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Malaysian J Path 01                                                                       August l980                     ...
serologically confirmed.
Malaysian J Path 01                                                                     August l980any member of the house...
OUTBREAK OF JAPANESE ENCEPHALITIS                           Laboratory investigations:                          in Pulau L...
Mala ysian J Pathol                                                                          August l980   The numbers and...
OUTBREAK 0 F JAPANESE ENCEPHALITIS29  have not shown this to be the case. Gross-       and   (7)   last, but not least, Pu...
Malaysian J Path01                                                                   August 1980       Malaya. Trans R Soc...
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investigation of a suspected outbreak of japanese encephalitis in pulau langkawi


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investigation of a suspected outbreak of japanese encephalitis in pulau langkawi

  1. 1. Malaysian J Path01 1980; 3: 23-30INVESTIGATION OF A SUSPECTED OUTBREAK OFJAPANESE ENCEPHALITIS I N PULAU LANG!<ANIR A N D E L FANG BSc(Hons)*, DR HSU MBBS* A N D T W L I M MBBS, FRCPath*** Summary An investigation was carried out on a suspected outbreak of Japanese encephalitis (JE) during the month of June 1979 in Pulau Langkawi, in the state of Kedah, Malaysia. Results incorporating the clinical features, laboratory and serologic findings, and brief epi- demiological survey showed 60% of the cases t o be positive for JE infection. Another 20% were suggestive of JE, but diagnosis could not be confirmed a death had occurred prior to the start s of the investigation. The outbreak appeared to be localized in 2 areas in Langkawi, and 90% of the cases affected were between the ages 5-1 5. The mosquito vectors for JE were shown to be present in Langkawi, but the link host between the normal animal cycle and man could not be determined. No virus isolation was attempted.INTRODUCTION caused by a Japanese encephalitis virus. InJapanese encephalitis (JE) virus is common 1951, however, an outbreak of equine encepha-over a wide part of Asia. It has been reported in litis among imported race horses, followedareas ranging from southern lndia to parts of closely by a fatal case of human encephalitis,S.E. Asia, and through to Japan and the islands was reported1 and later confirmed to be the ~ a c i f i c . " ~ The distribution of JE can be Subsequent work has demonstrated the exist-broadly categorized into 2 main regions - the ence of the virus in Peninsular Malaysia andareas in which JE epidemics are a serious and ~arawak.~, 3- The disease has been moni-regular occurrence; and the regions in which JE tored by the United States Army Medical Re-is believed to be e n d e m i ~ . ~ former include The search Team and the institute for Medical Re-Japan, Taiwan and ~ o r e a , ~while countries ,~ search, Kuala Lumpur; and the figures availableincluded in the latter are Malaysia, south-east indicate an endemic level of infection (Table 1). lndia and parts of haila and.^ As can be seen from Table 1, the incidence The virus is transmitted by several closely of JE i s low and fairly evenly distributedrelated species of Culex mosquitoes among the throughout the year. Hence, when 9 cases of wild vertebrate hosts. Evidence available indi- suspected JE were reported to the lnstitute forcates that the normal enzootic cycle of JE is a Medical Research in July, it was decided to wild-birdlmosquito cycle and that mammals investigate this probable outbreak.usually serve a dead-end hosts in the cycle.2 s The link between the natural cycle and the MATERIALS AND METHODS establishment of epidemics in man is believed to be via animals. Several workers, for example, Subjectshave shown the pig to aid in the transmission of The 9 reported cases were all from Pulau Lang- JE to man? O , kawi which had been referred by the district In Malaya, ~ruickshank, in a retrospective hospital there to the general hospitals at Ka- study, attempted to show the existence of JE ngar, Perlis and Alor Star, Kedah. among British prisoners of war during the Of these 9 cases, 2 were excluded from the Japanese occupation. The study was based on study a bacterial meningitis and bronchopneu- s clinical reports only, and hence it could only be monia were shown to be the cause of disease. speculated that the symptoms studied were Further investigation revealed 3 additionalMicrobiologist, Virus Division, lnstitute for Medical Research, Kuala Lumpur (Address for reprint requests).**Medical Officer, Virus Division. lnstitute for Medical Research. Kuala Lumpur.***Consultant Virologist, lnstitute for Medical Research, Kuala Lumpur.
  2. 2. Malaysian J Path 01 August l980 TABLE 1 DISTRIBUTION OF LABORATORY CONFIRMED JE CASES BY MONTH BETWEEN 1974-1978 Figures obtained from the Institute for Medical ~esearch MONTHS 1974 1975 1976 1977 1978 January 1 1 - - 2 February 3 3 - - 1 March 1 4 2 - 1 April 4 - 4 - - May 2 2 I - - June 1 2 2 - July - 5 4 1 - August 1 - 1 4 September 1 2 - 2 2 October 1 1 3 2 2 November 1 2 3 - 2 December 3 1 - 4 2 TOTAL: 19 23 19 10 16cases with possible JE symptoms, making the and (ii) Their illnesses fell between thenumber of cases studied to 10. months of May and June 1979. Of the cases included in the study, thereLangkawi (with ref. to Fig. 1) were 2 deaths prior to the start of the investi-The Langkawi group of 99 islands i s situated 30 gation. No post-mortem had been carried out,kilometers west of Kuala Perlis, Perlis, at the and hence, no brain specimens were availablenorthern tip of Peninsular Malaysia. The rna- for study.jority of the islands are uninhabited with theexception of a few like Pulau Tuba. The largest Serologic Criteriaisland in the group is Pulau Langkawi on which The diagnosis of JE was serologically deter-the majority of the population is concentrated. mined using the microtitre Haemagglutination- The population in Pulau Langkawi is mainly Inhibition (HI) test. Eight units of eachrural, with only one main urban center - the haemagglutinating antigen were used in thetown of Kuah with a population of just over simultaneous testing for JE, Dengue 1, Dengue2,000. The main occupations are fishing and 2, Dengue 3, Dengue 4, Tembusu, Zika andrice cultivation. Some rubber cultivation is also Sindbis antibodies.carried out. Of the 10 cases, serologic tests were not car- ried in two instances a the patients had died sStudy Design prior to the arrival of the team and no bloodThe investigation was divided into two main specimen had been a diagnostic review based on the clinical No virus isolation was attempted due to thefeatures and serologic investigations; and a brief lack of facilities on the island.epidemiological survey. Epidemiological SurveyClinical Criteria The survey consisted of investigations of thePatients who satisfied the following criteria patients household and surroundings.were included in the study: Note was taken of the sex-age distribution of (i) They had been clinically diagnosed the patients. Other factors considered included as encephalitis, meningitis or determining the movements of the patients meningo-encephalites. prior to the onset of the disease and whether
  3. 3. serologically confirmed.
  4. 4. Malaysian J Path 01 August l980any member of the house-hold had been ill isation was 3.2 days, reflecting upon the acute-prior to, during or subsequent to the patients ness of the illness.illness. There was some difficulty in evaluating the The animals reared or present in the immedi- physical signs due to the impairment of sen-ate vicinity of the household were also noted. sorium. However, based on the studies of caseParticular attention was paid to determine if records, 70% showed signs of meningeal irri-there was a link or amplifier host present. For tation (nuchal rigidity and Kernigs sign), 20%example, an attempt was made to bleed water showed pupillary changes (pupil constriction).buffaloes to see if residual JE antibodies were One case showed a mild papilloedema on (L)present, a no pigs were observed due to the s fundus. 20% had extensor planter being almost entirely Muslim. 50% of them developed hemiplegia during the The investigators also attempted to deter- course of the disease, most of them recoveredmine the different mosquito species present in subsequently (see below). 2 cases developedthe area. aphasia.R ESU LTS Sequelae Out of the 2 reported deaths, one case died onClinical Evaluations the 6th day of illness (3rd day of hospitalis-Signs and Symptoms: ation). The other case died on 13th day of ill-The clinical manifestations of the 10 cases are ness at home, after the patient was dischargedsummarised in Table 2. The onset and course of a t own risk (AOR) about one week earlier.the illness were similar t o that reported in the Apart from the 2 deaths, one case was stillseries of JE studies around this region.421 2 3 - critically ill at the time this study was done.All cases (100%) presented with an acute onset The patient was in deep coma, with spasticityof high fever; 50% of which were above 104°F of all 4 limbs, right conjugate gaze and briskafter admission. Other presenting symptoms reflexes with extensor plantar. The remainingwere headache (go%), nausea and vomiting cases regained their consciousness. The majority(70%) and convulsions (60%). There was cloudi- of them were discharged between 9th-18thness of the sensorium and shortly after ad- day of hospitalisation. One case however has amission, all cases became drowsy or comatose. residue (R) sided hemiparesis. Another case was40% had upper respiratory tract complaints. mentally retarded after the illness. The average duration of illness before hospital- TABLE 2 CLINICAL MANIFESTATIONS OF 10 CASES OF ENCEPHALITIS STUDIED Clinical Manifestations No. of Cases % of total Fever 10 100% Headaches 9 90% Arthralgialmyalgia 1 10% Coughlrhinitis 4 40% Nausea or vomiting 7 70% Drowsiness or coma 10 100% Convulsions 6 60% Paralysis 5 50% Meningeal signs 7 70% Pupil changes 2 20% Papilloedema 1 10% Extensor Plantar 2 20% Aphasia 2 20%
  5. 5. OUTBREAK OF JAPANESE ENCEPHALITIS Laboratory investigations: in Pulau Langkawi. No other reported casesThe -average white blood cell count was came from Pulau Tuba, and inquiries among the8,5801~~ millimeter, and ranged from 6,300to villagers there did not reveal any further cases18,100. None of the cases showed any signifi- with encephalitic symptoms.cant alteration in differential count. The cases were from two main areas - the Lumbar puncture was done in 7 of the 10 villages around the town of Kuah, and the areapatients. Two cases had a normal picture on around Padang Masirat (Fig. 1).microscopic and biochemical examination. The These two localities were low-lying withcerebral spinal fluid was clear in all cases. Three extensive rice fields in close proximity. In thepatients had a cell counts of more than 100, vicinity of Kuah, rubber and coconut plan-with lymphocytes ranging from 50-90%. CSF tations were also present. The houses were ofproteins were raised in 2 patients (above 45 gm wood and palm-thatch construction, with many%). Sugar levels was normal in all cases. Gram raised on stilts. The surroundings of the housesstaining, AFB staining and Indian Ink staining visited were generally well kept, and the houseswere negative in all cases. were built on sandy ground. The animals common to all the houses wereSerologic Results water buffaloes, chickens, ducks, cats and dogs.From the serologic results, 4 cases were shown The attempt to bleed water buffaloes was un-to be positive to Group B Arbovirus (Flavivirus) successful, a the co-operation of the villagers sinfections, while the remainder did not show was not obtained.any significant rise in titre. The survey also revealed that no other mem- A positive result was accepted when a four- bers of the respective household had been illfold rise in titre was obtained from paired sera prior t o or during the period of illness. Thein a clinically diagnosed case. disease was also of local origin as none of the patients or their families had travelled t o theEpidemiological Findings mainland in the month preceding the onset of The age and sex distributions of the patients are disease. There appeared to be no additional un- shown in Table 3 Two cases were below 5 reported cases with JE symptoms, although . years old; 2 cases between 6-10 years old; 3 reference was made to one care who had died patients were between 11- years, while the during the month of June. This particular 20 remainder were over 20 years. The majority of patient was included in the survey because he the cases (80%)were male. had presented with symptoms suggestive of The survey also showed that the cases were encephalitis. He had been discharged AOR and all confined to the main island of Pulau Lang- had subsequently died at home. This particular kawi. The one patient whose address was given case lived in the vicinity of Padang Masirat, and a Pulau Tuba was shown to have contacted the was only several houses away from another s disease while studying at the residential school reported case. TAB LE 3 AGE AND SEX DISTRIBUTION Age Group No. of Cases Sex Distribution Male Female 0- 5 2 2 0 6 - 10 2 1 l 1 1 - 20 3 2 1 21 -40 2 2 0 40 andabove 1 1 0 TOTAL 10 8 2
  6. 6. Mala ysian J Pathol August l980 The numbers and various species of mos- tion. I t was, however, not possible to determinequitoes caught are given in Table 4. The main if this was the case in Pulau Langkawi as thevectors for JE virus - C tritaeniorhynchus and . villagers did not permit the water buffaloes t oC. pseudovishnui, were present in the area of be bled for serologic examination. The otherconfirmed JE. The numbers of mosquitoes domestic animals present - chickens, ducks,trapped were small, but this could have been cats and dogs - have not been previouslydue to the several consecutive days of heavy implicated a hosts; although both Pond and srainfall prior to the investigation, and also to Simpson have demonstrated serologic evi-the fact that the staff of the Health Department dence of JE infection in dogs.had carried out extensive fogging (Reslin in Results of the HI tests shoved a character-diesel) operations as a preventative measure. istic rising titre indicative of a primary JE infec- tion. There were two clinically diagnosed casesDISCUSSION of JE whose HI results failed to show a charac-The outbreak in Pulau Langkawi can be con- teristic rise in titre. This may be explained bycluded a JE based on the clinical comparability s the fact that the first sera were only collectedof the cases with JE, the serologic findings and approximately 2 weeks after the onset of dis-the presence of the probable vector mosquitoes. ease. As the characteristic rising titre is usually The link or amplifier host in the transfer of only demonstrable within the first week ofthe disease to man was not established during infection, it is possible that in these two casesthis investigation. The usual host-the pig -was the HI test would be inconclusive.absent on the island. Of the animals present in This particular outbreak was confinedLangkawi, the most common was the water mainly to children, a 90% of the confirmed s zbuffalo. However, several workers 4 - 2 6 have cases were between the ages of 5-1 5 years. Thesuggested that the buffalo, and bovines in majority of those affected were also males,general, are not important amplifying hosts for thereby suggesting a possible sex-related suscep-JE and may even act in suppressing JE infec- tibility to JE. However, several workers2 " - TABLE 4 MOSQUITO SPECIES AND NUMBERS CAUGHT ON PULAU LANGKAWI "Indicates possible vector species for J E ~ Mosquito Species No. Caught Culex annulus * 26 bitaeniorhy nchus 4 fuscoecphalus * 4 pseudovishnui 3 sinensis 13 sitiens 7 tritaeniorhynchus 15 Aedes albopictus 8 Armigeres subalbatus 1 Anopheles barbirostris korwari philippenensis vagus
  7. 7. OUTBREAK 0 F JAPANESE ENCEPHALITIS29 have not shown this to be the case. Gross- and (7) last, but not least, Puan Rajeswariman3 has suggested that the reason for the Thavarajah for kindly typing outhigher incidence of clinical illness in males was this report.because males were more likely to be outsidelate in the evening and hence be exposed to JE REFERENCESvirus-infected mosquitoes. 1. Warren J. Epidemic encephalitis in the The incidence of disease among children i s Far East, a review. Am J Trop Med 1946;similar to the outbreaks in Korea and Taiwan 26: 417-36.where JE is almost entirely a disease of young Miles JAR. Epidemiology of the arthro- children5 and also in in gap ore.^ 3 3 Figures pod-borne encephalitis. Bull WHO 1960; 22: 339-71.available from the lnstitute for Medical Re-search for the years 1970-1978 show that the Grossman RA, Gould DJ, Smith TJ,age group mainly affected is between 5-14 Johnsen DO, Pantuwatana S. Study ofyears, thus showing this outbreak to be similar Japanese encephalitis virus in Chiangmaiin pattern. The only difference was that in this Valley, Thailand. I. Introduction andinstance, the children affected were all Malay in study design. Am J Epidemiol 1973; 98:origin; whereas the cases for the past 8 years in 111-20.Malaysia show a higher incidence rate among Tigertt WD, Hammon WMcD, Berge TO,the Chinese population. This may be due in et al. Japanese B encephalitis: a completepart to the fact that Pulau Langkawi is basically review of experience on Okinawaa rural area with a predominantly Malay popu- 1945-1949. Am J Trop Med 1950; 30:lation. pau13 has stated that the disease 689-722.appears to be more marked in rural areas in Kono R, Kim KH. Comparative epidemi-Singapore a a result of the high mosquito s ological features of Japanese encephalitispopulation and pipbreeding. However, this in the Republic of Korea, China (Taiwan)would not necessarily apply to Pulau Langkawi and Japan. Bull WHO 1969; 40: 263-77.where the population is almost entirely Muslim Hale JH, Lim KA, Chee PH. Japaneseand hence there is no pig rearing. It would be of type B encephalitis in Malaya. Ann Tropinterest, therefore, if further studies were to be Med Parasitol 1952; 46: 220-5.carried out in order to determine the reservoir Work TH, Shah KV. As cited by Mileshost in Pulau Langkawi. JAR: Epidemiology of the arthropod- borne encephalitides. Bull WHO 1960;ACKNOWLEDGEMENTS 22: 339-71. Yamada T, Rojanasuphot S Takagi M, et ,The authors would like to express their appreci- al. Studies on an epidemic of Japaneseation and thanks to the following people: encephalitis in the northern region of (1) Dr. GF de Witt, Director of the Thailand in 1969 and 1970. In: Viral dis- lnstitute for Medical Research for ease in the Southeast Pacific Area and permission to publish this paper. Africa. Tokyo: International Medical (2) Dr. Dora Tan for her advice and Foundation of Japan, 1973: 37-54. encouragement. Hale JH, Lirn KA, Colless DH. Investi- (3) Dr. RG Pillay, Pengarah Perkhid- gation of domestic pigs as a potential matan Perubatan & Kesihatan, reservoir of Japanese B encephalitis virus Kedah, for his invaluable help. on Singapore Island. Ann Trop Med Para- (4) Mr. S Mahadevan for collecting and sitol 1957; 51 :374-9. identifying the mosquitoes. Gresser I, Hardy JL, Hu SMK, et al. Fac- (5) Mr. TK Chew, Puan Hani binte tors influencing transmission of Japanese ltam Ali Hussein and Encik Oth- B encephalitis virus by a colonized strain man b. Mohd Said for their help in of Culex tritaeniorh ynchus Giles, from the serologic investigations. infected pigs and chicks to susceptible (6) The staff of the district hospital pigs and birds. Am J Trop Med Hyg 1958; and public health centre on Pulau 7: 365-73. Langkawai. Cruickshank EK. Acute encephalitis in
  8. 8. Malaysian J Path01 August 1980 Malaya. Trans R Soc Trop Med Hyg 1951; Voodhikul P Siriwan C. Study of Ja- , 45: 113-8. panese encephalitis virus in Chiangmai12. Paterson PY, Ley H L Jr, Wisseman CL Jr, Valley, Thailand. 11. Human clinical infec- et al. Japanese encephalitis in Malaya. I. tions. Am J Epidemiol 1973; 98: Isolation of virus and serologic evidence 121-32. of human and equine infections. Am J Phoon WO, Lim KA. Japanese encepha- Hyg 1952; 56: 320-30. litis in Singapore children. Singapore Med13. Pond WL, Russ SB, Lancaster WE, Audy J 1963;4: 11-7. JR, Smadel JE. Japanese encephalitis in Gould DJ, Edelman R, Grossman RA, Malaya. 11. Distribution of neutralizing Nisalak A, Sullivan MF. Study of Ja- antibodies in man and animals. Am J Hyg panese encephalitis virus in Chiangmai 1954; 59: 17-25. Valley, Thailand. IV. Vector studies. Am14. McCrumb FR. Japanese encephalitis in J Epidemiol 1974; 100: 49-56. t h e F e d e r a t i o n o f Malaya and Johnsen DO, Edelman R, Grossman RA, neighbouring countries. In: Annual re- Muangman D, Pomsdhit J, Gould DJ. port of the institute for Medical Re- Study of Japanese encephalitis virus in search, Malaya, 1955: 95-6. Chiangmai Valley, Thailand. V. Animal15. Simpson DIH, Bowen ETW, Platt GS, e t infections. Am J Epidemiol 1974; 100: al. Japanese encephalitis in Sarawak: virus 57-68. isolation and serology in a Land Dyak Carey DE, Myers RM, Reuben R, Webb village. Trans R Soc Trop Med Hyg 1970; J KG. Japanese encephalitis in South 64: 503-1 0. India. A summary of recent knowledge. J16. Simpson DIH, Bowen ETW, Way HJ, e t Indian Med Assoc 1969; 52: 10-5. al. Arbovirus infections in Sarawak, Octo- Pieper SJ Jr. Kurland LT. Sequelae of ber 1968 - February 1970: Japanese Japanese B and mumps encephalitis. Am encephalitis virus isolations from mos- J Trop Med Hyg 1958; 7: 481-90. quitoes. Ann Trop Med Parasitol 1974; Schneider RJ, Firestone MH, Edelman R, 68: 393-404. Chieowanich P Pornpibul R. Clinical ,17. The Institute for Medical Research, Kuala sequelae after Japanese encephalitis: a Lumpur, Malaysia. Annual reports, one year follow-up study in Thailand. 1974-1978. Southeast Asian J Trop Med Public18. van Rooyen CE, Rhodes AJ. Virus dis- Health 1974; 5: 560-8. eases of man. New York: Thomas Nelson Grossman RA, Edelman R, Willhight M, & Sons, 1948. Pantuwatana S, Udomsakdi S. Study of19. Clarke DH, Casals J. Techniques for Japanese encephalitis virus in Chiangmai haemagglutination and haemaggluti- Valley, Thailand. III. Human seroepi- nation-inhibition with arthropod-borne demiology and inapparent infections. Am viruses. Am J Trop Med Hyg 1958; 7: J Epidemiol 1973; 98: 133-49. 561-73. Grossman RA, Edelman R, Gould DJ. 20. Sever JL. Application of a microtech- Study of Japanese encephalitis virus in nique to viral serological investigations. J Chiangmai Valley, Thailand. VI. Sum- lmmunol 1962; 88: 320-9. mary and conclusions. Am J Epidemiol 21. Ming CK, Swe T, Thaung U, Lwin TT. 1974; 100: 69-76. Recent outbreaks of Japanese encepha- Paul FM. Japanese B. encephalitis in litis i n Burma. Southeast Asian J Trop Singapore children. J Singapore Paediatr Med Public Health 1977; 8: 113-20. SOC 1978; 20: 13-7. 22. Grossman RA, Edelman R, Chiewanich P,