Chandipura virus (CHPV), initially thought to be an orphan virus, was later reported to cause sporadic cases of fever with arthralgia, Reye’s syndrome, and. Chandipura virus (CHPV; genus Vesiculovirus, family Rhabdoviridae) is an emerging tropical pathogen with a case fatality rate of 55 to 75% that predominantly. Chandipura virus: A virus that causes fever, symptoms similar to those of flu, and acute encephalitis (inflammation of the brain). Chandipura virus was first.
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Rhabdoviridae garnered global attention as an emerging neurotropic pathogen inflicting high mortality in children within 24 h of commencement of symptoms. The outbreaks in Central India witnessed case fatality rates ranging from per cent in Andhra Pradesh and Gujarat with typical encephalitic symptoms. Due to the acute sickness and rapid deterioration, the precise mechanism of action of the virus is still unknown. Recent studies have shown increased expression of CHPV phosphoprotein upto 6 h post infection PI demonstrating CHPV replication in neuronal cells and the rapid destruction of the cells by apoptosis shed light on the probable mechanism of rapid death in children.
Phlebotomine sandflies are implicated as vectors due to their predominance in endemic areas, repeated virus isolations and their ability to transmit the virus by transovarial and venereal routes. Significant contributions have been made in the development of diagnostics and prophylactics, vaccines and antivirals. Two candidate vaccines, viz. Rhabdomyosarcoma and Phlebotomus papatasi cell lines as well as embryonated chicken eggs have been found useful in virus isolation and propagation.
Despite these advancements, CHPV has been a major concern in Central India and warrants immediate attention from virologists, neurologists, paediatricians and the government for containing the virus. Chandipura virus CHPVan arbovirus belonging to genus Vesiculovirus in the family Rhabdoviridae has gained global attention as an encephalitis causing virus after the outbreaks in central India 12345.
A total of child deaths; in Andhra Pradesh APin Maharashtra and 24 in Gujarat were reported during the outbreaks. In majority of the cases, mortality was reported within 24 h of commencement of symptoms. The disease was characterized by sudden onset of high fever followed by seizures, altered sensorium, diarrhoea and vomiting followed by death in majority of the cases 45.
The rapid deterioration and death among the patients could not be explained satisfactorily to date though several hypotheses have been postulated 678.
Changing clinical scenario in Chandipura virus infection
The cause of death was interpreted as encephalitis, acute catastrophic event in the brain, spasm or transient obstruction due to vasculitis. However, none of these could be confirmed scientifically 3. The presence of CHPV in the brain biopsy specimens as detected by immunofluorescent antibody technique during the early investigations pointed towards the probable association of CHPV 4. But the role of CHPV and the precise mechanism of action could not be explained 678.
The investigators reported rapid apoptosis vkrus infected neurons though FAS-associated death domain via an extrinsic pathway following the activation of caspases -8 and -3 as well as prominent cleavage of ADP-ribose polymerase 7. The disease was predominant in the lower income strata of the population and the affected age group ranged from 2.
Advances in Virology
Though the outbreaks were contained, sporadic cases were reported from Warangal district of Andhra Pradesh now Telangana and Vidarbha region of Maharashtra with a few case fatalities 910 Family Rhabdoviridae of Order Mononegavirales comprises negative sense, single stranded viruses with a bullet shaped virions of approximately 11kb. Amongst the 10 genera, genus Lyssavirus and genus Vesiculovirus are of public health importance. Rabies virus, the prototype virus of genus Lyssavirusis the most important pathogen of Rhabdoviridae with a worldwide distribution.
Genus Vesiculoviruscomprises viruses of human and veterinary importance; the prototype specimen being vesicular stomatitis Indiana virus, which infects cattle, horses, pigs, etc.
Majority of the viruses in the genus are transmitted by Phlebotomine sandflies. Though CHPV was first isolated init was considered as an orphan or concomitant virus due to low pathogenicity to cause infections in man and domestic animals 1.
No efforts were, therefore, made to develop diagnostics or prophylactics. However, post outbreak in central India, CHPV garnered global attention as a human pathogen of public health importance and significant advances were made in basic understanding of the virus as well as in the development of diagnostics and vaccines.
The present review is focused on the studies conducted since on virus vector interactions and development of diagnostics and prophylactics with a special mention on the changing clinical scenario observed during the recent outbreaks. No attempt is made to review the studies conducted at the molecular level though significant contributions have been reported 3612 Characterization of the agent subsequently revealed it as a new virus.
It was named after the place of isolation and placed under the Chandipurq group, genus Vesiculovirusfamily Rhabdoviridae CHPV was characteristic with its unique pattern of pathogenesis as it killed infant mice within 10 h of inoculation through intracerebral route as well as produced cytopathic effect CPE in vertebrate cell lines within h of inoculation, a probable reason for missing the agent on earlier occasions The chancipura was subsequently isolated from Phlebotomine sandflies, the incriminated vector of CHPV, collected from Aurangabad district, Maharashtra, India, during After its discovery in and subsequent isolation from sandflies, no cases of human involvement or any outbreak of public health importance were reported from the area or elsewhere for approximately two decades.
Seroprevalence studies carried out in retrospective samples collected since from different parts of chansipura country demonstrated prevalence of neutralizing N antibodies in humans Table I. N-antibodies were also detected in animals 1 Potential of CHPV to cause mortality in humans was detected when the virus was held solely responsible for the death of an 11 yr old child in Raipur district, Madhya Pradesh now in Chhattisgarh State.
The child developed complications and died within 24 h of admission due to CHPV induced encephalopathy The rapid progression and the fatality rates were so confusing that the outbreak was referred to as killer brain disease or mystery disease In the following year, a focal outbreak with similar virua was reported from Gujarat with CFR exceeding 75 per cent 5.
Though no outbreak with high CFR was reported sincerecurring sporadic cases were reported from Warangal district of Andhra Pradesh now in Telangana and Vidarbha region of Maharashtra 9 Presence of neutralizing antibodies to CHPV in human and animal samples collected since substantiates this chamdipura and points towards the circulation of CHPV or a closely related virus across the country 1 Apart from India, CHPV activity was prevalent in West Africa since as the virus has been isolated from a hedgehog and wild caught phlebotomine sandflies from Nigeria and Senegal, respectively 19 Retrospective studies with human serum samples collected from to from different parts of the country showed prevalence of N-antibodies in humans and domestic animals across the country except in Kashmir and Arunachal Pradesh N-antibody prevalence ranged from a minimum of 6 per cent in Kerala to a maximum of 89 per cent in Uttar Pradesh while other places showed varying percentages Table I.
Changing clinical scenario in Chandipura virus infection
N-antibodies to CHPV were also detected in animals serum samples including domestic animals, camels, Rhesus monkeys, etc. Serological studies also demonstrated presence of N-antibodies in pigs and other domestic animals in the affected areas 1. However, none of these animals exhibited sickness. Experimental studies with Phlebotomus papatasi showed their potential not only to replicate the virus but also to transmit the virus through vertical, venereal and horizontal routes 23 The potential of P.
This mechanism could have helped the virus to remain dormant for prolonged periods and initiate outbreaks when sandfly population increased under favourable conditions. However, their role as vector is still not confirmed. However, the role of Sergentomyia spp.
Members of genus Sergentomyia are predominantly peridomestic in nature and seldom come in contact with humans unlike Phlebotomus sandflies. Studies in Vidarbha region showed a reverse trend in which Phlebotomus sandflies were being replaced by Sergentomyia spp.
This was in contrast to that recorded during s and s from the area when the former was predominant However, more systematic studies on the bionomics of Sergentomyia spp.
Mosquitoes were not found to be involved in the transmission of CHPV though several chandipra of mosquitoes replicated and transmitted the virus experimentally 1. Among the different mosquito species studied, Aedes aegypti was found to be highly susceptible and could transmit the virus more efficiently than others through vertical and venereal chandipuura under laboratory conditions The probability of Ae.
A large number of vertebrate and insect cell lines replicated CHPV giving high yields. Vertebrate cell lines showed distinct chanvipura effects CPE while insect cell lines did not. CPE was distinct and characterized by rounding of cells followed by detachment and rapid deterioration. Chick embryo was also found susceptible to CHPV and yielded high titre An animal model for studying the pathogenesis was developed using Swiss albino mice by Jadi He demonstrated infant mice mortality when inoculated with CHPV by intracranial ICintraperitoneal, subcutaneous, intradermal, nasal and oral routes.
Adult mice showed age related susceptibility as adults above the age of 17 days survived CHPV infection through IC route, but those below firus days succumbed to infection.
The infected mice showed convulsions followed by paralysis of front or hind limbs.
Elucidating the Interacting Domains of Chandipura Virus Nucleocapsid Protein
Ruffled fur, hunched posture, rapid running movements when stimulated were other symptoms. Urine retention was also observed in certain cases. Histopathological analysis showed moderate perivascular cuffing in brain, mild congestion and collapsed areas in lungs, increased intracellular spaces in heart and focal degenerative changes in liver.
Blood brain barrier breakage and virus replication in central nervous system was observed when inoculated through IC or intravenous routes RNA viruses are known for mutation as it provides evolutionary advantages over their host organisms in survival. The first indication of enhanced virulence of the virus was observed in An 11 yr old child was presented with high grade fever, vomiting and loose motion and developed unusual complications and collapsed within 1 h of admission.
The patient experienced convulsions lasting for min at an interval of min and had generalized hypertonia of the limbs, hyper-reflexia, bilateral extensor plantar response with sudden drop in blood pressure. The investigators felt it a case of encephalitic syndrome and needed further studies to confirm the role of CHPV. The outbreaks in Andhra Pradesh APMaharashtra and Gujarat were explosive due to a large number of cases and deaths.
Another characteristic was that only children below 15 were involved in the outbreaks. The outbreaks reported the death of children; in AP, in Maharashtra and 24 in Gujarat. In AP also, the clinical progression of the disease was similar to that of the index case. Considering the high case fatality in the outbreaks, it was presumed that the virus genome might have mutated to produce enhanced virulence.
However, sequence analysis of N, P and G proteins of the prototype strain and the recent isolates showed no significant change at the amino acid level Vesicular eruptions were seen in a few cases during Gujarat outbreak, which developed to hyperpigmentation on healing 5. Another clinical manifestation observed was bilateral crepitations on auscultation of lungs in a majority of patients. Tachycardia, another typical clinical manifestation of CHPV was also present among the patients.
Palpable liver and elevated levels of alanine aminotransferase and aspartate aminotransferase were also detected in a few cases. Subsequent outbreaks reported from Warangal district 9 and Nagpur, Maharashtra 10 also had identical clinical manifestations.
However, a low CFR was observed.
chandipurs Tremendous progress has been made in the development of diagnostics and prophylactics The significant findings are reviewed here for ready reference:. Immunofluorescent antibody technique IFA and virus isolation using cell lines: Jadi et al 28 demonstrated the application of sandfly and mosquito cell lines for early detection of CHPV as the virus antigen could chanripura detected within 2 h of inoculation using IFA.
The application of cell culture systems has also been successfully employed to detect and isolate the virus as CHPV produced characteristic CPE in vertebrate cell lines 411 Diagnosis with molecular tools: Since the progression of disease in children is rapid causing death within h of commencement of symptoms, the need for rapid diagnosis was felt.
A highly sensitive diagnostic RT-PCR targeting N gene bp with a detection limit of plaque forming units pfu has been developed and is virua used for routine diagnosis of human and sandfly samples 10 ,