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