Dickinson, D.B.

Malherbe, H.

McGillivray, G.M.

McIntosh, B.M.

English

AJOL - African Journals Online

S.A. MEDICAL JOURNAL2 May 1964ILLNESS CAUSED BY SINDBIS AND WEST NILE VIRUSES IN SOUTH AFRICA*291B. M. MCOOOSH, G. M. McGILLIVRAY, D. B. DICKINSON, Arbovirus Research Unit, South African Institute forMedical Research, Johannesburg .. AND H. MALHERBE, Poliomyelitis Research Foundation, JohannesburgAntibody surveys on sera from persons resident in differentparts of South Africa have revealed the wide distributionof Sindbis and West Nile viruses in this country andindicated that man is fairly frequently infected. Theseinfections are especially prevalent in the highveld regionof the Transvaal and Orange Free State and along theOrange River, where high temperatures 'and irrigation haveapparently created favourable conditions for the vector.1-5The presence of these viruses in South Africa has alsobeen demonstrated by their isolation from mosquitoes andwild birds collected in northern Natal and on the high-veld ;6-8 and West Nile virus has been isolated from a sickhuman being in northern Natal.6Despite these findings, little definite evidence has hithertobeen obtained to indicate the extent to which Sindbis andWest Nile viruses are a cause of illness in man in SouthAfrica. Furthermore, although Sindbis virus has beenknown since 1952 and has been isolated in several parts ofthe world from birds and mosquitoes, it was only in 1961that it was recovered for the first time from man when itsisolation from blood specimens taken from 5 ill Africansin Uganda was reported.9 The signs and symptoms shownby these patients included fever, headache, malaise, jaun-dice, widespread body pains and pain in the chest andjoints.l°It was thus of considerable interest when, in January1963, Sindbis virus was isolated from the skin lesions of aperson ill in Johannesburg.l1 This patient showed fever,malaise, pains in the joints and tendons, a maculopapularrash over the trunk and limbs, and vesicles on the fingersand toes. Subsequently, further cases with somewhatsimilar clinical features were brought to our notice atseveral localities in the Transvaal and Orange Free Statefrom March to April 1963. Although no virus was isolatedfrom these patients, paired sera, collected from the sameindividuals during the acute and convalescent stages ofthe illness, were available from 16 patients, thus enablinga,diagnosis ef Sindbis or West Nile infection to be made onserological evidence. This report describes the clinical andserological findings in these patients, as well as in an addi-tional 5, from whom only convalescent-phase sera wereavailable.We are indebted to the medical practitioners and medicalofficers of health, listed below, for informing us of thesecases; for the submission of blood samples from them, andfor clinical observations on the patients not seen by us.METHODS AND MATERIALSThe methods used in the haemagglutination-inhibition (HI)test are those described by Clarke and Casals,12 in whichserial, two-fold dilutions of serum were tested against 8units of viral antigen and the results expressed as the reci-·'Ihe studies and observations on which this paper is basedwere financed jointly by the South African Institute forMedical Research, the Poliomyelitis Research Foundation, theSouth African Council for Scientific and Industrial Researchand the Rockefeller Foundation.procal of the highest serum dilution, causing inhibition.The lowest serum dilution tested was 1/20.In the neutralization (N) test, undiluted serum wasmixed with an estimated 100 LDso of virus and, afterincubation for 1 hour at 37°C, the mixture was inoculatedintracerebrally into 6 mice. Mouse survival ratios of 6/6,5/6, 4/5 or 4/4 were' recorded as positive, provided thevirus dose was at least 50 LDs., as shown by titration atthe time of the test.In the complement-fixation (CF) test, serum dilutions of1/4, 1/8, 1/16 and 1/32 were tested against approximately8 units of antigen. The antigens were prepared by acetone-ether or sucrose-acetone extraction of infective infant-mouse brain.l2Following our usual procedure, sera were initiallyscreened in an HI test with antigens from the followingarboviruses :Group A: Sindbis, chikungunya; Middelburg; GroupB: H 336, Wesselsbron, West Nile, Spondweni (selectedsera only) ; Bunyamwera group: Bunyamwera, Gerrniston ;Ungrouped: Rift Valley fever.Depending upon the outcome of this test, sera were thentested with the Nand CF tests. In some instances thesetests could not be done on account of lack of serum. SinceNdumu virus, a member of Group A, does not readilyproduce a satisfactory haemagglutinin, certain sera posi-tive for Sindbis virus antibody were tested against Ndumuvirus with the N test only.LABORATORY RESULTSVirus IsolationAttempts at isolation of virus were made from 11 casesof Sindbis and from 4 cases of West Nile infection asindicated in Tables I and 11. The specimens used includedblood (14 cases), throat swabs (5), skin lesions (7), andstool (3). These were tested in 1 - 2 days-old white mice,and most specimens were also tested in vervet monkeykidney· tissue cultures. None of the specimens has yieldedvirus, although it is intended to repeat some of theseattempts.It will be seen from Table' I that attempts to isolatevirus from Sindbis cases were made in 6 cases within 4days of onset of the illness, and in 3 of these Sindbis virusID antibody was absent in the blood at the time the speci-mens were collected. A further case in which time of onsetwas uncertain was also negative for antibody at the timethe specimens were collected for virus isolation. An attemptto isolate the virus was made in one West Nile case within4 days of onset and at a time when the blood was free fromWest Nile antibody.Failure to isolate the virus in these cases was probablydue to low concentration or the absence of virus at the timeof collection of the specimens, or to loss of viability duringconveyance and storage of the specimens, since the hostsystems used possess a high degree of susceptibility to bothviruses.292 S.A. TYDSKRIF VIR GENEESKUNDE 2 Mei 1964TABLE I. RESULTS OF ANTIBODY TESTS ON SERA FROM PERSONS SUSPECTED OF HAVING BEEN INFECTED WITH Sfi''DBIS VIRUSCaseNo.234567891011121314LocalityJohannesburgVereenigingVanderbijlparkCarletonvilleWelkomPatientM.L.·J.D.·L.P.·M.W.·M.B.·L.B.·M.E.·J.H.·A.W.·M.K.R·B.·V.L.C.B.·S.M.Days afteronset bloodcollected527312615716216215214431?>181039320620543220SindbisHI NN N1,280 P80 N>1,280 P80 N>1,280 P1,280 P2,560 PN320 PN64080 N2,560 P20 N640 PN1,280 P80 N640 PN N320 P320 P1,280 PN640 PN640 PGroup A virusesChikungunya Middel-burgHINNNNNNNNNNNNNNNNNNNNNNN20NNNNNdumuNNNNNNNNNNNGroup BvirusWest NileHI NNN>1,280 P>1,280 PNNNN80 P20 PNNNN1,280 P1,280 PNNNNN N40 NN N40 NN N40N·Cases on which virus isolation was attempted. N = negative. - = not tested.Serological Findings(a) Sindbis infections. Paired sera from 14 patientsshowed a diagnostic rise in titre against Sindbis virus. Theresults of the antibody tests on these sera with West Nileand 4 Group A viruses are shown in Table I. The resultsagainst other viruses· tested are excluded, since these wereeither negative or -due to obvious immunological overlapwith West Nile virus.In all cases HI antibody against Sindbis virus eitherappeared or rose during convalescence. The results showeda high degree of specificity in: that only cases 5 and 12showed HI antibody against the other A viruses includedin this test, and this antibody was of much lower titre thanthat against Sindbis.The 13 convalescent sera tested with the N test againstSindbis virus were all positive, and there was conversionfrom negative to positive antibody status in 7 of the 9cases from which paired sera were subjected to this test.The CF test was carried out· on 12 convalescent sera,and 8 of these were positive. In 6 cases there was a conver-sion from negative to positive CF antibody status duringconvalescence.HI antibody against West Nile virus was observed in 6cases. In 3 of these N antibody was present, and HI anti-bOdy was present at approximately the sanTe levels in theacute and convalescent phases. It is therefore concludedthat in these 3 cases the presence of antibody to West Nilevirus was the result of a previous infection. In the remain-ing 3 cases the HI antibody was at a low level and 2 ofthem were negative to West Nile virus with the N tests.(b) West Nile infections. Sera were obtained from 7cases which were negative for HI antibody against Sindbisand th.e. other Group A viruses and in which HI antibodiesagainst West Nile virus were higher than against the otherGroup B viruses tested. The results on the sera are shownin Table 11. Results with Spondweni virus are omitted sincethese were either negative or of low titre and obviouslydue to immunological overlap. _Significantly, sera with HIantibody· against H 336 and Wesselsbron viruses werenegative for N antibody against these viruses, and with oneexception (No. 16) were positive for N antibody againstWest Nile virus. Although the convalescent serum fromcase 16 was recorded as negative for N antibody againstWest Nile virus,'2 of the 6 mice inoculated in this testsurvived, indicating the presence of low titre N antibody.Paired sera were available from only 2 patients, but bothshowed a rise in West Nile HI antibody and one alsoshowed a rise in CF antibody.CLINICAL FEATURES(a) SindbisA full description of the case encountered in January,has already been given.!l While this case was unusually2 May 1964 S . A. MED 1 C A L J.O URN A L 293TABLE 11. RESULTS OF ANTIBODY TESTS ON SERA FROM PERSONS SUSPECTED OF HAVll'G BEEN INHCTED WIlH WEST NILE VIRUSDays after Group AGroup B virusesCase Locality Patient onset blood virus West Nile H336 WesselsbronNo. collected SindbisHI HI N CF HI N CF HI N CF15 Vereeniging D.e.- 13 N 80 P N 80 N22 N 1,280 P N 320 N 816 Middelburg J.B.- 4 N N N N N N N21 N 320 N 32 40 N N17 Welkom T.H.- 10 N 320 P 32 80 N 160 N N18 S.H.- 21 N 40 P 4 40 N N 20 N19 S.P. 10 N 320 P 32 40 N N 160 N N20 V.K. 28 N 640 P 32 80 N 16 320 N 821 Vanderbijlpark RA 14 N 320 P 32 40 N N 160 N·Cases on which virus isolation was attempted. N = negative - = not tested.severe, essentially the same clinical features were observedas in the others. The patients were all adults with agesranging from 18 to 56 years.bicubation period. Since most of the patients had beenexposed to mosquitoes over a prolonged period, it was notpossible to determine the incubation time of the infection.Prodromal symptoms. The onset of illness was usuallymarked by the sudden appearance of the rash; but 4patients experienced, for 1 or 2 days before the rash,symptoms which included lassitude, headache, joint painsand generalized body aches.Exanthem. The rash involved chiefly the trunk andlimbs, being most profuse over the buttocks and legs. Itaffected the palms and soles; but the head was usually,though not invariably, spared. Lesions occurred in cropsfor the first few days and lasted up to 10 days, leavingbrown stains.The spots remained discrete, appearing first as maculesbut soon becoming papular. The papules were usuallyabout 3 mm. in diameter, but much variation in size wasnoted. Vesicles could be discerned in nearly half the cases,occurring chiefly on the hands and feet; but removal ofthe skin over papules elsewhere on the body frequentlyreve~led a small amount of clear fluid. The lesions tendedto be pruritic, and were occasionally very irritating,especially on the extremities.Enanthem. Evidence of lesions in the oro-pharynx wasusually lacking, although small ulcers irregularly distributedin the mouth or pharynx were seen in 4 cases. Somepatients complained of sore throat, and mild inflammationof the pharynx was occasionally observed.Other clinical features. Low fever not much exceeding100°F and lasting only for the first few days was noted ina number of cases. Lassitude and fatigue on slight exertionwere early symptoms which tended to persist throughconvalescence. Rigors were not observed, but alternatingfeelings of heat and cold were experienced by a number ofpatients.Muscle tenderness and deep aches in the limbs wereoccasionally encountered. Pains in the small joints of the~~nds and feet were almost invariably present, and larger)omts were frequently affected. There was a tendency forthe extremities to become swollen. Pain in the extensor ten-dons on the dorsum of the hand and in the tendo calcaneus(Achillis) was occasionally present.Several patients had periocular pain, but photophobiawas not common and conjunctivitis was not seen. Headachewas frequently present, but it was usually mild and therewas no clinical evidence of involvement of the centralnervous system. A few patients complained of paraesthe-siae such as pricking or tingling sensations, particularly inthe hands; and shooting pains in the limbs were noted in2 cases.Lymphadenopathy was usually absent, although enlarge-ment of inguinal, occipital and posterior cervical nodes wasencountered. In one case the spleen could be felt. Rightsubcostal tenderness was experienced by several patients,but the liver was not palpable. Anorexia was usual, butnausea and vomiting uncommon. Bowel function was notmarkedly disturbed.The respiratory system did not appear to be involved. Inone case extrasystoles were a notable feature of the acuteillness, and during convalescence this patient experiencedan anginal attack with pain radiating from the chest downthe left arm, but there was no electrocardiographic evidenceof myocardial damage.In most cases the symptoms disappeared within 10 days,but a few patients experienced fatigue and tendon painsfor several weeks.Laboratory investigations. Blood counts performedduring the acute phase on 10 patients were within normallimits, but the erythrocyte sedimentation rate, as measuredby the Wintrobe method, was markedly raised in 5 cases(13 - 31 mm. in one hour). Liver-function tests were carriedout in 2 cases, but were normal, except for positive colloi-dal red reactions.Pathological changes. The histological changes occurringin suckling mice inoculated with virus recovered from thefirst case seen have already been described.ll With duereservations concerning extrapolation from mouse to man,it may be postulated that the joint pains and swelling ofextremities are probably due to necrobiosis and oedema insubcutaneous, periarticular and tendinous tissues, ratherthan to pathology within the joint cavities.Cb) West NileFeatures common to both Sindbis and West Nile infec-tions were lassitude, generalized body pains, headache,joint pains, and a maculo-papular rash; and it was notpossible to distinguish between the two infections onclinical grou.nds.

Illness caused by Sindbis and West Nile viruses in South Africa

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Illness caused by Sindbis and West Nile viruses in South Africa

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