A retrospective study of 107 cases of serologically proven chikungunya (CHIK) virus infection was undertaken. All respondents had contracted the disease at least 3 years previously; 87,9% had fully recovered, 3,7% experienced only occasional stiffness or mild discomfort, 2,8% had persistent residual joint stiffness but no pain, while 5,6% had persistent joint pain and stiffness and frequent effusions. Synovial fluid from 3 patients was analysed. All the patients with persistent joint pain and, stiffness had very high antibody titres against CHIK virus

Brighton, S.W.

de la Harpe, A.L.

Prozesky, O.W.

English

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We wish to thank the following firms for donating the high-fibrefoods used in the study: Bokomo Foods, Gants Foods, the SA DriedFruit Board and Sasko.We also wish to thank Annette Mason and Debbie Feldman forgeneral organiz~tion, Kamalie Samsodien, Magsie Paul and MarilynTyler for techlllcal assistance, and Rozanne Simpson for secretarialassistance.This study was funded by the South African Medical ResearchCouncil.SA MEDICAL JOURNAL VOLUME 63 26 FEBRUARY 1983 313REFERENCESI. Jenkins DJA, Goff DV, Leeds AR er al. Unabsorbable carbohydrates anddiabetes: decreased postprandial hyperglycaemia. Lancer 1976; ii: 172-174.2. Jenkins DJA, Wo1ever TMS, Hockaday TDRer 01. Treatment ofdiabetes withguar gum. Lancer 1977; ii: 779-780.3. Miranda PM, Horwitz DL. High-fibre diets in the treatment of diabetesmellitus. Ann Intern Med 1978; 88: 482-486.4. Anderson JW, WardK. High-<:arbohydrate, high-fibre diets for insulin-treatedmen with'diabetes mellitus. Am] Clin NUlr 1979; 32: 2312-2321.5. Anderson JW, Ward K. Long-term effects of high-<:arbohydrate, high-fibredIets on glucose and lipid metabolism: a preliminary report on patients withdiabetes. Diaberes Care 1978; 1: 77-82.6. Paul AA, Southgate DAT. The Composilion ofFoods. 4th ed. London: HMSO,1978.Chikungunya •VIrUS infectionA retrospective study of 107 casesS. W. BRIGHTON, O. W. PROZESKY, A. L. DE LA HARPESumm~ryA retrospective study of 107 cases of serologicallyproven chikungunya (CHIK) virus infection wasundertaken. All respondents 'had contracted the'disease at least 3 years previously; 87,9% had fully.recovered, 3,7% experienced only occasional stiff-ness or mild discomfort, 2,8% had persistent resi-dual joint stiffness but no pain, while 5,6% had per-sistent joint pain and stiffness and frequenteffusions. Synovial fluid from 3 patients was ana-lysed. All the patients with persistent joint pain and., stiffness had very high antibody titres against CHIKvirus.S Afr Med J 1983; 63: 313-315.The disease was ·first described in 1955 by Robinson2 andLumsden3 from Tanzania, where it occurred in epidemic form.Other outbreaks have been described in the Transvaal,4 Zam-bia,' south-eastern Rhodesia,6 and Zaire.' Antibody studies onhuman sera have indicated human infection in Mozambique,Caprivi, Botswana and Angola,6 and epidemics have been des-cribed in Thailand,8 Viemam9 and India. IQThe earl(l~linical course. of the disease has previously beendescnbed. . It IS charactenzed by severe con)unctIvltls, a macu-lar rash, fever, low back pain and a symmetrical polyarthritis ofvarying severity, the most commonly involved joints being themetacarpophalangeal joints, wrists, elbows, shoulders, knees,ankles and metatarsal joints.Stiffness is a prominent feature. To date follow-up studiesseem to have been limited to 18 months and no long-term studieshave been reported. Cases of longer duration are the subject ofthis report.The name chikungunya is derived from the Swahili, meaning 'hewho walks bent up'. The severe crippling pains encountered inthe acute stages of the disease make this name particularly apt.The chikungunya (CHIK) virus is an alphavirus of the familyTogaviridae of the arbovirus epidemiological group. The alpha-virus group includes among others the Sindbis and CHIKviruses.The virus is transmitted by a mosquito reported to be Aedesaegypti, but in the southern Mrican epidemics of 1975, 1976 and1977 A. furclfer-taylori appeared to be the main veCtaL lDepartments of Physical Medicine, Rheumatology andMicrobiology, H. F. Verwoerd Hospital and University ofPretoriaS. W. BRIGHTON, M.B. CH.B., F.F. PHYS. MED., M.MED. (pHYS. MED.),Head, Deparzmenc of Physical Medicine and RheumalOlogyO. W. PROZESKY, M.D., Deparlmenc of Medical MicrobiologyA. L. DE LA HARPE, M.B. CH.B., Medical Officer, Deparlmenc ofRheumalOlogyDate received: 29 April 1982.Patients and methodsA list of all patients who had had serologically proven CHIKvirus infections during epidemics in the northern Transvaalduring 1975, 1976 and 1977 was obtained from Dr B. M. McIn-tosh, National Institute of Virology, Johannesburg. From thislist 107 patients were traced either by telephone or personally.All were contacted after August 1980, the duration from the timeof contracting the disease thus being 3-5 years.ResultsThe 107 cases were divided into 4 groups.Group 1Group I consisted of 94 patients fully recovered from theinfection. They were now free of any joint pain or stiffness, butall could still vividly describe the severe pain of the acute attack.314 SA MEDIESE TYDSKRIF DEEL 63 26 FEBRUARIE 1983Although many could only vaguely recall how long their jointshad taken to recover fully, 38 apparently recovered within amatter of weeks of the acute attack; 41 stated that they hadrecovered slowly over a period ofup to a year and 15 said that therecovery period was 2-3 years. It is ofpossible significance that ofthese 94 patients now recovered, 42 were under the age of 17, themean age ofall patients being 37. It has previous\( been reportedthat the disease has a milder course in children..13.14Group 2Group 2 consisted of 4 patients retaining only occasionalstiffness or mild discomfort. The youngest was 45 and the oldest60 years (mean age 54). Occasional stiffness or mild discomfort inthe proximal interphalangeal (PIP) joints was experienced by all4 patients, in the metacarpophalangeal (MP) joints (3 patients),in the wrists (3 patients) and in the knees (3 patients). Thestiffness appeared to be very intermittent, but 3 of the 4 patientssaid the stiffness was noticeably aggravated by exercise. All 4patients claimed to have had no joint pains or stiffness before theCHIK virus infection. None of the 4 cases showed objectiveabnormality of the joints, such as joint deformity, palpable syno-\'itis or joint effusion.Of the 4 patients, 2 were examined during a period when theywere free ofdiscomfort; no joint tenderness could be elicited. Ofthe other 2, both with joint discomfort and stiffness at the time ofexamination, one had very mild tenderness of the MP joints ofboth hands, while the other had none. On radiographs theinvolved joints appeared normal, as were results ofspecial inves-tigations and the ESR. The CHIK antibody titres were 1:40 and1:80.Group 3Group 3 consisted o'f 3 patients with persistent residual stiff-ness but no pain. Their ages were 65, 60 and 55 years. The65-year-old patient stated that the joint pains had settled rapidlyafter the acute attack, but stiffness remained in the wrists, MPjoints, PIP joints, knees and ankles. This gradually improved butshe retained some stiffness in the ankles and knees, this beingpresent in the morning for over an hour and aggravated by.exercise. No abnormalities were noted on examination of theinvolved joints or on radiographs. The other 2 patients hadresidual morning stiffness in the wrists, MP joints and knees,lasting for 15-30 minutes. There was also no objective evidenceof joint damage on physical examination or radiography. Specialinvestigations were negative and CHIK antibody titres were1:160,1:80 and 1:40 in the 3 cases.Group 4Group 4 consisted of 6 patients with persistent joint pain andstiffness with or without swelling (Table I). Pain was graded on ascale of 4: 0 = no pain; 1= pain, but no tenderness on palpationof the involved joint; 2 = pain and tenderness on palpation of thejoint; 3 = pain and tenderness on palpation sufficient to causewincing from pain; 4 = pain on palpation causing withdrawal ofthe limb. These 6 cases are reported in detail below.CaseIIn a 60-year-old woman the duration of the disease was 3 yearsand 2 months. The pain was always present but tended to fluc-tuate in severity over fairly lengthy periods. She was examinedduring a painful period. Wrists, MP joints, PIP joints, shoulder,neck, knees, ankles and subtalar joints were all involved. A mildsynovitis was present in the ankles and wrists, but the patientwould not consent to synovial biopsy. Aspiration of:the kneeyielded synovial fluid of reduced viscosity, with poor mucin clotformation, slight turbidity and 5 000 leucocyteslIll. Insufficientfluid was obtained for complement function tests. Morning stiff-ness persisted for 30 minutes and exercise, particularly climbingstairs, aggravated the pain and stiffness on the following day.The blood count was normal on four occasions, and on fouroccasions the ESR was between 20 and 25 mmlh (Westergren).The antinuclear factor test was negative, normal serum comple-ment levels were found, the HelIer test was negative, investiga-tions ofkidney and liver function gave normal results and immu-noglobulin (IgG, IgA, IgM) levels were all normal. Markedlyraised antibody titres against CHIK virus were encountered onthree occasions: 1:2560, 1:640 and I:640. Investigations forother arbovirus infections were negative.Case 2A 16-year-old girl had complained of persistent pain sincecontracting CHIK infection in 1976. She apparently had hadsevere pain during the acute stage for several weeks; this settleddown into a steady pain and tenderness (grade 1-2) of the knees,wrists, ankles and small joints (MPs and PIPs) ofthe hands. Shehad morning stiffness for 20 minutes each day. The joint symp-toms were markedly aggravated by exercise.Special investigations showed a normal full blood count, anESR of 18 mmlh (Westergren), a negative rheumatoid factortest, "and a C-reactive protein level of 13,2 Ilg/ml. Liver andkidney function tests were all negative, the urine was microscopi-cally and biochemically normal, and the serum complement andimmunoglobulin levels were within normal limits. Synovial fluidanalysis revealed straw-eoloured fluid of reduced viscosity andwith poor mucin clot formation. Complement levels were normaland the white cell count was 20001Ill. Radiographs of the jointswere normal. Arthroscopy was performed on the right knee by anorthopaedic surgeon experienced in this technique. A very thin,pale, atrophic-looking synovium was found but a specimen takenwas reported as being normal.TABLE I. GRADING OF JOINT PAIN IN 6 PATIENTS WITH PERSISTENT PAIN AND STIFFNESSWrists MP PIP DIP Elbow Shoulder Neck Hip Knee Ankle Subtalars ToesCase L R L R L R L R L R L R L R L R L R L R L R1 2 2 1 1 1 1 0 0 0 0 1 1 1 0 0 2 2 2 1 1 1 0 02 2 2 1 1 1 1 0 0 0 0 0 0 0 0 0 2 2 2 2 0 0 0 03 1 1 0 0 1 1 1 1 0 0 1 1 0 0 0 0 0 2 2 0 0 0 04 2 2 2 2 1 1 1 1 1 1 0 0 1 0 0 1 1 1 1 1 1 0 05 1 1 1 1 1 1 1 1 0 0 0 0 0 0 0 0 O. 1 1 1 0 0 06 2 2 1 1 0 0 0 0 0 0 0 0 0 0 0 2 2 1 1 0 0 0 0DIP = distal interphalangeal joints.Case 3A 54-year-old man had developed CHIK infection in 1977,with fever, severe joint and muscle pains and a mild rash. Thesevere pain slowly receded and 4 years after infection he was leftwith involvement of the wrists, PIP joints, distal interphalangeal(DIP) joints, shoulders and ankles and morning stiffness for 15minutes. The blood count was normal, and the ESR 20 mmlh(Westergren). The rheumatoid factor and antinuclear factor testswere negative. Liver and kidney function and serum comple-ment levels were all within normal limits. The serum antibodytitre against CHIK virus was 1:640.Case 4A 52-year-old woman had contracted the infection in 1975,and was completely bedridden for 4 weeks with severe joint pain.Thereafter the pain subsided but left her, 6 years after theinfection, with residual symptoms in the wrists, MP joints,ankles and subtalar joints and morning stiffness of 15 minutes'duration. There was no soft-tissue swelling of the joints but mildeffusions were present in both knees. The patient did not consentto joint aspiration. The full blood count, liver and kidney func-tion and serum immunoglobulin levels were all normal, whilerheumatoid factor and antinuclear factor tests were negative.The ESR was 20 mmlh (Westergren). The antibody titre againstCHIK virus was 1:160. No erosions could be demonstrated onradiography.Case 5A 52-year-old man had contracted CHIK infection in 1976.The severe, acute pain gradually subsided over a period ofseveral months, but left him with pain in the PIP, DIP and MPjoints, including the thumbs, wrists and ankles, with morningstiffness of30 minutes' duration. Mild synovial thickening of thewrists and MP joints was noted. The full blood count, rheuma-toid factor and antinuclear factor tests, and tests of liver andkidney function gave results within normal limits. The ESR was15 mm/h (Westergren) and the CHIK antibody titre 1:160.Case 6A M-year-old man had contracted CHIK infection in 1976and had been left with constant pain in the knees, ankles, wristsand MP joints and morning stiffness of 15 minutes' duration.Marked effusions were noted in both knees. On aspiration syno-vial fluid with a low viscosity, poor mucin clot formation, verylow complement levels and a total white cell count of 4 0001 J-LIwas found.The serum complement level, the full blood count, and liverand kidney function were all normaL The rheumatoid factor testwas negative and the ESR 15 mmlh (Westergren).DiscussionThis study was conducted to investigate the incidence and natureof residual symptoms in patients who had contracted CHIKvirus infection at least 3 years previously. Of the 107 patientsinvestigated 94 (87,9%) had fully recovered and had no residualsymptoms 3-5 years after the infection. Of the remainder, 4(3,7%) had only occasional stiffness or mild discomfon, 3 (2,8%)had persistent stiffness but no pain, and 6 (5,6%) had persistentpain and stiffness with or without joint swelling.The patients were a selected group of people, i.e. those whohad sought medical help during the acute phase of the diseaseand whose infection had been proved serologically. The possibi-SA MEDICAL JOURNAL VOLUME 63 26 FE·SRUARY 1983 315lity that a larger group with milder disease had not consulted adoctor must be considered. Epidemiological studies to identifythis group are in progress. Further investigations were onlycarried out on symptomatic patients. None had any abnormali-ties of the full blood count. Only in the 6 patients with persistentpain and stiffness was the ESR accelerated. All the symptomaticpatients had serum antibodies against CHIK virus, as expected,but of panicular interest were the high titres encountered in thepatients with persistent joint symptoms (group 4). Whether thisis indicative of persistent virus antigen or due to some othermechanism is not clear. Virus could not be cultured from theblood or synovial fluid of the patients with high titres. Serologi-cal investigations of the fully recovered, asymptomatic patientsshould be of interest. To date only 4 of the 94 patients in thisgroup have been investigated for CHIK antibody titres. All 4had levels of 1:40, which is indicative of their immune status.None of the patients had any radiological evidence of bonydestruction, although one report of possible bony erosions fol-lowing CHIK infection has appeared in the literature. 12 Morn-ing stiffness appears to be a major feature in those with residualsymptoms. Stiffness persisted for a mean of 35 minutes inpatients with no joint pain, and for 24 minutes in patients withjoint pain.Synovial fluid analysis was carried out in 3 patients, all withpersistent joint symptoms; the fluid was of reduced viscosity andshowed poor mucin clot formation. Total white cell counts in thethree samples were between 2000 and 50001J-LL In one samplethe complement levels were reduced but in the remaining twosamples these were within normal limits ..The most commonly involved joints are the wrists and ankles,followed by the knees and the MP and PIP joints of the hands.Three patients had involvement of the DIP joints of the hands.No evidence of any destructive process could be found in thejoints.This project was financed in part by a gram from the SouthAfrican Medical Research Council. We thank Dr B. M. McInroshand the staffof the National Institute of Virology for performing theserological studies.REFERENCES1. Mclntosh BM. The epidemiology of arthropod-borne viruses in South Africa(D.5c. thesis). Pretoria: University of Pretoria, 1980: chapt 7, 72-95.2. Robinson MC. An epidemic ofvirus disease in Southern Province, TanganyikaTerritory, in 1952-53: clinical features. Trans R Sac Trap Med Hyg 1955; 49:28-32.3. Lumsdep WHR. An epidemic of virus disease in Southern Province, Tanga-nyika Territory, in 1952-53: general description and epidemiology. Trans R SacTrap Med Hyg 1955; 49: 33-57.4. Gear J. The occurence ofa dengue-like fev'er in the north-eastern Transvaal: 1.Clinical features and isolation of virus. S Air Med] 1957; 31: 253-257.5. Roger LM. An outbreak of suspected Chikungunya fever in Northern Rhode-sia. S Air Med] 1961; 35: 126-128.6. Mclntosh BM, Ham'in RM, Paterson HE, Westwater ML. An epidemic ofChikungunya in south-eastern Rhodesia. Cent Air] Med 1963; 9: 351-359.7. Osterrieth PM, Deleplanque-Liegeois P. Presence d'anticorps vis-a-vis des\'ieus rransmises pour arthropods chez le chimpanze. Comparaison de leur elatimmunitaive a celui de Thomme. Ann Sac Beige Med Trap 1961; 41: 63-72.8. Nummannitya S. Halstead SB, Cohen SN, Margiona MR. Dengue and Chi-kungunya virus infection in man in Thailand 1962-1964. Am] Trap Med Hvg1969; 18: 954-971. .9. Deller Jj, Russel PK. Chikungunya disease. Am] Trap Med Hyg 1968; 17:107-111.10. De Ranitz CM, Myers RM, Varkey Mj, Isaac ZH, Carey DE. Clinical impres-ions of Chikungunya in Vellore gained from study of adult patients. Indian]Med Res 1965; 53: 756-763.11. Fourie EO, Morrison jGL. Rheumatoid arthritic syndrome after Chikungu-nya fev·er. S Air Med] 1979; 56: 130-132.12. Kennedy AC, Fleming J, Solomon L. Chikungunya viral arthropathy: a clini-cal description.] Rhelllllarol 1980; 7: 231-236.13. Moore DL, Reddy S, Akinkugbe FM. An epidemic of Chikungunya fever atIbadan, Nigeria, 1969. AmI Trap Med Parasiro/1974; 68: 59-68.14. Hal tead SB, Nimmannitya S, Margiona MR. Dengue and Chikungunya virusinfection in man in Thailand, 1962-1964: observations on disease in out-patients. Alii] Trap Med Hyg 1969; 18: 972-983.

Chikungunya virus infection - A retrospective study of 107 cases

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Chikungunya virus infection - A retrospective study of 107 cases

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