WHO TECHNICAL ADVISORY MISSION ON INTRADERMAL RABIES VACCINATION: FLORES ISLAND RABIES OUTBREAK, INDONESIA (December 3-10, 2000) Henry Wilde MD, FACP Professor of Medicine (Infectious Diseases) Queen Saovabha Memorial Institute and Department of Medicine, Chulalongkorn University Hospital, Bangkok, Thailand INTRODUCTION The Island of Flores, Indonesia experienced an outbreak of canine rabies starting in early 1998. This coincided with a severe economic depression in Indonesian and the devaluation of the local currency causing much hardship. Prior to traveling to Flores, I was briefed in Jakarta by officials of the Communicable Disease Directorate of the Ministry of Health and by their counterparts in the Livestock Services, Ministry of Agriculture. We also had a lively discussion of rabies problems in Asia at the Infectious Disease Hospital (Sulianti Saroso) in Jakarta. All of these meetings were very productive since I then went to Flores with some understanding of the overall rabies situation in Indonesia. GEOGRAPHIC AND SOCIAL BACKGROUND Flores Island is located west of Bali, Lombac and Sumbawa islands, east of Timor. It is approximately 350 X 60/20 Km long and wide. The provincial capital of Nusa Tenggara (name of the province) is at Kupang on West Timor and there are 6 districts on the island with Maumere being the main one. The Komodo Islands (home of the dragons) are part of this province and are often visited by more adventurous tourists. Flores had, in the past, been influenced greatly by Portugal and Holland; the latter being the last colonial power prior to the Japanese occupation during World War II. It became part of the Republic of Indonesia under President Sukarno in 1945. Maumere has a good airport and there are daily flights to and from Denpasar, Bali and Kupang, West Timor by Merpati/Indonesia Airline using ancient F-27 propjet aircraft. Flying time from Bali to Maumere is approximately 2 hours. Flores has a population of 1.5 million of which approximately 70% are Catholics and the rest Moslem, Hindi or Protestant. There are also some 10,000 refugees from East Timor scattered in camps, mostly at Maumere. Before the current rabies outbreak, there were an estimated 800,000 dogs on the island. These were not strays but almost all were owned but had not been vaccinated against rabies. Flores dogs are the same mix of many breads seen over most of South and Southeast Asia. Dog meat has a traditional place in the diet and culture of the people of Flores and they are kept as watchdogs and for food as well as trade. The island is mountainous (an old vulcano is 2,000 meters high) and has lush vegetation with growths of bananas, many other tropical fruits, vegetables, coffee and cocoa. Flores is one of the ancient “spice islands” and many are still grown here. People are, nevertheless, poor and seem to live mostly off subsistence farming. 30-40.- US$ per month is a starting wage for a government clerk or elementary teacher and I was told it takes about US$ 40.- to feed and dress a family of 2 adults and 2 children. A junior doctor, serving at a district hospital or clinic, receives a monthly salary of US$ 140.- including free housing. This is not enough to attract staff to an isolated island with limited educational facilities. Goats, Bali-cows and chickens are everywhere and, with rice and taro, are the main ingredients of the diet. Fishing is also an active industry from virtually all beaches around the island. There is apparently little control over movements of the fishermen and they also participate in trade with neighboring islands. The Island has a good infrastructure of district and sub-district health centers. The EPI program was said to function well with over 80% of infants and children receiving the WHO recommended vaccines (including measles, Hepatitis B and BCG (the latter is given intradermally by nurses and midwives). Endemic diseases include a significant malaria problem (P.falciparum and P.vivax) which may still be sensitive to most drugs including Fansidar. Tuberculosis and intestinal parasites are also common (See later for more details of the health care delivery system). Though people in Flores are poor, it is a very peaceful, friendly and beautiful island with little crime or violence Names of Flores Districts with names of capital cities: Sikka District: Maumere East Flores: Larantuka Ende: Ende Ngada: Bajawa Manggaray: Ruteng Lenbata: Kalabahi RABIES IN FLORES This island has never reported animal or human rabies prior to 1997 when the virus was presumably introduced. At the end of that year, retrospective investigations by local health and life stock officers, revealed that fisherman in East Flores district had imported 3 dogs from Butung Island (Sulawesi), north of Flores, a rabies endemic region. These dogs died but had not been examined. Dogs then came down with rabies and several had been diagnosed later by Seller stain (and/or FAT) at the Regional Animal Diseases Research Center, Diagnostic Laboratory (Lifestock Department) at Maros-Sulawesi. Soon the first human cases appeared in East Flores: 10 in 1998, 4 in 1999 and 2 in 2000. The decision to combat the epidemic among dogs was first made in East Flores district in early 1998. It was to eliminate all dogs in the district. The killing of dogs was implemented after an educational campaign and consultation with political, religious and health care leaders. The public was first asked to kill their own dogs. This was accepted quite well as many persons had lost friends or neighbors to rabies. However, a few responded by moving their dogs to the next district and by selling them on the market alive. This may well have hastened the spread of rabies westward. There were now also 13 human cases in Sikka District in 1999 and 3 in 2000 with the last case in November of 2000. Rabies appeared in Ende District first in 2000 (3 human cases). Ngada District (further west) had a severe outbreak with 50 human cases in 2000 (1,306 PET cases and 1770 dog bite reports). Manggarai had 2 cases in 2000 and Lenbata (an other island East of Flores, had none so far. A total of 81 person had been reported as dead from rabies between 1998 and December 2000. All known cases had encephalitic rabies and all were presumably acquired from dogs. Worldwide, approximately 30% of human rabies are of the paralytic (GBS type) and these can be difficult to diagnose clinically. Thus, there probably were more cases of human rabies than had been identified. INNITIAL RESPONSE TO THE OUTBREAK The local lifestock, health and political authorities were confronted with a catastrophe and a justifiably anxious population. They considered several options and consulted community, religious and cultural leaders regarding an appropriate and acceptable response. Options were: 1) To conduct a rapid island-wide dog vaccination campaign. This was discarded as an immediate response. There was not enough vaccine on hand and not an adequate number of trained vaccinators or facilities (transport, coolers etc) to initiate an island-wide dog vaccination effort quickly. Furthermore, it was felt that many dogs had already been infected and were incubating rabies and vaccination alone would be to late to arrest further spread. 2) To eradicate all dogs. This could be done by the public and using local low- level officials and inexpensive hired staff. Many of the dogs would also be killed and eaten by the owners which is an ancient local custom accepted by most of the population. Option 2 was therefore selected as a first response. It was implemented first in East Flores and later in most of the other districts after the first human cases appeared there. There was some criticism from some members of the public but no serious resistance was encountered as many had witnessed the demise of neighbors from rabies. Approximately 500,000 dogs were killed by teams of workers who went from house to house (without weapons or police threats), caught the dogs with bamboo poles and slings and quickly clubbed them to death. This, apparently, was the same mode of “execution” that is used by Flores inhabitants to kill dogs destined for human consumption and thus did not represent a deviation from local customs. It is only the numbers that are awesome. MANAGEMENT OF HUMANS EXPOSED TO RABIES Local health officials quickly set up rabies prevention centers and purchased Purified Vero Cell Vaccine. A very limited quantity of human rabies immune globulin was also obtained by donation but was not used. Following are the numbers of postexposure treatment vaccine doses given: Intramuscular vaccine administered (number of doses): 1998 1999 2000 = 1,600 = 756 = 7,293 Rabies immune globulin administered: None (up to December 2000. A small stock of human rabies immune globulin has now arrived at Flores and will be used where indicated). Approximately 75,000 US$ was spent on vaccine, using imported Purified Vero Cell vaccine from France. An additional donation of vaccine and immune globulin from abroad (donated by Italy) was received and helped greatly. However, fearing that this need for postexposure treatment (PET) in previously rabies free Flores might continue indefinitely, introduction of the reduced dose and effective intradermal PET method was suggested. This consultant was therefore instructed to introduce the Thai Red Cross (WHO approved) intradermal postexposure vaccine regimen and the proper use of immune globulin (including that of the purified equine products to health care workers in Flores). An additional problem was that many persons presented after rabies exposures that had occurred months earlier. Management of such cases was controversial but most seemed to have been vaccinated but not given immune globulin. Number of deaths who had no vaccination 81 Number of deaths who had vaccine and no immune globulin 0 Number of deaths who had vaccine and immune globulin 0 RABIES WORKSHOP AT MOMERE, DECEMBER 7, 2000 This workshop was held at the Hotel May Wali in Maumere. It was opened by the District Chief of Maumere Mr. Paulus Mao who gave a history of the outbreak and the reasons why a decision was made to eliminate all dogs from the district. Dr. Henyo Kerong, the very able district health officer, chaired the meeting. Mrs. Caecilia Windi, Head of Zoonoses treatment at the CDC in Jakarta, was the co-chair and did much of the required interpretation and prior organization for this well run conference. Also present was Dr. Ir Felix from the Lifestock Services, Ministry of Agriculture at Maumere. Participants from all districts (over 30 doctors and nurses) were enrolled. Dr. Stuart Collins (WHO-Tuberculosis project-Flores) contributed greatly by helping in interpretation and by adding comments. The morning was spent by giving a review of rabies, the disease. The following topics were covered: Basic virology of lyssaviruses, mode of infection, progression of infection and pathophysiology of the disease, clinical manifestations in man (encephalitic and paralytic forms), clinical diagnosis of rabies, laboratory diagnosis, management of a patient and of contacts. The afternoon was spent on discussions of postexposure measures to prevent the disease. A supply of some 20 copies of relevant publications was distributed. This included data documenting the safety and efficacy of the intradermal postexposure regimens. The scientific basis for the use of rabies immune globulin and for the importance of injecting it into the bite sites was presented verbally and in the form of literature. The Foundation Merieux VIDEO film, showing the use of the Thai Red Cross intradermal regimen, was then shown and discussed. Following this, participants (virtually all) practiced the intradermal injection technique by giving each other the first of a 3 injection series for preexposure vaccination using Verorab at 0.1 mL per dose at one site. None of the participants who injected the intradermal vaccine missed producing the required "intradermal bubble". Ms. Caecilia Windi then collected blood from 19 volunteers for follow up antibody titer determination. Samples will be coded and blinded and send either to an Indonesian reference lab or to QSMI in Bangkok for neutralizing antibody determination by RFFIT. At the end of the long day, there was much discussion dealing with methods to eradicate rabies from the island. Most of us felt that this could be accomplished and that Flores could again become rabies free. VISITS ON FLORES OUTSIDE MAUMERE Visits were made to Ende where we met with the district chief Dr. Juris Paulinus Domi and Dr. Johanes Don Bosco, the district health officer. To travel from Maumere to Ende (about 120 Km), over a narrow winding and mountainous road built by the Dutch some 70 years ago, requires about 4 hours. Much the same views were expressed there by the doctors and district chief. The real concern was how to develop an appropriate follow up to the initial dog eradication efforts that would eliminate rabies from Flores. The next visit was to Lela (on the Southern side of Flores) and to the 100 bed Catholic St. Elizabeth Hospital (see section on health care facilities). They had seen one human case this year. I was impressed by the sincerity, motivation and seriousness of the staff that I met at Ende and Lela (see later). On traveling by car to Ende and Lela, we observed 10 dogs along the highway, one of which was a puppy not older than 4-6 month. However, no dogs were seen in any of the townships that we visited. Over one hour was also spent at Lela being interviewed by 2 local newspaper reporters who wanted a full review of what is known about rabies. DIAGNOSTIC RESOURCES FOR RABIES AT FLORES There is presently no laboratory support for rabies diagnosis on the island. Samples are sent to the Institute for Animal Diseases Research at Maros, South Sulawesi by air and it usually takes several days to obtain results. They do perform Sellers stains and FAT. Antibody determinations are not available in the region. Rabies diagnosis of dogs and humans was thus mostly based on clinical impressions but 150 dog brains had been examined at Maros. HEALTH CARE DELIVERY FACILITIES AT FLORES Hospitals: Each of the districts has a 100-120 bed government hospital. I visited the ones at Maumere and Ende. The physical plants were clean and functional. There is, however, a great need for more resident specialist staffing. Modern laboratory services were virtually absent. Only very basic tests could be done. . None of the laboratories are doing blood, urine or other cultures. Lab staffing is mostly by "on the job trained" technicians with barely a high school education. The reason for this appears to be an inability to recruit and retain qualified staff. There is no blood banking on Flores and, when needed, blood is collected from donors (usually family or friends of the patient). I had the impression that there is no reliable routine testing for HIV, hepatitis B or C. Both Maumere and Ende hospitals have basic x-ray units and a radiologist works currently at Maumere Hospital. There is no CT on Flores. Surgeons, internists, OB-GYN specialists etc rotate to Flores from other Provinces (Sulawesi?) and usually only on 3 month terms; a situation that does not encourage growth and development. However, both Maumere and Ende have a resident ophthalmologist who perform cataract extractions (but no lens implantations). The permanent staff of the hospitals and health centers consist mostly of recently graduated doctors who serve 2 year tours, receiving a small bonus for working in the outlying islands. Both the Maumere and Ende government hospitals appeared underutilized to me. Most outpatient services are thus rendered at the health centers. I was impressed by the Catholic mission hospital at Lela (one hour by road from Ende). It is run virtually single-handed by one elderly nun Sister (Dr.) Conchita Cruz. She does, medicine, surgery, OB-Gyn and pediatrics and is on duty 24 hours daily, 7 days a week for the last 30 years. The hospital has some 100 beds and has become something of a referral center for citizens able to travel there. It looks attractive and clean. A nursing school (3 year diploma) is also operated there and attracts local students who mostly remain on Flores. The hospital's laboratory appeared to be the nearest to a professional one that I had seen on Flores. It was able to do routine blood chemistries and had at least one technician with some formal training. Limited microbiology could also be performed here. Blood, when needed, was collected from a "walking blood bank" but was not routinely tested for HIV or hepatitis C. District and sub-district health centers: There is a good network of health centers that each have a few beds, provide primary care and deliveries and are staffed by a young doctor, nurses, midwives and assistant nurses. They also carry out general and nutritional education as well as EPI immunizations. Much of the PET was administered at such centers and at the district hospitals. Rabies educational posters were prominently displayed. Laboratory support here was virtually absent. Disease reporting: This appeared to be well organized and allowed early recognition of the dangers of this rabies outbreak. This may well have been one reason why drastic action was initiated early and this surely saved hundreds of human lives. OVERALL IMPRESSIONS This was a unique outbreak that probably resulted from the importation of 3 dogs from a rabies endemic region. Rabies then spread rapidly from the East to the West of Flores. The outbreak was contained by drastic action, similar to the one the Malaysians took when confronted with the Nipha virus epidemic among pigs and humans in 1998 (over 1 million pigs were killed and bulldozed into pits at that time). There was a rapid decrease in the number of new rabies exposures after dog elimination was started and human deaths have also declined and are expected to decline further and stop eventually. The need for PET vaccine and immune globulin will therefore also decline and management of human exposures should not pose any great future economic burden on local resources. The main problem is how to make Flores again rabies free and how to keep it in that state. This issue has been discussed at great length with all participants in Flores and with Ms. Caecilia Windi from the CDC/Jakarta. I expect that Dr. Bingham's recommendations will also be noted. Ongoing actions by local authorities will, most likely, consist of: 1) Further reduction of the dog population in West Flores and isolated regions where the initial elimination efforts have not been fully implemented. 2) Continuation and expansion of the educational efforts already implemented. 3) Vigorous dog and cat vaccination as soon as a sufficient number of trained vaccinators can be trained and dog vaccine supplies are adequate. Dogs and cats will be vaccinated annually and must have a collar or be eliminated on sight. There may also be drafting of new laws which would allow fining of dog owners who do not comply or resist vaccination. 4) No dogs or cats without valid vaccination certificates will be allowed to enter Flores and, even when they have been vaccinated elsewhere, the dog or cat should be re-vaccinated again on arrival and equipped with a Flores rabies vaccine collar. CONSULTANT'S RECOMMENDATIONS 1) There is a real need to improve hospital services in Flores. This is not only for the good of the local population but also important for tourism, a growing income generating industry in Flores. Staffing and existing staff education are the most important issues. Securing permanent experienced physicians, who are willing to remain on Flores and build up the health care services, should be a high priority of the local government. Assistance from outside and special incentives will be required to implement this. 2) Improvement of laboratory diagnostics is mandatory. The Ende hospital is currently negotiating with the German "Entwicklungsdienst" for help in securing better lab equipment. This will only be useful if there is also trained staff to operate it (there is apparently none now). Might it not also be possible to recruit a German, Australian, American volunteer laboratory technologist who could remain in Flores for at least 2 years and train local staff (Peace Corps, VISTA, German Entwicklungsdienst etc) ? 3) There is an urgent need for a rabies diagnostic laboratory facility at Flores island. It would be needed to follow the current outbreak to the end as well as be available for future surveillance in order to prevent reintroduction of rabies. One might consider establishing it in or near a district hospital compound. This will assure better communication between medical and veterinary staff, full utilization of scarce qualified technical personnel and will enable rapid diagnosis and save time and some postexposure treatments where the biting animal was found to be FAT negative. Requirements for such a laboratory are: a qualified and well trained technician, a fluorescent microscope in a dark room, refrigerator/freezer, a biohazard hood, a separate incubator and an incinerator for infected material. Ideally, such a laboratory should be a joint effort of the public health and animal health departments. It should serve as a clinical diagnostic facility for animal and human samples. Fluorescent microscopy has many other than rabies applications which may be needed later in Flores as well. Such a joint utilization has worked well at the Thai Red Cross Institute (next door to a university hospital) as well as in provincial centers in Thailand. 4) Establishment of a "rabies telephone hot-line" for health care providers at Flores should be considered. This should be manned by one or more physicians who are knowledgeable in rabies PET and who can give competent advice when special or unusual situations are encountered at one of the rabies treatment centers. Such a responder will, in our experience, prevent much unnecessary PET and assure that unusual types of exposures are handled properly and in compliance with international guidelines. AN AFTERTHOUGHT: BALI I was able to visit with the Port Health Officer Dr. Murtiyasa and Dr. Budha of the Regional Health Office, Bali. at Denpasar on my overnight stay there going back to Bangkok. I was told that Bali has a population of 3 million, mostly Hindi citizens and thousands of tourists. The dog population is approximately 2-4 per household and few if any are vaccinated. There are many fisherman on many unsupervised beaches. Bali is now rabies free. There is no way in which Bali, confronted by a Flores type outbreak, could respond in a similar manner (such as by dog elimination). Dr Murtiyasa, who is also responsible for port quarantine, told us that an outbreak of rabies such as in Flores is one of his worst nightmares. He obviously intends to strengthen his dog and cat quarantine system and will try to appoint a task force to plan for management of such an outbreak, should it occur. General preventive dog rabies vaccination should also be initiated. COMPLIANCE BY THE CONSULTANT WITH HIS WHO INSTRUCTIONS The consultant was instructed by WHO-Geneva to: 1) advise local authorities in setting up a referral system for management of animal bites including vaccine and medical supplies delivery and distribution. 2) To provide training for trainers for intradermal vaccination and case management. Local health officials in Flores had already developed a good network of treatment centers for animal bites. They also had developed considerable experience in the management of patients in providing PET using the standard intramuscular regimen with tissue culture vaccine. One half day was spent on review of WHO recommendations for patient management, clinical and laboratory diagnosis of human and animal rabies. Local officials had a supply-line for purchasing vaccine and immune globulin. Donated vaccine was also received and helped greatly. The main remaining problems are the need for further reduction of the dog population and ongoing vaccination of remaining and new dogs. Prevention of a new introduction of rabies from neighboring islands was also discussed and a plan for this is evolving and will be developed further by Flores health authorities. This consultant feels that he has fulfilled his mission to the best of his abilities and with the excellent cooperation from local Indonesian staff at Flores. It is felt that Flores can again be made rabies free and the responsible authorities know how to do this and appear to be intent on accomplishing it. Other locations, particularly at other islands, can learn a great deal from this outbreak. ACKNOWLEDGEMENTS Our very knowledgeable team leader during this consultancy was epidemiologist Caecilia Windo Y, (CDC). She, Dr. Thomas Suroso (CDC), Dr. HS Widarso (CDC), Dr. Tata Neipospos(Animal health) Dr. Budi Tri Akoso (Director, Animal Health Div), Dr. Henyo Kerong (Maumere), Dr Johanes Don Bosco (Flores), Mr. Paulus Mao (Chief of Sikka District), Dr. Paulinus Domi (Chief of Ende District) Dr. Ir Felix (Head of Animal Services, Flores), Dr. George Petersen (WHO, Jakarta), and Dr. Kriangsak Charn (WHO,Jakarta) made this enlightening visit possible. I would like to thank them all for their efforts and hospitality. Bangkok, Thailand December 18, 2000 ___________________________ Henry Wilde