WORLD HEALTH ORGANIZATION
ORGANISATiON MONDIALE .DE LA . SANTt
-.~ r·:S~~~J~-~:336 .J ORIGINAL ENGLISH SURVEILLANCE REPORTS Epidemiological/serological evaluation of tropical yaws following mass penicillin campaigns * (Thailand, Philippines, Nigeria) by T. Guthe and J. L. de Vries
*
The present summary report is based on epidemiological/serological survey material from Thailand, Philippines and. Nigeria and has been obtained in co-operation between national health administrations and the World Health Organization. The data have been collected by the WHO Treponematoses Epidemiological team (Dr G. Antal, Teamleader; Mr J. D1Costa, Serologist; Mr J. Maxwell, field administrator). Serum specimen collections have been examined at the WHO Serulogical Reference Centre, State Serum Institute, Copenhagen (Director: Dr H. Aa. Nielsen), and Institut Alfred Fournier, Paris (Director: Professor A. Vaisman). The data have been collated and analysed by BHO Headquarters, Geneva (Dr T. Guthe, Chief Medical Officer, VDT, Dr J. de Vries, Medical Officer VDT; Dr S. Christiansen, WHO Consultant VDT and HSM; Mr K. Uemura, Chief Statistician and Dr B. Grab, Statistician, HSM).
Ths Issue of this doc."mert does not constitute formal pucilcatlon.
Ce document ne const!tue pas una publication. 11 ne dolt falre l'obj~;;t d'aucurr wmpte rendu ou
lt should not be reviewed,
abstracted or quoted without the agreement of the World Health Organization. Authors alone are responsible for views Elxpressed In signed articles.
resume nl d'aucune citatl.on Mns l'autorlsatlon de I'Organlsatlon Mond!ale de la Santa. Les opinions exprlmees dans les articles slgnes n'engagent que leurs auteurs.
,. GES/SR/66.2 WHO/VDT/66 .336 page iL' CONTENTS
1. 2.
OUTLOOK SURVEYS Immunological aspects 2.1.1 2.1.2 2.1.3 "False" seroreactors Treponema! artigen, fluorescent and immobilising antibody Antibody denaturation and specimen transport Clinical findings Serological findings .~
ell
2.2
Epidemiological aspects 2.2.1 2.2.2
3.
RELATIONSHIPS BETWEEN YAWS
SYPHILIS
4. 5.
MASS CAMPAIGNS AND GENERIIT. HEALTH SERVICES SUMMARY
'.. ·.: r.-.
GES/SR/66.2 1~0/VDT/66 .')36 page l l •. OUTLOOK :'""'
Yaws is a treponemal disease of childhood, highly prevalent-in rural 'tiopical countries until 15 - 20 years ago. Its 'manifestations in later l:ife include de'structive. and. in~alidirig b~rie and joint lesions which develo:p in ten per cer~t. of the patien:t.s dtiring 'the natural course of the untreated disease. Ih the last.l5 years some l50million people have.been .
exarni:ried and some 4.3 million treated, as clinical cases, latents and .
contacts, with long-acting penicillin (procairi penicillin G in oil and monostereate - PAIV!, or dibenzylethyldiamine penicillin - DBED) in WHO and UNICEF assisted yaws projects in 42 tropical countries •. A remarkably rapid and .ex,tensi ve regression of over:t clinical lesio.ns take.s community-wide application of .long-acting An extensive review of . penicill~n.
pl~c.e;
following
This is illustrated
by data from .Indonesia, Haiti, in South Pacific.islands and elsewhere. WHO endemic treponematoses programme in this . .. . . .. . context has recently been ,published (1) and details are. available els,et~e ~· .~
where (2, ), 4, 5). · With infectious lesions being reduced from some 20 .;. 30 pet' cent.· to a fraptton of one per: cent. in the community and with extensive interruption o( transmission beipg evident, t.he need became apparent fpr unde.r'tak;ing. epidemiological/serological eyalua:tions in the- surveillance of· thi.s disease, particularly since persistence of infection was also observed in many areas. To investigate prevailing imm~olog;ical
patterns in a disease with
an unknown potential of recrudescence following mass applica,tion of;· penicillin seemed of particular interest. tropical countries. However, the use of serological
methods is only possible on a limited scale in developing rural areas of Sampling· techniques must therefor:e be tlSed whereby the The findings in patterned surveys are referable to the population.
technical orientation of WHO in the continued surveillance of yaws following mass penicillin campaigns has therefore been to provide assistance in the
GES/SR/66.2 WHO/VDT/66.336 page 2 epidemiological/serological evaluation of yaws campaigns and to appraise statistical, serological and survey methodology on the basis of data collected so far in Thailand, the Philippines and Eastern Nigeria by the Interregional Epidemiolog.ical Team {TET). Northern Nigeria. A further study is under way in
Regional teams for similar purposes have been established
in the Western Pacific and African Regions of WHO, undertaking not yet completed epidemiological/serological evaluation surveys in the Western and 2 Mid West Regions of Nigeria; fn Togo and in Western Samoa3 . 2.
SURVEYS In these epidemiological/serological surveys the sampling units were
divisions, districts, villages and clusters of households.
A stratified
survey design related to geographical location of villages, population density, prevalence of infectious yaws and treatment at previous surveys in the mass campaign, has been the basis for the samples investigated. Details of the designs are available elsewhere (6, 7, 8, 9, 10). According
to the survey design the resulting clinically examined sample is made up of all members of the selected cluster of households and the serologically examined samples comprise all children and 20 per cent. adults (15 years and over). The number of sampling points, the populations examined etc.
in the TET surveys are given in the following table:
1
Teamleader, Dr N. Ruland; Serologist, Mr E. Levy-Lambert; field technician, Mr c. Bambara Medical Officer, Dr F. Vorst; Serologist, Mrs Heinze Serologist, Dr P. Wang
2
3 Teamleader, Dr W. Frohlich;
GES/SR/66.2 WHO/VDT/66 .336 page 3 I
Country
!
No. of sampling points
Clinically exam. popn.
VDRL
Serologically exam. popn. FTA TPI 1. !
Thailand 1960-62 Philippines 1962-63 E. Nigeria 1963-64 N. Nigeria 1965-
40 37 56 50
38 000 17 000 9 500 8 500
19 000 ~ 9 000
i
l
I 640 320 640 700 l 200 3 500
5000~1200
I i
12
5 000
3 500
The data and serum collections obtained are utilised also in the surveillance studies of several conditions other than yaws. Serum aliquots
have been deposited at the WHO Serum Reference Banks in Prague and New. Have~.
Multisubject exploitation of sera originating from several 1 treponematoses projects have thus been undertaken and are the subject of separate communications from the WHO Communicable Disease division.
The epidemiological/serological treponematoses surveys have also become a vehicle for other approaches to ePidemiological research. Thus~
in
co-operation with the WHO Virus programme, the malaria programme and Human Genetics programme, a study is made of sera from Northern Nigeria in regard to arbovi.ruses, malaria~
immunofluorescent antibodies and
1
The sera from Thailand originated fuom an additional survey supplementing the original epidemiological team survey.
GES/SR/66.2 page 4
,
WHO/VDT/66~-;J~6:.~.'.
-immunohaematological factor:s
.
·-· ·-
- ·- ---- -- - .
--
-1 .......... -· .................- ... ____ ......... ..
Th:_=_P~d=~~?.~?~~c_:-~/~~-r?~ogical evaluation of__ ;raws as a !!disappearing disease", as well as multisubject exploitation of random collections of sera from rural tropical countries, were envisaged by the \iHO Scientific Group ... on Haematnlogical studies . (24), were encouraged by the Scientific ,· . Groups on Treponernato'ses Resear-ch (25) and of Immunology (26), as well as by the WHO Aqvisory Committee on Medical Research in 196o (27).
2.1 ·2 .1.1
Immunological aspects ''False'; seroi-eactors: _In_ ~r.ep<me!TI~1;.oses the .. advent of chemical~y
defined cardiolipin-lecithin antigens and the subsequent establishment by WHO sorne years ago 6f international reference preparations for the cardiolipin'a:nd'iecitnin components; as well as for human reactive antisera~ repres'ent'ed steps forward in obtaining a measure of unif;rmity in serological . .
methods in this field.
Experience has shoWn that, when-properly used~
.
.,
reagents r:eferable to these standards will.gi;e a relatively small number· of s6-called "biologically false positive·" reactions (BFP) in European arid Ameri'can hospital patients and other selected populations.
It
was assumed
initially that, within limits, cardjolipin antigens would also be suitable in studies of 'troptcal yaws, althoUgh their use in the tropics had previously been.co:rlfined mainly to selected case rilateriai of ·syphilis arid yaws. These anti'ge'ns had not been used ih orgariised sample surveys in rural areas. However, evidence of the exlstence of a considerably higher.. number ..of .. reagin reactors than .~nti?ipated_in
..
tropical.countries- and non-related to
treponema! infection on·the basis of treponema! immobilisation testing (TPI)commenced to accumulate in syphilis studies from Ethiopia in l96o (11), Morocco in 1961 (12) and in 1964 with FTA as the reference test also in 1
These studies are undertaken in co-operation with the virus unit of the laboratory of Epidemiology and Public Health, Yale University, New Haven, USA, the Nuffield Institute f~r Medical Research, London, and the International Reference Centre for Abnormal Haemoglobins, London.
C3S/SR/66.2 WHO/VDT/66.336 page 5 Ethiopia (13) .. Applying f()r the first time TPI testing in proper, sampling of rural populati~~--WHO-.maGa--stmila:r. -:· ·•• '!' :.
·~
.•
.
':"<
.-~
obser:vati ons. in
y.rua~-- beginning
in
Thaita:na in 196o.
Th~·findirigs: in .North-East' 'l'haila.nd-<m the basis of TPI
results ·among ·a· subsampl~ of.--VDRL reactions--are shown. in.tha. .:fo.Uow~-----··· su;:nmary table: ~-::
--·
..
-Age ·grOU!)S ·- -"\··········· ····.·-. --· ····· --
!
VD11L
I ..
TPI Rce,ctiv3s ---i:~----
-:·1·--·--·--;% ·--·-- --·--·-. .
18.6
15 .Yi'S •. & OV21... ,
1
1
3s·~
35.3
!
)02
1· 33.3 ------·----~----L
I
-- -----The-- exce::;s.· r~~g-in reactivity by. VDFL in ...cllil.CL'2en ,~_...b.i~o~hi.._Q'J.:t.._in. __t_~is
table · az >Compared. to 'l'PI testing~ computed on the basis 'If.' th~ examinatio:-:-.s of 39-l-5 :
- --···-··r ·-·· --- ····--- -----l---···--····:·-- -·--- .. "~lv?.L. te~ted sera with -! ; • I : i
a. subsamp1e
of 723 ~SG
TP::··-tesc:;ed-~
-t:"'~.'1
~~ese
aspects are further illustrated by
distribu;tion in
follo-;qirlg table and in fig. l, con;p::.'ising 1181~ .sera from r~)ral areas of Ec.3~;c:;."n
Niceria <:;:::.d e;:aminscl con:p;;.:.."i.tlvely fo:> irr.::Jcbili3int; (':'i'I),
fluoresCent' (FTA), complement fixing (CWMR) and floccnlc.tin::;, antibodie::::; (VDRL) • T:te sera fo:;." TI:;::: testi~g
were dravm ao.:; rc:;,ndom from a serologicaJ.
sa.ilpi~ o:L. l~jS9 . .Scr·::J.,- a6cor(1ir:>g eo th3 st.r-~·e;;.- de:::;:i.,::n~ !' •.
GES/SR/66.2 ~IJHO/VDT/66.336
page 6 Tests Age in years less than 5 6 - 10 ~1 - 14 I
I i
TPI
FTA
CINRM
I iVDRL
Tested Reactive Tested Reactive TesteJ Reactive Teste!_ Reactive o/ i No. iNo. No. % % /0 tNo. I %
I 168
j ; 18 10.7 17.2 36.4 19.4 53.4 57.2 I 68.7
181 165
18
9.9
173 416 157 746 113 137 77
l I
-
4 24 21 49 28 29 16
2.31 5.8 13.4 6.6 24.8 21.2 20.6
167 I
34 20.4
436 f"75 162 r 59 ' 766 ~
454 i 50 11.0 51 l30.9 119 14.9 55 46.2 88 59.2 58168.2 20 6o.6 221 p7.6
I
433 109 22.8 155! 58 37.4 755 201 26.6 112 84 61 54.5 66 78.5
Children 115 - 29 30 - 44 45 - 59
49 ~
Boo 119 147 85 33 384
118 ~ 63 140 182 80
141 106 75.2 31 23 74.2 368 256 69.6 1123,457 40.6 i
~55
6o
.y
30 118 ;
160.0
30 357
4 13.3 77 21.6 11.4 ;
Adults Total sera
i 368 b1s 159 •2
. !
' 26 ' ' a - The smaller number of T.PI tests as compared to FTA arises from )
a' 'j 1134 ~67 !32.7 l
1184 t340 129.2 1103b . , ' I
inconclusive readings# etc. £ The smaller number of CWRM and VDRL tests as compared to FTA and TPI arises from unreadability# not enough serum# etc. Thus in these studies in rural tropical areas higq reagin rates in cardiolipin lecithin flocculation tests were found as compared to immobilising antibody. Accepting immobilising antibody reactivity as near specific in treponema! infections the excessive reagin reactor rates may be due to cross-reactivity from other infections# infestations, vaccinations# etc. to nutritional or genetic conditions. The findings suggest the This does not imply that considerable limitations of lipoidal antigen testing for screening purposes in random populations of rural tropical areas.
.:
..
-~·
.
·~
...
·-· ·.--··
GES/SR/66.2 WHO/VDT/66.336 page 7 _ ··-~-·
..
--·-" ......
card.lolipin·tests·{;qU.antitative technique) ar.e not useful in tt;te diagn(Dsis, management and control of individual clinical-cases of yaws (and~syphilis).
bri ·the other hand, a strikingly low complement' fixing antibody · reactivity by the cardiolipin Wassermann reaction (CWRM) ·is-cbs~rved- :f'~om the table. and ffg·e 1, a-phenomehen po-ssibly due to (i). Slnal.i.-aggri~gate '.:. ,·
particles characterising the antigen in complement fixation aicontrasted to the
.g.iant
antigen particles used in fl~cculation tests' and ·reacting ': · ·.
differently with serum, ( ii) differences
in
te.3t sensi tivHy in :!'eiatlori to
sta~ ah<;ldtirat1lon of disease, (iii) differences in-reactivity patterns in
yaws·: as ;ootnpared to· syphilis ete •., aspects which,
ar~
further
consid~r~st .~n lat~;r.,
the detailed analysis of this: type of material to be publisheq
, ...
2.1.2 1 I
~reponemal antigens, fluorescent and immobilising ~tibody:
Np significant titre differences have T~ .
'been fotind.
in Ta.bora~ory stud,ies <
:·"between
·pertenue· strains when exposed to homologous (pertenue.) ... and ......
heterolgdus (syphilis) serum, and vice versa (14), based oh immobilising· ' antibody! technique
(TPI).
Neither have laboratory studies1 using fluorescent
t-~~·P;~-~~-~i- ~~tibody. technfq~e· {FTA) with
T: .palliduin,
resp;ectlvery: ..
'I'. _pertemue,__ 130 far .. ~how_n significantly dHferent resul t_s_ (~~-· 16). Pathogenic T. pallidum (Nichols) appears to be as sensitive to yaws antibodies as is T. pertenue and standard TPi testing-based on pallidum antigen has been accepted as a specif~c reference procedure in epidemiological/ '
..
....,.._
serological surveys of yaws. · Since significant -correlation . ~
betw!'l~t;J._._,tne
··
occurrence of immobilising and f'l~orescent" antibodie's l.ii'"y_~~-~:~~~~-~e~.?~-~-ound in,tropical pop\).l~~ions '•;
.. .., .......--- .. --...
~~·~·-·.
···~.-
.......
~·····
......
(figs. l.and 2), . the less complex FTA test can also . . . . ... .. ··.. . be·utfHsed in irmriuriological studies of"·this. condition •. Studie::? ba.se<,i. on gradually increased FTA samples of the popuia.tio~ thus justified the determination of FTA reactor rates as an expression of yaws infection in the current Northern Nigerian survey. FTA testing is also gradually being
introduced in the field and recommended for use in tropical countries.
GES/SR/66.2 WHO/VDT/66 .336 page 8 2.1.3 Antibody deterioration and specimen transport: Flocculating
antibodies (reagins) as determined by cardiolipin-lecit¥in tests (VDRL) deteriorate easily during tropical transport, under adverse temperature exposures and variations as contrasted to fluorescent and immobilising antibodies. (a) Extensive studies have been undertaken of these problems:
Dried blood transport by mailing of blotting paper discs (rondelles) This 'simple antibody
was found suitable for FTA testing of the eluent. 1
preservation method, useful under field conditions, is based on finger prick blood without venipuncture (17, 18) . An example of a comparative study of rondelle eluent (FTAR ) in a random rural papula~ion 100 Eastern Nigeria is illustrated in the following table: serum (FTAS FTAR ·····-···· -·· lOO FTASl09. ~-.
) and 100 from six sample paints in
_,_
Reactive 107 7 114
I
TOTAL ----·- .. 108
Non-reactive -· -~
Reactive Non-reactive Total Concordance~
l 303
310 418
1
304
I l
Reactivity 410 . - .. = 98 per cent. Non-reactivity 418 Ca-positivity = 107/ll4 = 93.8 per cent~ eo-negativity= 303/304 = 99-7 per'cent. Prevalence of fluorescent trepanemal antibody: 23.6-24.8 per cent.
Such absorbent paper procedures are available also for neutralisation tests in poliomyelitis etc., for haemagglutination inhibition testing in mumps, and lately for rubella (see 17 and 18).
GES/SR/66.2 WHO/VDT/66.336 page 9 (b) peep freezing of sera in liquid nitrogen at mirius -l50-l96°C vras The details of this established as an optimal method for preservation and transport of specimen collections from the field to overseas laboratories. method-have been described elsewhere (19, 20). Prior experience in b~
transport or large serum collections from tropical countries to overseas laboratories had shown use of carbon-dioxide ice to of specimen infection and/or antibody decay. pa,~-ticu:Larly.
impractical and that:
"normal" sh:i,ppirtg procedures from tropical rural areas often entailed risk The latter was brought out
in a study in North-Ea.st Thailand (21) where a very wide
range of time/temperature exposures and differing thermo-regimens were established and which affected the thermo-sensitive reagins but apparently not the fluorescent and immobilising antibodies. Subsequent laboratory
experiments (22, 23) have confirmed this in regard to absolute temperature exposure as well as to temperatur: variations. The shipment of frozenserum collections by LR-lOA-6 refrigerator transporters at minus 150~196°C in liquid nitrogen from tropical countries to overseas reference laboratories has increasingly been found to b.e a practical, efficient,; safe and economical method to "bring the field into the laboratory" for immunological investigations of unaltered material. This procedure is
gradually being used also in other working areas (e.g. parasitic diseases, bacterial diseases, diarrhoeal diseases and subsequently as part of the methodology in 11/HO Surveilla.rtce and Serum Reference Barik Programmes).
GES/SR/66.2 WHO/VDT/66.336 page 10 2.2 2.2.1 Epidemiological aspects Clinical findings: In -the sample populations examined clinically in
the three completed surveys the following manifestations were found: lesions Thailand No. Infectious Yaws Other yaws * lesions Total persons with yaws Clin. popn. 19 1886 1905 38280 Philippines No. 4 417 421
I
Eastern Nigeria No. 6
% 0.05
% 0.02
% 0.07
4.9
2.4 17000
1146 1152
13.5 8500 I
'
*
Includes hyperkeratosis, gumma or gangosa, late bone lesions, juxtaarticular nodes, sabre tibiae, depigmentations and scars. Some observations as regards infectious yaws will be discussed briefly
in the following:
(a) In Thailand 15 of the infectious lesions and 143 of Only four
"other yaws lesions" were observed in Southern Thailand.
infectious and as much as 1743 of "other yaws" were diagnosed in North-East Thailand. All infectious cases were in children. {b) In the Bhilippines
infectious and other active lesions in children in the islands of Samar and Cotaba.;to pointed to the need for antiyaws measures in ,these areas, although the Philippines in general had been a low level prevalence area for a long time. (c) In Eastern Nigeria infectious yaws was diagnosed in four different The fact that they were found through a random cluster
village foci.
sampling procedure ba$ed on a small sampling fraction suggested that yaws may be more widespread than assumed, particularly in the Southern and SouthEastern part of Eastern Nigeria. The clinical material collected in these three completed surveys although comprising only a small number of infectious cases - confirms on the
GES/SR/66.2 WHO/VDT/66.336 page i l ..
one hand the results of the mass camp2igns to the effect that infectious _y9-ws h_as _])~en r~duced
fr()m _5 - 15 per cent. prevalence 'to a fraction of
one per cent., but signals clearly on th3 other hand that transmission of infection has not ceaseq and that 'focal cases of infectious. yaws continue :to.oqc'l;lr in chiidren~ .. The
clinical findings above cannot, however, explain
the ext;ent of the yaws problem andthe epidemiological characteristics of residual infection. evaluation. This emphasises the need for epidemiological/serological
2.2.2
§erological _findings: In the natural course of yaws in endemic The attack
areas very few cases occur in the first year or two of life. and ecological factors.
rate may reach its peak at 5 - 7 years depending on the endemicity,level In many' areas of Thailand, the Philil)p.ines:anO.,
EasternNigeria the initial.treatment surveys commenced more than ten years before the present epidemiological/serological evaluations.·. Most of: the children with recent. yaws infection at the time when the mass. ·campaigns started would now be 15 years old or more. amoUhts' of· long-acting p~nicillin
The relatively small
administered in the campaigns could not
be expected- to. influence substantially sero-reacti vi ty in yaws case.s of long ·duration, a duration which would increase with increasing age. ·.·If the mass· campaigns suppressed infectiousness completely in the young and interrupted..t:i:'a:rf$trrission, the young age groups should now show little or no immunological ·evidence of infection. Those below 15 years of age mu.st
therefore hold our particular attention in the surveillance studies of yaws. 'The age sp·ecific prevalence of treponemal antibodies (by FTt\ and TPI)
GES/SR/66.2 WHO/VDT/66.336 page 12 in the three completed surveys are summarised below: N.E. Thailand 11.5 % 30.9 % 1 Philippines 2 E. Nigeria3 1).2 %
Age
l
-
15 yrs
3.5
7D
&-f
Over 15 yrs 1 2
17.5 %
l
55.0 jb
Estimated preva'lence on the basis·of a TPI subsample of VDRL examined sera Estimated prevalence on the basis of a large FTA subsample confirmed by TPI test
3 FTA prevalence confirmed by TPI.test on a statistical subsample. Thus also the serological findings confirm that infection with T. pertenue persists in the age group below 15 years of age many years after penicillin mass campaigns in rural tropical areas, and that transmission continues in the child population at a considerably higher level than incidenta~
clinical
cas~s
would suggest.
These aspects are considered
_in_ some furtber detail in the following: .age~speciflc
In table 1 and figs. 3 and 4 the
antibody pattern in North and South Thailand is illustrated
by total VDRL seroreactors, sera titres of 8. dils, 16 dils and more. Partially reactive and low titre sera are particularly apt to.be nonspecific reactors in yaws, where9-s it is rare for a serum. reactive in dilutions e.g. 1:16 or more to be non-specific. The_ Thailand yaws ,surveillance study t.,as the first of its kind and only very limited subsampling was part of the survey design for direct comparison of TPI results to age-specific reagin titre curves. immunological profil~s
In fig. 2 from the Philippines The
estimating flocculating (by dilution} fluorescent
and immobilising antibodies cru1, however, be compared by age groups.
findings are compatible with the Thailand experience in regard to the level at which VDRL reactivity may possibly be considered as a meaningful
expression of treponemal infection in the rural tropical community -
GES/SR/66,2 \\'JIO/VDT/66 -336 p<".ge
13 In a
as contrasted to indi'ridual;:; withm.It history or Gigns of yaws" previous table as \'lell as in fig basis of. FTA tes-c.ing f:2om r
.l immunologi-cal ag·e profiles e .g ,, on the were already illustrated on
~aS-tern N2-_~eri::::-_
·the basis. of a random 1'?I subsarl}p2"e .,
In the: t'oll<=h·TL1g tablB a ·further
FTA .profile is compared tc the age ant:i.body patte:·n.:: of ec;nplement fixation (CWRM) and i'locculation (V,)l'lL) covering all J984 :;.~andom ·sera examined in the P':.:'A test. The pattcr~l.
::L;::; similar to
t.h.r.~
in fig" l. The
table shows that conside:;:-able in children in the 2;;3
fl~orG-Gcent ~<\nb:Lbod;s'
rc:ac".:.:lvlty i;:; pr...;sent a. steep rise
grcu:;>s G .-- 4, an:·: 5 - 7
yea-..~;.:;. Hi tll
The asses~tnent of the o1..lt.come oi' m.:.es campaigns dcper..ds on several factors taken into ac~ount
j:n: the sur7ey design, inclucUr.:..; geogr'lphy,
population density, previouE p:c"'evalence of inft•ction, extent of tl'eatment etc., aspects already briefly referred to but which in reports under prepa:L~a·c-ion.
ar~
evaluated in extenso
Ho\';ever, :' t i.s beliwreo to b<2 of some
GES/SR/66.2 WHO/VDT/66.336 page 14 interest in the present summary report to seek answers to some questions of 1 particular interest . Was the sampling design adequate in relation to previous yaws prevalence to judge the outcome of the mass campaign and was yaws in fact distributed in different population groups as reported from the lesions at that time? It was already indicated that a measure of the outcome of mass campaigns by definition is the prevalence of FTA {and TPI) seroreactivity in children belo~r campa~gns?
Has a substantial reduction taken place in relation to strata of infectious
7 - 8 years of age.
Seroreactivi ty in older children and The following
adults implies acquisition of infection before that age.
data from Eastern Nigeria shows correlations permitting an affirmative answer in regard to the yaws distribution in different population groups
---------------------------,----------------------T------------------------, Percentage infectious yaws found initially in mass campaign surveys 1. '· 5% prevalence 2. 2 - 5% North East 3. 2 - 5% North West 4. ·. 2% Re surveyed areas Percentage FTA serareactors in children 8 - 14 years Percentage FTA serareactors in adults 15 years and over
as reported by the mass campaigns.
S6%
59% 12% 14% 6%
83% 83% 55% 55%
5. :. 2% not re surveyed areas 6. No campaign, previously "no yaws"
25%
5%
l
Special acknowledgement is made to Dr S. Christiansen, Scientific Adviser to the WHO Serological Reference Centre, State Serum Institute, Copenhagen for some of the considerations presented in this and other contexts.
GES/SR,/66.2 irJHOlVDT/66 .336 page 15 The low rate in {3) North West is explained by the fact that the mass campaign staPted first therf>, ll years·prior to the epidemiological/ serological survey and was per·.3istent and intensive. between e.ges. 1 - 7 would now be 10 - 17 years ·or over. All children treated Furthermore,
accepting a peak a.ttack rate at 5 - 7 years, nearly all children with recent infection at tbe time w-ould be 15 yC;ars or more at the time of the pr13sent study • The following material (also from Eastern Nigeria) permits an affirmative anS\1er in ::._~egard
to whether or not a substantial reduction of
yaws has taken place in the populations where it was reported prevalent at the time of the mass campaign:
Percentage infectious yaws at the time of mass campaign
·--1.
Percentage FTA seroreactors in children 1 - 7 years
2. ).
5% prevalence 2 - 5% North East ·2 5% North West '2% re surveyed
(.6%
i
3.0%
4.
5.
• 2% not re surveyed
I acp~pt.able are~likely
5.6% 6.1%
Except for North East, an
reduction in the prevalence of The· early untreated yaws
recent yaws _is considered to have taken place. . FTA reactivity can, of course, not be directly equalled.to infectious lesions. sequently disapp3ar. Relapses outbreaks of lesions last for a considerable time and lesions may subto occur one or more times. Infectious leslons found on inspection of a community represent therefore only a fraction of the nUITlber of ear)y infections in the population. FTA test will plck .up close to all early lnfections.present. The
GES/SR/66.2 WHO/VDT/66.336· page 16
Experimental researc:n
.tll huniC:U'lS
t...a.s de;nonstrated a large measure of As a result of ~eronegatives
protective cross-immunity between yaws and syphilis (29). the penicillin mass campaigns against yaws the number of
in rural tropical populations has increased substantially as compared to 10 - 15 years ago. At the time seroprevalence below 15 years of age
exceeded 50 - 60 ?er cent. in some areas, with only 40 - 50 per cent. of those reaching puberty being susceptible to infection with venereal syphili~
In the Philippines, Northern Thailand and Eastern Nigeria it was shown in the epidemiological/serological evaluation surveys that 3.5 per cent., 11.5 per cent. respectively 12.2 per cent. below 15 years of age were FTA seroreactive and that conversely some 96.5 per cent., 88.5 per cent. respectively 87.8 per cent. of those reaching puberty are now seronegative. The relative protective cross-immunity from yaws possessed by the previous generation against venereal syphilis is thus present to a much lesser extent in the age groups now reaching puberty and an ncreasing large number of adolescents are thus susceptible to infection with T. pallidum at a time when urbanisation, migration, industrialisation, and rapid soc oeconomic and other ecological changes are taking place, aspects known to favour spread of venereal syphilis. In one tropical area, the
occurrence of venereal syphilis in previous yaws regions has been reported. Health administrations may wish to consider these aspects in their future · communicable disease planning, particularly in view of the manifest recrudescence of venereal syphilis in many developed cbuntries already recognised (l).
4.
MASS CAMPAIGNS AND GENERAL.HEALTH SERVICES
With decreasing numoer of clinical yaws cases being found by mobile teams in the mass campaign in Thailand, trials to decentralise epidemiological vigilance as a function of growing rural health services were unsuccessful in 1956-58.· Subsequent efforts became, however, the
GES/SR/66.2 li1HO/VDT/66.336 page 17 basis for expanding assimilation of the surveillance activities by rural health services in llQ
pruvinces ba.sed on tr,dnir::g of' persoru'lel and focusing s~hool
attention on the younger age groups through
programmes (28, 30).
In the Philippines the mass campaign itself was from 1953 part of the activities of the :i'ap::.dly ex:.:;and:iDg rural health services~ supported by special anti-Yaws teams. Withthe observed regression of yaws, only two In Eastern_Nig!:ria_ advantage was taken by such teams remained by 1962,
the widespread disappearance of yaws lesions in the early stages of the campaign for the creation of a niunber of rural heaith centres by popular support.· At th8 same ".:.ime gradual decentralisation· of vigilance through local yaws anu newly trained health scouts attached at the rural health service level took place·. In Thailand, the Philippines and Eastern Nigeria a number of other activities were undertaken as part of the mass campaigns or of the postcampaign activities. Thus in Tflailand 3 12 million smallpox vaccinations 250 000 anticholera vaccinations etc. were undertaken 1959-63, and in Eastern Nigeria more than a million smallpox vaccinations have, in the last few years, been undertaken in co-operation with the yaws programme, on the structure of which much of the smallpox eradication programme is planned to go forward" The yaws programmes in ThaHand, the Philippines and Eastern Nigeria demonstrate the diff:iculties involved :i.n the transfer of responsibilities for the terminal stage of mass campaigns to growing local health services. Continued and adequate vigilance in the community is required to diagnose and treat rapidly new cases (indigenous and imported cases, relapses.),.: i; and contacts. tp occur. Otherwise further outbreaks of the disease must be expected
The recrudescence potential of.yaws following .community-wide
application of long-acting penicillin in mas8 campaigns is likely to build up further with time i f such vigilance is not. exercised and general epidemiological services remain inadequate~ o~
from lack
GES/SR/66.2 WHO/VDT/66.336 page 18 facilities, personnel and personnel training, and little or no improvement of environmental conditions (28).
5.
SUfvllVJ_I.\RY
(i)
The findings in epidemiological/serological surveillance of
tropical yaws following mass penicillin campaigns against this treponematosis of childhood in Thailand, Philippines and Eastern Nigeria are discussed on the basis of large scale clinica~
and immunological
studies based on stratified random samples of the rural population. (ii) A substantial reduction of the number of infectious cases to a fraction of one per cent. prevalence, as well as important decreases in the prevalence of infection - as measured by immunological tests (VDmL,
WR, FTA, TPI) - is described following such campaigns.
However, low
level transmission of T. pertenue is shown to continue 10 years or so after the beginning of the campaigns, along with focal outbreaks of infectious yaws cases, mainly in children. The serological findings
reinforce the outlook that much higher levels of infection prevail than . . can be estimated from incidental clinical cases diagnosed at rural health centres or reported to health services. Fluorescent treponemal antibody (FTA) seroreactor rates in children below 15 years of age were 3.5 per cent. in the Philippines, 11.5 per cent. in Thailand and 12.2 per cent. in Eastern Nigeria, it having been established that FTA reactivity is very close to treponema! immobilising antibody (TPI) reactivity, the latter being considered as a specific immunological test in yaws. (iii) The epidemiological/serological evaluation of yaws following
penicillin mass campaigns is emphasised as being of direct importance to health adiniriistrations (a) by indicating immediate action needed in the health programme when foqal outbreaks of disease or high seroprevalence areas are recognised, (b) by providing knowledge to determine the nature and extent of the infection as a basis for emphasis needed in the surveillance of the infection and as part of the planning process in communicable
GES/SR/66.2 W.tiU/ Vill'/00._?.)0
page 19 disease control and public health admini3tration, Cc)· by furnishing valuable material in the study or' "disappeari-ng disease 11 and epidemiological methodology. (iv) The advent in tropical countries - :'allowing mass penicillin campaigns - of a new generation now~:reaching puberty without the relative cross-immunity from yaws possessed by the previous generation against venereal syphilis is discuss_ed. While only 40 - 50 per cent. of those over r~ral
15 years of age were susceptible to s¥philis 10 - 15 years ago 96.5 per cent.,
88.5 per cent •. and 87.8 per cent. in
Philippines, Thailand respectively . .
Eastern Nigeria are now susceptible to infection with T. pallidum, an aspect Which health 13,C1IllirJ,i_stration.'s_ maywish to consider in future communicable disease control planning in view of p:r;evailing urbanisation, migration, industrialisation and other ecological changes known to favour spread of ' • '' . ; ; :.;· ·' . . ,. .- .. ~ ~· -~->
venereal disease C1-P.4- ip the<ii,grit of the r~co.g;nised general recrudescence ·- . of syphilis in many countries._ ir:t' recent. years. (v) Methods used for transport of dried blood specimens in absorbent • • • ' I • •
paper (rondelles) an<i of deepfrozeri
s~runi
specimens by liquid nitrogen
refrigerators at minus 150 -_l96°C are briefly reviewed in this summary . ··'· . . . . ·-· ..... -report. The utilisation - in addition to immunological examination for yaws - of ~he
serum collections from rural tropical areas for multisubject
_exploitation at WHO-reference centres WHO in its virus, malaria, human
or
laboratories collaborating with se.r.Ym. reference bank. and global
gen~tics, .
surveillance programmes is described.·. 'Such information is of value to health administ':rations· e .g ~ _in the __ p1~ning of surveillance of communicable diseases, in determi-ning the· need for,. or extent of, vaccination programmes (e.g. poliomyelitis, measles) in gauging the nature and· extent of preventive (e.g. strdptococcal infectio_ns) me_asur.es etc.. . of sources. Immuno~ogical
information of
this type can obvi'ou::;ly be_ obtain:e.d on the_ basis of sera from a wid.e variety The experl.ence described in the present summary report on the base~i.
utilisation of large scale sertim ·c.ollections
op. stratified random
sampling from rural tropical populations demonstrates, 'however, that rnultisub,iect exploitation can usefully be organised,_ ,i.n e+dd;i ttor1 to the primary purpose of the. epideriliological/serolc)gical activity.
(iB~/-·~)rt,' Q;_) c_ M
WHO/VDT/66.336 page 20 l.
REFERENCES
WHQ_Chron~le, 1965, 18, 19
2. 3. 4. 6. 7. 8. 9. 10. 11.
Guthe} T.Acta Derm.-venereol. (Stockh.), 1964, 44, 169. Racket, C .J. &. Guthe . T. 1956, Bull. Wld Hlth Org. 15, 869. Wld Hl~h Org. tee~ Rep_.Ser. 1953, 63, 9. _g~_:_:~e~hn. Rep. Ser. 1960, 19~. \-JOl1
5. TJIJ19:_!_ilth
Unpublished INHO
king document INT/VDT/163, 1961.
Unpt.;.blished 1'17HO i.vorking document INT/VDT/167, 1962. Unpublished vJHO working document ll'JT/VDT/169, 1962. UnpubJi::;hed 11\JHO "tvor king document INT /VDT /196/Rev .1, 1964. Unpublished WHO tvorking document TNT /VDT/206 .65, Rev .1, 1965. Schm:i.dt>
H.,
1964, Bull. \"Ild Hlth. Org. 30, 369.
12. · Ninard, A. & Christiansen, S., 1961, Unpublished communication to WHO. 13. 14. 15. Buck) A.A. & Spruyt, D.J., 1964, Amer. J. Hyg. 80, 91. Turner, T .B. & Hollander, D .H., 1957, Wld Hlth Org. Monograph Ser. WHO Treponernatoses Research Programme, Communication from Professor C .W. Chacko, National Serological Reference Centre, M:1<iras, India .
35,
227
16. 17. 18. 19. 20. 21. 22 . 23.
WHO Trcponerr.atoses Research Programme, Communication from , Professor A. Vaisman, Institute Alfred Fournier, Paris, France.
..
Vaisman,'A., Hamelin, A. & Guthe, T., 1963, Bull. Wld Hlth Org. 29, 1. Gutbe, T., Vaisman, A. & Paris-Hamelin, A., 1964, Bull. Wld Hlth brg·. 31,·~ 87 .. Unpubl,is~ed WHO tvqrking document, 1965, 11lHO/VDT/RES/81.65.
.,. .
Guthe, T ~ 1965, Bull. WldHlth Org. 33, 864. De Vries ,. J .-L.• Unpublished WHO working document -INT/VDT/201.64, 1964. Vaisr.J3_n, A. & Paris -Hamelin, A., Bull., Wld Hlth Org • In press . 1JY1:IO Treponematoses Rese?:rch Programrr.e, Communication from Dr B. Hederstedt 1 National Bacteriological Laboratory, Stockholm, · · Si.;redeh. ~ld
24.
Hlth · Org • techn . ,Rep. Ser • , 181, ·10, 1959 •
25. WHO Scientific Group on Treponematosis Research, Unpublished WHO document, ll~T/VDT/148, 1960. 26. tJld HL~h Org_.. techn. Rep. Ser. 1964, 286, 3L 27. WHO lmpubli:Jhed document ACIVJR2/8, 1960.
28. Wld Hlth O:rg. techn. Rep. Ser., 294, 1965. 29. 30. Medina, R., 1964, Unpubli$hed \'.fHO document WHO/VDT/RES/63 .64. Gonz8le3 5 C.L., Wld Hlth Org. Publ. Hlth. Papers, 1965, 29.
ID
(\J
1'\ 1'\
Epidemiological 2erolo~ical evaluation Thailand., 1960-62. Clinical &nd serolot.ical sample population. VDRL ·eroreactor rates, etc. North Ea'~ t
•
\0 \0 \0 ...........
• ID
Tha ilsnd ~ero-.% -------~----·
Southern Thailand
~~ ........._ -..........w. the~e
,'\ge
CfJ ObD
t:l
j:il ~(lj
Clinical te[te( ;.
o; reactive
~ .
% _erol.: No. [ero- Clinical reactive exam.
0..
I No.
E ere-
% , eroreactive
-·----reactive
c,;~a.In.
~erol.exdm,
.
-------··-----,-...._
_______ ______
Of theE:e ; % ~:erol. ;Perol.exam. tested
··---------·-----
FIG. 1
SEROREACTQRS BY AGE GROUPS IN 1134 RANDOM SAMPLE SERA EXAMINED BY'THE TPI TEST.
Eastern Nigeria epidemiological serological study of yaws. Several years after mass penicillin campaign
80
70
60
.__. 50
~
VI
....
0
-
u
e
Q) ....
0
40
Q)
Vl
30
20
/ .... / #.
,.
,
CWRM ....--------------- --------··---
10
#
./ 15-29 30-44 Age groups
---45-49 60 + Oi~O 5C~ 7~
,- . /
0~--~----~--~----
--
0-5
6-1011-14
FIG. 2
EPIDEMIOLOGICAL SEROLOGICAL EVALUATION OF YAWS 10 YEARS AFTER MASS PENICILLIN CAMPAIGNS: PHILIPPINES Prevalence patterns of reagin, fluorescent and immobi Iising antibodies based on 4447 random sera
100
gal Total VDRL reactors VDRL 8 dils or more VDRL 16 dils or more FTA 200 reactors TPI 18 reactors
80
1-
0
-----
0
..................
70
I
>. :!:
60
~
>
m
(.)
~
Q)
m
I:ID
50
t :::
............. ......······ .. ····· ········· •··········· ..··..·· .. ·· ......···
Q)
c...
Q)
~
40
......••········································· .. .. .. ........
30
20
10
0
.... -
0-4
5-7 8-10 11-14
15-29
30-44 Age-group
45-59
60+ WHO 50'+81
FIG. 3 SEROREACTOR RATES, VDRL NORTH EAST THAILAND (Survey 1-24)
90
Seroreactors
-80
Sera titres 8 dils. or more Sera titres 16 dils. or more
------·
...J 0:: 0
60
>
~
> -.;::; (.J
Cl)
50
0::
"'
Cl)
40
0·4
5·7 8-10 11-14
15·29
30-44 Age groups (years)
45· 59
60 + WHO 605 79
FIG. 4 TOTAL SURVEY POPULATION SEROL. TESTED - SOUTHERN THAILAND (1-16 Survey)
70~------------------------------------~------------------------~
. 60 Sera- titres 16 dils. or more
____..__
Seroreactors Sera titres 8 dils. or more
50
~
>
c
0::::
40
//
~
//
~,....,.... r _,,/ ,~
> ....... (..)
Q)
/ ,,,................ ,,, ,,,,,,
Q)
ro
30
0::::
_____ _,.. _,,. ,,,'' 1
..............
20
10
.,..,----15-29
~/ , , ,,''
/
/
/
,,,,,-----------------' -----~'-----------I
0
I ~ -~----' . ---r---r ~~~~-LI_ _
I
0- 4
5-7 8-10 11-14
30-44 Age groups (years)
45-59
60 + WHO 60580