Journal ofNeurology, Neurosurgery, and Psychiatry 1990;53:4-10

A cluster ofHTLV-1 associated tropical spasticparaparesis in Equateur (Zaire): ethnic andfamilial distribution

K Kayembe, P Goubau, J Desmyter, R Vlietinck, H Carton

AbstractIn Lisala, Equateur province, Zaire, 25patients from 21 pedigrees were iden-tified with human T-lymphotropic virustype 1 (HTLV-1) associated tropical spas-tic paraparesis (TSP). In the 10 (48%)pedigrees with additional genuine TSPcases established mainly by history, sevenof 10 patients' mothers, no fathers orspouses, one of 59 surviving offspring, fiveof 105 siblings, and six other close bloodrelatives had TSP. A child may developTSP before its mother. Three familialcases were in paternal relatives only. Intotal, 39 cases (11 men, 28 women) wereidentified in this population of about50,000. Half were in the Mundungaminority of < 10% (p < 0-001). Thedata suggest maternal transmission ofHTLV-I and enhanced TSP susceptibilityin those infected due to familial, probablygenetic factors.

CentreNeuropsychopatholo-gique, University ofKinshasa, Kinshasa,ZaireK KayembeRega Institute andDepartment ofMicrobiology,University Hospitals,Leuven, BelgiumP GoubauJ DesmyterDepartment ofHuman Genetics,Catholic University ofLeuven, Leuven,BelgiumR VlietinckDepartment ofNeurology, UniversityHospitals, Leuven,BelgiumH CartonReceived 16 December 1989and in revised form 10 April1989Accepted 9 June 1989

Correspondence to:Professor H Carton, AfdelingNeurologie, UZGasthuisburg, Herestraat 49B-3000 Leuven, Belgium.

Human T-lymphotropic virus type 1

(HTLV- 1), the first human retrovirus isolatedand a causative agent of adult T-cell leukaemia(ATL),' is also associated with slowly progres-sive myelopathy,2 a disease called tropical spas-tic paraparesis (TSP) in the tropics, andHTLV- 1 associated myelopathy (HAM) inJapan.3 Numerous cases ofHTLV-1 associatedTSP have been detected in the Caribbean(Martinique, Jamaica, Trinidad), in theTomaco lowlands on the Pacific coast ofColombia and in the Seychelles."5 A possiblelink between these tropical regions is thepresence of a population of black Africanancestry and where people of different ethnicorigin live together, the highest prevalence ofanti-HTLV-1 is found amongst the blackpeople.9 Thus HTLV- I could have beenimported to these various areas from theirAfrican population. This is consistent with asuggested sero-prevalence of HTLV- 1 of1-10% in African countries (Gabon, Ghana,Ivory Coast, Kenya, Nigeria, Senegal)'O'4 andwith the isolation ofHTLV-1 from at least oneAfrican patient, a Zairian treated for ATL inFrance.'5 However, there are technicalproblems in obtaining exact seroprevalencedata, particularly on stored African sera,1216and the above figure is lower than that in theendemic areas in the Caribbean or Japan.Reported cases of HTLV- 1 associated ATLand TSP are conspicuously few in Africans. Noclusters of TSP and only four sporadic TSP

patients have been reported, two from theIvory Coast,'718 one from Senegal,'9 and onefrom Ethiopia.20 An extensive serological andneurological survey in Gabon has shown asubstantial seroprevalence ofHTLV- 1, but noTSP cases.2'We describe an important cluster of

HTLV-1 associated TSP in the tropical rainforest of Equateur province, Zaire, and itsstriking familial and ethnic distribution.

Material and methodsLocation of the studyThe study was conducted at the TelemaRehabilitation Centre in Lisala (Zaire) inDecember 1987. Lisala is located in theEquateur province, on the right bank of theZaire river, in the tropical rain forest, 2° northand 220 east, at a mean altitude of 300 m (fig 1).The city has 30,000 inhabitants, but patients ofthe neighbouring villages at a distance ofup to20 km are also treated as outpatients at theTelema Rehabilitation Centre bringing thetotal population served by the centre to anestimated 50,000. Seventy five per cent of thispopulation are Ngombe, 10% are Budja, 10%are Mundunga and 5% Mongo or other. Mostpeople marry in their own ethnic group butnever marry with close relatives.

Study populationAt the Telema Rehabilitation Centre, 28subjects suspected by the local physiotherapistof having a spastic paraparesis were examinedby two neurologists (KK and HC) either at thecentre or in their homes in the villages sur-rounding Lisala up to a distance of 20 km. Anadditional four spastic patients belonging to afamily which moved from Lisala to Kinshasawere examined by KK at the Centre Neuro-psychopathologique (CNPP) in Kinshasa. Apedigree covering at least three generations wasobtained of all 32 patients examined. Thecriteria defined by Roman8 and more recentlyby Arango7 were used to identify patients withTSP. However, two important identificationcriteria proposed by Arango were not takeninto account: onset of the disease after 15 yearsof age and absence of a history of neurologicaldiseases in previous generations. On the con-trary, histories were taken and pedigrees wereconstructed with the aim of identifyingrelatives with TSP. Serum samples wereobtained from 32 paretic patients and CSFfrom 22 patients. Serum was obtained from 29neurologically intact blood relatives and twohealthy spouses.

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A cluster ofHTL V-i associated tropical spastic paraparesis in Equateur (Zaire)

Figure I Map of Zaire

ControlsThe seroprevalence of antibodies to HTLV-1was tested in sera of neurologically intactsubjects (NIS) and patients with otherneurological or psychiatric disorders thanchronic TSP (OND) from different regions ofZaire. Two groups of 100 subjects each were

selected on the basis of their HIV status inDungu, a remote area in Haut-Zaire (fig 1).The second population consisted of 211mothers with their young children visitingoutpatients in Kinshasa. Sera of 119 ONDpatients were obtained at the NeuropsychiatricCentre as well as serum of 61 patients of theMedical Clinic of the University of Kinshasa.In the analysis patients originating fromEquateur are considered separately. Finally 18patients with acute epidemic spasticparaparesis and three NIS from Kidima andother places in South Bandundu (fig 1) were

also tested.22

Laboratory testsSerum and CSF samples were collected inLisala and Kinshasa between December 1987and May 1988 and shipped frozen to Leuven(Belgium). Screening for HTLV-1 antibodieswas performed with a commercially availableELISA (DuPont, Wilmington, United States).All positive samples and all samples from TSPpatients and their families were also tested byWestern blotting (strips from DiagnosticBiotechnology, Singapore). A serum samplewas considered positive when reacting withmolecular weight bands of 19 kD and 24 kDtogether with at least one other virus specificband. In fact all samples corresponding to thiscriterion displayed an almost complete patternof bands. Samples with virus specific bandsother than p19 and p24 or with only one ofthese two in Western blotting were consideredindeterminate. Negative samples displayed no

bands or bands outside the specific molecularweights. Indeterminate and negative sampleshave been grouped in the analysis.

Titres of HTLV- 1 antibodies in serum

and CSF were defined with an indirect im-munofluorescence assay, using a continuousHTLV- 1 producing cell-line, MT-2, as theantigen (provided by L Montagnier). Albuminand IgG concentrations were assayed by

nephelometry. Isoelectric focusing was perfor-med according to the method described byDelmotte."

All serum samples were also tested for HIVantibodies with two different ELISAs (Well-come, Dartford, United Kingdom; Abbott,Wiesbaden-Delkenheim, FRG). Positive sam-ples were confirmed by indirect immuno-fluorescence against HIV-1 and HIV-2 by acompetitive ELISA against recombinant coreand envelope antigens (Abbott) and by Wes-tern blotting for HIV-1 and HIV-2 (strips fromDiagnostic Biotechnology).

ResultsClinicalfeatures and presence of anti-HTL V-1Of 32 patients screened for chronic symmetricspastic paraparesis, 29 had gradual onset ofslowly progressive disease (table 1). Amongthese 29, 26 had clinically typical TSP, and 25(96%) had anti-HTLV-1 in their serum (table1). In addition to their paraparesis, most ofthese nine men and 16 women complained ofincreased urinary frequency or retention and ofconstipation. Most males complained ofimpotence. Spastic paraparesis, absence of sen-sory level and absence of systemic disease wereconfirmed by examination (table 2). Otherfeatures will be discussed below. The seron-egative TSP patient also lacked antibody in hisCSF, but he had a typical TSP history andpresentation.

Three other patients (table 1) also hadprogressive weakness of the lower limbs, andanti-HTLV-1 in their serum and CSF. In onespastic patient, the main reason for the gaitdisturbance was cerebellar ataxia. In the twoothers, proximal weakness of the four limbsand hyporeflexia were present without signs ofcorticospinal tract, sensory or cerebellarinvolvement, or bladder or sexual dysfunction.The two patients were unrelated ethnicNgombe. One was a 55 year old man whosedisease had started a year earlier. He was thesole child of nonconsanguineous parents andthere was no similar disease or TSP in his bloodrelatives. The other patient, aged 52 years, alsohad onset of disease a year before and hadnonconsanguineous parents. These, his eightsiblings and 12 children did not have similardisease or TSP, but a half brother from thesame father had TSP. The remaining threepatients had HTLV-1 negative spasticparaparesis with a history of incompletelyrecovered acute myelopathy, one traumatic,one post-infectious and one ofunknown origin.

Familial and epidemiologicalfeatures ofHTLV-I positive TSPThe 25 HTLV-1 positive patients first iden-tified were from 21 families that were notclosely related. Four relatives indicated bythem as having the same disease could beexamined, and they had HTLV-1 positiveTSP. Of the 25 patients, 13 (10 pedigrees) wereethnic Mundunga, 11 (10 pedigrees) were

Ngombe and one was Budja. Since the Mun-dunga constitute less than 10% of the Lisalapopulation, this indicates strong ethnic cluster-ing (p < 0-001). Half of the patients lived in

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Kayembe, Goubau, Desmyter, Vlietinck, Carton

Table 1 Lisala patients screenedfor chronic symmetric spastic paraparesis

HTL V-i -pos OligoclonalIgG banding

Clinicalfeatures Number Serum CSF in CSF HIV-1-pos serum

1. Slowly progressive paresis 29Spastic paraparesis + sphincter dysfunction 26 25 13/16 13/14 0Paraparesis + cerebellar ataxia 1 1 1/1 1 0Quadriparesis + proximal atrophy + areflexia 2 2 2/2 2 0

2. Sequelae of acute myelopathy 3 0 0/3 0 0

Table 2 Neurologicalfindings in 25 patients with HTLV-I-positive trparaparesis

Neurologicalfindings

Motor:Cranial nervesUpper limbs: weakness

increased tendon reflexesLower limbs: weakness

increased tendon reflexesspasticityextensor plantar responsecontractures

Muscle atrophy

Sensory:Upper limbs: pin-prick sensation impaired

vibration, proprioception impairedLower limbs: pin-prick sensation impaired

vibration, proprioception impairedCerebellarBladder dysfunctionBowel constipationPenile impotence (male)

Figure 2 Year of onset(upper graph) and age atonset (lower graph) of 25cases ofHTL V-I positivetropical spasticparaparesis.

No

2-

1970 1975 1980Year

10

No

5.

0

Years

Lisala city, and half along patlforest. No patient lived close to a

for a mother and a daughter bot]the same house. No patient had i

transfusions. Ages were betweyears, median 35 (fig 2). Agebetween 7 and 51 years, medianmedian disease duration beforcneeded aid for walking was ninbecame unable to walk after a

years and the longest disease cyears.

Familial occurrence of TSP win close relatives by examinationby history only. We considerhighly reliable, given the typicpresentation of the disease, and i

proved correct in the four patiexamine. Familial cases were fou

ropical spastic 21 TSP pedigrees. In seven pedigrees, themother of a TSP case had died of TSP or still

Npositive (0n) had the disease (figs 3 and 4). None of the 21fathers had TSP.

0 (00 ) Serum was obtained from two neurologically4 (16°o) intact fathers, and one had anti-HTLV-1.

24 (5680) When both mother and child had TSP, it25 (100%) usually occurred much earlier in the mother,24 (96Oo, but in two cases, TSP had started in the child25 (1ooo09 (360%) five and nine years before the mother; in one0 (0o0) case, it started the same year. Age of onset was

not different in seven patients whose mother1 (40'o) had TSP and in 11 patients whose mother was0 (0."o)1 (40o) alive and well.2 (80o) Five out of 105 siblings of the 25 patients had0 (oco0)

20 (800o) TSP. One of their 59 living children had TSP.14 (560o) None of the 15 regular spouses of the 257 (80%0)

patients had TSP. Ten spouses ofTSP patientsnot examined by us, but from the samepedigrees, did not have TSP.

o SerologyThe CSF of 18 seropositive patients (15 TSP,one cerebellar ataxia, two with muscle atrophy)were examined. HTLV- 1 antibodies werepresent in all but two CSF samples, withalmost complete Western blot patterns similarto those in serum (see examples on fig 5). Thetwo patients without HTLV-1 antibodies intheir CSF were moderately disabled withtypical TSP for seven and nine years.

Increased IgG/albumin ratios and oligo-clonal banding of IgG on isoelectrofocusingwere present in all HTLV-1 positive CSFsamples. No relationship was found betweenthe IgG/albumin ratios and the severity orduration of the disease.

Seven paired CSF and serum samples could50 60 be further investigated (six typical TSP and

one with cerebellar ataxia). All had an intactblood-brain barrier as shown by normal serum/

hs in the rain CSF albumin ratios (lowest was 181, normalnother, except values > 105). Specific CSF anti-HTLV-lh with TSP in antibody titres by immunofluorescence werereceived blood 10 to 40. Six patients had a serum/CSF specificen 11 and 55 antibody ratio of 5 to 40 (normal values: 150-of onset was 750) indicating intrathecal anti-HTLV-131 (fig 2). The production.24 On this basis, intrathecal synth-e the patients esis could not be demonstrated in one TSPte years. They patient (ratio: 320).median of 13 Anti-HTLV-1 antibodies were found in 18-ourse was 17 out of 29 (62%) neurologically intact first or

second degree blood relatives of TSP patients.ras established Among these 4/8 children of affected mothers,(see above), or 5/8 siblings and 1/2 fathers of TSP patientsthe histories were seropositive. One tested husband and two

al course and children of a father with TSP were seron-these histories egative. Two wives of TSP patients were bothents we could positive.ind in 10 of the The results of screening for HTLV-1

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A cluster ofHTLV-1 associated tropical spastic paraparesis in Equateur (Zaire)

Figure 3 Pedigrees ofeightfamilies with morethan one member affectedby tropical spasticparaparesis.

921y

9 46y

0" 27y

9 55y

9 24y 923y

049y

Table 3 HTLV-I seroprevalence in Zairian reference groups

Neurologically Non-TSPintact neurologicalsubjects diseases*

Npos/N tested Npos/N tested

Dungu (1987-88):HIV-negative 2/100 NAHIV-positive 6/100 NA

Kinshasa (1986-88):mothers of young children 8/211 NApatients admitted to hospital

(not from Equateur) 1/51 8/109patients admitted to hospital

(originating fromEquateur) 2/10 2/10

South Bandundu (1986) 0/3 0/18

*Various neurological diseases in Kinshasa; acute epidemic spastic paraparesis in SouthBandundu.

antibodies in various groups are given in table3. In inhabitants of the Dungu the prevalenceof HTLV-1 tends to be somewhat higher inHIV-seropositive subjects (6%) than in HIV-seronegative subjects (2%), but numbers aretoo small to reach the significance level. Eightout of21 1 mothers tested in Kinshasa had anti-HTLV-1 antibodies. Among a group of 20patients admitted to hospital in Kinshasa,originating from the Equateur province, fourwere HTLV-1 positive (20%) while there werenine seropositives among 160 other patients(5-6%) (p = 0-034, Fisher's exact test). Thediagnosis of 10 seropositive OND patients wasepilepsy, subacute sclerosing panencephalitis,senile dementia, facial palsy, trypanosomiasisin one patient each and five had less welldefined (neuro)psychiatric illnesses. Allpatients from Bandundu with acute epidemicspastic paraparesis were seronegative.HTLV-1 antibody titres by immunofluores-

cence in serum ofTSP patients, oftheir healthyseropositive family members and ofseropositive OND patients are presented intable 4. Two thirds of TSP patients had titres> 400, whereas all of the OND in Kinshasa hadtitres below 400.No relationship was found between HIV

seropositivity and the presence of HTLV-1antibodies or HTLV-1-associated disease.None of the paretic patients examined nor anyof their family members and none of thecontrols from Equateur but seen in Kinshasa(table 3) and none of the South Bandunducontrols had anti-HIV. One out of eightHTLV-1 positive mothers (12-5%) and 17 outof 203 HTLV-1 negative mothers (855%) hadanti-HIV (p > 0-1). In the patients admitted tohospital in Kinshasa but not from Equateur,anti-HIV was found in 12 HTLV-1 negatives(six with and six without neurological disease)and in one HTLV-1 positive with herpes zosterand facial palsy.

Figure 4 Pedigree of theMfamily from Lisala,examined at Kinshasa.

I

II

III

V

M. FAMILY

\-/' ' ..J NJ/ L'J \-/' L'.' * Examined067 079 072 076 078 °82pos neg pos neg pos neg TSP

pos/neg HTLV-I antibodies

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Table 4 HTLV-i immunofluorescence antibody titres in different groups

Anti-HTL V-I antibody titres

Subjects 50 100 200 400 >800 N total

TSP* Lisala - 5 3 6 10 24Healthy relatives of TSP, Lisala 1 6 3 5 2 17ONDt Kinshasa 5 3 1 - - 9

*Tropical spastic paraparesis.tPatients with other neurological diseases.

Figure S HTLV-IWestern blot patterns inpaired serum and spinalfluid samples of tropicalspastic paraparesispatients. Lane a: positivecontrol; lane b: negativecontrol; lanes c, e, g:serum samples of threedifferent patients; lanesd,f, h: spinalfluidsamples of same patients. P 3.-

gp 46-p 42-

p 36-p 32-

p 28-p 26-p 24-p) 21 -

p 19-

p 1 5-

b*!.O.It .1N@. .1N-.-1

.C

.o _

__..,.

-

L._

.s3}X rX X

... 4E_.

w

m_ ._

..s_ __ _

-_

d f g h

co -; CO

.i.

_ -s

Discussion

The clinical presentation of typical TSP casesin Lisala is similar to that of TSP in theCaribbean and HAM in Japan.25 The HTLV- 1seropositivity in Lisala cases (96% ) is thehighest reported so far for TSP in endemiccountries, but all of the 11 patients born in theWest Indies and seen in the United Kingdom

26were seropositive. Intrathecal synthesis ofanti-HTLV-l occurs in most but not all of theLisala patients which agrees with similar find-ings in 14 of 19 (74%) TSP patients of variousorigin." One patient had cerebellar signs inaddition to the pyramidal syndrome, a combin-ation which has been previously noted5 andmay be a variant of HTLV-1 associated TSP,particularly since high serum anti-HTLV-1was associated with intrathecal production ofantibody in our patient. In two patients withproximal muscle atrophy of lower and upperlimbs and weak or absent tendon reflexes,clinical examination could not distinguish bet-ween neurogenic or myopathic atrophy. Alth-ough both had anti-HTLV-1 in the serum andCSF, it remains to be seen whether this isanother expression of HTLV- 1 associatedmyelopathy or a coincidence.The Telema outpatient facility reaches an

estimated population of 50,000. Every fiveyears, it sees about seven new cases of TSP,suggesting an annual incidence of three per

100,000. Furthermore a prevalence of at least50 cases per 100,000 is shown by our study.These figures are almost certainly an underes-timate of TSP in the area, with a bias towardthe more severe cases. The true incidence andprevalence of HTLV-1 associated TSP, andthe geographical extent of the cluster, remainsto be established. One pedigree (fig 4) includesHTLV-1 positive TSP patients who hadmoved from Lisala to Kinshasa. Spot inquiriesamong hospital physicians in different parts ofZaire did not suggest TSP clusters outsideEquateur, but sporadic cases or smaller clustersmay have gone unnoticed.The youngest ages of TSP onset in Lisala

were 7, 8 and 9 years, and one third of ourpatients started their disease before age 20years. In other tropical regions, TSP rarely ifever starts before age 20.25 In Japan, HAM hasbeen seen as early as the age of six.25 It wouldappear from our study that case definitionsexcluding cases with onset before 15 andexcluding cases with neurological disease inprevious generations78 are inappropriate.HTLV-1 positive TSP was found in the

three ethnic groups constituting 95% of theLisala population, but half of the cases and ofthe families with one or more cases were in theMundunga minority of 10% (p < 0 001).While the other groups are Bantu-speaking andhave long been established in Lisala, theMundunga only arrived about 150 years or sixgenerations ago from Southern Sudan and havekept their Sudanese language. They live insmall settlements dispersed among those of theNgombe majority. Cultural habits which mightexplain the difference with the other groupswere not evident. In Dungu, north-easternZaire (table 3), the inhabitants are Azande, aSudanese-speaking people who also exist inSudan; their anti-HTLV- 1 prevalence was notunusual for Central Africa, and TSP cases havenot been reported.

Besides ethnic aggregation, there was astrong familial aggregation of TSP cases inLisala. The 21 HTLV-1 positive TSP casesfound by direct search were from 21 differentfamilies and they reported 18 TSP cases in firstor second degree relatives they knew person-ally, four of whom we could examine andconfirm as HTLV-1 positive TSP. Additionalmild or incipient cases may have beenoverlooked. Ten of the 21 families (48%) hadmore than one TSP case. A survey in the Kiipeninsula of Japan showed four familial cases

28~~~~~~~~~~~~~in 18 patients,2 and uvyi the Seychellesshowed five familial cases in 21 patients.8Remarkably, evidence for familial clusteringdoes not appear in the data from the Caribbeanand Colombia.' Familial occurrence of TSP

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A cluster ofHTL V-i associated tropical spastic paraparesis in Equateur (Zaire)

and in particular the high rate of occurrence inmothers of TSP patients in Lisala, cannot beexplained by HTLV-1 transmission alone,even if all family members were HTLV-1positive, since the prevalence of TSP inHTLV-1 positives has been estimated at lessthan one in 1000 in Japan.29 In Africa, given thepaucity of reported TSP cases among a largepopulation of HTLV-1 positive subjects, itcould not possibly be higher.

Strikingly, seven mothers but no fathers ofour 21 original TSP cases had TSP (figs 3 and4). Fathers of other TSP patients in ourpedigrees were also free of TSP, and not asingle conjugal case was detected. Althoughmost familial associations were through thematernal lineage, three were through the pater-nal lineage: a paternal uncle or aunt in two maleTSP patients (fig 3) and a paternal great unclein a female patient (pedigree not shown). Thisseems to preclude cofactors which areexclusively maternal in favouring the develop-ment of TSP in HTLV-1 infected subjects,unless one accepts incomplete penetrance inthe mothers.HTLV-1 is thought to be transmitted sex-

ually, by blood-to-blood contact and frommother to child at an early age."' The latter hasbeen well shown in epidemiological studies inJapan and could occur transplacentally,intrapartum, or via milk during lactation."32The few serological data we have (anti-HTLV-1 in two healthy mothers of TSP cases and infour of eight healthy children of TSP mothers)are compatible with this mode of transmission,as are the diseased mother-child pairs. If thechild is at highest risk of acquiring HTLV-1from its mother, then it becomes difficult todistinguish cofactors favouring the develop-ment of TSP which are of maternal or otherorigin.The highest anti-HTLV- I titres were found

in the serum of TSP patients in contrast to thelow titres in the healthy HTLV-1 carriers inKinshasa where TSP is rare, while in healthyfamily members of TSP patients both high andlow titres could be found (table 4). Similarly,high anti-HTLV-l titres were observed byothers in TSP patients compared to theirhealthy relatives and to ATL patients." Astudy in Japan'4 suggests that different HLAhaplotypes are associated with HAM and ATLand that these HLA haplotypes may alsosegregate high and low in vitro responsivenessof lymphocytes to HTLV-1 antigen. Dalgleishet al found, however, no evidence of a relation-ship between HLA type and seroconversion ordisease in a study of West Indian TSP patientsand their relatives in the United Kingdom."Besides a possible immunogenetic background,other genetic cofactors could be involved. Thetransmission cannot be autosomal recessive,since vertical transmission was very frequentand consanguinity was never present in Lisala.X-linked dominant transmission of the cofac-tor by itself could explain the female/male ratioof 1 8, but is not compatible with the finding ofTSP in the paternal branch of male TSPpatients, since in this hypothesis the fathercould only transmit the cofactor to a daughter,

not a son. A mitochondrial cofactor, transmit-ted exclusively by the mother, does not explainthe few cases of TSP in the paternal branch,nor the skewed sex distribution of TSP cases(nine girls, three boys) in children of TSPmothers. If the cofactor is genetic, it is mostlikely a polygenetic influence.Environmental familial factors predisposing

toward TSP are entirely speculative. There isalso a remote possibility that familial TSPclusters in an area arise from locally evolvedHTLV- 1 mutants with increased neuro-virulence.There is some evidence that a virus related to

HTLV-1 could be involved in multiple scleros-is.'5 The high frequency of affected mother/child pairs in familial multiple sclerosis'6evokes a comparison with that of familial TSP.

We thank the staffofthe Telema RehabilitationCentre at Lisala for help with this study.

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7 Arango C, Concha M, Zaninovic V, et al. Epidemiology oftropical spastic paraparesis in Colombia and associatedHTLV-1 infection. Ann Neurol 1988;23(Suppl): 161-5.

8 Roman GC, Schoenberg BS, Madden DL, et al. Human T-lymphotropic virus type I antibodies in the serum ofpatients with tropical spastic paraparesis in the Seychelles.Arch Neurol 1987;44:605-7.

9 Miller GJ, Pegram SM, Kirkwood BR, et al. Ethniccomposition age and sex together with location andstandard of housing as determinants ofHTLV-1 infectionin an urban Trinidadian community. Int J Cancer1986;38:801-8.

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12 Fleming AF, Maharajan R, Abraham M, et al. Antibodies toHTLV-1 in Nigerian blood donors, their relatives andpatients with leukemias, lymphomas and other diseases.Int J Cancer 1986;38:809-13.

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16 Editorial. HTLV-1 comes of age. Lancet 1988;i:217-9.17 Gessain A, Francis H, Sonan T, et al. HTLV-1 and tropical

spastic paraparesis in Africa. Lancet 1986;ii:698.18 Giordano C, Dumas M, Hugon J, et al. Neuromyelopathies

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