Volume 58, Number 4Printed in the U.S.A.

(ISSN 0148-916X)

INTERNATIONAL JOURNAL OF LEPROSY

INTERNATIONALJOURNAL OF LEPROSY

And Other Mycobacterial Diseases

VOLUME 58, NUMBER 4^

DECEMBER 1990

A Longitudinal Study of the Incidence ofLeprosy in a Hyperendemic Area in Zaire, withSpecial Reference to PGL-Antibody Results'

Guido Groenen, Stefaan R. Pattyn, Peter Ghys,Kayembe Tshilumba, Luk Kuykens, M. Joseph Colston,

and the Yalisombo Study Group 2

Yalisombo (YAL) is an old leprosariumon the left bank of the Zaire River 25 kmdownstream from Kisangani. Up to 1960,treatment of leprosy patients was assuredby the nearby missionary hospital. After in-dependence in 1960, troubled times causeda breakdown of medical services. As a re-sult, the leprosy patients received very ir-regular dapsone (DDS) treatment, if treat-ment was given at all. The policy of isolationof the patients in leprosaria was abandonedin 1960, but the local authorities have con-

' Received for publication on 30 October 1989; ac-cepted for publication in revised form on 29 March1990.

2 G. Groenen, M.D., Bureau National de la LCpre,Kinshasa, Zaire. S. R. Pattyn, M.D., Professor of Mi-crobiology, University of Antwerp and Institute ofTropical Medicine, Nationalestraat 155, 2000 Ant-werpen, Belgium. P. Ghys, M.D.,; L. Kuykcns, M.D.,Damien Foundation, Kisangani, Zaire. T. Kayembe,M.D., University of Kisangani, Zaire. M. J. Colston,Ph.D., National Institute for Medical Research, MillHill, London NW7 I AA, U.K. Yalisombo Study Group:Mwanasangezi, Mwinyihali (University of Kisangani),E. Nollet, M. Vermander, L. Coussens, J. Verlinden,R. De Raedt, L. Van Laeken, L. Breugelmans (DamienFoundation, Kisangani).

Reprint requests to Professor S. R. Pattyn.

tinued, on their own initiative, to send man-ifest and suspected leprosy cases to YAL.

The Damien Foundation reactivated lep-rosy control in the city of Kisangani in Sep-tember 1982. It soon became evident thatYAL constituted a hyperendemic leprosyfocus: up to July 1984, 7.4% of the patientsregistered in Kisangani were living in or hadbeen living in YAL, and 36% of them weremultibacillary (MB) compared with a 15%MB proportion elsewhere in the area. In1984 a total population survey for leprosywas organized at YAL. Thereafter, the pop-ulation would be re-examined yearly. Theresults of the annual surveys from 1984 to1988 are presented here.

MATERIALS AND METHODSA preliminary demographic survey was

undertaken by two students of the Facultyof Psychology, University of Kisangani,during 1 week in 1984. YAL is a cluster offour villages: Yalisombo proper, Yakake(immediately adjoining Yalisombo), Yand-jali (2 km from YAL), and Bukukwana (4km from YAL; can only be reached by boat).Each house was visited and its inhabitants

641

642^ International Journal of Leprosy^ 1990

listed on a family record, noting name, sex,date of birth, relation to the head of thefamily, and date of arrival at YAL.

The initial leprosy survey was carried outduring 1 week in August 1984. Each indi-vidual was examined clinically by an ex-perienced leprosy worker (complete skin in-spection and nerve palpation, and sensoryand motor function testing if leprosy wassuspected). For all cases suspected of MBleprosy, as well as for all new and old MBcases, skin smears were examined on thespot. A skin biopsy was taken from all sus-pected cases, all new cases, and all old caseswith residual skin lesions. The biopsies, fixedin 10% Formalin, were sent to the Instituteof Tropical Medicine, Antwerp, Belgium.

Two thick blood drops were collected onfilter paper from all individuals examined.The filter papers were kept at 4°C and sentto the National Institute for Medical Re-search, London, where the phenol glycolip-id antibody (PGL-A) titers were deter-mined, following the procedure describedby Brett, et al. ( 2). Each blood spot was elut-ed in 4 ml of phosphate-buffered saline(PBS)-Tween 80 + 3% bovine serum al-bumin (BSA) (equivalent to an 80-fold di-lution), and antibodies against a syntheticantigen were determined. This synthetic an-tigen consisted of the terminal disaccharideof phenolic glycolipid (3,6-di-O-methy1-0-D-glucopyranosyl-(1 4)-2,3-di-O-meth-yl-a-L-rhamnopyranose) which was coupledto BSA using the allyl aglycone. This antigenwas kindly provided by Dr. R. Gigg, Lab-oratory of Lipid and General Chemistry,National Institute for Medical Research,London. Each sample was tested in tripli-cate, plus a "no-antigen" control. The re-sults were recorded as the difference in op-tical density units (ODU) between the testreading and the "no-antigen" control read-ing (z ODU). A A ODU of 0.20 or greaterwas considered to be positive; a A ODU of0.10-0.19 was considered to be doubtful.

A lepromin test (WHO lepromin H con-taining 4 x 10' bacilli per ml was suppliedby the National Institute for Medical Re-search) was performed on all children under15 years of age, and on old cases of uncertainclassification, by administering 0.1 ml oflepromin intradermally. The tests were readafter 28 days, and an induration of 3 mm

and more was considered positive.All leprosy cases received appropriate

multidrug therapy.All results were entered on the family rec-

ord, and allowed each individual to be clas-sified as to his/her leprosy status: no leprosy,old case (existing record or intake of lep-rostatics in the past, regardless of regulari-ty), new case (never treated before), pauci-bacillary (PB) or multibacillary (MB), activeor inactive. New cases were classified as MBif a bacterial index (BI) of 2 or more wasfound at any site. The classification of theold cases was based on whatever informa-tion was available: either the smear result(all positive skin smears being consideredas MB), the biopsy result, the initial clas-sification or a lepromin result of > 3 mm.The criteria for activity were: all new casesand old PB cases = inflamed skin lesions orpainful enlarged nerves with a skin biopsyrevealing a tuberculoid granuloma; old MBcases = a positive skin smear.

Follow-up surveys were carried out inSeptember 1985 and in August 1986, 1987,and 1988. Two months prior to each follow-up survey, the village chiefs and elders werecontacted, and in 1986 two students fromthe University of Kisangani visited all ofthe families at home 1 month prior to thesurvey in order to stimulate them to par-ticipate in the survey. All inhabitants pre-viously known to be free of leprosy, as wellas all newly arrived inhabitants, were ex-amined according to the 1984 survey, ex-cept that lepromin tests were not performedand blood samples for PGL-antibody de-termination were not taken.

Statistical analysis included the Student ttest for comparing means, the X 2 test withYates' continuity correction for comparingproportions, and the Mantel-Haenzel X 2 testfor comparing rates.

RESULTSLeprosy prevalence (Table 1). Of the 1768

individuals registered during the prelimi-nary demographical survey, 1394 (78.8%)and 198 new, unregistered individuals wereexamined; a total of 1592 people from 282families.

All PB cases were confirmed by histo-pathology. Three of the 30 newly diagnosed

58, 4^Groenen, et al.: Leprosy Incidence and PGL Antibodies^643

TABLE 1. Leprosy prevalence in each village according to type of leprosy.

Villages'Total

YAL YAK YAN BAK

No. examined 1066 15 48 63 1592PB leprosy

Activeb 45 13 I I 60Residual lesions 55 4 59No lesions 103 6 109Total 203 23 1 1 228

88.7%MB leprosy

Active' 16 17Inactive (BI neg.) 12 — 12

Total 28 1 2911.3%

Total PB + MB 231 24 25721.7% 5.8% 2.1% 1.6% 16.1%

Active cases 61 14 1 1 775.7% 3.4% 2.1% 1.6% 4.8%

YAL = Yalisombo; YAK = Yakake; YAN = Yandjali; BAK = Bukukwana, Zaire.b New cases + old cases with clinical and histological lesions.Old cases with a positive BI and new cases with a BI > 2+.

PB cases without signs of leprosy in the bi-opsy were nevertheless considered as caseson clinical grounds because there was an-esthesia and motor function impairment.No misclassifications between PB and MBleprosy have been made in the field.

The overall prevalence as well as theprevalence of active cases is very high, butthis is mainly due to the extremely highprevalence in Yalisombo village, the origi-nal leprosarium. In the three other villages,which were founded later, the prevalencediminishes as a function of the distance fromYalisombo. Thirty of the PB patients(13.2%) and 1 of the MB patients (3.4%) arenewly detected cases (no existing records,no known previous treatment). The otherpatients had records at the Yalisombo dis-

pensary or claimed to have received DDSin the past. However of these "old" casesonly 14 PB (47% of the old active PB cases)and 9 MB cases (56% of the old MB cases)were receiving treatment in Kisangani at thetime of the survey.

Leprosy patients are older than the gen-eral population (median age general popu-lation = 19; leprosy patients = 41). Thisdifference is mainly due to the old cases whohave a median age of 44, against 24 for thenew cases, while 26% of the new cases arechildren under 15 years of age. There is asignificant (0.005 > p > 0.001) predomi-nance of males in the leprosy population(57%), compared with the nonleprosy pop-ulation (47%), for PB (57%) as well as forMB (59%) patients.

TABLE 2. Distribution of leprosy cases among the families.

Cases/family No. families No. individuals Membersper family

No. leprosypatients Leprosy prevalence

4 7 64 9.1 28 43.8%3 10 67 6.7 30 44.8%2 54 373 6.9 108 29.0%1 91 516 5.7 91 17.6%0 120 572 4.8

Totals 282 1592 5.6 257 16.1%

644^ International Journal of Leprosy^ 1990

100

90

80

70

60

..!.■ 50

•••

040

30

20

10

2^3^4^5^6^7^8^9^10

Lepromin result (mm)

THE FIGURE. Distribution of skin test results.

Of the 282 families examined, 162 (57.4%)had at least one case of leprosy: Yalisombo,79.9%; Yakake, 28.4%; Yandjali, 12.5% andBakukwana, 38%. Seventy-one (42.5%) ofthe leprosy families had more than one caseof leprosy. The family composition in re-lation to the number of leprosy cases in the

family is given in Table 2. The families withthe most cases are also the largest ones. Inthe 3-case and 4-case families almost halftheir members have leprosy.

Results of lepromin tests. Seventy-fivepercent (543) of the 725 lepromin tests wereread. Among the leprosy patients, the threeMB cases had a lepromin result of 0 mm.Among 48 PB cases, 44 were lepromin pos-itive, with a mean diameter of 5.9 mm. Ofthe 4 lepromin negative PB cases, 1 had areading of 2 mm, and 3 had no induration.Two of the latter had a BI of 1+, and oneof these relapsed 2 years later as BL with aBI of 4; the other one was lost to follow-up.The two other lepromin-negative PB caseshad a satisfactory evolution.

The lepromin results of the 492 individ-uals without leprosy are presented in TheFigure. Based on this graph, a 3-mm in-duration was used as the cut-off point forlepromin positivity. Thus, 87.6% of the in-dividuals without leprosy were leprominpositive and 12.4% were lepromin negative.The mean diameter in the lepromin-posi-tive individuals was 5.6 mm; negative re-sults diminish with increasing age, while themean diameter in lepromin-positive indi-viduals increases.

PGL-A results. A total of 1524 bloodsamples were tested for PGL-A. Table 3presents the results according to leprosy sta-tus. The percent positive corresponds to thesensitivity of the test. If the doubtful resultsare included among the positives, the sen-sitivity increases from 51.1% to 87.7%among active MB patients, from 38.5% to57.7% among all MB patients, and from7.6% to 14.9% among all leprosy patients.

TABLE 3. Phenolic glycolipid (PGL) antibody results.Clinical leprosy

classification No. tested No. negative No. doubtful No. positive° (%)

MB active 14 4 8 (57)Inactive 12 9 1 2 (16.7)

PB actived 58 50 4 4 (6.9)Inactive 165 151 9 5 (3)

No leprosy 1275 1193 53 29 (2.3)1524 1405 71 48 (31)

a A ODU = 0.10-0.19.b A ODU = ^0.20.Old cases with a positive BI and new cases with a BI ^ 2+.

d New cases + old cases with clinical and histological lesions.

58, 4^Groenen, et al.: Leprosy Incidence and PGL Antibodies^645

TABLE 4. Follow up per annual cohort of individuals without leprosy.

Cohort 1984 Cohort 1985 Cohort 1986 Cohort 1987 Total

No. No. No. ova No. No. ova

1984No leprosy

1985DiedLostNew casesNo leprosy

1986DiedLostNew casesNo leprosy

1987DiedLostNew casesNo leprosy

1988DiedLostNew casesNo leprosy

1335

30229

31073

171024

950

31603

787

3265

515

17.2%

9.5%

16.8%

33.8%

197

5680

124

531088

029

58

34.5%

25.0%

32.9%

165

866091

027064

40.0%

26.7%

181

195

184

52.5%

1335

302293

1270

221704

1239

162573

1144

44163

721

17.2%0.28%

13.4%0.37%

20.7%0.31%

36.4%0.41%

The specificity of the test, as measuredamong the YAL inhabitants without lep-rosy, is 97.7%.

The positive predictive value of the testis 39.6% for discriminating between leprosypatients (all types, prevalence = 16.1%) andhealthy controls; 20.8% for discriminatingbetween MB patients (active and inactive,prevalence = 1.7%) and other individuals

(PB patients and healthy controls); and16.7% for discriminating between active MBpatients (prevalence = 0.92%) and all otherindividuals (inactive MB patients and PBpatients and healthy controls). For the ac-tive MB patients no correlation between thePGL-A result and the BI could be demon-strated.

The age distribution of the PGL-A pos-

TABLE 5. New cases detected during 1985-1988 surveys.

Year Patient no. Sex Age Bacterialindex

Histologicalresult PGL-A Lepromin

(mm)

1985 1 F 45 BT7 M 5 0 BT 0 ? 0

3 F 18 0 BT 0

1986 4 M 5 0 BT 05 F 9 0 06 F 24 0 BT 07 F 30 0 BT 0

1987 8 M 32 0 TT 09 M 8 0 0 9

10 M 13 0 BT 0 81988 11 F 12 0 BT 0 8

12 M 11 013 F 48 0 BT

— = Not done.? = Result unknown.

646^ International Journal of Leprosy^ 1990

TABLE 6. Incidence of leprosy among individuals previously without leprosy accordingto number of leprosy cases already present in the family.°

No. individ- Person-yearsuals without^(py) of

leprosy^follow up

Mean py of^Newfollow up^cases Incidence

Families with 4 cases 42 104 2.48 19.2%Families with 3 cases 47 108 2.30 0 0Families with 2 cases 343 611 1.78 2 3.3%Families with 1 cases 551 1337 2.43 3 2.2%Families with 0 cases 895 1884 2.11 6 3.2%

4 case families vs all other families = 0.01 < p < 0.001.4 case families vs 0 case families = 0.025 < p < 0.01.4 case families vs 1 case families = 0.01 < p < 0.001.4 case families vs 2 case families = 0.05 < p < 0.025.

itives is comparable to that of the PGL-Anegatives, among nonleprosy individuals aswell as among leprosy patients. The PGL-A-positive individuals without leprosy werenot preferentially found in the families withleprosy cases, nor had the type of leprosypresent in the family any influence (data notshown).

Follow-up surveys. The individualswithout leprosy were re-examined annually.Each year individuals not seen before wereincluded in the study. Table 4 presents dataon the annual follow-ups. The 1984 cohorthas been followed for 3333 person years (py)out of a possible 5340; the 1985 cohort, for271 py out of a possible 591; the 1986 co-hort, for 155 py/330; the 1987 cohort, for55 py/181; or a total of 3814 py/6442.

Between 1985 and 1988, no new cases ofMB leprosy were detected while the meanyearly incidence rate of PB leprosy was0.34%-variations in yearly incidence rates(from 0.28 to 0.41%) are not statisticallysignificant-and no new cases from Yali-sombo were seen in Kisangani. The partic-ulars of the new cases are given in Table 5:they are young (mean age 20 years), 7 outof 13 (54%) are under 15; 6 are male and 7,female. All are PB cases (one case had a BIof 1): 3 indeterminate (23%), 1 TT (8%), 9BT (69%). In all three of the new cases inwhom a lepromin test was done in 1984, itwas strongly positive.

Table 6 presents the new cases accordingto the number of leprosy cases already pres-ent in the family. The incidence in the 4case families is significantly higher than inthe other families (0.01 > p > 0.001). Beinga member of a 4-case family in YAL is

associated with a relative risk of 6.5 of de-veloping leprosy.

PGL-A had been determined in 1984 for11 out of the 13 new cases; only one had adoubtful positive result of 1+. The 82 PGL-A-positive individuals of the 1984 cohortwithout leprosy have been followed for 189py out of a possible 328 (mean = 2.31 years),and the 1193 PGL-A-negative individualsfor 3018 py out of a possible 4772 (mean= 2.53 years; the difference is slightly sig-nificant, 0.05 > p > 0.025. Among thePGL-A positives, one new case (patient 1,Table 5) was diagnosed but with a doubtfulpositive result of 1+.

The overall incidence of leprosy amongPGL-A positives (if the 1+ results are in-cluded) is 1/189 (0.53%) compared to 10/3018 (0.33%) among PGL-negatives; the dif-ference is not statistically significant.

The 37 PGL-A-positive patients diag-nosed in 1984 were followed for 106 py outof a possible 148 (mean = 2.86 years. Thisis significantly longer than the disease-free,PGL-positive persons). Of these 37 patients6 were never seen again (4 died, 2 disap-peared). One patient, classified as old in-active PB with a PGL-A result greater than1.0 A ODU, relapsed as MB in 1985. Asecond patient, classified as old inactive PB(biopsy = arrested BT lesions) and a PGL-A result of 0.20 A ODU, presented a reac-tivation of his BT lesions in 1987. No otheraggravations were observed. The remaining29 patients showed a satisfactory evolution,26 being considered cured at their last fol-low-up examination.

The 212 PGL-A-negative patients of the1984 cohort were followed for 656 py out

58, 4^Groenen, et al.: Leprosy Incidence and PGL Antibodies^647

of a possible 848 (mean = 3.09 years, com-parable to the PGL-A-positive leprosypatients). Seven patients died and 10disappeared. Six patients showed an unsat-isfactory evolution. Three patients present-ed a PB relapse; they had clinically activePB leprosy in 1984 and a negative biopsyafter treatment in 1986, but relapsed in 1987or 1988 with BT leprosy. Two patients withactive PB leprosy in 1984 did not respondto treatment and showed persistent activitywith a positive biopsy in 1987. One patient,diagnosed in 1984 as old inactive PB, pre-sented a reactivation of the lesions in 1986.The remaining 189 patients showed a sat-isfactory evolution and 133 were consideredcured at their last follow-up examination.

DISCUSSIONYAL constitutes a hyperendemic leprosy

focus. In 1984 the overall prevalence ratewas 22% in Yalisombo village, 6% in Ya-kake, and 2% in both Yandjali and Bakuk-wana. Many of the patients were old casesno longer in need of antibacterial treatment.Taking into consideration only the activecases who needed such treatment, the prev-alence rate was still as high as 6% in Yali-sombo village, 3% in Yakake and 2% inboth Yandjali and Bakukwana. By com-parison the prevalence rate in the adjoiningareas is between 0.4% and 0.6% ( 3). Thereason for this extremely high prevalence isthe active segregation policy in use until1960, and even later on when a considerablenumber of patients were sent to YAL by thecivil authorities, or came there on their owninitiative. Thus there has been a huge influxof leprosy patients from outside: 146 out ofthe 257 patients had leprosy when they ar-rived in YAL. This high concentration ofuntreated or insufficiently treated cases con-stituted a potent source of transmission: outof 1446 individuals who showed no signsof leprosy when arriving in YAL, 1 1 1 (7.7%)developed the disease. Even if we allow forsome of those cases to have contracted thedisease before their arrival, transmission inYAL must have been intense.

In spite of the heavy river traffic betweenYAL and Kisangani, and in spite of the factthat the Kisangani leprosy service was wellknown in YAL, only 14 out of the 61 activePB cases and 9 out of the 16 active MB caseshad sought treatment on their own initia-

tive. Thus, through spontaneous presenta-tion only 23% of the PB cases and 56% ofthe MB cases were detected. Among the YALpatients treated in Kisangani 36% were MB,but the YAL survey revealed an overall MBproportion of 11.3%, and an MB proportionof 22% among the active cases, comparableto the MB proportion found in the adjoiningareas of between 14% and 23% (3). The highnumber of MB cases observed in Kisanganiis thus caused by a presentation bias. Theresults of the surveys also suggest that theMB rate in a population remains constant,in spite of the high infection pressure.

Among the new cases (never treated be-fore), 26% were children, as compared to achild proportion of 12% ( 3) in the adjoiningareas. This is most probably the result ofearlier detection during active case-finding.The male predominance among both PBand MB patients remains unexplained. Inthe adjoining areas a male predominance isfound among MB patients, but among PBcases the sexes are distributed equally.

Sixty-two of the disease-free individualshad a negative lepromin test. There are twoexplanations for a negative lepromin resultin an endemic area: a) either infection withMycobacterium leprae has not yet occurred,or b) it did occur but the individual doesnot react and is incubating or at risk of de-veloping a MB form of the disease. It isunlikely that there were many cases incu-bating a MB form of the disease in this pop-ulation, since no new cases were detectedduring the next 4 years. An argument infavor of the first mechanism can also befound in the age and family distributions ofthe results; negative results decrease withage, while the mean diameter of indurationincreases. Exposure to M. leprae could beexpected to be highest in families with ac-tive MB cases and in families with multipleleprosy patients. However, no relation couldbe found between the prevalence of lepro-min negativity and the number of patientsin the families. This seems to indicate thatthe infection pressure in YAL is equal forthe whole population, the prevalence of dis-ease being so high that differences betweenfamilies do not play any role, leaving age asthe only limiting factor to exposure (beyondthe age of 10 years almost all inhabitants ofYAL have a positive lepromin test).

The PGL-A-positivity rate decreases from

648^ International Journal of Leprosy^ 1990

MB to PB to "no leprosy," whether aODU of 0.10 or of 0.20 is taken as the cut-off value for positivity. This decrease is mostdramatic between active and inactive MBcases. The test managed to pick up 12 outof 14 active MB cases but at a cost of manyfalse-positives, resulting in a low positive-predictive value. This predictive value willbe even lower in an area with a lower MBprevalence. For a MB prevalence of 0.092%,as in many Central African areas, the pos-itive predictive value for active MB caseswould be 1.1%.

No relation could be found between PGL-A positivity and the bacterial index, age, orthe presence of leprosy cases in the family.

The limited value of the PGL-A test as adiagnostic and prognostic tool found in thepresent study confirms the observations ofother studies in the field. Seropositivity isconsistently higher in MB patients than inPB patients ( 1,4), and in leprosy patients thanin nonleprosy individuals ( 1 ' 4 ' 5 ). Seroposi-tivity in contacts of known leprosy cases ishigher than in healthy controls in somestudies ( 1,4) but not in others ( 5), or it ishigher in contacts of more than 1-year du-ration of lepromatous patients than in othercontacts or healthy controls ( 6). However,the number of false-positives is always con-siderable and makes interpretation of in-dividual results in the field very difficult.One study ( 5) actually found that antibodiesagainst M. tuberculosis provide a better dis-crimination between leprosy patients (alltypes) and healthy subjects than do IgM an-tibodies against M. leprae PGL-I. The lattertest had a sensitivity of 43% and a specificityof 95%, but this specificity was arbitrarilyfixed by the investigators. Two studies ( 1 . 4 ),determining IgM antibodies against the nat-ural disaccharide coupled with an octylspacer arm to BSA (ND-O-BSA), yielded asensitivity of 100% for detecting MB pa-tients, and of 44% and 57.4%, respectively,for discriminating between leprosy and nor-mal individuals. The specificity as deter-mined from endemic noncontact personswas 95.5% and 98%, respectively. But inthese studies the group sizes were deter-mined by the investigators, and no predic-tive values can be calculated.

The 0.34% yearly incidence rate of lep-rosy in YAL is much higher than the de-tection rates of between 0.03% and 0.06%

in the adjoining areas ( 3). However, the lat-ter figures are based on passive case-findingwhich may represent 1/2 or 1/4 of the truenumber. The active case-finding in the YALsurveys also results in early detection; 54%of the new cases were children as comparedto 12% in the adjoining areas.

The incidence rates obtained during the1985-1988 surveys are probably a reflec-tion of the transmission before the 1984survey. In 1984 all leprosy cases, active aswell as inactive, were treated with bacteri-cidal therapy, and all new cases and relapsesfound thereafter were also treated right away,thus reducing the infection sources consid-erably. It is therefore thought that almostall new cases found during the follow-upsurveys were already infected in 1984 andincubating the disease in 1984 or later. Ifthis is the case, the PGL-A test was notuseful at all in detecting subclinical infec-tion: only 1 out of 11 new cases had a doubt-ful positive result. It may be of interest tonote that this patient also had a BI of 1+.

All new cases are PB. If the proportion ofMB among newly detected cases is com-parable to that in the adjoining areas (be-tween 9% and 12%), one new MB case couldbe expected. No new MB cases have beendetected so far, but further follow-up is in-dicated.

The family distribution of the new casessuggests clustering of the disease. But, asshown by the lepromin results and the veryhigh overall prevalence of the disease, itseems unlikely that members of 4-case fam-ilies are more heavily exposed to infection.However, it is possible that there is a familypredisposition for the development of dis-ease after infection. Speculations about thenature of this predisposition are beyond thescope of the present paper.

The follow-up of the 1984 cohort in re-lation to PGL-A results shows very incon-clusive results. Although 1 old PB case witha PGL-A result of 10+ relapsed as MB, 7other leprosy patients with a high positivePGL-A result (between 6+ and 14+) didnot relapse, and 6 highly positive (between6+ and 14+) individuals without leprosydid not develop the disease.

Among the cohort without leprosy, thePGL-A positives (including the doubtful 1+results) showed a leprosy incidence of 0.53%compared to 0.33% among the PGL-A neg-

58, 4^Groenen, et al.: Leprosy Incidence and PGL Antibodies^649

atives. This is remarkably comparable toobservations in French Polynesia ( 4), where3 new cases were observed among 631 sero-negative contacts followed for 1262 py (in-cidence = 0.23%), and 1 new case among93 seropositive contacts followed for 186py (incidence = 0.53%). It is of interest tonote that the three seronegative contacts whodeveloped leprosy (all of the PB type) re-mained seronegative after developing thedisease.

Among the leprosy cohort, 6.25% of thePGL-A positives, again including thedoubtful 1+ results, compared to 3.1% ofthe PGL-A negatives showed an unsatisfac-tory evolution, but 81.2% of the PGL-Apositives were considered cured by 1988 ascompared to 70.4% of the PGL-A negatives.None of the differences between the PGL-Apositives and PGL-A negatives arestatistically significant. If only the PGL-Aresults of at least 2+ are considered, theleprosy incidence is 0 among PGL-A posi-tives and 0.35% among PGL-A negatives.Among the PGL-A-positive patients, 9%presented an unsatisfactory evolution while75% were considered cured by 1988. Amongthe PGL-A-negative patients, 2.9% pre-sented an unsatisfactory evolution while71.8% were considered cured by 1988.Again, none of the differences are statisti-cally significant.

In spite of the efforts of the survey team,many people have been lost to follow-up.Of the 1984 cohort only 39.4% were fol-lowed for 4 years. This is partly due to themobility of the population; each year thereis about a 15% immigration and emigration.However, quite a few people seem to dropout due to lack of interest in the survey.This was investigated in 1986, when a psy-chology student at Kisangani University in-terviewed 100 absentees ( 7). The main rea-son for absenteeism seemed to be adisappointment in the survey team; thepopulation expected the survey team to pro-vide general medical care. There was alsosome dissatisfaction about the timing of thesurvey and, surprisingly, in view of the veryhigh leprosy prevalence in YAL, many ofthe interviewees manifested very inade-quate knowledge of the disease. The surveyteam subsequently tried to improve collab-oration through health education cam-paigns, through extensive explanation of the

purpose of the study to the village chiefsand elders, and even through individualhome visits. The timing of the survey wasalso rearranged. However, attendance didnot improve and, in view of the efforts made,it is probably the best that can be achieved.

From the present study the following con-clusions can be drawn: a) In the hyperen-demic Yalisombo situation with a leprosyprevalence of 16.1%, exposure to infectionis uniform but there is a suggestion of familyclustering of cases. b) The annual incidencerate is very high (0.34%) and 54% of thenew cases are children, indicating an intensetransmission. c) There is no decrease of theincidence during the first 4 years after theelimination of the known infection reser-voir by bactericidal treatment. d) The PGL-A test does not contribute to the diagnosisor classification of leprosy; it does not giveprognostic indications and does not detectincubating forms of the disease.

SUMMARYBetween 1984 and 1988, yearly surveys

for leprosy were done among the 1500 peo-ple living in a previous leprosy segregationvillage in Zaire. In 1984 lepromin tests andphenolic glycolipid (PGL) antibody testswere done in a significant part of the pop-ulation. The prevalence of the disease atthat time was 16.1%, the proportion of mul-tibacillary cases was 11.3% overall and 22%among active cases. Prior to 1984, 23% ofpaucibacillary cases and 56% of multiba-cillary cases had presented themselvesspontaneously to the Leprosy Service. Theexposure to the infection is uniform, butthere is a suggestion of family clustering ofcases. In spite of a rapidly bactericidal treat-ment of all known cases in 1984 and there-after, the annual incidence of 0.34% did notdecrease during the 4 years of the study. ThePGL antibody test did not contribute to thediagnosis, classification or prognosis of thedisease.

RESUMENEntre 1984 y 1988 se hicieron examenes anuales para

detectar lepra entre los 1500 habitantes de un cam-pamento en Zaire, utilizado en el pasado para segregara los pacientes con esa enfermedad. En 1984 se hicieronpruebas dermicas de lepromina y pruebas serolOgicaspara anticuerpos contra glicolipido fenOlico (PGL) enuna gran pane de la poblaciOn. En ese tiempo la pre-

650^ International Journal of Leprosy^ 1990

valencia de Ia enfermedad fue del 16.1%, la proporciOnde casos multibacilares fue del 11.3% en general, y del22% en los casos activos. Antes de 1984, el 23% de loscasos paucibacilares y el 56% de los multibacilares sehabian presentado al Scrvicio de Lepra de manera es-pontimea y voluntaria. Actualmente, aunquc Ia expo-siciOn a la infecciOn es uniforme, hay evidencias deagrupamiento familiar de los casos. No obstante eltratamiento bactericida de todos los casos cn 1984 (yposterior), Ia incidcncia anual del 0.34% no disminuy6durantc los 4 anos del estudio. La prueba del PGL nocontribuy6 al diagnOstico, a Ia clasificaciOn, ni al pro-nOstico de la enfermedad.

RÉSUMÉ

Entre 1984 et 1988, des enquetes annuelles pour Ialepre ont Cie realisees parmi les 1500 personnes vivantdans un ancien village d'isolement des malades lepreuxau Zaire. En 1984, des tests A Ia lepromine et de re-cherche des anticorps contre le glycolipide phénolique(PGL) ont Cite effectuês dans une partic significative deIa population. La prevalence de Ia maladie a cette ("Toqueetait de 16.1%, Ia proportion des cas multibacillairesetait de 11.3% parmi l'cnscmblc des cas, et de 22%parmi les cas actifs. Avant 1984, 23% des cas pauci-bacillaires et 56% des cas multibacillaires s'etaient pre-sentes spontanement au Service de la Lepre. L'expo-sition a l'infeciton est uniforme, mais it y a une ebauchede regroupement familial des cas. En &pit d'un trai-tement rapidement bactericide de tous les cas connusen 1984 et par Ia suite, l'incidence annuelle de 0.34%n'a pas diminue au cours des 4 ans de l'etude. Le testde recherche des anticorps anti-PGL n'a pas aide au

diagnostic, a la classification ni au pronostic de la ma-ladie.

REFERENCES1. AGIS, F., SCHLICH, P., CARTEL, J.-L., GUIDI, C. and

13AcH, M.-A. Use of anti-M. leprae phenolic gly-colipid-1 antibody detection for early diagnosis andprognosis of leprosy. Int. J. Lepr. 56 (1988) 527-536.

2. BRETT, S. J., DRAPER, P., PAYNE, S. N. and REES,

R. J. W. Serological activity of a characteristic phe-nolic glycolipid from Mycobacterium !viva(' in serafrom patients with leprosy and tuberculosis. Clin.Exp. Immunol. 52 (1983) 271-279.

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4. CHANTEAU, S., CARTEL, J.-L., GUIDI, C., PLICHART,

R. AND BACH, M.-A. Seroepidemiological study of724 household contacts of leprosy patients in FrenchPolynesia using disaccharide-octyl-BSA as antigen.Int. J. Lepr. 55 (1987) 626-632.

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7. MWANASANGEZI, B. M. and GROENEN, G. Reasonsfor non-response during an ongoing leprosy surveyin northern Zaire. Ann. Soc. Belg. Med. Trop. 67(1987) 271-275.