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PLoS Neglected Tropical Diseases Nov 2023Neglected tropical diseases (NTDs) affect most impoverished communities in developing countries, like Myanmar in Southeast Asia. NTDs have been understudied and...
BACKGROUND
Neglected tropical diseases (NTDs) affect most impoverished communities in developing countries, like Myanmar in Southeast Asia. NTDs have been understudied and underreported in Myanmar.
METHODS
A systematic review of published and grey literature (1900-2023) on neglected tropical diseases (NTDs) in Myanmar was conducted. The literature search included five international databases: PubMed, EMBASE, Ovid Global Health, and Web of Science Core Collection and one national database: the Myanmar Central Biomedical Library (locally published papers and grey literature). The selection criteria included articles with all types of study designs of current or previous infections conducted in humans, that reported NTDs, recognised by WHO, US CDC, and listed in PLoS NTDs. We included melioidosis and rickettsioses which we consider also meet the definition of an NTD.
RESULTS
A total of 5941 records were retrieved and screened, of which, 672 (11%) met the selection criteria and were included in this review. Of the included articles, 449 (65%) were published after 2000 and 369 (55%) were from two regions (Yangon and Mandalay) of Myanmar. Of the included articles, 238 (35%) reported bacterial NTDs, 212 (32%) viral NTDs, 153 (23%) helminth NTDs, 25 (4%) protozoal NTDs and 39 (6%) reported more than one aetiology. Based on reported frequency in descending order, the bacterial NTDs were leprosy, Escherichia coli enteritis, salmonellosis, cholera, shigellosis, melioidosis, leptospirosis and rickettsioses; the viral NTDs were dengue, chikungunya and Japanese encephalitis virus (JEV) infection; the protozoal NTDs were amoebiasis, giardiasis and leishmaniasis, and the helminth NTDs were ascariasis, trichuriasis, hookworm disease, filariasis and strongyloidiasis.
CONCLUSION
This review summarises NTDs reported in Myanmar over the past 100 years. The findings suggest that most NTDs are likely to be under reported, especially from the majority of the country which is far from academic centres. Research capacity building together with strengthening of laboratory systems would lead to better understanding of the true burden of NTDs in Myanmar.
TRIAL REGISTRATION
PROSPERO registration ID: CRD42018092627.
Topics: Animals; Humans; Myanmar; Melioidosis; Ascariasis; Helminths; Neglected Diseases; Tropical Medicine; Encephalitis, Japanese; Rickettsia Infections
PubMed: 37910592
DOI: 10.1371/journal.pntd.0011706 -
BioRxiv : the Preprint Server For... Aug 2023A diverse group of RNA viruses including Rabies, Polio, La Crosse, West Nile, Zika, Nipah, Eastern and Western equine encephalitis, Venezuelan equine encephalitis,...
A diverse group of RNA viruses including Rabies, Polio, La Crosse, West Nile, Zika, Nipah, Eastern and Western equine encephalitis, Venezuelan equine encephalitis, Japanese encephalitis, and tick-borne encephalitis viruses have the ability to gain access to and replicate in the central nervous system (CNS), causing severe neurological disease. Current treatment for these patients is generally limited to supportive care. To address the need for a generalizable antiviral, we utilized a strategy of mutagenesis to limit virus replication. We evaluated ribavirin (RBV), favipiravir (FAV) and -hydroxycytidine (NHC) against La Crosse virus (LACV) which is the primary cause of pediatric arboviral encephalitis cases in North America. NHC was more potent than RBV or FAV in neuronal cells. Oral administration of molnupiravir (MOV), the 5'-isobutyryl prodrug of NHC, decreased neurological disease development by 32% following intraperitoneal (IP) infection of LACV. MOV also reduced disease by 23% when virus was administered intranasally (IN). NHC and MOV produced less fit viruses by incorporating predominantly G-to-A or C-to-U mutations. Furthermore, NHC also inhibited two other orthobunyaviruses, Jamestown Canyon virus and Cache Valley virus. Collectively, these studies indicate that NHC/MOV has therapeutic potential to inhibit virus replication and subsequent neurological disease caused by this neurotropic RNA virus.
PubMed: 37662274
DOI: 10.1101/2023.08.22.554316 -
Frontiers in Neurology 2023Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is an inflammatory demyelinating disease of the central nervous system (CNS) with the... (Review)
Review
Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is an inflammatory demyelinating disease of the central nervous system (CNS) with the presence of conformation-sensitive antibodies against MOG. The spectrum of MOGAD includes monophasic/relapsing optic neuritis, myelitis, neuromyelitis optica spectrum disorder (NMOSD) phenotype without aquaporin 4 (AQP4) antibodies, acute/multiphasic demyelinating encephalomyelitis (ADEM/MDEM)-like presentation, and brainstem and cerebral cortical encephalitis. There is no apparent female preponderance in MOGAD, and MOGAD can onset in all age groups (age at onset is approximately 30 years on average, and approximately 30% of cases are in the pediatric age group). While prevalence and incidence data have been available for AQP4+ NMOSD globally, such data are only beginning to accumulate for MOGAD. We reviewed the currently available data from population-based MOGAD studies conducted around the world: three studies in Europe, three in Asia, and one joint study in the Americas. The prevalence of MOGAD is approximately 1.3-2.5/100,000, and the annual incidence is approximately 3.4-4.8 per million. Among White people, the prevalence of MOGAD appears to be slightly higher than that of AQP4+ NMOSD. No obvious latitude gradient was observed in the Japanese nationwide survey. The data available so far showed no obvious racial preponderance or strong HLA associations in MOGAD. However, precedent infection was reported in approximately 20-40% of MOGAD cases, and this is worthy of further investigation. Co-existing autoimmune disorders are less common in MOGAD than in AQP4+ NMOSD, but NMDAR antibodies may occasionally be positive in patients with MOGAD. More population-based studies in different populations and regions are useful to further inform the epidemiology of this disease.
PubMed: 37789888
DOI: 10.3389/fneur.2023.1260358 -
No Shinkei Geka. Neurological Surgery Nov 2023Status epilepticus(SE)is defined as a prolonged seizure and is a common neurological emergency with high morbidity and mortality rates. As uncontrolled SE causes...
Status epilepticus(SE)is defined as a prolonged seizure and is a common neurological emergency with high morbidity and mortality rates. As uncontrolled SE causes irreversible neurological damage, prompt diagnosis and treatment are required. If anti-seizure medications and benzodiazepines, which are initial treatments for SE, are not effective and SE deteriorates to refractory, anesthetic drugs are needed to suppress seizure activity under electroencephalogram(EEG)monitoring. Continuous EEG monitoring is useful not only for evaluating the control of SE but also for diagnosing non-convulsive SE(NCSE)and psychogenic non-epileptic seizures. New-onset refractory status epilepticus is defined as refractory SE in a patient without active epilepsy and without a clear acute or active structural, toxic, or metabolic cause. Because autoimmune encephalitis is the most frequently identified cause, immunotherapy can be attempted in addition to antiepileptic treatment within 2 weeks. Although NCSE is the major cause of unconsciousness, diagnosis is difficult because of uncertain clinical symptoms. Continuous EEG monitoring over 24 h is crucial for diagnosis, although arterial spin labeling-magnetic resonance imaging is alternatively useful. Finally, the building of a multidisciplinary cooperation system is required for prompt diagnosis and intensive treatment for controlling SE.
Topics: Humans; Status Epilepticus; Anticonvulsants; Encephalitis; Electroencephalography
PubMed: 38011881
DOI: 10.11477/mf.1436204853 -
Brain, Behavior, and Immunity Jul 2023The molecular pathological mechanisms underlying schizophrenia remain unclear; however, genomic analysis has identified genes encoding important risk molecules. One such...
The molecular pathological mechanisms underlying schizophrenia remain unclear; however, genomic analysis has identified genes encoding important risk molecules. One such molecule is neurexin 1α (NRXN1α), a presynaptic cell adhesion molecule. In addition, novel autoantibodies that target the nervous system have been found in patients with encephalitis and neurological disorders. Some of these autoantibodies inhibit synaptic antigen molecules. Studies have examined the association between schizophrenia and autoimmunity; however, the pathological data remain unclear. Here, we identified a novel autoantibody against NRXN1α in patients with schizophrenia (n = 2.1%) in a Japanese cohort (n = 387). None of the healthy control participants (n = 362) were positive for anti-NRXN1α autoantibodies. Anti-NRXN1α autoantibodies isolated from patients with schizophrenia inhibited the molecular interaction between NRXN1α and Neuroligin 1 (NLGN1) and between NRXN1α and Neuroligin 2 (NLGN2). Additionally, these autoantibodies reduced the frequency of the miniature excitatory postsynaptic current in the frontal cortex of mice. Administration of anti-NRXN1α autoantibodies from patients with schizophrenia into the cerebrospinal fluid of mice reduced the number of spines/synapses in the frontal cortex and induced schizophrenia-related behaviors such as reduced cognition, impaired pre-pulse inhibition, and reduced social novelty preference. These changes were improved through the removal of anti-NRXN1α autoantibodies from the IgG fraction of patients with schizophrenia. These findings demonstrate that anti-NRXN1α autoantibodies transferred from patients with schizophrenia cause schizophrenia-related pathology in mice. Removal of anti-NRXN1α autoantibodies may be a therapeutic target for a subgroup of patients who are positive for these autoantibodies.
Topics: Mice; Animals; Schizophrenia; Calcium-Binding Proteins; Neural Cell Adhesion Molecules; Autoantibodies; Phenotype
PubMed: 37004758
DOI: 10.1016/j.bbi.2023.03.028 -
Nature Communications Jan 2024Cytoskeleton is extensively recruited by flaviviruses for their infection. In this study, we uncovered an essential role of a nuclear membrane protein, SAD1/UNC84 domain...
Cytoskeleton is extensively recruited by flaviviruses for their infection. In this study, we uncovered an essential role of a nuclear membrane protein, SAD1/UNC84 domain protein 2 (SUN2) linking cytoskeleton and nucleoskeleton in the flavivirus replication. CRISPR/Cas9-mediated knockout of SUN2, but not SUN1, significantly reduces the replication of Zika virus (ZIKV), dengue virus (DENV), and Japanese encephalitis virus (JEV). In contrast, SUN2 does not affect the infection of non-flaviviridae RNA viruses. All three regions of SUN2 are required for its proviral effect. Mechanistically, SUN2 facilitates rearrangement of cytoskeleton and formation of replication organelles induced by viral infection, and hence promotes viral RNA synthesis. SUN2 is required for the interaction between cytoskeleton actin and ZIKV nonstructural protein 1 (NS1). Expression of dominant negative Nesprin-1 and Nesprin-2, which connect SUN2 to cytoskeleton proteins, alleviates the interaction between actin and NS1 and reduces viral replication levels. In a neonatal mouse infection model, SUN2 knockout dramatically alleviates the in vivo ZIKV replication and development of neuropathology. This work elucidates that recruitment of cytoskeleton proteins by flavivirus is coordinated by nuclear membrane proteins SUN2 and Nesprins, providing evidence for a link between nuclear membrane proteins and flavivirus infection.
Topics: Animals; Mice; Actins; Cytoskeleton; Membrane Proteins; Viral Nonstructural Proteins; Virus Replication; Zika Virus; Zika Virus Infection
PubMed: 38177122
DOI: 10.1038/s41467-023-44580-6 -
Annals of Medicine and Surgery (2012) Mar 2024Japanese encephalitis virus (JEV), an RNA virus transmitted by Culex mosquitoes, primarily cycles between aquatic birds and mosquitoes with pigs as amplifying hosts,... (Review)
Review
Japanese encephalitis virus (JEV), an RNA virus transmitted by Culex mosquitoes, primarily cycles between aquatic birds and mosquitoes with pigs as amplifying hosts, posing a significant global encephalitis threat. The emergence and spread of the JEV in new epidemiological regions, such as recent cases in Australia and nonendemic areas like Pune, India, raise significant concerns. With an estimated 68 000 clinical cases and 13 600 to 20 400 deaths annually, JEV poses a substantial global health threat. The virus primarily affects children, with a case-fatality ratio of 20-30% and long-term neurological sequelae in survivors. The changing epidemiology, influenced by factors like bird migration, climate change, and increased urbanization, contributes to the geographic expansion of JEV. The recent outbreaks underscore the potential for the virus to establish itself in nonendemic regions, posing a threat to populations previously considered at low-risk. With limited treatment options and high rates of neurological complications, continued surveillance, traveler vaccination, and research into treatments are crucial to mitigate the impact of JEV on human health. The evolving scenario necessitates proactive measures to prevent and control the spread of the virus in both endemic and newly affected areas.
PubMed: 38463109
DOI: 10.1097/MS9.0000000000001739 -
Nature Communications Jan 2024To curb viral epidemics and pandemics, antiviral drugs are needed with activity against entire genera or families of viruses. Here, we develop a cell-based multiplex...
To curb viral epidemics and pandemics, antiviral drugs are needed with activity against entire genera or families of viruses. Here, we develop a cell-based multiplex antiviral assay for high-throughput screening against multiple viruses at once, as demonstrated by using three distantly related orthoflaviviruses: dengue, Japanese encephalitis and yellow fever virus. Each virus is tagged with a distinct fluorescent protein, enabling individual monitoring in cell culture through high-content imaging. Specific antisera and small-molecule inhibitors are employed to validate that multiplexing approach yields comparable inhibition profiles to single-virus infection assays. To facilitate downstream analysis, a kernel is developed to deconvolute and reduce the multidimensional quantitative data to three cartesian coordinates. The methodology is applicable to viruses from different families as exemplified by co-infections with chikungunya, parainfluenza and Bunyamwera viruses. The multiplex approach is expected to facilitate the discovery of broader-spectrum antivirals, as shown in a pilot screen of approximately 1200 drug-like small-molecules.
Topics: Humans; Antiviral Agents; High-Throughput Screening Assays; Viruses; Virus Diseases; Cell Culture Techniques; Virus Replication
PubMed: 38168091
DOI: 10.1038/s41467-023-44339-z -
Veterinary Microbiology Dec 2023N6-methyladenosine (mA), the most common modification in mammalian mRNA and viral RNA, regulates mRNA structure, stability, translation, and nuclear export. The Japanese...
N6-methyladenosine (mA), the most common modification in mammalian mRNA and viral RNA, regulates mRNA structure, stability, translation, and nuclear export. The Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus causing severe neurologic disease in humans. To date, the role of mA modification in JEV infection remains unclear. Herein, we aimed to determine the impact of mA methylation modification on JEV replication in vitro and in vivo. Our results demonstrated that the overexpression of the mA reader protein YTHDF1 in vitro significantly inhibits JEV proliferation. Additionally, YTHDF1 negatively regulates JEV proliferation in YTHDF1 knockdown cells and YTHDF1 knockout mice. MeRIP-seq analysis indicated that YTHDF1 interacts with several interferon-stimulated genes (ISGs), especially in IFIT3. Overall, our data showed that YTHDF1 played a vital role in inhibiting JEV replication. These findings bring novel insights into the specific mechanisms involved in the innate immune response to infection with JEV. They can be used in the development of novel therapeutics for controlling JEV infection.
Topics: Humans; Mice; Animals; Encephalitis Virus, Japanese; Host-Pathogen Interactions; Encephalitis, Japanese; Cell Line; RNA, Messenger; Virus Replication; Mammals; RNA-Binding Proteins
PubMed: 37925877
DOI: 10.1016/j.vetmic.2023.109887 -
Indian Journal of Pediatrics Oct 2023The study compared the clinical profile and outcomes of Japanese encephalitis (JE) and acute encephalitis syndrome (AES) in children. Fifty-six consecutive children with...
The study compared the clinical profile and outcomes of Japanese encephalitis (JE) and acute encephalitis syndrome (AES) in children. Fifty-six consecutive children with symptoms fulfilling the WHO clinical case definition of AES from June 2018 to June 2020 were included in the study. All patients who tested positive for either serum or cerebrospinal fluid (CSF) anti-JE-IgM antibodies were JE patients (n = 24) and compared with non-JE AES cases (n = 32). Fever, seizures, and altered sensorium were the most common presenting symptoms. Low GCS, status epilepticus, meningeal irritation, raised CSF protein, and INR > 1.5 of JE children showed significant association with mortality (p value < 0.05), whereas only low GCS showed significant association in non-JE AES cases. The JE-specific mortality rate was 29%, which was less than the mortality rate of non-JE AES children at 41%. Both JE and non-JE AES children had a similar clinical profile, but only the JE children's poor clinical and laboratory parameters were associated with adverse outcomes.
Topics: Child; Humans; Encephalitis, Japanese; Acute Febrile Encephalopathy; Seizures; Fever; Status Epilepticus; Antibodies, Viral
PubMed: 36765003
DOI: 10.1007/s12098-022-04424-5