AFRICAN TICK TYPHUS (MEDITERRANEAN …david.grove/119.pdfvarious hard ticks. In neither of the two cases presented here was the patient aware of a tick bite. The most common vector

Australas J. Dermatol 1988; 29: 141-145

AFRICAN TICK TYPHUS(MEDITERRANEAN SPOTTED FEVER)

IN AUSTRALIAN TRAVELLERS

DAVID I. GROVEPerth

SUMMARY

Two cases of infection with Rickettsia conorii in Australian travellers returned from Africaare reported in order to heighten awareness of this condition. The major clinical featuresare fever, an eschar, and a maculopapular rash. Diagnostic methods and treatment withtetracyclines are reviewed.

Key words: Rickettsia conorii, African tick typhus, Mediterranean spotted fever,Boutonneuse Fever, travellers.

INTRODUCTION

Rickettsia conorii causes an acute febrile illnesswith characteristic cutaneous manifestations var-iously known as African tick typhus, Kenyan tick-bite fever, Mediterranean spotted fever, Fievreboutonneuse or Febre escaro-nodular. Althoughthe organism is endemic only in theMediterranean littoral, Africa and the MiddleEast through to India, the infection is acquiredfrom time to time by travellers and imported caseshave been recognised in the United States ofAmerica' ^ With the current increase in the in-cidence of infection in endemic areas'"* andgreater rapid international travel, practitioners inAustralia need to be aware of this treatablemalady. The purpose of this paper is to reportone proven case and one presumptive case ofinfection with R. conorii seen recently in Perth.

CASE REPORTS

Case 1. A 44 year old radiologist presented in1985 with a four day history of excruciatingmuscle pains, most marked behind the knees.Two days later he noticed a skin lesion on hisright shin. Twenty four hours before admissionto hospital he developed a high fever (reaching40 °C), rigors, delirium and a generalised rash.Four.weeks earlier he had attended a radiological

Dr. David I. Grove, MD, FRACP. Director of PostgraduateMedical Education, Sir Charles Gairdner Hospital.

Address for correspondence: Dr. D.I. Grove, Departmentof Postgraduate Medical Education, Sir Charles GairdnerHospital, Verdun St., Nedlands, W.A. 6009.

conference in London then had returned toAustralia via Kenya. He had spent ten days in thatcountry and had taken a safari around the lakesand through a game reserve. His illness began oneweek after leaving Kenya. He had takenchloroquine and maloprim as antimalarialprophylaxis. On examination, his temperaturewas 37.8 °C. An eschar was present on his rightleg (Figure 1). In addition, there was a generalisedrash with scattered erythematous papules up tothree or four millimetres in diameter (Figure 2).The remainder of the physical examination wasnormal. The haemoglobin concentration andplatelet count were normal as was the white cellcount (7.1xlOVlitre) with normal differential; theerythrocyte sedimentation rate (ESR) was 14mmin one hour. Plasma electrolyte and creatininelevels and liver function tests were within normallimits except for a slightly elevated AST level of46 units/litre (normal: 6-42). A chest X-ray andmid-stream specimen of urine were normal whilethree sets of blood cultures were sterile and a swabof the eschar grew no pathogens. Serologicaltesting for a variety of arboviruses, respiratoryviruses and enteroviruses was negative. The Weil-Felix reaction at the time of presentation gavenon-diagnostic antibody titres to Proteus OX19,OXK and OX2 antigens of 1 in 80, 320 and 40,respectively. Repeat testing two weeks latershowed no change in titres. Specific serology wasnot available at that time. A clinical diagnosis ofKenyan tick typhus was made and the patient wastreated with tetracychne, 500mg four times dailyfor one week. The fever resolved within 24 hours

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DAVID I. GROVE

FiGLiRE 1—Eschar on the leg of the first patient FIGURE 2—Scattered erythematous papules on the chest ofthe first patient

FIGURE 3—Eschar on the wrist of the second patientFIGURE 4—Close-up view of erythematous papules severalmillimetres in diameter on the trunk of the second patient

AFRICAN TICK TYPHUS IN TRAVELLERS

of beginning antibiotic therapy and the eruptionfaded over the next few days.

Case 2. A 41 year old geologist made threetrips during a six week period to South Africaand Botswana in 1988. While on his way backto Australia on the third occasion, he feltlethargic and noticed a small skin lesion on hiswrist. Two days later he became severely ill withhigh fever (up to 40 °C), rigors, sweats, headacheand a rash. He had not taken antimalarialprophylaxis. On examination, his temperaturewas 37.6 °C. An eschar was present on his leftwrist (Figure 3). A widespread rash similar to thatseen with the first patient was apparent (Figure4). The remainder of the examination was normalapart from one palpable, slightly tender leftaxillary lymph node. The haemoglobinconcentration and platelet count were normal butthere was a mild leucopenia of 3.0x10' whitecells/litre (neutrophils 46%, lymphocytes 36%,monocytes 18%). The ESR was 12 mm/hour.Plasma electrolyte and creatinine levels werenormal as were liver function tests and a mid-stream specimen of urine. Blood cultures revealedno growth. No changes occurred in the Weil-Felixreaction but a positive titre to the spotted fevergroup of rickettsiae was seen four weeks after theonset of the illness (Table 1). These tests wereperformed in the State Health LaboratoryServices, Perth. Before positive serology wasobserved, a clinical diagnosis of African ticktyphus was made and the patient was treated withtetracycline, 500 mg four times daily for oneweek. The fever resolved within 48 hours ofbeginning antibiotic therapy and the eruptionfaded over the next few days.

TABLE 1

Weil-Fetix reaction and specific rickettsiat antibody titres inthe second patient at various times after the onset of theitlness.

Daysofillness

31931

Weil-Felix reaction

ProteusOX19

-ve-ve

•••. - v e -

ProteusOX2

808080

ProteusOXK

-ve-ve-ve

Rickettsial immuno-fluorescence

Spotted Typhusfever

group group

-416 -41632 -^16

128 -416

Results are expressed as the reciprocal of the titre. For therickettsial immunofluorescent test, titres of ="^32 areconsidered negative, 64 as equivocal and •128 as indicativeof previous or recent infection. A fourfold rise in titre isdiagnostic of current infection.

DISCUSSION -

R. conorii infection is a zoonosis in which dogsare the prime reservoir of infection althoughother mammals may also be infected. Theorganism is generally transmitted by the bite ofvarious hard ticks. In neither of the two casespresented here was the patient aware of a tick bite.The most common vector in the Mediterraneanregion is the dog tick, Rhipicephalus sanguineus.In Kenya, Amblyomma hebraeum, Haemaphys-alis leachi and R. simus are also reported asvectors while in South Africa, A. hebraeum, H.leachi, Hyalomma rufipes, R. appendiculatus andR. evertsi have been found to be infected. InEthiopa, R. conorii infects another three speciesof Amblyomma^. The propensity of R. conoriito infect various species of Amblyomma is ofsome relevance as the tick that most commonlybites humans in the Perth region of WesternAustralia is Amblyomma triguttatum^. Althoughthe susceptibility of this tick to R. conorii hasnot yet been proven, it is conceivable that the in-fection could become endemic if it were intro-duced.

The illness now recognised as being due to thisorganism was first described by Conor and Bruchin Tunis in 1910 (cited in'). The incidence ofinfection appears to have been rising in theMediterranean region over the past decade. Threelarge series of approximately 200 patients havebeen described recently from Spain\ France"* andPortugal*. All patients had a fever and this wasmarked in almost all of them. More than 90%of patients had a generalised maculopapular rashwhich usually erupted around the third day offever and affected the trunk, limbs and face. Ina few patients, the rash was predominantlymacular in nature. Petechiae were present in asmall proportion of cases. An eschar (tache noire)was observed in three-quarters of patients andconsisted of a small ulcer with a black centresurrounded by a red halo. Eschars were seen onall parts of the body but were most common onthe lower limbs in adults. Myalgias and headachewere prominent symptoms, being seen in morethan half of the patients while a lesser numbercomplained of other systemic symptoms. Haema-tological studies revealed a normal ESR andwhite cell count in most patients; 20% of patientshad either a leucopenia or leucocytosis. Half ofthe patients had a mild elevation in liver enymes.Thus, the two patients described here had clinical

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DAVID I. GROVE

and laboratory features similar to those describedin large series.

A diagnosis of tick typhus is most frequentlyconfirmed serologically. Glassically, antibodiesappear against the OX19 and OX2 strains ofProteus vulgaris but not the OXK strain of P.mirabilis in R. conorii infections'. Rising titresto these antigens were not seen in either of mypatients but this is not exceptional as a positiveWeil-Felix reaction was seen in only 78% ofpatients in one series'. Recently, an immuno-fluorescent antibody assay for rickettsial infec-tions which is both more sensitive and specifichas become available "° . In the assay employ-ed in Perth, sero-reactivity can distinguishbetween but not within two groups of species ofRickettsia". The spotted fever group antigen testcan be used to diagnose infections with R.rickettsii, R. conorii, R. australis, R. siberica andR. akari while infections with R. typhi (=mooseri) and R. prowazekii are diagnosed withtyphus group antigens. No specific assay is yetavailable for the diagnosis of scrub typhus dueto R. tsutsugamushi. Rickettsial antibodies weresought in the second patient and a diagnostic risein titre was found.

An alternative method of diagnosis is to per-form immunofluorescent staining of R. conoriiin cryostat sections of skin biopsy specimens ofeither the eschar or papular lesions'^". Thishas the advantage of permitting prompt diagnosisbut requires the availability of appropriateantisera and was not used in these cases. Font-Creus et al.' have reviewed the histologicalappearances. Studies of the eschar have shownepidermal ulceration covered by necroinflam-matory material, endothelial hyperplasia of thesmall dermal arterioles and a mixed perivascularIeucocytic infiltrate. Examination of the maculo-papular lesions revealed a dermal perivascularlymphohistiocytic infiltrate and diffuse vasculitiswith partial or complete thrombosis of thevascular lumen with microinfarction andextravasation.

Mediterranean spotted fever has generally beenconsidered to be a benign condition. Untreated,the natural duration of the illness is 12-20 days'\However, deaths have occurred in 2.5% of 199patients in France'' and 2.4% of 247 patients inPortugal*. The majority of patients in reportedseries have been treated with tetracycline althougha few have received either chloramphenicol, co-trimoxazole or erythromycin'"". In vitro stud-

ies have indicated that the minimum inhibitoryconcentrations for a Moroccan strain of R.conoriiwere less than or equal to 0.25 fig/xnl for doxy-cycline, tetracycline, chloramphenicol,ciprofloxacin and rifampicin but that it wasrelatively resistant to erythromycin (4 ^g/ml) andco-trimoxazole (10 ;Ug/ml)". A recent randomisedtrial has shown that two oral doses of doxycyline200 mg twelve hours apart was as effective as 500mg tetracycline given four times daily for tendays".

REFERENCES

' Schlaeffer F, Lederer K, Mates SM. Mediterranean spottedfever in an American woman. Arch Int Med 1985;145:1733-1734.

' Harris RL, Kaplan SL, Bradshaw MW, Williams TW.Boutonneuse fever in American travelers. J Infect Dis 1986;153:126-128.

' Font-Creus B, Bella-Cueto F, Espejo-Arenas E et al.Mediterranean spotted fever: a cooperative study of 227cases. Rev Infect Dis 1985; 7:635-642.

' Raolut D, Weiller PJ, Chagnon A, Chaudet H, Gallais H,Casanova P. Mediterranean spotted fever: clinical,laboratory and epidemiological features of 199 cases. AmJ Trop Med Hyg 1986; 35:845-850.

' Ormsbee RA. Related spotted fevers and rickettsioses. In:Hunter GW, Swartzwelder JC, Clyde DF, eds. TropicalMedicine. Fifth ed. Philadelphia: WB Saunders andCompany, 1976; 118-121.

' Pearce RL, Grove DI, Tick infestation in soldiers who werebivouacked in the Perth region. Med J Aust 1987;146:238-240.

' Olmer D, Olmer J. Fievre boutonneuse: fievre exanthem-atique du littoral mediterranean. Paris: Masson, 1933

' Proenca R, Morgado A, Codinho A, Pachecho F, FerreiraN, Barreros T. Boutonneuse fever (febre escaro-nodular):an analysis of 247 cases during the period 1977-1986.Proceedings of the International Congress for InfectiousDiseases, Rio de Janiero, Brazil, Abstract No. 397, April,1988; 397

' Mansueto S, Vitale G, Tringali G, Pintagro C, OcchinoC, Miceli MD. Studi sieroimmunologici nella febbrebottonosa. 1. Valutazione di un kit del commercio permicro-immunofluorescenza nella diagnostica sierologicadella febbre bottonosa. Quad Sclavo Diagn 1983;19:262-270

'° Mansueto S, Vitale G, Tringali G et al. Studi sieroimmuno-logici nella febbre bottonosa. II. Ampiezza, cinetica,durata e dislocazione immunoglobulinica (lgA, IgG e IgM)olella risposta anticorpale anti-/?. conorii (metodo dimicroimmunofluorescenza indiretta). G Mai Inf Paras1983; 35:723-730.

" Hechemy KE, Raoult D, Eismann C, Yangsook Han, FoxJA. Detection of antibodies to Rickettsia conorii with alatex agglutination test in patients with Mediterraneanspotted fever. J Infect Dis 1986; 153:132-135

" Raoult D, de Micco C, Gallais H, Toga M. Laboratorydiagnosis of Mediterranean spotted fever byimmunofluorescent demonstration of Rickettsia conoriiin cutaneous lesions. J Infect Dis 1984; 150:145-148

AFRICAN TICK TYPHUS IN TRAVELLERS

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