ICP/BVD/Oll ~RD MEETING OF THE TECHNICAL ADVISORY I(COMMITTEE ON DENGUE HAEMORRHAGIC FEVER
ENGLISH ONLY
Jointly sponsored by the
WORLD HEALTH ORGANIZATION, GENEVA WORLD HEALTH ORGANIZATION REGIONAL OFFICE FOR THE AMERICAS WORLD HEALTH ORGANIZATION REGIONAL OFFICE FOR THE EASTERN MEDITERRANEAN WORLD HEALTH ORGANIZATION REGIONAL OFFICE FOR SOUTH-EAST ASIA WORLD HEALTH ORGANIZATION REGIONAL OFFICE FOR THE WESTERN PACIFIC !
REPORT
NOT FOR SALE PRINTED AND DISTRIBUTED by the
REGIONAL OFFICE FOR THE WESTERN PACIFIC of the World Health Organization Manila, Philippines
NOTE The views expressed in this report are those of the consultants and members of the Technical Advisory Committee on Dengue Haemorrhagic Fever and do not necessarily reflect the policies of the Organization.
This report
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CONTENTS
INTRODUCTION •••••••••••••••••••••••••••••
<I •
•
•
•
•
•
•
•
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1
EPIDEMIOLOGICAL STITUATION, 1975-1978 •••••••••••••••• 1.1
1 1
1.2
1.3
South-East Asian Region •••••••••••••••••••••••• Western Pacific Region ••••••••••••••••••••••••• Diagnosis ...•...........•..•.••.•••••.••..•.•..
2 2 2
PATHOGENESIS OF DENGUE HAEMORRHAGIC FEVER •••••••••••• 3. CLINICAL DIAGNOSIS AND TREATMENT
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3
4.
LABORATORY DIAGNOSIS ••••••.••••••••••••••••••••••••••
4
4.1 4.2 4.3
Serological tests •••••••..••••••••••••••••••••• Test for dengue antigen •••••••••••••••••••••••• Virus isolation ••••••.•••••••••••••••••.•••••••
4 4 4
SITUATION REGARDING VECTORS
6.
VACCINE DEVELOPMENT
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4 5 6 6 6 6 6
7.
SURVEILLANCE •••••••••••••••••••••••••••••••••••••••••
Morbidi ty reporting •..••.......•.......••••..••
Laboratory investigation .••••••••••••.••••••••• Vector and environmental surveillance •••••••••• Research •••••••••••••••••••••••••••••••••••••••
8.
PROGRESS IN THE IMPLEMENTATION OF PREVIOUS RECOHH:ENDATIONS ••••••••••••••••••••••••••••••••••••••
7
9.
RECOMMENDATIONS
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8 8 8 9 10
9.1 9.2
9.3 9.4 9.5
Pathogenesis ••••••••••••••••••••••••••••••••••• Clinical diagnosis and management •••••••••••••• Public health laboratory technology •••••••••••• Vector surveillance and control •••••••••••••••• Publio health problems •••••••••••••••••••••••••
10
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INTRODUCTION The Committee convened in Manila on 6 December 1978. In opening the proceedings, Dr Dy, Regional Director for the Western Pacific, spoke of the importance of this relatively new syndrome. Dr Gunaratne, Regional Director for South-East Asia, presented an overview of the condition, particularly as seen in his Region. Dr Charles spoke on behalf of the Regional Director for the Americas, Dr Husseini, for the Regional Director for the Eastern Hediterranean (Dr Taba, Director of the Region addressed the meeting on arrival later in the day) and Dr Bres for WHO, Geneva. Dr Natth Bhamarapravati was nominated Chairman, Dr Veronica Chan, Vice-Chairman and Dr J.A.R. Hiles, Rapporteur. After some minor modifications and addition of one presentation, the agenda was approved. 1. EPIDEMIOLOGICAL SITUATION, 1975-1978
There has been a considerable increase in reported human dengue infections in the years 1975-1978 in various countries of the South-East Asian and the Western Pacific Regions. 1.1 South-East Asian Region In the South-East Asian Region, hospitalized cases and deaths due to suspected DHF in children show this to be a major problem in Burma, Indonesia and Thailand. In these countries, respectively, there have been a total of 17 251 (772 deaths), 21 818 (916 deaths) and 71 312 (1676 deaths) hospitalizations for the period from 1975 into 1978. Formerly, DHF was largely confined to large cities, now it is increasingly involving provincial cities and towns, spreading to all or most portions of each country. •
A pattern of major epidemic activity at two-year cycles, once dominant in Thailand, is being replaced by irregular epidemic cycles. In Bangkok, where since 1968, there has been a trend towards reduced attack rates (constant hospital admissions with increased population), the modal age of hospitalized children has risen to 7; throughout the rest of Thailand, the modal age is 4-6. Sri Lanka has dengue activity as monitored by serological studies, but only sporadic DHF/DSS esses. India has serologiesl and virological evidence of dengue infections mainly in the east of the country. In the 1960's, all four types were identified by a laboratory in Madras State. Despite this epidemiological situation, epidemics of DHF/DSS occurred mainly in Calcutta in 1963-65, but no cases have been recorded since then.
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1.2
Western Pacific Region
In the Western Pacific Region, DHF reports have been received from Malaysia, the Philippines, Singapore and the Socialist Republic of Viet Nam. For the 1975-1978 period there were, respectively, 1288, 836, 533 1 and 66 372 (1976, 1977 only) DHF cases. Case fatality rates in Malaysia have varied between 7.8J and 9.2J; in Singapore they were about IJ and in the Socialist Republic of Viet Nam in 1977, 1.6J. Both in Singapore and the Philippines, many adults are reported with DF/DHF with some evidence that the age range of dengue infections is increasing. A very large number of island areas in the Western Pacific Region were involved in a dengue 1 pandemic in 1975. Smaller numbers of dengue fever were reported in 1976-1977. 1.3 Diagnosis
There is a need to differentiate between different clinical types of dengue infection. Shock cases, if known to national authorities, are apparently not being reported to WHO. The reported case fatality rates can give an indication of the relative number of DSS cases, but until it is known that the minimal rate in shock cases is similar throughout all countries in both regions, dengue death rates cannot be used as an absolute reporting index. 2. PATHOGENESIS OF DENGUE HAEHORRHAGIC FEVER
Recent studies on the various blood cell responses in DHF and the morphological expression of dengue virus blood cell interactions were focused mainly on peripheral leukocytes especially the lymphocytes and monocytes. Studies were made in clinical as well as experimental situations. Using material obtained from patients, it was shown that there was an increase in the number and percentage of transformed lymphocytes in DHF, especially in those with secondary dengue infections. This phenomenon could be used to help in the clinical diagnosis of DHF in the epidemic area since the number of transformed lymphocytes was higher than those found in febrile cases related to other viral agents. The number and percentage of T lymphocytes was found to be decreased in DHF by as much as 20J about the time of shock but recovered to near normal in 3-4 days. Dengue antigen-antibody complexes were found to be fixed on the surface of B lymphocytes probably through the complement receptor. This happens in a subpopulation of B lymphocytes (about 2J) and the number of cells bearing dengue antigen peaked at the time of shock. Experiments were made using human lymphocytes cultured in vitro to show that human B lymphocytes which were stimulated by mitogen-or cultured for three days, supported dengue virus replication. It was also shown that Raji cells, a human lymphoblastoid cell line of B cell origin, could support dengue virus replication. T lymphocytes could adsorb dengue virus but showed no viral replication. Polymorphomuclear leukocytes did not support dengue virus replication. lIncludes- dengue fever cases.
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It has been shown and confirmed by several groups of workers that a subpopulation of monocytes could support dengue replication and this was enhanced by the presence of anti dengue IgG. Further investigation is required to establish whether there is anything special about the virus strains producing DSS/DHF in South-East-Asia in contrast to those in areas of the world from which DHF has not been recorded. Is the level of viraemia higher in the former, or is the timing of infections or some other factor more important? Also, there is still some confusion on the differentiation of primary and secondary dengue infections, and this is of great importance for studies of pathogenesis. It is therefore recommended that further studies designed to clarify the problem including development of a simple test for IgM antibodies be undertaken. 3. CLINICAL DIAGNOSIS AND TREATMENT
Diagnostic criteria have been followed as adopted in Chapter II of the Guide. So far, in typical cases of DHF, the clinical picture has remained the same during the past 20 years. Cases with liver enlargement did not always show enzyme changes similar to those found in hepatitis as measured by $OPT. Unusual manifestations in DHF may be caused by interourrent or preceding pathological conditions. Suoh manifestations may suggest that (1) the severe liver damage may not be caused by dengue infection and pre-existing liver damage may have some effect, (2) other concurrent infections (leptospirosis, hepatitis) may predispose to encephalopathy and jaundice. There was a discussion on whether hepatomegaly could be related to infection with particular dengue types. While hepatomegaly varied in different epidemics even in the same area, it was difficult to make a convincing correlation with a particular type especially because most epidemics involved more than one type of virus. In Indonesia, sinoe 1975, there has been a partioularly large number of fatal cases of dengue showing encephalopathy. While the symptoms in some of 24 cases reported suggested a true dengue encephalitis, no post-mortems had been possible and the possibility that intracerebral haemorrhages and coagulation had been responsible rather than a true encephalitis could not be excluded. It was also reported that most DHF oases were adequately nourished. applied also to other countries. This
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4.
LABORATORY DIAGNOSIS
A number of new techniques for dengue diagnosis have been developed during the last three years and improvements have been made to dengue virus isolation techniques. 4.1 Serological tests
The use of the capacity of staphylococcus protein A to bind IgG has been developed into a staphylococcal agglutination inhibition test which enables dengue antibody to be detected in a three-minute plate test. This test appears suitable for use in small laboratories and Should be given an extensive trial. 4.2 Tests for dengue antigen
The realization that large amounts of dengue antigens are present in acute sera of cases of classical dengue and DHF has led to studies to develop tests for presence of antigen. The thin-layer immunoassay (TIA) test applied to dengue by Dr V. Chan shows considerable promise. Counter-immunoelectrophoresis (CIE) also shows promise and is likely to prove a useful technique in suitable laboratories. It is also desirable that attempts be made to develop an enzyme-linked immuno-assay (ELISA) test. Development of all these tests should be encouraged. 4.3 Virus isolation
Dengue viruses can now be readily isolated using mosquito or suckling mouse inoculation, killing the animals after seven days and staining antigen with fluorescent antibody in salivary glands and brain, respectively. The use of leukocyte suspensions as a source of virus also improves the virus isolation rate. Further studies in Japan suggest that a focus count assay using F.A. or PAP staining of BHK 21 cell cultures incubated for 48 hours after inoculation with dengue viruses will demonstrate micro-foci of dengue antigen accumulation. The method offers advantages of speed and economy over plaque assay methods. 5. SITUATION REGARDING VECTORS
Since the second meeting in 1975, Member States have recognized that (1) outbreaks of DHF occur even in areas where the density of Aedes aegYpti is extremely low, as exemplified by Singapore in 1977; (2) cases of DHF continue to occur in areas when control measure are undertaken, as in Thailand. In view of the above, it has been difficult for Member countries to carry out routine control programmes using insecticides. Emphasis continues to be placed on (1) identification of predominant vectors in different geographical areas; (2) inventory of spray equipment and stock of insecticides for emergencies.
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In the two regions of WHO, South-East Asia and Western Pacific, Ae. aegypti is widely distributed, and the most important vector especially in densely populated urban areas. Dengue outbreaks also have been attributed to Ae. albopictus, Ae. polynesiensis and several other species of the Ae. scutellaris complex. -In some Member countries, temephos (Abate) is available for preventive measures. This chemical is safe for use in drinking water. Portable vehicle-mounted ground equipment for ULV application is provided in some areas. In Malaysia, as in Singapore, legislation is being used to deter those who allow mosquito breeding in their premises. Public health education is an important but long-term control measure. For this reason, the Western Pacific Regional Office continues to work with Member States (1) to complete inventory of spray equipment or stocks of insecticides for emergency use; (2) to encourage training of personnel and participating in national control programmes; (3) to develop methods of covering water drums; and (4) on the use of mass media for public health education. It was further emphasized that greater community participation is an important aspect of the efforts to obtain vector control especially in areas lacking an indoor piped water supply.
6.
VACCINE DEVELOPMENT
Substantial progress is being made on the development of a tetravalent dengue vaccine. The possibility of sensitization rather than protection if a vaccine fails to immunize against all four types necessitates great care at all steps to ensure tetravalent immunity. Previous work has shown that killed dengue virus does not give good protection and, therefore, all efforts are being concentrated on producing suitable attenuated strains.
An attenuated type 2 clone has been developed to the stage where a first phase trial has been undertaken on six volunteers. The vaccine was immunogenic and only one volunteer had a pyrexia over lOloF and one had a rash. A further trial on eleven volunteers has shown that a lower dose is less reactogenic. An experimental batch of attenuated type 4 virus is being prepared and the attenuation of type 3 has now been completed. Several laboratories using various attenuation strategies are attempting to develop candidate vaccine strains of type 1. Although good progress can be reported, it will be several years before an acceptable vaccine for mass use can be available.
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7. 7.1 Morbidity reporting
SURVEILLANCE
It is not possible to obtain laboratory confirmation of all cases reported, but a sample may give an approximation of the accuracy of clinical diagnosis, which, outside main centres, is usually based on fever and a positive tourniquet test. In Thailand in 1976, 54~ of cases tested were confirmed by HI and in the high incidence year 1977, 72~ were confirmed. Hospitalized cases of PUO were made notifiable and 42~ of a sample of these cases proved to be dengue infections. 7.2 Laboratory investigation
Because of the difficulties in clinical diagnosis, serological confirmation is very important. Further laboratory monitoring leads to improvement in clinical diagnosis. The clinical diagnosis of dengue shock syndrome is nearly always confirmed to be due to dengue viruses and surveillance of shock cases will indicate the extent of the problem. 1.3 Vector and environmental surveillance
Recent studies have failed to show a good correlation between certain Ae. aegypti indices and incidence of the disease. For example, in Bangkok where the larval indices of aegypti do not vary greatly at any time of the year, there is an annual peak of DHF inCidence in the wet season in July or August. Several factors may be involved in this. Firstly, in the wet season there is a higher landing rate for female Ae. aegypti and this may be related to the then prevailing high humidity. Secondly, they may survive longer in humid conditions and therefore have a greater chance of becoming infected and transmitting. Thirdly, human behaviour alters in the wet season and people stay indoors more and therefore are more exposed to the vector. It was reported that during a dengue epidemic in Dacca, in a multi-storey student hostel, the infection rate was much higher in those living on the ground floor. This probably correlates with the biting habits of ~. aegypti. 1.4 Research
Serological surveys for the immunity status of different populations are highly desirable, but the interpretation of results where multiple flavivirus infections occur is very difficult. Further research into methods to clarify this problem would increase the value of such surveys (see also section 2).
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8.
PROGRESS IN THE IMPLEMENTATION OF PREVIOUS RECOMMENDATIONS
The Committee considered the recommendations which were may made during the second meeting of the Technical Advisory Committee at their meeting in 1975 (document VIR/75.2). 8.1 The recommendation on coordination of research has been fully implemented by the designation of a WHO Collaborating Centre for Research and Training in Immunopathology of Dengue Haemorrhagic Fever at the Mahidol University, Bangkok, Thailand, which serves for both South-East Asian and Western Pacific Regions. Coordination of research has also been implemented by the creation of a technical advisory group on dengue haemorrhagic fever in the Philippines and a similar committee in Indonesia. In addition, two study groups met in New Delhi in February 1978: one concerning the development of dengue virus vaccine (document SEA/RES/7) and the other one, the characterization of arbovirus infections (SEA/RES/9). Roth were attended by scientists from the two Regions together with conSUltants. 8.2 Regarding laboratory diagnosis, specific reference antisera are available from the Resource Research Branch of the NIAID, USA. However, working antisera have not yet been made available. Quality control antisera could probably be obtained from the National Institute of Virology in Poona. 8.3 Information on vector densities has appeared in the issues of the Dengue Newsletter (7 issues since 1975). Little has been done in the correlation of vector densities, serological data and results of vector control operations to document the risk and severity of DHF. Although desirable such studies have been found difficult to carry out. It was mentioned that the interpretation of the serology could be difficult in areas where Japanese encephalitis and flaviviruses were prevalent. 8.4 The designation of a repository for new strains isolated has not been implemented. Logistical problems would have to be solved. 8.5 The need for a micro test suitable for clinical diagnosis may well be fUlfilled by the very interesting preliminary results obtained with the thin layer immuno-assay method in Manila. 8.6 The technical guide on diagnosis, treatment and control of DHF has met with considerable success. 8.7 A conference on DHF held in Singapore in October 1977 under the auspices of the University of Singapore and the International Development Research Centre of Canada implemented the recommendation for an international conference. A most valuable scientific documentation and recommendations have been compiled in two issues of the Asian Journal of Infectious Diseases (1978, Volume 2 Numbers 1 and 2). The production of a film, which was recommended by the Committee at its first session in 1974, has been made by Dr Y.C. Chan and was projected during the present session and found to be an excellent review of the different aspects of DHF.
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6.6 The development of a vaccine is in progress and was considered during the study group in New Delhi in February 1976 and during the present session. 9. 9.1 Pathogenesis RECOMMENDATIONS
9.1.1 There is need for systematic registration and documentation of complicated dengue-virus infections and autopsy findings. There is also need for research in the following areas: 9.1.2 Is the fall in blood platelets in DHF due to lysis in the circulation, uptake in disseminated microthrombi or some other mechanism? 9.1.3 Can two distinct pathogenetic mechanisms be recognized: increased vascular permeability and consumptive coagulopathy? The former would be present in the pure shock syndrome and the latter in dengue-virus infections with a haemorrhagic component, while the usual DSS/DHF syndrome in South-East Asian children represents a variable mixture of the two. 9.1.4 Do mediators from transformed lymphocytes playa role in the pathogenesis of DSS/DHF or are mononuclear phagocytes necessarily involved in mediator production? 9.1.5 Is DHF/DSS due mainly to an increased number of infected cells, resulting from antibody-mediated enhancement, a greater number of susceptible cells or some other mechanism1 Is activation of monocytes resulting in increased production of mediators also important? 9.1.6 9.2 What, if any, is the role of immune complexes and circulating antigens? Clinical diagnosis and management
9.2.1 The CNS manifestations associated with dengue infections require further detailed clinical investigation. Several dengue-related, or possibly dengue-related manifestations including febrile convulsions, toxic encephalopathy, brain haemorrhage and Reye's syndrome have been reported. Further studies are required to prove dengue relatedness of CNS manifestations and differentiate from iatrogenic cerebral edema or CNS infections with other agents such as JE, leptospirosis, enterovirus and other. 9.2.2 Further studies of liver involvement and liver function in DHF are needed especially in severe cases to better define the role of liver involvement in encephalopathy and bleeding. 9.2.3 Further studies of DIC and modes of treatment of DIC are recommended.
9.2.4 Research is recommended on the observed relationship between nutrition and susceptibility, to investigate the hypothesis that undernourished children are relatively protected from DHF/DSS.
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9.2.5 Studies to evaluate the therapeutic value of oral rehydration solutions are recommended. Of special interest is the usefulness of oral fluids given early in the illness in the prevention of shock. 9.3 Public health laboratory technology
9.3.1 When possible, haematocrit and platelet counts should be made. Where platelet counts are not practicable, stained films showing gross lack of platelets indicate thrombocytopenia and can be recommended as an alternative. Where microhaemocrits are not available, these should be provided if necessary through WHO. Studies on the development of a test for complement depletion which can be used in small laboratories should be encouraged. 9.3.2 It is recommended that WHO facilitate trials of the use of the staphylococcal agglutination inhibition test as a serological test for dengue infections for use in small laboratories and field surveys. 9.3.3 Promising tests for the demonstration of dengue antigen in the sera of patients in the early stages of DHF are being developed. It is recommended that encouragement be given to further development of TIA (thin-layer immunoassay) and CIE (counterimmuno-electrophoresis) tests. Further, laboratories should be encouraged to develop an ELISA test (enzyme-linked immuno-assay) for antigen and antibody. 9.3.4 There are substantial differences in methods used and results obtained from serological tests for dengue antibodies in different laboratories. Greater standardization of methods is desirable. Further, it is important that facilities for quality control be provided. It is recommended that WHO designate a suitable laboratory to act as a centre for quality control for dengue serolOgy. 9.3.5 It has now been proved that mosquito inoculation is the cheapest and perhaps the most satisfactory and sensitive means of isolation of dengue viruses. It is recommended that WHO organize as soon as possible interregional training courses on mosquito inoculation and processing to enable further laboratories to use this technique. 9.3.6 There is still lack of laboratory personnel trained in methods required for dengue diagnosis. It is recommended that WHO organize interregional courses to train both graduates and technicians in these method~. 9.3.7 There is need for the preservation of a wide range of dengue isolates. It is recommended that WHO implement the recommendation 8.7 of VIR/75.7 report of the second meeting of the Technical Advisory Committee on Dengue Haemorrhagic Fever on the establishment of a repository at the National Institute of Virology, Poona and of another in some other country in the Regions. It is further recommended that a reference laboratory study a representative range of virus strains to confirm their identity and investigate their biological and serological variation. Implementation of these recommendations should be actively explored.
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9.3.8 The preparation of standardized typing sera on the scale required for routine use is an urgent need. New techniques such as the development of monoclonal antibodies from hybridomas should be explored. 9.4 Veotor surveillanoe and control
9.4.1 Ae. aegypti should be the main target of surveillanoe and control activities wherever it occurs. 9.4.2 WHO should stimulate and ooordinate research to determine the oritical density of Ae. aegypti in relation to dengue transmission and improved surveillance techniques should be developed to provide an index which relates well with disease, and which can be used to foreoast an impending outbreak or the severity of the outbreak. 9.4.3 Sinoe there can be many families in a single dwelling, a house should be defined as a single unit of aocommodation irrespective of the number of people therein. 9.4.4 Pilot studies should be organized to determine the cost-effeotiveness of health education and community participation in comparison to oonventional control methods. 9.4.5 Manufaoturers of spray equipment should be encouraged to produce equipment whioh is lighter, less noisy and less vibrating than equipment presently used. 9.4.6 WHO should oontinue to support national training oourses on Ae. aegypti surveillanoe on request from the government and provide fellowships for national health inspectors and related personnel who are involved in Aedes control. 9.4.7 WHO should oontinue to encourage governments to obtain adequate supplies of insectioide and spray equipment for emergenoy use. 9.4.8 WHO should continue to maintain and update the list of equipment and insecticides available at the country level so that cooperation between countries can be speeded up in case of emergenoies. 9.5 Public health problems
9.5.1 Active surveillance for DHF/DSS cases should be strengthened for the purpose of increasing the completeness and accuraoy of reporting and also as a mechanism for alerting the public and physicians to promote early recognition of DHF/DSS oases. 9.5.2 The previous recommendation on reporting of DHF should be followed but because admission oriteria differ widely from hospital to hospital, country to country and during the progress of epidemics, shock cases should also be reported nationally and to WHO as the best available standardized criterion for monitoring dengue haemorrhagic fever.
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9.5.3 Reported acute febrile HF Or shOck syndromes must be regarded as of presumptive dengue etiology. Serological confirmation should be obtained particularly for new or remote outbreaks. The filter paper method of blood collection has proven to be useful in Thailand and tndonesia aR a practical method for sending serum specimens to the l.abor~tory for this purpose. 9.5.4 Coordinated interregional epidemiological studies in several countries with DHF/DSS and in silent areas should be planned and supported bv WHO. These longitudinal studies will have as their goal the definition of risk factors in DHF/DSS. The study requires at a minimum one epidemiologist and one virologist but might also include observations on vectors. 9.5.5 Since dengue viruses are transmitted global1v in the tropical areas, WHO should promote i.nterchange of technical information between countries and regions with dengue infection, but without DHF/DSS. tn particular, dengue newsletters should be distributed to all Member countries. Future WHO-sponsored meetings on DHF should be attended by appropriate representatives of areas with endemic dengue, which are, in fact, "receptive" areas for DHF/DSS outbreaks. 9.5.6 WHO should encourage a standardized method for analysis of clinical and laboratory findings, either in reports developed from WHO-supported research Or in working papers submitted to regional meetings. At a minimum, all analyses of clinical data should specify syndromes by the WHO grading system. Virus isolation, when successful, should be described with attention to the isolation method and the method of identification of virus, including attempts to verify isolates (e.g. by re-isolation, by back-up identifi.cation methods, etc.). Serological reports should include the percentage of patients with adequate paired serum collection and an indication of the number of cases by type of antibody response, e.g. primarY, secondary, inconclusive or not dengue.
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ANNEX 1
LIST OF MEMBERS. CONSULTANTS. SECRETARIAT AND OBSERVERS Members Dr U Thaung. Deputy Director (Epidemiology). Directorate of Health Services. Rangoon. Burma Dr Imam Zaghoul Imam. President. Egyptian Organization for Biological and Vaccine Production. Cairo. Egypt Dr J.K. Sarkar. Emeritus Scientist and Officer-in-charge. ICMR Virus Unit School of Tropical Medicine. Calcutta. India Dr Sumarmo. Department of Child Health. University of Indonesia. Jakarta. Indonesia Professor K. Fukai. Institute of Infectious Diseases. Osaka University. Osaka. Japan Professor J.A.R. Miles. Professor of Microbiology. UniverSity of Otago. Dunedin. New Zealand Major-General M.I. Burney, Director. National Health Laboratories. Islamabad. Pakistan Dr J.C. Baltazar. Associate Professor. Department of Epidemiology and BiostatistiCS, Institute of Public Health. University of the Philippines. Manila. Philippines
,
Dr V.F. Chan. Associate Professor. Department of Microbiology. Institute of Public Health. University of the Philippines. Manila. Philippines Dr Chan Kai Lok, Chief Vector Control Officer. Vector Control and Research Ministry of the Environment, Princess House, Alexander Road, Singapore, Singapore Dr Chan Yow Cheong. Senior Lecturer, Faculty of Medicine, University of Singapore, Singapore, Singapore Dr Natth Bhamarapravati, Professor and Chairman, Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Bangkok, Thailand Dr Sujarti Jatanasen. Director. Division of Epidemiology, Ministry of Public Health, BangkOk. Thailand Dr Suchitra Nimmannitya, Senior Paediatrician, Children's Hospital,
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Annex 1 Consultants Dr A.C. Allison, Clinical Research Centre, Division of Cell Pathology, Harrow, Middlesex, England Dr S.B. Halstead, Professor and Chairman, Department of Tropical Medicine and Medical Microbiology, School of Medicine, Leahi Hospital Honolulu, Hawaii Dr P.K. Russell, Deputy Director, Walter Reed Institute of Research, Walter Reed Army Medical Centre, Washington, D.C., United States of America Secretariat Dr Y. Bang, Project Leader, WHO Vector Biology and Control Research Unit No.2, Jakarta, Indonesia Dr P. Br$s, Chief Medical Officer, Virus Diseases Unit, World Health Organization, Geneva Dr J. Hamon, Director, Division of Vector Biology and Control, World Health Organization, Geneva Dr G. Torrigiani, Chief Medical Officer, Immunology Unit, World Health Organization, Geneva Dr L.J. Charles, Sr, Temporary Adviser on Communicable Diseases, WHO Regional Office for the Americas, WaShington, D.C. Dr A.H. Taba Regional Director, WHO Regional Office for the Eastern Mediterranean, Alexandria Dr V.T.H. Gunaratne, Regional Director, WHO Regional Office for South-East Asia, New Delhi - I Dr C. Kampanartsanyakorn, Regional Adviser on Communicable Diseases, WHO Regional Office for the South-East Asia, New Delhi - 1 Dr F.J. Dy, Regional Director, WHO Regional Office for the Western Pacific Manila, Philippines Dr R. Lindner, Regional Adviser in Communicable Diseases, WHO Regional Office for the Western PaCifiC, Manila, Philippines Dr L.S. Self, Regional Adviser in Vector Biology and Control, WHO Regional Office for the Western PaCific, Manila, Philippines
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Dr A.D. Rajkovic, Regional Adviser in Health Laboratory Technology, WHO Regional Office for the western Pacific, Manila, Philippines Observers Dr T. Kuberski, Epidemiologist, South Pacific Commission, Noumea, New Caledonia Dr John Woodall, Director, San Juan Laboratories, Center for Disease Control, San Juan, Puerto Rico Dr Chiriboga, Assistant Secretary for Environmental Health, Department of Health, San Juan, Puerto Rico Dr Marietta Diaz, Assistant in-Charge, Dengue Fever Project, Children's Memorial Hospital, Manila, Philippines Dr H. Penafiel, Assistant in-Charge, Dengue Fever Project, Children's Memorial Hospital, Manila, Philippines
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• AGENDA Wednesday 6 December 08.00 - 09.00 09.00 - 10.00 10.00 - 10.30 10.30 - ]2.00 12.00 - 13.30 13.30 - 1.4.00 14.00 - 14.30 14.30 - )5.00 15.00 - 15.30 15.30 - 16.00 16.00 - 17.00
Registrati.ons Opening ceremonv roffee bl"p.ak Bpidemtologtcal si.tuaUon 1975-1 Q7f', Lunch bl"eak F.oi.l'!p.miologi cal ",Uuation (Fmd) ~~o",p~tI!Int.:=t t; VP:C:;
f)f
I"!ount,..;.p.s
Advances in p,.thology and haematology Present aspects of patllo-ollysio1l)gv Tea break Advance in virology and vaccines rUni.cal experience (diagnosis and treatment) nl" A11 i ,,"011
Thursday 7 Decp.mber 08.30 - 09.00 09. 00 - 09. 30 09.30 - 10.09 10.00 - 10.30 10.30 11.00 •
Laboratory dhgnosis Research on new labol"atory methods Review of vectol"S and advancp.s in control methods roffee break Surveillance methods r1inica1 a~pects
Dr
v.
r""n
-
11.00 11.30
of DqF in Inrtone",ia
11. 30 - 12.00
Development and usP. of vaccines Lunch bl"eak
12.00 - 13.30
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Annex 2
• Thursday 7 December 13.30 - 15.00 15.00 - 15.30 15.30 - 17.00
Tea break Draftin~
of group" for the gu1.cle (continuation)
Friday 8 December 08.00 - 10.00 10.00 - 10.30 10.30 - 12.00 12.00 - 13.30 l3.30 - 15.00 15.00 - 15.30 15.30 - 16.30 16.30 Draftin~
of
~port
and recommendations
Coffee break Draftin~
of report ann (continuation)
recommen~ation~
Lunch break Ac1opti.on of Tea break Ac1optl.on of ~ui.de, report ann recomm",.,clati.on" (continuation) Closing ceremony ~ui.de,
report ann recommenrlat. ion"