Spatiotemporal variation in risk of Shigella infection in childhood: a global risk mapping and prediction model using individual participant data.

BACKGROUND: Diarrhoeal disease is a leading cause of childhood illness and death globally, and Shigella is a major aetiological contributor for which a vaccine might soon be available. The primary objective of this study was to model the spatiotemporal variation in paediatric Shigella infection and map its predicted prevalence across low-income and middle-income countries (LMICs). METHODS: Individual participant data for Shigella positivity in stool samples were sourced from multiple LMIC-based studies of children aged 59 months or younger. Covariates included household-level and participant-level factors ascertained by study investigators and environmental and hydrometeorological variables extracted from various data products at georeferenced child locations. Multivariate models were fitted and prevalence predictions obtained by syndrome and age stratum. FINDINGS: 20 studies from 23 countries (including locations in Central America and South America, sub-Saharan Africa, and south and southeast Asia) contributed 66 563 sample results. Age, symptom status, and study design contributed most to model performance followed by temperature, wind speed, relative humidity, and soil moisture. Probability of Shigella infection exceeded 20% when both precipitation and soil moisture were above average and had a 43% peak in uncomplicated diarrhoea cases at 33°C temperatures, above which it decreased. Compared with unimproved sanitation, improved sanitation decreased the odds of Shigella infection by 19% (odds ratio [OR]=0·81 [95% CI 0·76-0·86]) and open defecation decreased them by 18% (OR=0·82 [0·76-0·88]). INTERPRETATION: The distribution of Shigella is more sensitive to climatological factors, such as temperature, than previously recognised. Conditions in much of sub-Saharan Africa are particularly propitious for Shigella transmission, although hotspots also occur in South America and Central America, the Ganges-Brahmaputra Delta, and the island of New Guinea. These findings can inform prioritisation of populations for future vaccine trials and campaigns. FUNDING: NASA, National Institutes of Health-The National Institute of Allergy and Infectious Diseases, and Bill & Melinda Gates Foundation.

Associations Between Eight Earth Observation-Derived Climate Variables and Enteropathogen Infection: An Independent Participant Data Meta-Analysis of Surveillance Studies With Broad Spectrum Nucleic Acid Diagnostics.

Diarrheal disease, still a major cause of childhood illness, is caused by numerous, diverse infectious microorganisms, which are differentially sensitive to environmental conditions. Enteropathogen-specific impacts of climate remain underexplored. Results from 15 studies that diagnosed enteropathogens in 64,788 stool samples from 20,760 children in 19 countries were combined. Infection status for 10 common enteropathogens-adenovirus, astrovirus, norovirus, rotavirus, sapovirus, Campylobacter, ETEC, Shigella, Cryptosporidium and Giardia-was matched by date with hydrometeorological variables from a global Earth observation dataset-precipitation and runoff volume, humidity, soil moisture, solar radiation, air pressure, temperature, and wind speed. Models were fitted for each pathogen, accounting for lags, nonlinearity, confounders, and threshold effects. Different variables showed complex, non-linear associations with infection risk varying in magnitude and direction depending on pathogen species. Rotavirus infection decreased markedly following increasing 7-day average temperatures-a relative risk of 0.76 (95% confidence interval: 0.69-0.85) above 28°C-while ETEC risk increased by almost half, 1.43 (1.36-1.50), in the 20-35°C range. Risk for all pathogens was highest following soil moistures in the upper range. Humidity was associated with increases in bacterial infections and decreases in most viral infections. Several virus species' risk increased following lower-than-average rainfall, while rotavirus and ETEC increased with heavier runoff. Temperature, soil moisture, and humidity are particularly influential parameters across all enteropathogens, likely impacting pathogen survival outside the host. Precipitation and runoff have divergent associations with different enteric viruses. These effects may engender shifts in the relative burden of diarrhea-causing agents as the global climate changes.

Kawasaki Disease like Multisystem Inflammatory Syndrome in a Toddler during SARS-CoV-2 Pandemic in Nepal.

Multisystem inflammatory syndrome in children is a new childhood inflammatory disorder associated with respiratory syndrome coronavirus 2 (SARS-CoV-2). This illness of elevated inflammatory markers and multiple organ involvement similar to Kawasaki disease is not commonly reported from Asia. A 17-month-old boy presented with acute onset fever, rash, non-exudative conjunctivitis and swellings of hands and legs. In x-ray chest there was infiltration on the right lower lobe and echocardiography showed evidence of coronary arteritis. The diagnosis of multisystem inflammatory syndrome in children was confirmed on the basis of characteristic clinical features and laboratory parameters fulfilling standard case definition for multisystem inflammatory syndrome in children. The child responded to treatment with intravenous immunoglobulin and high dose aspirin. Hence, amidst SARS-CoV-2 pandemic, multisystem inflammatory syndrome in children should be suspected and effectively treated even in a country like Nepal. Keywords: Kawasaki disease; multiple inflammatory syndrome in children; Nepal; respiratory syndrome coronavirus 2.

Infectious Etiologies of Intussusception Among Children <2 Years Old in 4 Asian Countries.

BACKGROUND: The etiology of intussusception, the leading cause of bowel obstruction in infants, is unknown in most cases. Adenovirus has been associated with intussusception and slightly increased risk of intussusception with rotavirus vaccination has been found. We conducted a case-control study among children <2 years old in Bangladesh, Nepal, Pakistan, and Vietnam to evaluate infectious etiologies of intussusception before rotavirus vaccine introduction. METHODS: From 2015 to 2017, we enrolled 1-to-1 matched intussusception cases and hospital controls; 249 pairs were included. Stool specimens were tested for 37 infectious agents using TaqMan Array technology. We used conditional logistic regression to estimate odds ratio (OR) and 95% confidence interval (CI) of each pathogen associated with intussusception in a pooled analysis and quantitative subanalyses. RESULTS: Adenovirus (OR, 2.67; 95% CI, 1.75-4.36) and human herpes virus 6 (OR, 3.50; 95% CI, 1.15-10.63) were detected more frequently in cases than controls. Adenovirus C detection <20 quantification cycles was associated with intussusception (OR, 18.59; 95% CI, 2.45-140.89). Wild-type rotavirus was not associated with intussusception (OR, 1.07; 95% CI, 0.52-2.22). CONCLUSIONS: In this comprehensive evaluation, adenovirus and HHV-6 were associated with intussusception. Future research is needed to better understand mechanisms leading to intussusception, particularly after rotavirus vaccination.

Low population Japanese encephalitis virus (JEV) seroprevalence in Udayapur district, Nepal, three years after a JE vaccination programme: A case for further catch up campaigns?

The live attenuated Japanese encephalitis (JE) vaccine SA14-14-2 has been used in Nepal for catch-up campaigns and is now included in the routine immunisation schedule. Previous studies have shown good vaccine efficacy after one dose in districts with a high incidence of JE. The first well-documented dengue outbreak occurred in Nepal in 2006 with ongoing cases now thought to be secondary to migration from India. Previous infection with dengue virus (DENV) partially protects against JE and might also influence serum neutralising antibody titres against JEV. This study aimed to determine whether serum anti-JEV neutralisation titres are: 1. maintained over time since vaccination, 2. vary with historic local JE incidence, and 3. are associated with DENV neutralising antibody levels. We conducted a cross-sectional study in three districts of Nepal: Banke, Rupandehi and Udayapur. Udayapur district had been vaccinated against JE most recently (2009), but had been the focus of only one campaign, compared with two in Banke and three in Rupandehi. Participants answered a short questionnaire and serum was assayed for anti-JEV and anti-DENV IgM and IgG (by ELISA) and 50% plaque reduction neutralisation titres (PRNT50) against JEV and DENV serotypes 1-4. A titre of ≥1:10 was considered seropositive to the respective virus. JEV neutralising antibody seroprevalence (PRNT50 ≥ 1:10) was 81% in Banke and Rupandehi, but only 41% in Udayapur, despite this district being vaccinated more recently. Sensitivity of ELISA for both anti-JEV and anti-DENV antibodies was low compared with PRNT50. DENV neutralising antibody correlated with the JEV PRNT50 ≥1:10, though the effect was modest. IgM (indicating recent infection) against both viruses was detected in a small number of participants. We also show that DENV IgM is present in Nepali subjects who have not travelled to India, suggesting that DENV may have become established in Nepal. We therefore propose that further JE vaccine campaigns should be considered in Udayapur district, and similar areas that have had fewer vaccination campaigns.

Hospital based surveillance and molecular characterization of rotavirus in children less than 5 years of age with acute gastroenteritis in Nepal.

BACKGROUND: Rotavirus remains a significant causative agent of childhood acute gastroenteritis, particularly among children less than 5 years of age. Although precise data on childhood mortality associated with diarrheal disease in Nepal is not available, it is estimated that22% of all rotavirus deaths globally occurs in neighboring country of India. In spite of the substantial burden of rotavirus gastroenteritis in the Indian subcontinent, rotavirus vaccine has not been introduced in Nepal. Continuous surveillance for monitoring rotavirus disease burden and molecular characterization is needed prior to rotavirus vaccine introduction in Nepal. METHODS: A total of 3310 stool samples (2849 hospitalized cases and 461 non-hospitalized cases), were collected from patients <5 years of age from January 2013 to December 2016 and tested for rotavirus antigen by ELISA (ProSpecT, USA). A subset of ELISA positive stool samples was genotyped. Demographic data were collected. RESULTS: During the four-year surveillance period, the overall burden of rotavirus infection was 24% among hospitalized children which was much higher than among non-hospitalized children (12%). The majority of children hospitalized with rotavirus gastroenteritis were less than 2 years of age (86%). Rotavirus-associated gastroenteritis hospitalizations occur year-round in Nepal, but a distinct peak in winter (up to 40% among hospitalized) was observed. Of 735 ELISA positive samples, 492 were genotyped by RT-PCR. The most prevalent genotype was G12P[6] (45.3%), followed byG2P[4](12.2%), G1P[8] (9.6%), G9P[4](7.3%), and G9P[8](4.5%). Mixed infection accounted for 4.4% of cases, 6.2% were partially typed and 10.5% of the samples were G and P untypable. CONCLUSIONS: A high burden of rotavirus gastroenteritis and a diversity of circulating rotavirus strains in Nepal were observed. Recommendation to introduce a rotavirus vaccine with known vaccine effectiveness would help in reducing the severity of Rotavirus diarrheal disease in children less than 5 years of age.

Preparing for safety monitoring after rotavirus vaccine introduction - Assessment of baseline epidemiology of intussusception among children <2 years of age in four Asian countries.

Intussusception is the invagination of one segment of the bowel into a distal segment, characterized by symptoms of bloody stool, vomiting, and abdominal pain. Previous studies have found regional differences in incidence but the etiology of most intussusception cases is unknown. Rotavirus vaccines were associated with a slightly of increased risk of intussusception in post-licensure evaluations in high- and middle-income countries, but not in low income African countries. To describe the baseline epidemiology of intussusception in young children prior to rotavirus vaccine implementation, active sentinel hospital surveillance for intussusception in children < 2 years of age was conducted in 4 low income Asian countries (Bangladesh, Nepal, Pakistan and Vietnam). Over a 24-month period, 15 sites enrolled 1,415 intussusception cases, of which 70% were enrolled in Vietnam. Overall, 61% of cases were male and 1% (n = 16) died, ranging from 8% in Pakistan to 0% in Vietnam. The median age of cases enrolled ranged from 6 months in Bangladesh and Pakistan to 12 months in Vietnam. The proportion of cases receiving surgical management was 100% in Bangladesh, 88% in Pakistan, 61% in Nepal, and 1% in Vietnam. The high proportion of males and median age of cases around 6 months of age found in this regional surveillance network are consistent with previous descriptions of the epidemiology of intussusception in these countries and elsewhere. Differences in management and the fatality rate of cases between the countries likely reflect differences in access to healthcare and availability of diagnostic modalities. These baseline data will be useful for post-rotavirus vaccine introduction safety monitoring.

Preparing for rotavirus vaccine introduction - A retrospective assessment of the epidemiology of intussusception in children below 2 years of age in Nepal.

BACKGROUND: Rotavirus is the most common cause of severe diarrhea in Nepali children, accounting for 25-33% of childhood diarrhea hospitalizations. Two rotavirus vaccines recommended for inclusion in national immunization programs have been associated with a low risk of intussusception in post-marketing studies conducted in several countries. Data on the epidemiology of intussusception hospitalizations are lacking in Nepal. Thus, we aimed to describe the epidemiology of intussusception-associated hospitalizations among Nepali children in preparation for rotavirus vaccine introduction. METHODS: A retrospective review of intussusception hospitalizations for a three year period was conducted at two major pediatric hospitals in Kathmandu, Nepal. Possible intussusception cases were identified through admission, discharge, and operation theater logs and ultrasound registers. Cases with a diagnosis of possible intussusception were selected for medical record review and classified as confirmed if they met the Brighton Collaboration level 1 criteria of diagnostic certainty and the child was aged < 24 months. Data on demographics, clinical course, and outcome were abstracted and analyzed. RESULTS: Eight-five confirmed intussusception cases were identified; most (96%) were confirmed at surgery. The number of intussusception cases peaked between ages 4-7 months; no cases occurred in children 0-2 months. Fifty-nine (64%) case-patients were male. The median duration of symptoms before admission was 2 days (range: 0-14). Abdominal pain, bloody stool, and vomiting were the most common clinical features. All cases underwent surgical treatment; there was only one death. CONCLUSIONS: This is the first study to evaluate the epidemiology of intussusception hospitalizations among children aged < 24 months in Nepal. Because the public health impact of rotavirus vaccination could be substantial in Nepal, where childhood diarrhea-related morbidity and mortality are high, this baseline knowledge of intussusception prior to introduction of rotavirus vaccine in the national immunization schedule will provide useful information for post-vaccine introduction safety monitoring.

The inter-rater reliability and prognostic value of coma scales in Nepali children with acute encephalitis syndrome.

Background Acute encephalitis syndrome (AES) is a common cause of coma in Nepali children. The Glasgow coma scale (GCS) is used to assess the level of coma in these patients and predict outcome. Alternative coma scales may have better inter-rater reliability and prognostic value in encephalitis in Nepali children, but this has not been studied. The Adelaide coma scale (ACS), Blantyre coma scale (BCS) and the Alert, Verbal, Pain, Unresponsive scale (AVPU) are alternatives to the GCS which can be used. Methods Children aged 1-14 years who presented to Kanti Children's Hospital, Kathmandu with AES between September 2010 and November 2011 were recruited. All four coma scales (GCS, ACS, BCS and AVPU) were applied on admission, 48 h later and on discharge. Inter-rater reliability (unweighted kappa) was measured for each. Correlation and agreement between total coma score and outcome (Liverpool outcome score) was measured by Spearman's rank and Bland-Altman plot. The prognostic value of coma scales alone and in combination with physiological variables was investigated in a subgroup (n = 22). A multivariable logistic regression model was fitted by backward stepwise. Results Fifty children were recruited. Inter-rater reliability using the variables scales was fair to moderate. However, the scales poorly predicted clinical outcome. Combining the scales with physiological parameters such as systolic blood pressure improved outcome prediction. Conclusion This is the first study to compare four coma scales in Nepali children with AES. The scales exhibited fair to moderate inter-rater reliability. However, the study is inadequately powered to answer the question on the relationship between coma scales and outcome. Further larger studies are required.

Emergence or improved detection of Japanese encephalitis virus in the Himalayan highlands?

The emergence of Japanese encephalitis virus (JEV) in the Himalayan highlands is of significant veterinary and public health concern and may be related to climate warming and anthropogenic landscape change, or simply improved surveillance. To investigate this phenomenon, a One Health approach focusing on the phylogeography of JEV, the distribution and abundance of the mosquito vectors, and seroprevalence in humans and animal reservoirs would be useful to understand the epidemiology of Japanese encephalitis in highland areas.

A preliminary randomized double blind placebo-controlled trial of intravenous immunoglobulin for Japanese encephalitis in Nepal.

BACKGROUND: Japanese encephalitis (JE) virus (JEV) is a mosquito-borne flavivirus found across Asia that is closely related to West Nile virus. There is no known antiviral treatment for any flavivirus. Results from in vitro studies and animal models suggest intravenous immunoglobulin (IVIG) containing virus-specific neutralizing antibody may be effective in improving outcome in viral encephalitis. IVIG's anti-inflammatory properties may also be beneficial. METHODOLOGY/PRINCIPAL FINDINGS: We performed a pilot feasibility randomized double-blind placebo-controlled trial of IVIG containing anti-JEV neutralizing antibody (ImmunoRel, 400mg/kg/day for 5 days) in children with suspected JE at two sites in Nepal; we also examined the effect on serum neutralizing antibody titre and cytokine profiles. 22 children were recruited, 13 of whom had confirmed JE; 11 received IVIG and 11 placebo, with no protocol violations. One child (IVIG group) died during treatment and two (placebo) subsequently following hospital discharge. Overall, there was no difference in outcome between treatment groups at discharge or follow up. Passive transfer of anti-JEV antibody was seen in JEV negative children. JEV positive children treated with IVIG had JEV-specific neutralizing antibody titres approximately 16 times higher than those treated with placebo (p=0.2), which was more than could be explained by passive transfer alone. IL-4 and IL-6 were higher in the IVIG group. CONCLUSIONS/SIGNIFICANCE: A trial of IVIG for JE in Nepal is feasible. IVIG may augment the development of neutralizing antibodies in JEV positive patients. IVIG appears an appealing option for JE treatment that warrants further study. TRIAL REGISTRATION: ClinicalTrials.gov NCT01856205.

The functional, social and economic impact of acute encephalitis syndrome in Nepal--a longitudinal follow-up study.

BACKGROUND: Over 133,000 children present to hospitals with Acute Encephalitis Syndrome (AES) annually in Asia. Japanese encephalitis (JE) accounts for approximately one-quarter of cases; in most cases no pathogen is identified and management is supportive. Although JE is known to result in neurological impairment, few studies have examined the wider impact of JE and AES on patients and their families. METHODOLOGY/PRINCIPAL FINDINGS: Children (aged 1 month-14 years) with AES were assessed 5-12 months after discharge from two Nepali hospitals. Assessment included clinical examination, the Liverpool Outcome Score (LOS) - a validated assessment of function following encephalitis, questionnaires about the child's social participation since discharge, and out-of-pocket costs to the family. Children were classified as JE or 'other AES' based on anti-JE virus antibody titres during acute illness. Contact was made with the families of 76% (73/96) of AES children. Six children had died and one declined participation. 48% (32/66) reported functional impairment at follow-up, most frequently affecting behaviour, language or limb use. Impairment was more frequent in JE compared to 'other AES' cases (68% [13/19] versus 40% [19/47]; p = 0.06). 49% (26/53) had improvement in LOS between discharge and follow-up. The median out-of-pocket cost to families, including medical bills, medication and lost earnings was US$ 1151 (10 times their median monthly income) for children with severe/moderate impairment and $524 (4.6 times their income) for those with mild/no impairment (P = 0.007). Acute admission accounted for 74% of costs. Social participation was limited in 21% of children (n = 14). CONCLUSIONS/SIGNIFICANCE: Prolonged functional impairment was common following AES. Economic impact to families was substantial. Encouragingly, almost half the children improved after discharge and most reported sustained social participation. This study highlights a need for long-term medical support following AES. Rationalisation of initial expensive hospital treatments may be warranted, especially since only supportive treatment is available.

Clinical and prognostic features among children with acute encephalitis syndrome in Nepal; a retrospective study.

BACKGROUND: Acute encephalitis syndrome (AES) is commonly seen among hospitalized Nepali children. Japanese Encephalitis (JE) accounts for approximately one-quarter of cases. Although poor prognostic features for JE have been identified, and guide management, relatively little is reported on the remaining three-quarters of AES cases. METHODS: Children with AES (n = 225) were identified through admission records from two hospitals in Kathmandu between 2006 and 2008. Patients without available lumbar puncture results (n = 40) or with bacterial or plasmodium infection (n = 40) were analysed separately. The remaining AES patients with suspected viral aetiology were classified, based on positive IgM antibody in serum or cerebral spinal fluid, as JE (n = 42) or AES of unknown viral aetiology (n = 103); this latter group was sub-classified into Non-JE (n = 44) or JE status unknown (n = 59). Bad outcome was defined as death or neurological sequelae at discharge. RESULTS: AES patients of suspected viral aetiology more frequently had a bad outcome than those with bacterial or plasmodium infection (31% versus 13%; P = 0.039). JE patients more frequently had a bad outcome than those with AES of unknown viral aetiology (48% versus 24%; P = 0.01). Bad outcome was independently associated in both JE and suspected viral aetiology groups with a longer duration of fever pre-admission (P = 0.007; P = 0.002 respectively) and greater impairment of consciousness (P = 0.02; P < 0.001). A higher proportion of JE patients presented with a focal neurological deficit compared to patients of unknown viral aetiology (13/40 versus 11/103; P = 0.005). JE patients weighed less (P = 0.03) and exhibited a higher respiratory rate (P = 0.003) compared to Non-JE patients. CONCLUSIONS: Nepali children with AES of suspected viral aetiology or with JE frequently suffered a bad outcome. Despite no specific treatment, patients who experienced a shorter duration of fever before hospital admission more frequently recovered completely. Prompt referral may allow AES patients to receive potentially life-saving supportive management. Previous studies have indicated supportive management, such as fluid provision, is associated with better outcome in JE. The lower weight and higher respiratory rate among JE patients may reflect multiple clinical complications, including dehydration. The findings suggest a more systematic investigation of the influence of supportive management on outcome in AES is warranted.

The spatial heterogeneity between Japanese encephalitis incidence distribution and environmental variables in Nepal.

BACKGROUND: To identify potential environmental drivers of Japanese Encephalitis virus (JE) transmission in Nepal, we conducted an ecological study to determine the spatial association between 2005 Nepal JE incidence, and climate, agricultural, and land-cover variables at district level. METHODS: District-level data on JE cases were examined using Local Indicators of Spatial Association (LISA) analysis to identify spatial clusters from 2004 to 2008 and 2005 data was used to fit a spatial lag regression model with climate, agriculture and land-cover variables. RESULTS: Prior to 2006, there was a single large cluster of JE cases located in the Far-West and Mid-West terai regions of Nepal. After 2005, the distribution of JE cases in Nepal shifted with clusters found in the central hill areas. JE incidence during the 2005 epidemic had a stronger association with May mean monthly temperature and April mean monthly total precipitation compared to mean annual temperature and precipitation. A parsimonious spatial lag regression model revealed, 1) a significant negative relationship between JE incidence and April precipitation, 2) a significant positive relationship between JE incidence and percentage of irrigated land 3) a non-significant negative relationship between JE incidence and percentage of grassland cover, and 4) a unimodal non-significant relationship between JE Incidence and pig-to-human ratio. CONCLUSION: JE cases clustered in the terai prior to 2006 where it seemed to shift to the Kathmandu region in subsequent years. The spatial pattern of JE cases during the 2005 epidemic in Nepal was significantly associated with low precipitation and the percentage of irrigated land. Despite the availability of an effective vaccine, it is still important to understand environmental drivers of JEV transmission since the enzootic cycle of JEV transmission is not likely to be totally interrupted. Understanding the spatial dynamics of JE risk factors may be useful in providing important information to the Nepal immunization program.

First-episode versus recurrent acute rheumatic fever: is it different?

BACKGROUND: Recurrent episodes of acute rheumatic fever (RF) can lead to rheumatic heart disease with considerable disability and mortality in children. RF can recur in the absence of secondary prophylaxis. The differences in clinical manifestations and outcome between first-episode and recurrent RF have been less studied. METHODS: A cross-section of patients under 14 years was studied for 2 years (2003-2005) in order to compare the clinical, laboratory, echocardiographic profile and outcome of first-episode RF with recurrent attacks, and risk factors for recurrence and mortality. Patients without a previous history of RF and/or mitral stenosis (MS) and/or aortic stenosis (AS) were defined as first-episode patients, and patients with previous history of RF and/or MS and/or AS, were defined as recurrent RF patients based on the Jones criteria. RESULTS: Of 51 patients in total, 26 had first-episode RF and 25 had recurrent RF. Arthritis occurred in a significantly higher number of first-episode patients (P = 0.047) whereas shortness of breath (SOB; P = 0.003), palpitation (P = 0.034), and aortic regurgitation (AR; P = 0.001) occurred in a significantly higher number of recurrent RF patients. Audible murmur of corresponding echocardiographic regurgitation was present in all recurrent RF patients whereas audible murmur was present in 61.5% and echocardiographic regurgitation in 81% in first-episode patients (P = 0.007). Palpitation, SOB, audible murmur, thrill, age and AR on admission were independent predictors of recurrence. Palpitation, age and AS on admission were independent predictors of mortality. CONCLUSIONS: Subclinical carditis occurred only in the first-episode patients, which requires further evaluation for clinical significance. Because all deaths occurred in recurrent RF group (P = 0.02), secondary prophylaxis and management of sore throat need re-emphasis.

Study of Japanese encephalitis and other viral encephalitis in Nepali children.

BACKGROUND: A hospital-based prospective cross-sectional study was conducted in children aged 1 month-14 years to identify the proportion of viral encephalitis due to Japanese encephalitis (JE) and compare the clinico-laboratory profile and outcome of JE with that of other viral encephalitis (non-JE). METHODS: All probable cases of viral encephalitis on clinical and laboratory evaluation were confirmed as JE on anti-JE IgM in cerebrospinal fluid (CSF) and/or serum. Patients not having anti-JE IgM in CSF and/or serum were diagnosed as having non-JE. RESULTS: Of 94 cases, 58 were JE and 36 non-JE. Although practice of rearing pigs at home was associated with JE (P = 0.0001), significantly higher serum creatinine, protein, aspartate aminotransferase and CSF protein levels were observed in non-JE. Longer duration of fever was associated with complete recovery in JE whereas shorter duration of fever was associated with recovery in non-JE. Risk of neurological sequelae (P = 0.01), especially hemiparesis (P = 0.03) was significantly more in JE. Sequelae were observed at 6 weeks follow up in 18.8% of JE and 13.9% of non-JE. CONCLUSION: JE was the most common cause of viral encephalitis in eastern Nepal and should be suspected in encephalitic patients having pig rearing at home and neurological sequelae. Although duration of hospitalization and complication were higher in JE, final outcome was similar to non-JE. Longer duration of fever in JE and shorter duration of fever in non-JE correlated with recovery, while altered sensorium and focal neurological deficit were independent predictors of sequelae at 6 weeks only in JE and not in non-JE.

Clinical, laboratory and echocardiographic profile of acute rheumatic fever in Nepali children.

BACKGROUND: Acute rheumatic fever (RF) is a common, preventable health problem in developing countries. Sporadic outbreaks and the prevalence in some indigenous populations have renewed interest in RF in developed countries also. AIMS: To describe the clinical, laboratory and echocardiographic features, outcome and value of echocardiography in detecting valvular disease in RF. METHODS: A prospective, cross-sectional study was conducted over 2 years. Patients under 14 years admitted to the cardiology unit of Kanti Children's Hospital, Kathmandu with RF using the Jones criteria were recruited consecutively. RESULTS: The median age (range) of the 51 patients was 11 (5-14) years, the male:female ratio was 1.6:1 and 39% had a history of a sore throat. Clinical and laboratory features detected were as follows: carditis 92%, arthritis 33%, chorea 8%, subcutaneous nodules 4%, fever 51%, arthralgia 37%, elevated antistreptolysin O titre 94%, elevated CRP 78%, prolonged PR interval 45%, pericardial effusion 22% and cardiac failure 28%. In total, 36 patients (71%) complained of joint pains. A murmur on auscultation was significantly associated with underlying diseased valves confirmed by echocardiography (p=0.001). A murmur was audible in 78.4% and diseased valves were confirmed by echocardiography in 88.2%. The mitral valve was the most commonly involved valve (82%) and mitral regurgitation the commonest lesion (24%). A thickened mitral valve predicted carditis (p=0.007). Five (10%) patients died. CONCLUSION: Inclusion of echocardiographic evidence of carditis and possibly arthralgia as major criteria would improve case detection.

Clinico-laboratory profile and outcome of Japanese encephalitis in Nepali children.

BACKGROUND: Japanese encephalitis (JE) is associated with high mortality and neurological sequelae. The unpredictable course and lack of specific treatment pose major challenges in management. The tropical climate and paddy ecosystem in Nepal provide a suitable setting. AIMS: To determine the aetiology of febrile encephalopathy and describe the clinico-laboratory profile and outcome of JE in Nepali children. METHODS: A hospital-based prospective and observational study was conducted over a 1-year period (2000-2001). Children aged from >1 month to 14 years with fever >38 degrees C for <2 weeks and altered sensorium were recruited. JE was confirmed by anti-JE IgM in cerebrospinal fluid and/or serum. RESULTS: Of 117 consecutively enrolled patients, 58 had JE. Ten patients had concomitant infections, four with malaria and six with bacterial meningitis, and were excluded from analysis. Clinical findings were as follows: boys, 69%; age 4-14 years, 71%; presentation during summer and autumn, 83%; fever >3 days, 69%; altered sensorium <2 days, 50%; Glasgow coma score 8-12, 63%; seizures, 58%. Four (8.3%) died. At discharge, neurological sequelae were detected in 24 (50%) and hemiparesis was the most common form. Longer duration of vomiting, altered sensorium and focal neurological deficit on admission were independently associated with sequelae at discharge. Sequelae persisted in nine (18.8%) at 6 weeks follow-up. Long duration of altered sensorium (beta co-efficient 0.35, odds ratio 1.4, p=0.042) and presence of focal neurological deficit on admission (beta co-efficient 1.6, odds ratio 5.2, p=0.049) were independent predictors of sequelae at 6 weeks. CONCLUSION: JE was the commonest cause of febrile encephalopathy. Neurological sequelae were common but resolved in two-thirds of cases.