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Area under influence of Chandipura epidemic in India. 

Area under influence of Chandipura epidemic in India. 

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Chandipura Virus (CHPV), a member of Rhabdoviridae, is responsible for an explosive outbreak in rural areas of India. It affects mostly children and is characterized by influenza-like illness and neurologic dysfunctions. It is transmitted by vectors such as mosquitoes, ticks and sand flies. An effective real-time one step reverse-transcriptase PCR...

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... the data obtained from Hospitals, Primary Health Cen- ters (PHC's), published and unpublished work it was found that in the Central and South Indian states of Maharashtra, Gujarat, Mad- hya Pradesh, Orissa, Uttar Pradesh, Bihar, Tamil Nadu, Karnataka, Andhra Pradesh and in few parts of Kerala Chandipura, the virus has spread its vicious web (Fig. 2). Statistical analysis of the epidemic shows an increase in cases from 2003 to 2010 (Fig. ...
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... Control (CDC), USA. Scientists at the CDC inferred it to be a rabies virus on the basis of electron microscopy study. The patient recovered from disease within week and his second CSF sample showed no virus but had virus-neutralizing antibody. This observation led CDC scientists to classify the virus as a member of Rhabdoviridae family and finally identified it as CHPV. Furthermore, it was studied that the patient got infected in the hospital, most probably by mosquito- bite, most likely Aedes aegypti . NIV scientists had earlier proved the vectorial capacity of mosquitoes to transmit CHPV (Rao et al., 1967). In 2003, CHPV came to the limelight with a report published by NIV scientists. On a large outbreak of an acute neurological illness of young children with high case-fatality, diagnosed as encephalitis and putatively associated with infection with the virus (Rao et al., 2004a,b). The illness was characterized by an acute onset fever, altered sensorium, seizures, diarrhea, and vomiting. Death or recov- ery occurred rapidly, within 2–3 days, and there was no sequel in survivors. These findings led to the clinical diagnosis of ‘brainstem encephalitis’ partly to explain the lack of increase of cells in the CSF, the etiology was described as CHPV (Rao et al., 2008). Some experts have raised doubts about the validity of evidences for CHPV etiology of epidemic encephalopathy (Commentary, 2010). An arbovirus expert in CDC has stated: Large outbreaks of viral encephalitis were attributed to the Chandipura Virus, an infre- quently recognized rhabdovirus. However, compelling evidence suggests that the relationship between illness and the virus are “questionable” (Sejvar, 2006). The detailed neurological findings were interpreted to demonstrate that the outbreak was not one of ‘encephalitis’, but an acute catastrophic event in the brain. The site of lesion was pinpointed to the brain supply territory of the mid- dle cerebral artery. The nature of the arterial pathology was not investigated, but it was suggested to be spasm or transient obstruc- tion due to vasculitis, rather than thrombo-embolism (Rao et al., 2004a,b). That the ‘acute brain attack’ could occur was new infor- mation. There was no clinical evidence of invasion by any pathogen, or of inflammatory lesions in pathology. If CHPV etiology is correct, the disease would be mediated by vasculitis, not encephalitis (Rao et al., 2004a,b; Ismail, 2004). Yet another study of acute encephalitis in Andhra Pradesh has provided intriguing results. In a hospital in Hyderabad all cases of encephalitis in children from May 2005 to April 2006 were prospectively investigated. Of the 90 cases, 25 yielded evidence of CHPV infection by PCR, IgM antibody or sero- conversion. However, the virus was not isolated. Among contacts of cases that were <15 years of age, 71–73% and among those who were >15 years, 94–97% had antibody evidence of past CHPV infection (Tandale et al., 2008). The role of CHPV in an epidemic brain attack was evaluated in Andhra Pradesh in 2003. This was the first report of infection related epidemic stroke. Both bacterial (especially Mycobacterium tuberculosis , Helicobacter pylori and Chlamydia pneumoniae ) and CHPV infection contribute to increased risk of stroke. Coagulation abnormalities and immunological reactions are among possible pathogenic pathways that link infection and stroke. There was a 13-fold increase in the incidence of pediatric stroke. There were 322 cases of stroke admitted in the hospital, and analyzed for age, sex, symptoms and signs. Out of 322 cases, 55 cases satisfied the inclusion and exclusion criteria and 28 cases were showing evidence of CHPV. Boys were affected more than girls and were in age group of 2–9 years. Possibly twenty-six encephalitis cases were reported in childrens between June 2004 to July 2004 (22 from Vadodara district and 4 from Punchamahal district). The male to female ratio was 1:1 and ages of patient range between 2 and 16 years. Eighteen of 23 patients have been died with a case fatality of 78.3% while 13 (72.25) of 18 died within 24 h of onset of disease. The remain- ing deaths occurred in 2–4 days post onset of illness (Chadha et al., 2005). Moreover, to confirm the etiology and to describe the clinico- epidemiological features, it was further investigated in Nagpur between June and September 2007. In Nagpur and nearby districts, a total of 78 cases were less than 15 years of age. Out of which 39 cases were found to be positive with CHPV. Among 39 Chandipura confirmed cases, 20 (51.3%) deaths were reported. There were 15 (38.4%) cases aged less than 5 years. From the data obtained from Hospitals, Primary Health Centers (PHC’s), published and unpublished work it was found that in the Central and South Indian states of Maharashtra, Gujarat, Mad- hya Pradesh, Orissa, Uttar Pradesh, Bihar, Tamil Nadu, Karnataka, Andhra Pradesh and in few parts of Kerala Chandipura, the virus has spread its vicious web (Fig. 2). Statistical analysis of the epidemic shows an increase in cases from 2003 to 2010 (Fig. 3). Under laboratory conditions, Phlebotomus papatasi is an efficient reservoir for the CHPV, showing growth, venereal and transovarial transmission (Mavale et al., 2006; Tesh and Modi, 1983). The experimental transmission of CHPV by P. (Euphlebotomus) argentipes has been recently demonstrated (Mavale et al., 2007). In natural conditions, it has been isolated from a pool of 253 unidentified phlebotomine sand flies ( Phlebotomus spp.) in the Maharashtra, India (Dhanda et al., 1970) and from unidentified sergentomyia in the Karimnagar district in Andhra Pradesh, India (Geeverghese et al., 2005). Four strains have also been isolated from batches of sand flies from Senegal, belonging to genus Sergentomyia (Ba et al., 1999; Fontenille et al., 1974). The data reveals about wide distribu- tion of the CHPV and important transmitters include Phlebotomus and Sergentomyia the two genera of sand flies (Depaquit et al., 2010). This was further confirmed by experiments, which demonstrates the susceptibility and transmission potential of P. argentipes (Annandale and Brunetti) for CHPV. In India, P. argentipes is one of the predominant species found in many areas endemic for CHPV, it was found that 65% of P. argentipes were susceptible to CHPV infection by the oral route. Transmission experiments were carried out by intra-thoracic inoculation because of re-feeding problems with this species. After incubation for 24 h, efficient transmission of CHPV to mice was observed. The estimated minimum transmission rate among the inoculated flies was 32%. CHPV in sand flies as well as in mice was detected and confirmed by immunofluorescent antibody assay and reverse transcription–polymerase chain reaction, respectively. The susceptibility of P. argentipes to CHPV and its potential to transmit the virus by bite has importance in epidemiology of CHPV. Similar laboratory experiments were conducted on Phlebotomus papatasi to determine the possible role of males in maintaining or sustaining the CHPV activity in nature. This study indicated that infected males are capable of passing on the virus to female sand flies while mating. The infection rate was found to be 12.5% in uninfected females when mated with infected males. The occurrence of venereal transmission of this virus may have epi- demiologic importance in the natural cycle of CHPV (Mavale et al., 2007). The original virus discovery was made in infant mice used for specimen inoculation (Bhatt and Rodrigues, 1967). NIV scientists have shown that CHPV inoculated in the brain causes fatal encephalitis in mice (Rao et al., 2004a,b). Chick embryos are also susceptible to infection (Pawar et al., 2005). These observations confirm the presence of virus receptors in a very wide range of host species, invertebrate and vertebrate, which may lead to the conclusion that from evolutionary viewpoint it is an ancient virus. Access of viruses to CNS can occur by either haematogenous or neuronal routes. Haematogenous spread is most common and can result in an altered BBB, as exemplified by arthropod-borne viral infections (Whitley and Gnann, 2002). Age dependent susceptibility of CHPV in Murrin model was reported by several authors. Research article reveals that CHPV is lethal to young mice by peripheral as well as central route of infection but adult mice are susceptible only through central route of infection. Thus, immature neuron is not a critical factor for CHPV pathogenesis. The virus is lethal to living system, as it produces vireamia and crosses the BBB to replicate in CNS. Virus specific IgM antibodies effectively clear the circulating virus but replicate in CNS continues. The virus affects immunity particularly by increasing secretion of pro-inflammatory cytokines in significant amount. It also reduces significant amounts of CD 4 , CD 8 and CD 19 cells. Cytokines also increase the permeabil- ity of BBB to allow the virus to enter the CNS, virus replication in CNS is responsible for neurological symptoms and mortality (Balakrishnan and Mishra, 2008). Vesiculovirus life cycle can be divided into discrete steps, namely 1. Adsorption of virus particle, penetration of virus into cell. 2. Uncoating and release of core RNP into the cytosol from late endosomal vesicles. 3. Transcription of the genome by viral polymerase. 4. Translation of viral mRNA. 5. Post-translational modifications of viral proteins. 6. Replication of viral genome. 7. Assembly of progeny particles and finally budding of mature virion. The entire vesiculovirus life cycle within an infected cell is cytosolic (Banerjee, 1987a). Genome RNA enwrapped with nucleocapsid protein N acts as a template for sequential transcription start- ing from 3 end of the genome to synthesize short leader RNA and five monocistronic capped and poly adenylated viral mRNAs. Viral RNA dependent RNA polymerase (RdRp) is composed of large protein L, the ...

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... Treatment is usually focused on managing complications such as increased intracranial pressure, seizures, and hyponatremia. Currently, there is no vaccine available and no specific antiviral medications are effective against this infection [2] . ...
... Symptoms and disease progression in Chandipura virus infection.[2] ...
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... The accelerated cell death of affected neurons through the FAS-linked apoptotic pathway has been identified as the mechanism responsible for this rapid fatality. Though the disease mainly affects children aged 2.5 months to 15 years, cases have been reported sporadically in Warangal, Andhra Pradesh (now Telangana), and Vidarbha, Maharashtra [2,3]. ...
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... Summary of recorded CHPV outbreaks. A total of 7 CHPV outbreaks have occurred since 2003, which tended to peak with the monsoon season and had case fatality rates between 28 and 79 percent[1,3,[9][10][11][12][13][14]. The table includes the date(s) of outbreaks, regions affected, total number of acute encephalitis syndrome (AES) cases, the age of affected patients, and the case fatality rate (CFR). ...
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... So far the disease has been restricted to India [2]. A few cases have also been suspected in Sri Lanka. ...
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... Humans: CHPV causes acute encephalitis in humans especially in children [9] . ...
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... It has five structural proteins which are coded by genome: the nucleocapsid protein (N), the phosphoprotein (P), the matrix protein (M), the glycoprotein (G) and large structural protein (L). These are produced in the form of five monocistronic mRNAs [3]. The available information suggests that sandflies are the vectors for this virus while antibodies against this have been detected in a wide range of vertebrate animals [4]. ...
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... Chandipura virus (CHPV) ( Table 2, Figure 2b,c) is an important cause of morbidity, primarily in India. However, apart from India, to date, CHPV has also been detected in Bhutan, Nepal, Sri Lanka, and African countries (Nigeria and Senegal) [179]. The virus was first discovered during a fever outbreak in 1965 in Nagpur, Maharashtra. ...
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... B esides its well-documented role in the skeletomuscular system, vitamin D also modulates protective immunity against viruses (1). Population-level observational studies argued that vitamin D deficiency elevates the risk of lung infection by the respiratory syncytial virus and influenza A virus and exacerbates inflammatory lung injuries (24). Similarly, a weakened vitamin D pathway escalated hepatitis C virus infections and the incidence of hepatocellular carcinoma (5). ...
... Chandipura virus (CHPV) is a neurotropic RNA virus belonging to the Rhabdoviridae family and vesiculovirus genera (23). This virus has been implicated in several recent epidemic outbreaks of acute encephalitis in the Indian subcontinent that were characterized by influenza-like illness, neurologic manifestations, and a high case fatality rate (24). It has been suggested that inadequate peripheral immune reactions, including those elicited by cells of the monocyte and macrophage lineage, allow the dissemination of CHPV to the CNS, triggering neuronal infection and widespread cell death (25). ...
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Besides its functions in the skeletomuscular system, vitamin D is known to alleviate viral-inflicted pathologies. However, the mechanism underlying protective vitamin D function remains unclear. We examined the role of vitamin D in controlling cellular infections by Chandipura virus, an RNA virus implicated in human epidemics. How immune signaling pathways, including those regulating NF-κB and IFN regulatory factors (IRFs), are activated in virus-infected cells has been well studied. Our investigation involving human- and mouse-derived cells revealed that vitamin D instructs the homeostatic state of these antiviral pathways, leading to cellular resilience to subsequent viral infections. In particular, vitamin D provoked autoregulatory type 1 IFN–IRF7 signaling even in the absence of virus infection by downmodulating the expression of the IFN-inhibitory NF-κB subunit RelB. Indeed, RelB deficiency rendered vitamin D treatment redundant, whereas IRF7 depletion abrogated antiviral vitamin D action. In sum, immune signaling homeostasis appears to connect micronutrients to antiviral immunity at the cellular level. The proposed link may have a bearing on shaping public health policy during an outbreak.