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Journal of Tropical Pediatrics May 2021Survivors of childhood encephalitis often suffer from physical and neurocognitive sequelae, particularly in tropical, resource-limited areas with a large burden of...
BACKGROUND
Survivors of childhood encephalitis often suffer from physical and neurocognitive sequelae, particularly in tropical, resource-limited areas with a large burden of arboviral, neurotropic pathogens and limited resources with which to address chronic morbidities. Research into overall and pathogen-specific outcomes following childhood encephalitis may help identify risk factors for poor outcomes, quantify the burden of sequelae, assist with resource allocation and help focus rehabilitative efforts. However, such research is limited. To this end, we systematically reviewed the literature on this topic to identify gaps in knowledge worthy of future investigation.
METHODS
A search of PubMed, Web of Knowledge and the Cochrane databases was performed 10 January through 20 February 2020, using 17 search terms for sequelae and 14 for tropical, arboviral pathogens. Eligible reports demonstrated post-discharge follow-up of ≥3 months and assessment of clinical outcome in a child with an arboviral encephalitis ≤18 years of age at diagnosis.
RESULTS
Of 1513 articles, 35 were eligible, comprising 693 children. Japanese encephalitis accounted for 18 articles and 93.2% of all subjects (646 total). Sequelae were documented in ∼60% of subjects overall and in those with Japanese encephalitis. For non-Japanese encephalitis virus encephalitides (47 children), sequelae were found in 78.1%. No studies utilized comprehensive neurocognitive testing or assessed the efficacy of rehabilitative efforts. Only nine studies reported data from ≥1 follow-up visit.
CONCLUSION
Investigation into long-term outcomes following tropical childhood encephalitis is limited, particularly for neurocognitive sequelae, serial assessments over time and the effect of rehabilitative measures.
LAY SUMMARY
Encephalitis, an infection of the brain, is frequently caused by arboviruses (viruses spread via the bite of infected arthropods, such as mosquitoes) in tropical locales. Following infection, surviving children may be plagued with severe physical and cognitive deficits. Unfortunately, research into the type of deficits, their frequency and their responsiveness to rehabilitative efforts is lacking. We identified and reviewed 35 studies describing outcomes in children recovering from tropical, arboviral encephalitis at least 3 months following hospital discharge. Poor outcomes were common and found in up to 60% of children. Long-term and serial follow-up visits were rare, as was the use of comprehensive neurocognitive testing. No studies assessed the efficacy of rehabilitative measures. Further study into these areas is recommended.
Topics: Aftercare; Animals; Child; Cognition Disorders; Encephalitis, Arbovirus; Humans; Patient Discharge
PubMed: 34109400
DOI: 10.1093/tropej/fmab028 -
International Journal of Infectious... Jan 2021Findings were published in 2015 that highlighted the endemicity of Japanese Encephalitis (JE) in the Philippines. The policymakers responded by conducting an...
BACKGROUND
Findings were published in 2015 that highlighted the endemicity of Japanese Encephalitis (JE) in the Philippines. The policymakers responded by conducting an immunization campaign and strengthening the surveillance system. Using data on the revitalized surveillance system, the epidemiology of JE in the country was updated.
METHODS
Electronic databases were searched, and conference proceedings related to JE in the Philippines were identified until 31 December 2018. Surveillance data from 01 January 2014 to 31 December 2017 were used. The 2015 population census was used to estimate the national and regional incidence for children aged <15 years.
RESULTS
Four studies reported the seroprevalence of JE in the Philippines, which showed increasing seroprevalence with increasing age. Seroprevalence rates were from 0% for infants (aged <1 year) to 65.7% in adolescents (12-18 years) before the immunization campaign. Among five studies on the clinical profile of JE, case fatality ranged from 0 to 21.1% and neurologic sequelae ranged from 5.2 to 81.8% of diagnosed cases. In the surveillance data, JE cases peaked annually from July to October, coinciding with the wet season. The national incidence was estimated at a minimum of 0.7 JE cases/100,000 among children aged <15 years, but higher rates were seen in the northern regions of the country.
CONCLUSION
Improved surveillance affirmed the burden of JE in the Philippines. A subnational immunization campaign in April 2019 was conducted in the northern regions of the country. This paper highlights the importance of including the JE vaccine in the immunization program and sustained high-quality surveillance to monitor its impact on JE control.
Topics: Databases, Factual; Encephalitis, Japanese; Humans; Immunization Programs; Incidence; Japanese Encephalitis Vaccines; Philippines; Seroepidemiologic Studies
PubMed: 33127505
DOI: 10.1016/j.ijid.2020.10.061 -
BMC Medicine Sep 2020In the absence of definitive diagnosis, healthcare providers are likely to prescribe empirical antibacterials to those who test negative for malaria. This problem is of...
BACKGROUND
In the absence of definitive diagnosis, healthcare providers are likely to prescribe empirical antibacterials to those who test negative for malaria. This problem is of critical importance in Southern Asia (SA) and South-eastern Asia (SEA) where high levels of antimicrobial consumption and high prevalence of antimicrobial resistance have been reported. To improve management and guide further diagnostic test development, better understanding is needed of the true causative agents of fever and their geographical variability.
METHODS
We conducted a systematic review of published literature (1980-2015) to characterise the spectrum of pathogens causing non-malarial febrile illness in SA and SEA. We searched six databases in English and French languages: MEDLINE, EMBASE, Global Health (CABI) database, WHO Global Health Library, PASCAL, and Bulletin de la Société Française de Parasitologie (BDSP). Selection criteria included reporting on an infection or infections with a confirmed diagnosis, defined as pathogens detected in or cultured from samples from normally sterile sites, or serological evidence of current or past infection.
RESULTS
A total of 29,558 records from 19 countries in SA and SEA were screened, of which 2410 (8.1%) met the selection criteria. Bacterial aetiologies were reported in 1235 (51.2%) articles, viral in 846 (35.1%), parasitic in 132 (5.5%), and fungal in 54 (2.2%), and 143 (6.0%) articles reported more than one pathogen group. In descending order of frequency, Salmonella Typhi, Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, and coagulase negative Staphylococcus were the commonly reported bacteria, while dengue virus, chikungunya virus, Japanese encephalitis virus, hepatitis B virus, and hepatitis C virus were common viral pathogens reported. Reports of rarely reported or emerging pathogens included a case report of Borrelia burgdorferi (Lyme disease) in India in 2010 and reports of Nipah virus in Singapore and India.
CONCLUSIONS
This review summarises the reported non-malaria pathogens that may cause febrile illness in SA and SEA. The findings emphasise the need of standardising the reporting of aetiological studies to develop effective, evidence-based fever management and improved surveillance. Research and development of diagnostic tools would benefit from up-to-date epidemiological reporting of the regional diversities of non-malaria fever aetiologies.
TRIAL REGISTRATION
PROSPERO registration, CRD42016049281.
Topics: Asia; Asia, Southeastern; Fever; History, 20th Century; History, 21st Century; Humans; Organizational Case Studies
PubMed: 32951591
DOI: 10.1186/s12916-020-01745-0 -
PharmacoEconomics Oct 2020Cost-of-illness data from empirical studies provide insights into the use of healthcare resources including both expenditures and the opportunity cost related to... (Review)
Review
BACKGROUND
Cost-of-illness data from empirical studies provide insights into the use of healthcare resources including both expenditures and the opportunity cost related to receiving treatment.
OBJECTIVE
The objective of this systematic review was to gather cost data and relevant parameters for hepatitis B, pneumonia, meningitis, encephalitis caused by Japanese encephalitis, rubella, yellow fever, measles, influenza, and acute gastroenteritis in children in low- and middle-income countries.
DATA SOURCES
Peer-reviewed studies published in public health, medical, and economic journals indexed in PubMed (MEDLINE), Embase, and EconLit.
STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS
Studies must (1) be peer reviewed, (2) be published in 2000-2016, (3) provide cost data for one of the nine diseases in children aged under 5 years in low- and middle-income countries, and (4) generated from primary data collection.
LIMITATIONS
We cannot exclude missing a few articles in our review. Measures were taken to reduce this risk. Several articles published since 2016 are omitted from the systematic review results, these articles are included in the discussion.
CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS
The review yielded 37 articles and 267 sets of cost estimates. We found no cost-of-illness studies with cost estimates for hepatitis B, measles, rubella, or yellow fever from primary data. Most estimates were from countries in Gavi preparatory (28%) and accelerated (28%) transition, followed by those who are initiating self-financing (22%) and those not eligible for Gavi support (19%). Thirteen articles compared household expenses to manage illnesses with income and two articles with other household expenses, such as food, clothing, and rent. An episode of illness represented 1-75% of the household's monthly income or 10-83% of its monthly expenses. Articles that presented both household and government perspectives showed that most often governments incurred greater costs than households, including non-medical and indirect costs, across countries of all income statuses, with a few notable exceptions. Although limited for low- and middle-income country settings, cost estimates generated from primary data collection provided a 'real-world' estimate of the economic burden of vaccine-preventable diseases. Additional information on whether common situations preventing the application of official clinical guidelines (such as medication stock-outs) occurred would help reveal deficiencies in the health system. Improving the availability of cost-of-illness evidence can inform the public policy agenda about healthcare priorities and can help to operationalize the healthcare budget in local health systems to respond adequately to the burden of illness in the community.
Topics: Child; Cross-Sectional Studies; Developing Countries; Humans; Income; Prospective Studies; Retrospective Studies
PubMed: 32748334
DOI: 10.1007/s40273-020-00940-4 -
ELife May 2020Japanese encephalitis (JE) is a mosquito-borne disease, known for its high mortality and disability rate among symptomatic cases. Many effective vaccines are available...
Japanese encephalitis (JE) is a mosquito-borne disease, known for its high mortality and disability rate among symptomatic cases. Many effective vaccines are available for JE, and the use of a recently developed and inexpensive vaccine, SA 14-14-2, has been increasing over the recent years particularly with Gavi support. Estimates of the local burden and the past impact of vaccination are therefore increasingly needed, but difficult due to the limitations of JE surveillance. In this study, we implemented a mathematical modelling method (catalytic model) combined with age-stratifed case data from our systematic review which can overcome some of these limitations. We estimate in 2015 JEV infections caused 100,308 JE cases (95% CI: 61,720-157,522) and 25,125 deaths (95% CI: 14,550-46,031) globally, and that between 2000 and 2015 307,774 JE cases (95% CI: 167,442-509,583) were averted due to vaccination globally. Our results highlight areas that could have the greatest benefit from starting vaccination or from scaling up existing programs and will be of use to support local and international policymakers in making vaccine allocation decisions.
Topics: Encephalitis, Japanese; Endemic Diseases; Global Burden of Disease; Humans; Japanese Encephalitis Vaccines; Vaccination
PubMed: 32450946
DOI: 10.7554/eLife.51027 -
International Journal of Infectious... Jun 2020Japanese encephalitis virus infection (JE) remains a leading cause of neurological disease in Asia, mainly involving individuals living in remote areas with limited...
OBJECTIVE
Japanese encephalitis virus infection (JE) remains a leading cause of neurological disease in Asia, mainly involving individuals living in remote areas with limited access to treatment centers and diagnostic facilities. Laboratory confirmation is fundamental for the justification and implementation of vaccination programs. We reviewed the literature on historical developments and current diagnostic capability worldwide, to identify knowledge gaps and instill urgency to address them.
METHODS
Searches were performed in Web of Science and PubMed using the term 'Japanese encephalitis' up to 13th October 2019. Studies reporting laboratory-confirmed symptomatic JE cases in humans were included, and data on details of diagnostic tests were extracted. A JE case was classified according to confirmatory levels (Fischer et al., 2008; Campbell et al., 2011; Pearce et al., 2018; Heffelfinger et al., 2017), where level 1 represented the highest level of confidence.
FINDINGS
20,212 published JE cases were identified from 205 studies. 15,167 (75%) of these positive cases were confirmed with the lowest-confidence diagnostic tests (level 3 or 4, or level 4). Only 109 (53%) of the studies reported contemporaneous testing for dengue-specific antibodies.
CONCLUSION
A fundamental pre-requisite for the control of JEV is lacking - that of a simple and specific diagnostic procedure that can be adapted for point-of-care tests and readily used throughout JE-endemic regions of the world.
Topics: Asia; Encephalitis Virus, Japanese; Encephalitis, Japanese; Forecasting; Humans
PubMed: 32205287
DOI: 10.1016/j.ijid.2020.03.039 -
Journal of Travel Medicine Mar 2020Japanese encephalitis is a disease caused by a flavivirus which is transmitted by mosquitos in endemic countries. Considering the potentially severe outcomes of the...
Japanese encephalitis is a disease caused by a flavivirus which is transmitted by mosquitos in endemic countries. Considering the potentially severe outcomes of the disease, vaccination is recommended for those at risk of exposure. During recent years, IC51 (IXIARO®, JESPECT®, JEVAL®) has increasingly been used to protect travellers from Europe and the USA. However, no systematic review exists that summarizes the currently available evidence on the immunogenicity and safety of this vaccine. We conducted a systematic review on the immunogenicity and safety of IC51, using the databases PubMed, MEDLINE, EMBASE and ClinicalTrials.gov (search date: 31 August 2019). Data extracted from included studies were grouped by outcomes and stratified by population and setting. Risk of bias (ROB) was assessed using the RoB 2 tool for randomized controlled trials (RCTs) and ROBINS-I for non-randomized studies. Due to high heterogeneity, meta-analysis was not performed. A total of 32 studies from 16 countries met the inclusion criteria (15 RCTs, 17 non-randomized studies). ROB was serious or high in the majority of studies. Seroprotection rates ranged from 93 to 100% in adults (seven studies) and from 91 to 100% in children (four studies). In the study involving adults aged 64 years and older, seroprotection was 65% with higher rates in persons who were previously vaccinated against tick-borne encephalitis virus. Safety was investigated in 27 studies. Rates of serious adverse events were below 5% in all age groups, with the majority not being causally related to the vaccine. IC51 is a safe vaccine with good seroprotective abilities in persons aged >2 months to <64 years. The body of evidence, however, is weakened by a large amount of heterogeneity in study and clinical trial methodology. Further well-designed RCTs with special risk groups are needed.
Topics: Encephalitis, Japanese; Humans; Japanese Encephalitis Vaccines; Vaccination
PubMed: 32043122
DOI: 10.1093/jtm/taaa016 -
Viruses Oct 2019Despite the existence of human vaccines, Japanese encephalitis (JE) remains the leading cause of human encephalitis in Asia. Pigs are described as the main amplifying...
Despite the existence of human vaccines, Japanese encephalitis (JE) remains the leading cause of human encephalitis in Asia. Pigs are described as the main amplifying host, but their role in JE epidemiology needs to be reassessed in order to identify and implement efficient control strategies, for both human and animal health. We aimed to provide a systematic review of publications linked to JE in swine, in terms of both individual and population characteristics of JE virus (JEV) infection and circulation, as well as observed epidemiological patterns. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement to select and analyze relevant articles from the Scopus database, 127 of which were included in the review. Pigs are central, but the implication of secondary hosts cannot be ruled out and should be further investigated. Although human vaccination cannot eradicate the virus, it is clearly the most important means of preventing human disease. However, a better understanding of the actual involvement of domestic pigs as well as other potential JEV hosts in different JEV epidemiological cycles and patterns could help to identify additional/complementary control measures, either by targeting pigs or not, and in some specific epidemiological contexts, contribute to reduce virus circulation and protect humans from JEV infection.
Topics: Animals; Communicable Disease Control; Culex; Disease Reservoirs; Encephalitis Virus, Japanese; Encephalitis, Japanese; Humans; Japanese Encephalitis Vaccines; Swine; Swine Diseases; Vaccination
PubMed: 31618959
DOI: 10.3390/v11100949 -
Journal of Travel Medicine Mar 2020Pregnant travellers and their offspring are vulnerable to severe outcomes following a wide range of infections. Vaccine-preventable diseases can have a particularly... (Meta-Analysis)
Meta-Analysis
Pregnant travellers and their offspring are vulnerable to severe outcomes following a wide range of infections. Vaccine-preventable diseases can have a particularly severe course in pregnant women, but little is known about the safety of travel vaccines in pregnant women. We performed a systematic review of all published literature concerning the safety of vaccines frequently given to travellers such as yellow fever, MMR (mumps, measles and rubella), influenza, Tdap (tetanus, diphtheria and pertussis), meningococcus, hepatitis A and B, rabies, polio, typhoid fever, tick-borne encephalitis and Japanese encephalitis vaccines. We included case series, cohort studies and randomized controlled trials (RCTs). For the meta-analysis, we included only RCTs that compared the administration of a vaccine to placebo or to no vaccine. Outcome measures included severe systemic adverse events, maternal outcomes related to the course of pregnancy, neonatal outcomes and local adverse events. We calculated the risk ratio and its 95% confidence interval as the summary measure. The safety of influenza vaccine is supported by high-quality evidence. For Tdap vaccine, no evidence of any harm was found in the meta-analysis of RCTs. A slight increase in chorioamnionitis rate was reported in 3 out of 12 observational studies. However, this small possible risk is far outweighed by a much larger benefit in terms of infant morbidity and mortality. Meningococcal vaccines are probably safe during pregnancy, as supported by RCTs comparing meningococcal vaccines to other vaccines. Data from observational studies support the safety of hepatitis A, hepatitis B and rabies vaccines, as well as that of the live attenuated yellow fever vaccine. We found little or no data about the safety of polio, typhoid, Japanese encephalitis, tick-borne encephalitis and MMR vaccines during pregnancy.
Topics: Female; Humans; Pregnancy; Travel Medicine; Travel-Related Illness; Vaccination; Vaccines
PubMed: 31616947
DOI: 10.1093/jtm/taz074 -
Parasites & Vectors May 2019Arboviruses represent a significant burden to public health and local economies due to their ability to cause unpredictable and widespread epidemics. To maximize early...
Arboviruses represent a significant burden to public health and local economies due to their ability to cause unpredictable and widespread epidemics. To maximize early detection of arbovirus emergence in non-endemic areas, surveillance efforts should target areas where circulation is most likely. However, identifying such hotspots of potential emergence is a major challenge. The ecological conditions leading to arbovirus outbreaks are shaped by complex interactions between the virus, its vertebrate hosts, arthropod vector, and abiotic environment that are often poorly understood. Here, we systematically review the ecological risk factors associated with the circulation of six arboviruses that are of considerable concern to northwestern Europe. These include three mosquito-borne viruses (Japanese encephalitis virus, West Nile virus, Rift Valley fever virus) and three tick-borne viruses (Crimean-Congo hemorrhagic fever virus, tick-borne encephalitis virus, and louping-ill virus). We consider both intrinsic (e.g. vector and reservoir host competence) and extrinsic (e.g. temperature, precipitation, host densities, land use) risk factors, identify current knowledge gaps, and discuss future directions. Our systematic review provides baseline information for the identification of regions and habitats that have suitable ecological conditions for endemic circulation, and therefore may be used to target early warning surveillance programs aimed at detecting multi-virus and/or arbovirus emergence.
Topics: Animals; Arbovirus Infections; Arboviruses; Arthropod Vectors; Disease Vectors; Encephalitis Virus, Japanese; Europe; Humans; Mosquito Vectors; Rift Valley fever virus; Risk Factors; West Nile virus
PubMed: 31133059
DOI: 10.1186/s13071-019-3515-7