japanese encephalitis (JE)-associated long-term functional and neurological outcomes, the extent of reduced social participation and predictors of poor outcomes among paediatric JE survivors. DESIGN: A retrospective cohort study. SETTING: Laboratory-confirmed JE-positive paediatric cases (<16 years of age) hospitalised at the paediatric ward of Baba Raghav Das Medical College, Gorakhpur, India, between 1 January 2017 and 31 December 2017, were followed up after 6-12 months of hospital discharge. PARTICIPANTS: 126 patients were included in the study; median age was 7.5 years (range: 1.5-15 years), and 74 (58.73%) were male. OUTCOME MEASURES: Functional outcome defined by Liverpool Outcome Score (LOS) dichotomised into poor (LOS=1-2) and good (LOS=3-5) outcome groups compared for demographic, clinical and biochemical parameters for prognostic factors of poor outcomes. Social participation of patients scaled on Child and Adolescent Scale of Participation score 2-5. RESULTS: About 94 of 126 (74.6%) children developed neurological sequelae at different levels of severity. Age-expected social participation was compromised in 90 out of 118 children. In multivariate logistic regression analysis, a combination of parameters, JE unvaccinated status (OR: 61.03, 95% CI (14.10 to 264); p<0.001), low Glasgow Coma Score (GCS) at admission (≤8) (OR: 8.6, 95% CI (1.3 to 57.1); p=0.026), malnutrition (OR: 13.56, 95% CI (2.77 to 66.46); p=0.001) and requirement of endotracheal intubation (OR: 5.43, 95% CI (1.20 to 24.44); p=0.027) statistically significantly predicted the poor outcome with 77.8% sensitivity and 94.6% specificity. The goodness-of-fit test showed that the model fit well (Hosmer-Lemeshow goodness-of-fit test) (χ 2=3.13, p=0.988), and area under the receiver operating characteristic curve was 0.950. CONCLUSION: This study estimates the burden of JE-presenting post-discharge deaths (15.4%) and disability (63.08%). Those who did not receive JE vaccine, were suffering from malnutrition, had GCS ≤8 at admission and required endotracheal intubation had poorer outcomes.

Genotypic Characterization of Orientia tsutsugamushi Isolated From Acute Encephalitis Syndrome and Acute Febrile Illness Cases in the Gorakhpur Area, Uttar Pradesh, India.

Scrub typhus infections caused by Orientiatsutsugamushi (OT), continue to remain underdiagnosed globally, due to the lack of distinctive symptoms. The elusive nature of the Acute Encephalitis Syndrome (AES) outbreak in Gorakhpur, Uttar Pradesh that claimed numerous pediatric lives was the driving force of this study which involved serological diagnosis (IgM-ELISA), isolation of OT in cell culture, confirmation by PCR, and characterization by Sanger sequencing. In total, 12 out of 36 patients were seropositive, of which 4 were positive by PCR. Upon enrichment in cell culture, additional 3 patients (including two seronegative) were detected positive by PCR. In total, three of these 7 patients were found to be infected with two strains of OT. Taken together, this study for the first time reports the occurrence of dual infections in addition to three circulating OT genotypes (Gilliam, Kato, and Karp-like) and highlights the significance of enriching OT in cell culture systems for efficient molecular detection.

Association of single nucleotide polymorphisms in the CD209, MMP9, TNFA and IFNG genes with susceptibility to Japanese encephalitis in children from North India.

Japanese encephalitis (JE), an acute encephalitis syndrome disease caused by infection with JE virus (JEV), is an important mosquito borne disease in developing countries. The clinical outcomes of JEV infection show inter individual differences. Only in a minor percent of the infected subjects, the disease progresses into acute encephalitis syndrome. Single nucleotide polymorphisms in the host immune response related genes are known to affect susceptibility to JE. In the present study, 238 JE cases and 405 healthy controls (HCs) without any known history of encephalitis were investigated for SNPs in the CD209 MX1, TLR3, MMP9, TNFA and IFNG genes which are important in the immune response against JEV by PCR based methods. The results revealed higher frequencies of heterozygous genotypes of CD209 rs4804803, MMP9 rs17576, TNFA rs1800629 and IFNG rs2430561 in JE cases compared to HCs. These SNPs were associated with JE in an over-dominant genetic model (Odds ratio with 95% CI 1.51 (1.09-2.10) for CD209 rs4804803, 1.52 (1.09-2.11) for MMP9 rs17576, and 1.55 (1.12-2.15) for IFNG rs2430561). The association of G/A genotype of TNFA rs1800629 with JE was confirmed in a larger sample size. The results suggest the association of CD209 rs4804803, MMP9 rs17576, IFNG rs2430561 and TNFA rs1800629 polymorphisms with susceptibility to JE.

Investigations of seasonal outbreaks of acute encephalitis syndrome due to Orientia tsutsugamushi in Gorakhpur region, India: A One Health case study.

Gorakhpur division consisting of Gorakhpur and neighboring districts Deoria, Kushinagar and Maharajganj in Uttar Pradesh, India, have been witnessing seasonal outbreaks of acute encephalitis syndrome (AES) among children for the last three decades. Investigations conducted during 2005 identified Japanese encephalitis (JE) virus as an aetiology of AES. With the introduction of JE vaccination and other control strategies, the incidence of JE in the region declined, however, outbreaks of acute febrile illness with neurological manifestations continued to occur. Subsequent investigations identified Orientia tsutsugamushi, as the major aetiology of AES outbreaks in the region. This review details clinical, epidemiological, animal and entomological investigations conducted for AES due to O. tsutsugamushi during 2015 and 2017 in Gorakhpur region. Surveillance of acute febrile illness among children attending peripheral health facilities identified scrub typhus as an important aetiology of febrile illness during monsoon and post-monsoon months. Population-based serosurveys indicated high endemicity of scrub typhus. Entomological studies demonstrated natural infection of O. tsutsugamushi in small animal hosts and vector mites. Children acquired this infection through recent exposure to outdoor environment, while playing, or visiting fields or defecating in open fields. A few of the children with scrub typhus progress to develop CNS manifestations. Hence, early administration of appropriate antibiotics is crucial in preventing progression of AFI due to scrub typhus to AES. The investigations conducted by the multi-disciplinary team helped understand the transmission dynamics of scrub typhus in Gorakhpur division and recommend strategies for its control.

The Outbreaks of Acute Encephalitis Syndrome in Uttar Pradesh, India (1978-2020) and Its Effective Management: A Remarkable Public Health Success Story.

INTRODUCTION: Acute encephalitis syndrome (AES) is a major public health enigma in India and the world. Uttar Pradesh (UP) is witnessing recurrent and extensive seasonal AES outbreaks since 1978. Government of India and UP state government have devised various mitigation measures to reduce AES burden and AES associated mortality, morbidity and disability in Uttar Pradesh. The aim of this study was to describe the public health measures taken in order to control seasonal outbreaks of AES in UP between 1978 and 2020. METHODS: We used literature review as a method of analysis, including the Indian government policy documents. This review utilized search engines such as PubMed, Google Scholar, Research Gate, Cochrane, Medline to retrieve articles and information using strategic keywords related to Acute Encephalitis Syndrome. Data was also collected from progress reports of government schemes and websites of Indian Council of Medical Research (ICMR), National Vector Borne Disease Control Programme (NVBDCP) and Integrated Disease Surveillance Programmes (IDSP). RESULTS: The incidence of AES cases in UP have declined from 18.2 per million population during 2005-2009 to 15 per million population during 2015-2019 [CI 12.6-20.6, P-value < 0.001] and case fatality rate (CFR) reduced from 33% during 1980-1984 to 12.6% during 2015-2019 [CI 17.4-30.98, P-value < 0.001]. AES incidence was 9 (2019) and 7 (2020) cases per million populations respectively and CFR was 5.8% (2019) and 5% (2020). This decline was likely due to active surveillance programs identifying aetiological agents and risk factors of AES cases. The identified etiologies of AES include Japanese encephalitis virus (5-20%), Enterovirus (0.1-33%), Orientia tsutsugamushi (45-60%) and other viral (0.2-4.2%), bacterial (0-5%) and Rickettsial (0.5-2%) causes. The aggressive immunization programs against Japanese encephalitis with vaccination coverage of 72.3% in UP helped in declining of JE cases in the region. The presumptive treatment of febrile cases with empirical Doxycycline and Azithromycin (EDA) caused decline in Scrub Typhus-AES cases. Decrease in incidence of vector borne diseases (Malaria, Dengue, Japanese Encephalitis and Kala Azar) i.e., 39.6/100,000 population in 2010 to 18/100,000 population in 2017 is highlighting the impact of vector control interventions. Strengthening healthcare infrastructure in BRD medical college and establishment of Encephalitis Treatment Centre (ETC) at peripheral health centres and emergency ambulance services (Dial 108) reduced the referral time and helped in early treatment and management of AES cases. The AES admissions increased at ETC centres to 60% and overall case fatality rate of AES declined to 3%. Under clean India mission and Jal Jeevan mission, proportion of population with clean drinking water increased from 74.3% in 1992 to 98.7% in 2020. The proportion of household having toilet facilities increased from 22.9% in 1992 to 67.4% in 2020. Provisions for better nutritional status under state and national nutrition mission helped in reducing the burden of stunting (52%) and wasting (53.4%) among under five children in 1992 to 38.8% (stunting) and 36.8% (wasting) in year 2018. These factors have all likely contributed to steady AES decline observed in UP. CONCLUSION: There is a recent steady decline in AES incidence and CFR since implementation of intensive AES surveillance system and JE immunization campaigns which is highlighting the success of interventions made by central and state government to control seasonal AES outbreaks in UP. Currently, AES incidence is 9 cases per million population (in year 2019) and mortality is 5.8%.

Sequelae Following Acute Encephalitis Syndrome Caused by Orientia Tsutsugamushi.

We evaluated 146 patients with acute encephalitis syndrome caused by Orientia tsutsugamushi, after median interval of 5 months of hospitalization, to estimate the proportion and spectrum of disability. Fifty-six (38.4%) had mild, whereas 19 (13%) had moderate to severe degree of disability. Most patients had impairment in the domain of cognition and behavior.

Effectiveness of Presumptive Treatment of Acute Febrile Illness With Doxycycline or Azithromycin in Preventing Acute Encephalitis Syndrome in Gorakhpur, India: A Cohort Study.

OBJECTIVE: To estimate effectiveness of presumptive doxycycline or azithromycin treatment in preventing progression of Acute Febrile Illness to Acute Encephalitis Syndrome in Gorakhpur. STUDY DESIGN: Prospective cohort study. STUDY SETTING: Primary healthcare centers and Community healthcare centers of Gorakhpur district, Uttar Pradesh. PARTICIPANTS: Children aged 1 year to less than 15 years with fever of 3 days to less than 15 days duration attending three selected peripheral health facilities in Gorakhpur during August to October, 2018. PROCEDURE: 35 medical officers in three selected Primary Healthcare Centers/Community Healthcare centers were sensitized on the treatment strategy. After sensitization, study participants were enrolled and information about prescription of doxycycline or azithromycin was collected. Participants were telephonically followed-up to know their progression status from AFI to AES. MAIN OUTCOME MEASURE: Incidence of acute encephalitis syndrome among acute failure illness patients who received presumptive doxycycline or azithromycin treatment and those who did not receive this treatment. RESULTS: Of the enrolled 930 AFI patients, 801 (86%) were prescribed doxycycline or azithromycin and 725 (78%) could be telephonically followed-up. Progression to acute encephalitis syndrome was seen in 6 of the 621 patients who received presumptive treatment, and 5 of the 104 who did not receive the treatment. The relative risk of developing acute encephalitis syndrome among acute febrile illness patients who were prescribed presumptive treatment with doxycycline or azithromycin was 0.20 (95% CI: 0.06-0.65). The effectiveness of presumptive treatment with doxycycline or azithromycin strategy was 79.9% (95% CI: 35.4-94). CONCLUSIONS: PDA treatment to children presenting with fever in peripheral health facilities of the study blocks in Gorakhpur during August-November, 2018 had good effectiveness in preventing progression of acute febrile illness to acute encephalitis syndrome.

Neonatal microbiome - a brief review.

The long-held concept of fetus being nurtured in a sterile environment has been challenged by many recent studies that have identified bacterial communities in meconium, amniotic fluid and the placenta concluding that the microbial colonization of fetal gut begins in utero and continues during the first 2 years of life. This microbial colonization of newborn's gut during prenatal, intrapartum, and postnatal period depends on multiple factors, e.g. maternal diet, stress, antibiotic exposure, mode of delivery, type of feeding (human milk versus formula), etc., and imparts a critical role in the development of gastrointestinal, immunological, and neural systems in newborns. This article briefly reviews the current state of knowledge of microbiome in the maternal fetal unit and its impact on subsequent neonatal health and diseases.

Association of single nucleotide polymorphisms in TNFA and CCR5 genes with Japanese Encephalitis: A study from an endemic region of North India.

TNFA, IL1B, HMGB1, IL10, CXCL8, CCL2 and CCR5 gene polymorphisms were investigated in 183 Japanese Encephalitis (JE) cases and 361 healthy controls from North India. Higher frequency of TNFA rs1800629 G/A, CCR5 rs1799987 genotypes with A allele and lower frequency of combination lacking TNFA rs1800629 A, CCR5 rs333 Δ32, andCCR5 rs1799987 A alleles and CCL2 rs1024611 G/G genotype was observed in JE cases. TNFA rs1800629 A and CCR5 rs1799987 A alleles were associated with susceptibility while combination lacking TNFA rs1800629 A, CCR5 rs333 Δ32, and rs1799987 A alleles and CCL2 rs1024611 G/G genotype was associated with protection to JE.

Acute Encephalitis Syndrome in Gorakhpur, Uttar Pradesh, 2016: Clinical and Laboratory Findings.

BACKGROUND: Seasonal outbreaks of acute encephalitis syndrome (AES) with high fatality have been occurring in Gorakhpur, Uttar Pradesh, India, for several years. We conducted investigations during the 2016 outbreak to identify the etiology. METHODS: We included 407 hospitalized AES patients with cerebrospinal fluid pleocytosis (>5 cells/mm) in our study. These patients were clinically examined; their blood and cerebrospinal fluid samples were collected and investigated for scrub typhus (ST), Japanese encephalitis virus (JEV), dengue virus and spotted fever group of Rickettsia by serology and/or polymerase chain reaction. RESULTS: Of the 407 AES patients, 266 (65.4%), 42 (10.3%) and 29 (7.1%) were diagnosed to have ST, JEV and dengue infection, respectively. Four patients were diagnosed to have spotted fever group of Rickettsia infection. A significantly higher proportion of ST patients with AES had hepatomegaly, splenomegaly and facial edema. The common hematologic and biochemical abnormalities among ST-positive patients include thrombocytopenia, raised liver enzymes and bilirubin levels. The case fatality ratio was significantly higher among ST-negative AES patients (36.2% vs. 15.2%; P < 0.05). CONCLUSIONS: ST accounted for approximately two third of the AES case-patients. Efforts are required to identify the etiology of AES case-patients who are negative for ST, JEV and dengue fever.

Acute Encephalitis Syndrome in Eastern Uttar Pradesh, India: Changing Etiological Understanding.

Seasonal outbreaks of acute encephalitis syndrome (AES) with high case fatality have been occurring in Gorakhpur division in Eastern Uttar Pradesh, India, for more than three decades. Japanese encephalitis virus (JEV) accounted for <10% of AES cases, while the etiology of the remaining cases remained largely unknown. Investigations conducted during the 2014 and 2015 outbreaks indicated Orientia tsutsugamushi (Haruo Hayashi 1920) (Norio Ogata 1929) Tamura et al. 1995 (Rickettsiales: Rickettsiaceae) as the etiology in about 60% of AES cases. Hospital-based surveillance studies indicated that about one-fifth of the patients with acute febrile illness were due to scrub typhus. Further studies are required to identify the etiology of about a third of AES cases that test negative for scrub typhus, JEV, or dengue.

Scrub Typhus as an Etiology of Acute Febrile Illness in Gorakhpur, Uttar Pradesh, India, 2016.

Seasonal outbreaks of acute encephalitis syndrome (AES) with high mortality occur every year in Gorakhpur region of Uttar Pradesh, India. Earlier studies indicated the role of scrub typhus as the important etiology of AES in the region. AES cases were hospitalized late in the course of their illness. We established surveillance for acute febrile illness (AFI) (fever ≥ 4 days duration) in peripheral health facilities in Gorakhpur district to understand the relative contribution of scrub typhus. Of the 224 patients enrolled during the 3-month period corresponding to the peak of AES cases in the region, about one-fifth had immunoglobulin M (IgM) antibodies against Orientia tsutsugamushi. Dengue and leptospira accounted for 8% and 3% of febrile illness cases. Treating patients with AFI attending the peripheral health facilities with doxycycline could prevent development of AES and thereby reduce deaths due to AES in Gorakhpur region.

Scrub Typhus as a Cause of Acute Encephalitis Syndrome, Gorakhpur, Uttar Pradesh, India.

Outbreaks of acute encephalitis syndrome (AES) have been occurring in Gorakhpur Division, Uttar Pradesh, India, for several years. In 2016, we conducted a case-control study. Our findings revealed a high proportion of AES cases with Orientia tsutsugamushi IgM and IgG, indicating that scrub typhus is a cause of AES.

Coverage & missed opportunity for Japanese encephalitis vaccine, Gorakhpur division, Uttar Pradesh, India, 2015: Implications for Japanese encephalitis control.

BACKGROUND & OBJECTIVES: Japanese encephalitis (JE) is an important aetiology of acute encephalitis syndrome in Gorakhpur division, Uttar Pradesh, India. Two doses of JE vaccine ( first during 9-12 months and second during 16-24 months of age) are administered under the Universal Immunization Programme. We conducted surveys to estimate the coverage of JE vaccine and magnitude of missed opportunity for vaccination (MoV) for JE in Gorakhpur division. METHODS: To estimate the JE vaccine coverage, cluster surveys were conducted in four districts of Gorakhpur division by selecting 30 clusters by probability proportional to size method in each district, seven children aged 25-36 months were selected from each cluster and their mothers were interviewed about JE vaccination. To estimate the magnitude of MoV, exit surveys were conducted in vaccination clinics in selected health facilities, mothers were interviewed about the vaccination status of their children and vaccines administered to the child on the day of interview. RESULTS: A total of 840 children were surveyed, 210 from each district. The coverages of one and two doses of JE vaccine in Gorakhpur division were 75 per cent [95% confidence interval (CI): 71.0-78.9] and 42.3 per cent (95% CI: 37.8-46.8), respectively. Facility-based exit survey indicated that 32.7 per cent of the eligible children missed JE vaccine. INTERPRETATION & CONCLUSIONS: The survey results showed that three of the four children aged 25-36 months in Gorakhpur division had received at least one dose of JE vaccine. The coverage of second dose of JE vaccine, however, was low. Failure to administer vaccination simultaneously was the most common reason for MoV for JE vaccine. Training vaccinators about correct vaccination schedule and removing their misconception about administering vaccines simultaneously would substantially improve JE vaccine coverage in Gorakhpur.

Predictors of Mortality in Paediatric Myocarditis.

INTRODUCTION: Paediatric myocarditis can present as mild flu like symptoms to fulminent form. Early identification of the severity of illness and prioritization of intensive care is helpful especially in developing countries with limited resources. AIM: To know the factors at admission that can predict mortality in paediatric myocarditis. MATERIALS AND METHODS: This was an observational study which enrolled children who presented with fever of acute onset (less than 15 days in duration), and were diagnosed as suspected myocarditis on the basis of clinical features, Troponin I and echocardiography, according to Expanded criteria for myocarditis in Paediatric ward at our institute over a period from August 2014 to December 2015. Their clinical features, cardiac biomarkers and echocardiography findings were compared between survivors and non-survivors. STATISTICAL ANALYSIS: All statistical analysis was done using graphpad Prism 5 and SPSS statistical software. A Fisher exact p-value <0.05 was regarded as significant. Multivariate Logistic Regression was carried out to quantify the relationship between cardiac death and other predictor variables. The logistic coefficients for the predictor variables and their exponents, that is, log odds were calculated. Statistical significance of these predictor variables was interpreted by p-values. RESULTS: A 17.7% (n=11/62) patients of paediatric myocarditis died in this study. New York Heart Association (NYHA) class IV dyspnea (p=0.0115) and hypotension (p=0.0174) were more in patients who did not survive. The mean value of Troponin I was more in the non-survivor group (0.958 ± 1.13ng/ml); (p=0.0074). More number of patients who died had Brain Natriuretic Peptide (BNP) levels increased in their plasma (p=0.0087) with higher mean value (p=0.0175). LV ejection fraction was decreased markedly in non survivor group with mean value of 37±8.09 % as compared to survivor group with mean value of 46.6±10.5%, (p=0.0115). On multivariate analysis, NYHA class IV dyspnea (p=0.0113), BNP (p=0.015) and ejection fraction (p = 0.0284) independently are the predictors of mortality in our study group. CONCLUSION: Children with myocarditis having hypotension, raised Troponin I, BNP and decreased ejection fraction are more prone to die. NYHA IV dyspnea, higher levels of BNP and decreased EF are independently related to worst outcome.

WHO/UNICEF recommended therapeutic food versus home based therapeutic food in the management of severe acute malnutrition: A randomized controlled trial.

Malnutrition is a major public health problem especially in the developing countries. The objective of the study was to compare WHO/UNICEF recommended therapeutic food with home based therapeutic food in the management of severe acute malnutrition. It was a randomized controlled trial at tertiary care level hospital with nutritional rehabilitation centre. Children (6 month to 5 years) having severe acute malnutrition were included in the study. Group A (n=74 children) was given WHO recommended therapeutic food and group B (n=75 children) was given home based therapeutic food. The mean rate of weight gain, gain in height and increase in mid-upper arm circumference were significantly higher (p<0.05) in the group received home based therapeutic food. Mean duration to achieve target weight was 21.44±3.33 days in group A and 16.28±2.11 days in group B (p