WORLD HEALTH ORGANIZATION
ORGANISATION MONDIALE DE LA SANT.
REGIONAL OFFICE FOR THE WESTERN PACIFIC
BUREAU REGIONAL DU PACIFIQUE OCCIDENTAL
REGIONAL COMMITTEE Twenty-third Session Guam 27 September - 5 October 1972 Provisional agenda item 21
WPR!RC23!14 30 June 1972 ORIGINAL: ENGLISH
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THE WHO SERUM REFERENCE BANK IN TOKYO, JAPAN 1. INTRODUCTION
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Epidemiological surveillance, which perhaps most aptly can be defined as "collection of information for public health action", is indispensable for the development and maintenance of sound public health programmes. The surveillance activities provide the basis for rational use of personnel and resources and adaptation of control programmes to changing epidemiological situations. In the field of communicable diseases the most important surveillance activities should be focused on prompt information about outbreaks, and a steady flow of information concerning the morbidity and mortality from specified diseases, by geographical area, age and sex. Experience shows, however, that routine reporting of morbidity and mortality from common infectious diseases is sometimes slow and incomplete and, therefore. of relatively limited value to the decision making authority who is responsible for the best possible utilization of health service facilities and funds. Furthermore, often hospital records constitute the sole or main source of information concerning the occurrence of communicable diseases, and such data are not always easy to interpret, because they are not representative of what goes on in the general population. One way of overcoming this difficulty is to carry out special surveys from time to time aiming at obtaining information that is relevant to public health action, and at the same time use this information for an evaluation of the routine reporting of morbidity and mortality. One type of such surveys is serological investigations in an epidemiological context. The use of serological techniques for this purpose rather than for individual diagnosis is of fairly recent date. 1.1 Brief Historical Background
Early examples of serum surveys were those listing the results of Wassermann tests in samples from normal populations. In the 1930's the first important geographical surveys of the prevalence of antibodies ,-
!against yellow
WPR/RC23/14 page 2 against yellow fever carried out, for the most part, in Brazil and Africa by the International Health Division of the Rockefeller Foundation, demonstrated the existence of jungle or sy1vatic yellow fever. Later in the 1940's serum surveys were used for mapping geographical distribution of the arthropod-borne virus encephalitides and soon afterwards they were applied to poliomyelitis. During the 1950' sand 1960' s, some investigators have examined the sera collected using batteries of tests, thus obtaining information regarding several diseases at little extra cost, since manl different antibodies can be demonstrated in a single 10 m1. sample of serua. This has proved useful, particularly in areas where routine morbidity and mortality reporting of common communicable diseases has been deficient or altogether lacking. In addition. serum collections have been used for investigation of biochemical, genetic and haemato10gica1 markers in an attempt to define high risk and low risk groups of populations with regard to infectious diseases. This has been extended to examinations of animal sera in relation to important zoonoses.
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In 1958 WHO convened a study group to make recommendations regarding immunological and haemato10gica1 surveys. The report of this group was 1 instrumental in the establishment of the WHO Serum Reference Bank programme. 1.2 The Establishment Serum Reference Banks
The report of the study group referred to above includes the statement that "the problem of providing for the rather extensive laboratory facilities required for large surveys be tackled without delay. Here the most urgent and important provision is for facilities for processing and storing sera in strategically situated laboratories allover the world. Suitable laboratories must be identified, their co-operation enlisted and necessary equipment and, probably, additional technical assistance provided for." During 1960-61 ·WHO Serum Reference Banks were established in the following institutes: The Department of Epidemiology and Public Health at Yale University, New Haven, Connecticut, United States of America; The Institute of Epidemiology and Microbiology, Prague, Czechoslovakia; The South African Institute of Medical Research, South Africa. Johann~sburg,
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The Serum Reference Bank in Johannesburg subsequently became detached from the WHO programme. /In 1970 a WHO •••
Immunological and Haemato10gica1 ReP.Ser., 1959, No. 181.
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SurveY8,WldHllhOt$~
techno
WPR/RC23/14 page 3 In 1970 a WHO Serum Reference Bank was established in the National Institute of Healt~ Tokyo. Japan. 2. THE WHO SERUM REFERENCE BANK IN TOKYO
The Serum Reference Bank in Tokyo works within the general scope of the WHO programme. The specific objectives of the WHO Serum Reference Banks have been described as follows. l
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1. Acceptance and storage of selected collections of sera and of data in a retrievable form. Acceptance depends on the origin· of the sera. the quality of the collection. and the reference bank's capacity to handle it. 2. With WHO approval, investigation of sera in the reference bank or co-operating laboratories. 3. Selection and storage of samples of sera for posterity studies.
4. With WHO approval, distribution of sera and other material to other laboratories for investigations. 5. Periodic dissemination and exchange of information about the collections of sera in the bank and ahout studies carried out in the hank or co-operating laboratories.
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6. Processing of data about collections of sera and the results of investigations, if possible by computer • 7. Participation in further research related in particular to the methodology of the collection. storage, transport. and investigation of blood sera and the processing and analysis of the results. 8. Direct participation in planning, making. and studying collections of blood sera. 9. Providing consultation and advice to national health services on immunological surveys. espeCially on the planning and carrying out of sampling and collecting material and on processing in the field. providing documentation on individual sera. and advising on community. ethnic. geographical, and other ecological aspects and on transport. The WHO serum reference banks also provide advice on different aspects of laboratory investigation and on standardized methods.
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Education •••
~ultipurpose Serological. Surveys and WHO Serum Reference Banks, WldHlth Ora.:tee.hn. Rep.Ser., 197Q. No. 454.
WPR/RC23/14 page 4 10. Education - the training of scientists and technical personnel from national health services. 11. Presenting, through WHO, the results of laboratory investigations organized under the auspices of WHO to the respective national ministries of health. First priority is given to activities which are directly related to operating WHO programmes. Specifically, emphasis and encouragement is placed on the use of .ero10gical techniques for the purpose of establishing the prevalence of important infections, as a means of determining the age specific distribution of susceptible individuals in a given population. This information, in turn, is intended to be used for rational planning of vaccination programmes, ideally followed by post-vaccination serological investigations to evaluate the vaccination programmes. In addition, repeated serological surveys will permit the trends in the prevalence of important communicable diseases to be followed, it being understood that the results of serological investigations should be assessed in relation to information on morbidity and mortality received from other sources.
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The WHO Serum Reference Bank in Tokyo has, during its first two years of existence, concentrated on work inside Japan with the purpose of permitting the staff of the National Institute of Health in Tokyo to develop operational methodology and acquire experience in this new field of activity, prior to undertaking international commitments. Therefore, since its inception the Bank has worked on collecting, transporting, storing, and examining sera coming from selected provinces of Japan. Table 1 gives a brief summary of the work carried out during 1970-71. The Bank has now the staff and equipment, as well as the necessary organizational experience to participate in international health programmes. To facilitate this international co-operation a document has been prepared entitled "Operational Guide for Users", and a copy of this document is attached (Annex 1). It gives a succinct explanation of the operational procedures related to the assistance that the Bank can give to Member States of WHO and individual research workers and institutes. The Serum Reference Bank in Tokyo has a Scientific Advisory Board consisting of Senior Medical Officers of the National Institute of Health and the Institute of Public Health, and selected Medical Officers in the Ministry of Health and Welfare as well as the Sapporo Medical College and the Research Institute of Medical Science. WHO is also represented on the Board. In addition, co-operation will be established with WHO Reference Laboratories throughout the world as required by the need and scope of specific studies and investigations and close contact and collaboration will be maintained with the other WHO Serum Reference Banks. /2.1 Future •••
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WPR/RC23/l4 page 5/6 2.1 Future Activities
A gradual implementation will be undertaken of an international programme of work which will include sero-epidemiological studies of the geographical distribution of common infections, including monitoring of such infections in selected index groups of man and animals. These studies will also be concerned with pre- and post-vaccination immunological assessment of child populations. It is hoped in this way that assistance can be given to the strengthening of international epidemiological surveillance in close co-operation with WHO-assisted projects and the United States/Japan Medical Programme.
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One aspect of the future programme of the WHO Serum Reference Bank in Tokyo, to which considerable importance is attached, is that of education and training. Facilities are available for microbiologists to acquaint themselves with new serological techniques at the Serum Reference Bank and training courses for laboratory technicians will also be arranged, either in Tokyo or in the country where they are to work. Courses in epidemiology will form part of this educational programme in the belief that the laboratory expert, on whatever level, must have a thorough understanding of the role of the laboratory in public health. These training and education programmes are ultimately geared to assist WHO in strengthening of national health services in Member States •
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WPR/RC23/l4 page 7 TABLE 1 Serum Collections received by the WHO Serum Reference Bank, Tokyo, 1970-1971 Collection No. 1970-1 No. of sera 100 50 200
Collection locality Sugito-cho, Saitama Prefecture Gyoda-shi, Saitama Prefecture Honjo-shi, Showamachi and Ogawamachi, Saitama Prefecture Chiba-shi and 17 other areas, Chiba Prefecture Matsuo-machi, Chiba Prefecture Chiba-shi and four other areas, Ch1ba Prefecture Tone-gun, Takasakishi and Tomioka-shi, Gunma Prefecture Fujioka-shi, Prefecture Gunma I
Purpose of collection Serological survey of Weil's disease Serological survey of rubella Serological survey of Sh. sonnei
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1970-2 1970-3
1970-4
Serological survey of toxoplasmosis Adult disease control Epidemiological surveillance Epidemiological surveillance Adult disease control Japanese encephalitis. patients Japanese encephalitis patients Epidemiological surveillance ..
221
1970-5 1970-6
74 35
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1970-7
469
1970-8 1970-9 1971-1 1971':"3
491 24 58
Fukuoka Prefecture Fukuoka Prefecture Maebashi-shi and Shihukawa-shi • GUDll& Prefecture
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WPR/RC23/14 page 8 TABLE 1 (continued)
Collection
No. 1971-4
Collection locality .
Purpose of collection .
No. of sera 48
Maebashi-shi and Shibukawa-shi. Gunma Prefecture Kitakawake-machi. Saitama Prefecture Omiya-shi and Ogawamach!. Saifama Prefecture Kumagaya-shi, Saitama Prefecture Yashio-machi, Saitama Prefecture Yoshida"'1lUlchi, Saitama Prefecture Chiba Prefecture Chiba Prefecture Chiba Prefecture Chiba Prefecture
Adult disease control
1971-5 1971-6
Health eXamination Epidemiological surveillance Serological survey of rubella Serological survey of Weilts disease Survey of anaemia Adult disease control Serological survey of toxoplasmosis Epidemiological surveillance Venereal disease control .
74 100
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1971-7 1971-8 1971-9 1971-10 1971-11 1971-12 1971-13
50 123 100 155 150 100 50
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Total number of sera received by the Bank during 1970-1971: 3072
WPR/RC23/14 page 9 February 1972 WHO SERUM REFERENCE BANK, TOKYO An Operating Guide for Users Serological investigations play an increasingly important role in epidemiological surveillance of communicable diseases. Immunological studies can serve as a basis for rational planning and evaluation of vaccination programmes and identification of high risk groups. Combined with other epidemiological information they can provide an objective guide for public health decisions. As a research tool multidisciplinary surveys may lead to a better understanding of biological conditions favouring communicable and non-communicable diseases and thus make forecast and prevention possible. Standard procedures in serological studies also facilitate international comparisons of disease problems. 2 An im~ortant by-product of Serum Reference Bank (SRB) activities is the long-term storage of serum aliquots for posterity studies. For these reasons the World Health Organization has established a SRB in Tokyo, Japan, in 1970, in addition to the two SRBs which have been operating since 1960 in New Haven, Connecticut, United States of America, and in Prague, Czechoslovakia. 1 The objectives of the WHO SRBs are as follows: I ANNEX 1
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1.1 Acceptance and storage of selected collections of sera and data in a retrievable form. Acceptance depends on the origin of the sera, the quality of the collection, and the Bank's capacity to handle it. 1.2 ... ," 1.3 Investigation of sera in the Bank or co-operating laboratories. Selection and storage of samples of sera for posterity studies.
1.4 With WHO approval, distribution of sera and other material to other laboratories for investigation. 1.5 Periodic dissemination and exchange of information about the collections of sera in the Bank and about studies carried out in the Bank or co-operating laboratories. 1.6 Processing of data about collections of sera and the results of investigations by computer. /1.7 Participation •••
Address: c/o National Institute of Health, 10-35, Kamiosaki, 2-chome, Shinagawa-ku, Tokyo, Japan (Cable: KOKURITSUYOKEN, Telephone: Tokyo 444-2181). 2Multipurpose Serological Surveys and WHO Serum Reference Banks, WId Hlth Org. techno Rep. Ser., 1970, No. 454.
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WPR/RC23/14 Annex 1 page 10 1.7 Participation in further research related in particular to the methodology of the collection, storage, transport, and investigation of blood sera and the processing and analysis of the results. 1.8 Direct participation in planning, making, and studying collections of blood sera. 1.9 Providing consultation and advice to national health services on immunological surveys, especially on the planning and carrying out of sampling and collecting materia~ and on processing in the field, providing documentation on individual sera, and advising on community, ethnic, geographical, and other ecological aspects and on transport. The Bank also provides advice on different aspects of laboratory investigation and on standardized methods. 1.10 Education - the training of scientists and technical personnel from national health services. 1.11 Presenting, through WHO, the results of laboratory investigations organized under the auspices of WHO to the respective national health administrations. 2 2.1 Organization Staff Director Acting Director Chief Epidemiologist Administrative Assistant Professional Assistant Epidemiologist and Statistician 2.2 Scientific Advisory Board Dr K. Yanagisawa Dr R. Kono Dr I. Shigematsu Mr M. Tsunashima Dr Y. Akao Mrs K. Miyamura Dr H. Yanagawa Mr M. Tanemura (National Institute of Health) (National Institute of Health) (Institute of Public Health) (Ministry of Health and Welfare) (National Institute of Health) (National Institute of Health) (Institute of Public Health) (Institute of Public Health)
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A representative of WHO Headquarters, chiefs of departments in the National Institute of Health and the Institute of Public Health, professors in the several medical schools and research institutes, and medical officers concerned in the Ministry of Health and Welfare are the members of the Board responsible for advising on all scientific matters related to the activities of the Bank. 2.3 Branch Laboratories
Divisions of the National Institute of Health are designated as Branch Laboratories of the Bank.
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Procedures •.•
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WPR/RC23/l4 Annex 1 page 11 3 3.1 3.1.1 Procedures (see also Process Chart) Deposit of serum collections Proposal of deposit
The health authorities or investigators making serum collections as part of epidemiological surveys of different population groups are encouraged to deposit such collections in the Bank. Prior arrangements and discussions with the Bank are desirable to meet the following criteria for acceptance of serum collections and make the collection useful for other investigators. Proposals for deposit can be made directly to the Bank or through the WHO Headquarters, Geneva. ~
3.1.2
Criteria for acceptance of serum collections
(a) Sampling of subjects for bleeding must conform with statistical procedures suitable for the main purpose of any given sero-epidemiological investigation. Preferably consultation between the SRB and the principal investigator should take place before field work is initiated. (b) Quantity and condition of sera: The Bank needs 6 aliquots each consisting of 0.5 ml of serum per one specimen so that 3.0 ml of serum is the s\fiflliest amount usually acceptable. For unique collections less will be considered but 1.0 ml or 2 a1iquots is the minimum. Sera should be sterile, free of hemolysis, and free of preservatives and anticoagulants. The use of a disposable blood-collecting system (VENOJECT) is recommended for this purpose. (c) Documentation: Investigators are requested to complete all the items on the form "INDIVIDUAL CARD FOR SERUM SPECIMEN" (see the attached form). • 3.1:3 Transportation
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After separation of the sera, each serum shall be transferred to 2 or 3 plastic tubes each of apprOXimately 1.5 ml and transported in Liquid Nitrogen Containers (LR-IOA-6 for 180 tubes) by air freight. Individual cards should also be sent to the Bank by air mail. 3.1. 4 Supply from the Bank
The following material can be supplied by the Bank without charge. Individual record forms Disposable blood-collecting system (10 ml Vacontainer, sterile disposable needle, reusable plastic holder) Plastic tubes Labelling materials Liquid Nitrogen Container will be placed at disposal to the principal investigator by the Bank, if not already available /3.2 Storage · ••
WPR/RC23/l4 Annex 1 page 12
3.2
Storage of serum collections
Each serum specimen received in the Bank will be given a storage number after being checked against the records available and divided into 6 aliquots each consisting of 0.5 ml. These aliquots will be stored at -70 o e. All the information on the individual forms will be transferred to computer input material together with storage number and number of aliquots. Thus, subsampling of sera for testing, linkage of the results of testing, tabulation, cataloguing, data storage for retrieval and inventory control will be done by computer. 3.3 Testing of sera
Priorities will be determined for the different examinations in relation to: (a) (b) (c) national health needs and the possibility of controlling the disease concerned; the need for epidemiological surveillance; and availability of laboratories capable of carrying out the particular tests.
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Reporting of the results of testing will be made through WHO. 3.4 Withdrawal of sera
The serum collections deposited in the Bank will be divided into three categories. The catalogues of these sera will be published. (a) (b) Open - available for investigators after review of study purpose by the Scientific Advisory Board. Restricted - exceptionally available because of unique collections such as small amounts of sera left or sera under active study. Posterity - only for future use. Two of 6 aliquots will be used for this purpose. Withdrawal can be authorized only by the Scientific Advisory Board.
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(c)
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WPR/RC23/14 Annex 1 page
13
PROcrss CIIMT FOR COI.L£CTION OF
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!IND O;\r,1
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Sr.pdrdtion of ~crum (2.500 r-. 10 m'n) .Quantity 0):. Y'" 's ,_. ..-----•...::J (til. 4 ml) :.,.e!!,!!,. _~ •• oJ
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Transfer to Teflon tubes (2 ml X 2)
TransportatiDn by L1aUid H, Container' (L ~10A·6. 180 tubes)
(By air to S.R.B.) I
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WPR/RC23/14 Annex 1 page 14
INDIVIDUAL CARD FOR SERUM SPECIMEN WHO
Serum Reference Bank, Tokyo Form A SRB/T
Write with ball pen or hard pencill (1) Ntlllle
1
ot invostigator:
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Reason for coU I:ction:
Family
First
(6) Name:
Other name (Initial)
7) Dete of
birth:
--n
Year
~2' "". ...... ,.... ~ (14)
~8) ~thnic group
19IflJ.14-1 .. __ ,_.:u (9) Occupation
1Oj-",\; ;;.;~ -.-t~-:-~-~! Fe.m~~~_ ..
. ___~b]jYr 13) Number of years spent of ....''Y ... in present reaidenCe~ I ;1 province) (province level) _ I -J,Yrs.
f" . . .1_
Q] -5 i-
Month
Date
II~
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Add-ress:
(Name
I li6)' E;~rie;;~~
of' prOVince~'c1ti-or'-'llS') Classification locality) of address \ Nnme of countrles
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Urban Town
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______________ tJ __~R~"~rAa&l ______~ Years of stay Yra. Yra.
DYes -..~ (If Yes, state name of countries and number of U No years of stay)
2. Tetanus Diphtheria Others (
17) Previous history of vaccinations:[] Poliomyelitis o Smallpox [J Whooping cough
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1---------------..,..---,.--------------1 JS) Remnrks on exaainee, if any: Quantity of serum: Rell18rks:
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.. ~rJ" ,. 2_~ i~
ml
Serial number written in the bottom of cach 'box'is'for convenience-of the Serum Dank. 'fhe followings are for computer use only: (Do not enter)
Note:
....