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Many mosquito-borne viruses (arboviruses) are endemic in Africa, contributing to systemic and neurological infections in various geographical locations on the continent. While most arboviral infections do not lead to neuroinvasive diseases of the central nervous system, neurologic diseases caused by arboviruses include flaccid paralysis, meningitis, encephalitis, myelitis, encephalomyelitis, neuritis, and post-infectious autoimmune or memory disorders. Here we review endemic members of the Flaviviridae and Togaviridae families that cause neurologic infections, their neuropathogenesis and host neuroimmunological responses in Africa. We also discuss the potential for neuroimmune responses to aide in the development of new diagnostics and therapeutics, and current knowledge gaps to be addressed by arbovirus research., Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Klein.)

Pancreas disease (PD) in salmonid fish is caused by an infection with Salmonid alphavirus (SAV) and remains as one of the major health problems in the European fish farming industry. Sequence studies have revealed a genetic diversity among viral strains. A subtype of SAV (SAV3) is causing an epizootic in farmed salmonids in Norway. Here we evaluate efficacy and safety of an inactivated virus vaccine based on ALV405, a strain of SAV3 that was isolated from Norwegian salmon. The vaccine provided an average relative percent survival (RPS) of 98.5 in an intraperitoneal challenge model, and induced nearly total protection against PD in a cohabitant challenge model. It provided significant protection against SAV-induced mortality also in a field trial under industrial conditions. Local reactions seen as melanization and adhesions in the visceral cavity were less severe than those induced by two commercial vaccines. Finally, we demonstrated that the protection is not impaired when the ALV405 antigen is combined with other viral or bacterial antigens in a polyvalent vaccine. The results confirm that efficient and safe protection against SAV infection and development of PD is possible using an inactivated virus vaccine, both alone and as a component in a polyvalent vaccine., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

In February 2008, a Mayaro fever virus (MAYV) outbreak occurred in a settlement in Santa Barbara municipality, northern Brazil. Patients had rash, fever, and severe arthralgia lasting up to 7 days. Immunoglobulin M against MAYV was detected by ELISA in 36 persons; 3 MAYV isolates sequenced were characterized as genotype D.

A transgenic cell line for the detection of salmon interferons (IFNs) has been established. It is based on a CHSE-214 cell line containing a reporter construct expressing firefly luciferase under the control of the rainbow trout promoter for the IFN-induced Mx1 gene. This cell line, named CHSE-Mx10, showed IFN-induced luciferase expression after more than 80 passages, confirming the stability of this cell line. Interestingly, the Mx promoter was shown to respond to both salmon IFN-alpha/beta and trout IFN-gamma in a dose-dependent manner, while there was no response to TNF-alpha and IL-1beta. IFN-alpha/beta activity could be measured at a range of 9-150 U/ml, and IFN-gamma showed activity between 10 and 100 ng/ml. The reproducibility of both responses was good. The CHSE-Mx10 reporter system constitutes a versatile tool to study the induction and regulation of IFN signaling in teleost fish. A preliminary study presented herein suggests that both infectious pancreas necrosis virus (IPNV) and salmon pancreas disease virus (SPDV) may block activation of the Mx promoter in CHSE-Mx10 stimulated with IFN-alpha/beta.

Una virus (UNAV), Togaviridae family, is widely distributed in South America, where infections have been detected in mosquitoes and vertebrate hosts (humans, birds and horses). We analyzed human sera from Córdoba inhabitants aged 44 to 89 years and using a neutralization test, we found a prevalence of UNAV antibodies of 3.8% (3/79). The low titers detected suggest past infections probably acquired in rural areas of the Province of Córdoba (central Argentina). None sera were found positive for MAYV neutralizing antibodies. This is the first report of human infections by UNAV in Argentina.

Objective: To isolate arbovirus from mosquitoes caught from Yantai., Methods: The isolated viruses were tested for their physico- chemical properties, examined by electron microscopy and specific immuno-reactivity., Results: Fifteen strains of virus were isolated from mosquitoes in 1994 from Yantai. Three of them were further assayed. The results showed that the viruses could multiply on C6/36 cell and produce typical cytopathogenic effect. The viruses couldn't cause regular sickness and death of suckling mice by intracerebral inoculation. The viruses were sensitive to ether, but resistant to 5, -Idu. One sample was examined with electron microscope, and spherical virus particles were observed. The diameter of the virus particles is about 55 +/- 2. 3nm. It did not react with the JBE virus and Bunyaviridae group specific immuno-ascitic fluids but cross-reacted with the group A Togaviridae specific immuno-ascitic fluid., Conclusions: The results showed that the viruses isolated from Yantai belong to alphavirus of togaviridae.

The development of the humoral immune response against porcine reproductive and respiratory syndrome (PRRS) virus was monitored by an indirect fluorescent antibody (IFA) test, immunoperoxidase monolayer assay (IPMA), enzyme-linked immunosorbent assay (ELISA), and serum virus neutralization (SVN) test over a 105-day period in 8 pigs experimentally infected with ATCC strain VR-2402. Specific antibodies against PRRS virus were first detected by the IFA test, IPMA, ELISA, and the SVN test 9-11, 5-9, 9-13, and 9-28 days postinoculation (PI), respectively, and reached their maximum values by 4-5, 5-6, 4-6, and 10-11 weeks PI, respectively, thereafter. After reaching maximum value, all assays showed a decline in antibody levels. Assuming a constant rate of antibody decay, it was estimated by regression analysis that the ELISA, IFA, IPMA, and SVN antibody titers would approach the lower limits of detection by approximately days 137, 158, 324, and 356 PI, respectively. In this study, the immunoperoxidase monolayer assay appeared to offer slightly better performance relative to the IFA test, ELISA, and SVN test in terms of earlier detection and slower rate of decline in antibody titers. Western immunoblot analysis revealed that antibody specific for the 15-kD viral protein was present in all pigs by 7 days PI and persisted throughout the 105-day observation period. Initial detection of antibodies to the 19-, 23-, and 26-kD proteins varied among pigs, ranging from 9 to 35 days PI. Thereafter, the antibody responses to these 3 viral proteins of PRRS virus continued to be detected throughout the 105-day study period.(ABSTRACT TRUNCATED AT 250 WORDS)

An indirect enzyme-linked immunosorbent assay was developed for rapid detection of serum antibodies against the virus responsible for the porcine reproductive and respiratory syndrome (PRRS). This test is more sensitive than the reference technique (immunoperoxidase test applied to cultures of alveolar macrophages), particularly for detecting animals at the stage of seroconversion. It is also very specific for PRRS virus, because all specific hyperimmune sera against other porcine viruses, and all serum samples taken from herds before the disease appeared in western France were negative. The test has been used for routine diagnosis of PRRS. The results obtained during nine months from over 21,000 samples have confirmed the value of the test for diagnosis and epidemiological surveillance of the disease.

We describe the first known occurrence in France of the porcine reproductive and respiratory syndrome (PRRS), a new porcine disease that first appeared in Germany in November 1990. Outbreaks of the disease appeared in November 1991 in Brittany (France), with comparable clinical features to those observed in other countries, were definitively confirmed by a serological analysis from the affected animals using an immunoperoxidase monolayer assay with PRRS-virus infected alveolar macrophages. Furthermore, we report the isolation from one serum of a filtrable agent that, in view of its cytopathic effect for porcine alveolar macrophages and of the serologic reactivity of the infected cells, appears similar to the Lelystad virus that has been implicated in the etiology of the disease.

An indirect enzyme-linked immunosorbent assay (ELISA) has been developed for the rapid detection of antibodies to the porcine reproductive and respiratory syndrome (PRRS) virus in pig sera. Compared to the immunoperoxidase monolayer assay (IPMA) which was the only test available up till recently for serodiagnosis of the disease, the ELISA test proved to be more sensitive, particularly for early detection of antibodies. The test was also highly specific for the PRRS virus inasmuch as it scored negative all the hyperimmune sera directed to other swine viruses and the field sera sampled before the outbreak of the disease in Brittany (France). This easy test now provides further possibilities for epidemiological surveys and could also be a reliable tool for new sanitary prophylaxis of the disease.

The incidence of Ockelbo disease and the prevalence of Ockelbo virus neutralizing antibodies were investigated in a sample of the Swedish population. The disease occurs throughout most of Sweden but with higher incidence and antibody prevalence rates in the central part of the country. It generally affects middle-aged men and women, with equal incidence between sexes, and is uncommon in people younger than 20 years of age. The disease occurs during a short period each year between the third week of July and the first week of October, with a peak during the second half of August. During the 8 years studied (1981-8), an average of 31 Ockelbo patients/year were diagnosed. The antibody prevalence rates in the oldest age groups were 20-40 times higher than the accumulated life-risk of being diagnosed and reported as an Ockelbo disease patient, which suggests that many cases are asymptomatic and/or unreported.

Treatment of adult mice with gold sodium thiomalate made the normally non-lethal Semliki Forest virus and Sindbis virus infections lethal and increased the virulence of Langat and West Nile viruses. These changes were associated with an enhanced virus invasion of the brain. Depression of the humoral antibody response was not observed.

Several Togaviridae of the alphavirus and flavivirus genera agglutinate trypsinized human group O erythrocytes (THOE) (Shortridge and Hu, 1976). Haemagglutinin titers of Semliki Forest virus (SFV) and Japanese encephalitis virus (JEV) measured with THOE were equivalent to, if not higher than, those obtained with Embden gander erythrocytes, even with unextracted haemagglutinin. Results obtained with THOE in JEV haemagglutination-inhibition tests on sera taken from a previously infected individual over a 20-yr period were similar to those measured during the initial JEV infection. The inhibition of SFV haemagglutinin production as measured with THOE was a very sensitive bioassay for chicken interferon: interferon titers were 6- to 10-fold higher than those obtained with the vesicular stomatitis virus plaque-reduction method. The generally greater availability of human erythrocytes (including those stabilized with glutaraldehyde), the simplicity of the trypsin treatment, and the possibility of using unextracted haemagglutinin recommend this technique for use with haemagglutinating Togaviridae.

Since 1977, the Pasteur Institute of madagascar has been studying, during six surveys, the arboviruses of Nosy-Be area, in the north-west of Madagascar. 47.2 p. 100 out of 271 human sera and 11.3 p. 100 out of 150 animal sera (mostly from Lemurs), tested for antibodies to 16 arboviruses by the haemagglutination inhibition test, are positive. The results show an important prevalence of Flaviviruses. West-Nile and Dengue 1 viruses were probably circulating some years before the surveys. Antibodies against Sindbis and Rift Valley Fever viruses, were found only in few subjects. Bunyamwera and Tahyna viruses are absent. The rate of positive Lemurs is weak, particularly in Lemur macaco species. Flaviviruses are the most frequent. 12262 haematophagous diptera (11965 Culicidae belonging to 40 species) were caught . Aedes aegypti and Aedes albopictus are both present. Arbovirus isolation attempts from 394 mosquito pools failed; only Mengo virus was isolated from four pools of Erethmapodites quinquevittatus and one pool of Aedes (Skusea) sp.

An enzyme-linked immunosorbent assay (ELISA) was developed for the detection of serum antibodies to equine arteritis virus (EAV). Results from this assay produced a good correlation with results from virus neutralisation tests in horses which had not been regularly vaccinated with commercially available mammalian tissue culture-derived viral vaccines. Vaccination of some horses with tissue culture-derived vaccines induced the formation of antibodies to bovine serum. These antibodies reacted with the bovine protein contaminants in the EAV ELISA antigen, producing false-positive results. Non-viral protein contaminants were found to be closely associated with EAV in that they co-purified with the virus during gradient centrifugation.

Lambs congenitally infected with border disease (BD) virus and sheep exposed to BD virus as adults were studied for one year to determine the pathogenesis of congenital exposure compared with adult exposure to the virus. Persistent BD virus was isolated in tissue culture and detected by immunofluorescence of the peripheral white blood cells, urine, and cerebrospinal fluid of lambs with congenital BD up to one year of age. These animals had no detectable serum neutralizing antibody response to the virus for the same interval. BD virus antigen was also detected by immunofluorescence in many central nervous system tissues of these lambs with congenital BD. Dysmyelination and glial proliferation in the central nervous system and microencephaly were noted in the lambs with congenital BD, and these lesions appeared to remain the same over a 12-month period.

The cord bloods of 30 congenitally malformed infants, born consecutively at the Worcester Royal Infirmary, were screened for serological evidence of infection with Border disease and bovine virus diarrhoea viruses as well as for the presence of rubella-, cytomegalovirus-, and measles-specific IgM. Despite Border disease and bovine virus diarrhoea being endemic among sheep and cattle in counties bordering Wales, none of the cord blood samples contained antibodies to Border disease or bovine virus diarrhoea viruses. No rubella-, measles-, or cytomegalovirus-specific IgM was detected. When the total immunoglobulins were estimated, 15 of the malformed infants and elevated levels, but in a control group of 35 infants born in the same unit, none showed significantly elevated immunoglobulin levels.

Experiments on mice demonstrated the ability of 3 flaviviruses and 1 bunyavirus to suppress the activity of the effectors of the graft-versus-host (GVH) reaction. The conditions of the suppression of the primary immunological recognition were shown to differ in infections caused by different viruses. In experimental flavivirus infections caused by Langat, dengue 2 or yellow fever (strain 17D) viruses T-suppressor cells were activated, and their activity was realized only in respect to syngeneic or semisyngeneic target cells. In mice infected with Tahyna virus (a bunyavirus) no suppressor cells capable of suppressing the activity of the effectors of the GVH reaction were detected. The suppression of this reaction, not linked with the activity of the detected T-suppressor cells, was observed in the Langat virus infection under conditions of bilateral incompatibility when both the donor and the recipient were infected.

The natural killer (NK) cell induced one to two days after Kunjin virus infection of BALB/c mice is cytotoxic for a wide range of syngeneic, allogeneic and xenogeneic cell lines. It is also weakly cytotoxic for some non-malignant cells including mouse fibroblasts, macrophages and thymocytes, but not lymph node cells. Levels of lysis of non-tumour target cells are dependent on their genotype. Furthermore, malignant cell lines may become resistant following transplantation in vivo then susceptible again after culture in vitro. The virus-induced NK cell is elicited as readily in athymic (nude) as in normal mice. X-irradiation inhibits its development if administered prior to infection. It is labile on culture at 37 degrees. The cell carries Fc receptors but its NK activity is not antibody-dependent.

Kunjin virus encephalomyelitis is described in a 49-year-old man who presented with an episode of acute encephalitis. He developed profound bulbar, truncal and proximal muscle weakness suggestive of damage to cranial motor nuclei and anterior horn cells. This resolved very slowly. A marked rise in antibody titres to Kunjin virus was shown by haemagglutination inhibition tests. Specific IgM antibodies were detected only against Kunjin virus.

An assay for antiviral antibody based on antibody-dependent plaque enhancement (ADPE) in the macrophage cell line P388D1 is described which is as sensitive as, or more sensitive than a radioimmune assay. The method is applicable to a range of Togaviridae and Bunyaviridae although not to Picornaviridae and Herpesviridae. The variables affecting the assay are investigated.

The successful application of the immunoperoxidase method of (IP) with light microscopy for rapid detection of certain togaviruses and orthopoxviruses and antibodies to them is described. A comparative evaluation of the IP and immunofluorescent (IF) method for these purposes was performed. The results indicate practically similar sensitivity and specificity of both methods. The detection of viral antigen directly depended upon the infective dose and time of examinations (within 4--12 hours postinoculation). In evaluating the IP method, however, the account should be taken of the fact that it does not require expensive equipment and therefore may be used in any practical laboratory or even under field conditions. Rapid detection of both viral antigens and antiviral antibody by this method opens approaches for its wide application in the future.

Devastating epizootics of simian hemorrhagic fever (SHF) have been iatrogenically initiated in captive colonies of macaque monkeys by strains of SHF virus emanating from asymptomatic persistently infected patas monkeys. We have found that persistently infected patas monkeys can be cleared of their infection by superinfection with strains of SHF virus which cause acute infections in this species. All 20 persistently infected animals subjected to this procedure have been cleared of their infection within 3 months. These animals were shown to be virus free by the most sensitive in vitro and in vivo tests currently available and periodic tests of serum from these animals over several years have shown them to remain virus free. Superinfection has in some cases caused some adverse clinical symptoms (anorexia, lethargy, facial edema, dehydration, and mild subcutaneous hemorrhages), but with supportive care, no fatal infections have occurred. Thus, superinfection with acute strains of SHF virus is a highly effective method of eliminating persistent infection in patas monkeys.

Complement-fixation test reactions to eight viruses of the family Togaviridae were studied in 372 serum samples (157 rodents, 172 domestic animals, 43 humans) from Pakistan. Antibodies to each tested virus were detected. The highest over-all prevalence rates were for West Nile (WN) (7.8%), Japanese encephalitis (JE) (3.2%) and Zika (ZIKA) (2.4%) viruses, followed by Sindbis (SIN), Chikungunya (CHIK), Uganda S (UGS) and Royal Farm (RF) viruses (1.6 to 1.3%). One human serum (male, age 58 years) reacted with Dengue-1 (DEN) virus antigen (titre 1:32). Antibodies to each virus except RF were detected in human sera; antibodies to RF virus were detected only in rodent and domestic animal sera. The roles of rodents in the epidemiology of WN, JE and ZIKA viruses should be investigated. At least six of these eight viruses cause fevers in humans (fevers of unknown origin comprise about one third of the febrile episodes recorded in Pakistan).

A total of 295 birds belonging to 19 species of 7 families of wild Passeriformes were examined by haemagglutination-inhibition test. The birds were caught for an international research program "Balt" at the time of autumn migration (August-September 1984). Their blood sera were examined for antibodies against 6 arbovirus antigens of the genera Alphavirus (Sindbis-SIN) and Flavivirus (tick-borne encephalitis-TBE, West Nile-WN) and family Bunyaviridae (Tahyna-TAH, Calovo-CVO and Bhanja-BHA). Antibodies against all studied viruses were detected at different frequencies: SIN 6.4%, TBE 7.1%, WN 9.7%, TAH 16.3%, CVO 12.1%, and BHA 1.0%.

In August-September 1981, in some areas of Karelia (on the border of northern and middle taiga) there occurred diseases with signs of fever, rash, and arthralgia developing in some patients into a chronic condition. Examinations of paired sera from patients with the acute disease and from convalescents using a set of Toga- and Bunya-viruses showed the etiology of the disease to be associated with a virus from the Togaviridae family, genus Alphavirus, of the antigenic Sindbis complex.

Simian hemorrhagic fever (SHF) virus is a member of the Togaviridae family which currently is unclassified to genus. We have studied the relatedness of four different SHF virus isolates obtained from infected macaque or patas monkeys. Differences were found among isolates in type and severity of disease produced in patas monkeys, cell sensitivity to infection, viral antigens, and levels of specific antibody induced in patas monkeys. Based on these criteria, the four isolates have been grouped in two categories: those producing acute infections in patas monkeys (LVR, P-180) and those producing persistent infections (P-248, P-741). The P-180 isolate induced the most severe disease in experimentally infected patas monkeys, but only occasionally were their infections fatal. Persistently infected patas monkeys were viremic over a period of years, but showed no signs or symptoms of infection. All four isolates were found to be antigenically related by use of enzyme-linked immunosorbent assay (ELISA); the P-248 isolate showing the weakest antigenic relationship. However, none of the four isolates induced cross-neutralizing antibodies in infected patas monkeys. High titers of specific IgG antibody (up to 31,250 as determined by ELISA) were induced in acutely infected patas monkeys (LVR, P-180), but antibody was barely detectable (less than or equal to 50) in persistently infected patas monkeys (P-248, P-741). LVR lytically infected USU-104 cells, patas monkey peritoneal macrophages (PMAC), and rhesus monkey PMAC. The P-180 isolate lytically infected both patas monkey PMAC and rhesus monkey PMAC, but not USU-104 cells. The isolates producing persistent infections (P-248, P-741) lytically infected only rhesus monkey PMAC. These results show that marked differences exist among isolates of SHF virus from naturally infected animals. These differences should be useful in categorizing new isolates.

The prevalence of border disease virus in a flock of Targhee sheep in southern Idaho was determined by serologic and virologic techniques. Of 249 ewes, 73 (29%) were seropositive to the antigenically related togavirus, bovine seropositive to the antigenically related togavirus, bovine viral diarrhea virus (BVDV). Concurrent testing of sera from 337 neonatal lambs indicated that 172 (51%) were seropositive for BVDV. It was observed that a high percentage (35%) of the BVDV-seropositive lambs were derived from seronegative ewes. Immunotolerance of the ewe was considered as the explanation for the lack of serologic relationship between seropositive lambs and their seronegative dams. Eleven cytopathogenic viruses were isolated from nasal and vaginal specimens obtained from 80 clinically healthy ewes within 24 hours of parturition. The viral isolates were demonstrated to be antigenically related to BVDV by direct immunofluorescence. Six of the 11 isolates were obtained from BVDV-seronegative ewes.

A survey for haemagglutination-inhibiting arthropod-borne virus antibody was carried out in the Kainji Lake area of Nigeria. Of 267 persons tested, 139 (52%) and 158 (59%) had alphavirus and flavivirus group HI antibody, respectively. The prevalence of antibody to individual virus antigen is as follows: Chikungunya, 45%; Semliki Forest, 25%; Sindbis, 33%, Yellow fever, 31%, Dengue type 2, 46%; and Zika 56%. The presence of high antibody rates to Chikungunya, Dengue type 2 and Yellow fever viruses is of public health significance. These viruses have been identified as the most important arthropod-borne viruses causing human infections in Nigeria.

Virus-like particles (60-70 nm) with spiked surfaces budding into cell vacuoles and rod-shaped inclusions were detected in nuclei of hepatocytes from a British patient transplanted for sporadic non-A, non-B fulminant hepatitis (NANB-FHF), probably contracted in Kenya. Identical particles were seen in two successive grafts (days 2 and 10) at regrafting for recurrent FHF. Ultrastructural features resembled those of the RNA-containing arbovirus, Rift Valley fever virus, but serological markers against a representative panel for arboviruses (Togaviruses) and transmission in mice proved negative. The particles shared features with the different arboviruses seen in the hepatectomy specimen of a second patient with NANB-FHF, and in both patients an insect vector was implicated in the clinical history. The particles were identical in size to those of a third patient with NANB-FHF, who had remained in the United Kingdom. These findings, together with the recent report of isolation of an RNA-containing virus resembling the Togaviridae, in parenteral NANB, suggest that several exotic virus-like agents resembling the arboviruses may be involved in the aetiology of NANB, including in the sporadic forms of FHF in the United Kingdom.

A seroepidemiological study of 16 842 human sera, collected in 1981 and 1982 from all health regions of New South Wales, was carried out using the haemagglutination-inhibition (HI) test and eight Australasian flaviviruses: Murray Valley encephalitis (MVE); Kunjin (KUN); Alfuy (ALF); Stratford (STR); Kokobera (KOK); Edge Hill (EH); Sepik (SEP); and Saumarez Reef (SRE). A limited survey was also carried out with two recently discovered flaviviruses, Gadgets Gully and CSIRO 946. Antibody prevalence rates were low on the coast and tablelands (around 2%-8%), moderate on the western slopes (6%-11%) and high on the western plains (26%-42%). Some centres had higher prevalence rates, Bourke being the highest at 78%. The survey indicated that SEP and SRE viruses are unlikely to infect humans in New South Wales. Similarly, there was no evidence for Gadgets Gully and CSIRO 946 infection of humans. HI antibody prevalence rates were highest to STR, MVE, KUN and ALF in that order, these agents being closely related antigenetically. Reactions to KOK and EH occurred less frequently. Serological tests of greater specificity will be required to identify the flaviviruses that elicit these HI antibodies.

The authors make a review of literature on viruses isolated from chiroptera's tissues. They study especially two of these viruses: a true arbovirus, the Japanese B encephalitis virus and a virus of the same genus but not arthropod-borne, the Rio Bravo virus. They consider successively for each virus: isolations from bats, serosurveys in bat and in man, and experimental studies with these viruses, allowing to estimate the role of chiroptera in the diffusion and the maintenance of some arboviruses. They also report some personal results of serosurveys in bats from Tunisia and Spain.

A seroepidemiological survey was performed on antibody against Getah virus in horses in Japan by the complement fixation test. The positive rate was 35 and 53% in two areas where an outbreak of the infectious disease was reported, whereas it was in a range of 3.3 to 24.2% in other areas, except in certain prefectures of the Kyushu district where a high positive rate was observed. In the Hokkaido district, the northernmost part of Japan, no reactors were found in horses under 6 years old, unlike in any other district. It was also suggested that Getah virus infection might have already been prevalent among horses in Japan before the outbreak of the disease in 1978. It remained to be elucidated, however, that the antibody detected might have been produced by some virus which was antigenically related to Getah virus.