AFRICAN TICK TYPHUS (MEDITERRANEAN SPOTTED FEVER) IN AUSTRALIAN TRAVELLERS

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Australas J. Dermatol 1988; 29: 141-145 AFRICAN TICK TYPHUS (MEDITERRANEAN SPOTTED FEVER) IN AUSTRALIAN TRAVELLERS DAVID I.

1 Australas J. Dermatol 1988; 29: AFRICAN TICK TYPHUS (MEDITERRANEAN SPOTTED FEVER) IN AUSTRALIAN TRAVELLERS DAVID I. GROVE Perth SUMMARY Two cases of infection with Rickettsia conorii in Australian travellers returned from Africa are reported in order to heighten awareness of this condition. The major clinical features are fever, an eschar, and a maculopapular rash. Diagnostic methods and treatment with tetracyclines are reviewed. Key words: Rickettsia conorii, African tick typhus, Mediterranean spotted fever, Boutonneuse Fever, travellers. INTRODUCTION Rickettsia conorii causes an acute febrile illness with characteristic cutaneous manifestations variously known as African tick typhus, Kenyan tickbite fever, Mediterranean spotted fever, Fievre boutonneuse or Febre escaro-nodular. Although the organism is endemic only in the Mediterranean littoral, Africa and the Middle East through to India, the infection is acquired from time to time by travellers and imported cases have been recognised in the United States of America' ^ With the current increase in the incidence of infection in endemic areas'"* and greater rapid international travel, practitioners in Australia need to be aware of this treatable malady. The purpose of this paper is to report one proven case and one presumptive case of infection with R. conorii seen recently in Perth. CASE REPORTS Case 1. A 44 year old radiologist presented in 1985 with a four day history of excruciating muscle pains, most marked behind the knees. Two days later he noticed a skin lesion on his right shin. Twenty four hours before admission to hospital he developed a high fever (reaching 40 C), rigors, delirium and a generalised rash. Four.weeks earlier he had attended a radiological Dr. David I. Grove, MD, FRACP. Director of Postgraduate Medical Education, Sir Charles Gairdner Hospital. Address for correspondence: Dr. D.I. Grove, Department of Postgraduate Medical Education, Sir Charles Gairdner Hospital, Verdun St., Nedlands, W.A conference in London then had returned to Australia via Kenya. He had spent ten days in that country and had taken a safari around the lakes and through a game reserve. His illness began one week after leaving Kenya. He had taken chloroquine and maloprim as antimalarial prophylaxis. On examination, his temperature was 37.8 C. An eschar was present on his right leg (Figure 1). In addition, there was a generalised rash with scattered erythematous papules up to three or four millimetres in diameter (Figure 2). The remainder of the physical examination was normal. The haemoglobin concentration and platelet count were normal as was the white cell count (7.1xlOVlitre) with normal differential; the erythrocyte sedimentation rate (ESR) was 14mm in one hour. Plasma electrolyte and creatinine levels and liver function tests were within normal limits except for a slightly elevated AST level of 46 units/litre (normal: 6-42). A chest X-ray and mid-stream specimen of urine were normal while three sets of blood cultures were sterile and a swab of the eschar grew no pathogens. Serological testing for a variety of arboviruses, respiratory viruses and enteroviruses was negative. The Weil- Felix reaction at the time of presentation gave non-diagnostic antibody titres to Proteus OX19, OXK and OX2 antigens of 1 in 80, 320 and 40, respectively. Repeat testing two weeks later showed no change in titres. Specific serology was not available at that time. A clinical diagnosis of Kenyan tick typhus was made and the patient was treated with tetracychne, 500mg four times daily for one week. The fever resolved within 24 hours

2 DAVID I. GROVE FiGLiRE 1 Eschar on the leg of the first patient FIGURE 2 Scattered erythematous papules on the chest of the first patient FIGURE 3 Eschar on the wrist of the second patient FIGURE 4 Close-up view of erythematous papules several millimetres in diameter on the trunk of the second patient

3 AFRICAN TICK TYPHUS IN TRAVELLERS of beginning antibiotic therapy and the eruption faded over the next few days. Case 2. A 41 year old geologist made three trips during a six week period to South Africa and Botswana in While on his way back to Australia on the third occasion, he felt lethargic and noticed a small skin lesion on his wrist. Two days later he became severely ill with high fever (up to 40 C), rigors, sweats, headache and a rash. He had not taken antimalarial prophylaxis. On examination, his temperature was 37.6 C. An eschar was present on his left wrist (Figure 3). A widespread rash similar to that seen with the first patient was apparent (Figure 4). The remainder of the examination was normal apart from one palpable, slightly tender left axillary lymph node. The haemoglobin concentration and platelet count were normal but there was a mild leucopenia of 3.0x10' white cells/litre (neutrophils 46%, lymphocytes 36%, monocytes 18%). The ESR was 12 mm/hour. Plasma electrolyte and creatinine levels were normal as were liver function tests and a midstream specimen of urine. Blood cultures revealed no growth. No changes occurred in the Weil-Felix reaction but a positive titre to the spotted fever group of rickettsiae was seen four weeks after the onset of the illness (Table 1). These tests were performed in the State Health Laboratory Services, Perth. Before positive serology was observed, a clinical diagnosis of African tick typhus was made and the patient was treated with tetracycline, 500 mg four times daily for one week. The fever resolved within 48 hours of beginning antibiotic therapy and the eruption faded over the next few days. TABLE 1 Weil-Fetix reaction and specific rickettsiat antibody titres in the second patient at various times after the onset of the itlness. Days of illness Proteus OX19. - Weil-Felix reaction Proteus OX Proteus OXK Rickettsial immunofluorescence Spotted Typhus fever group group ^ Results are expressed as the reciprocal of the titre. For the rickettsial immunofluorescent test, titres of ="^32 are considered negative, 64 as equivocal and 128 as indicative of previous or recent infection. A fourfold rise in titre is diagnostic of current infection. 143 DISCUSSION - R. conorii infection is a zoonosis in which dogs are the prime reservoir of infection although other mammals may also be infected. The organism is generally transmitted by the bite of various hard ticks. In neither of the two cases presented here was the patient aware of a tick bite. The most common vector in the Mediterranean region is the dog tick, Rhipicephalus sanguineus. In Kenya, Amblyomma hebraeum, Haemaphysalis leachi and R. simus are also reported as vectors while in South Africa, A. hebraeum, H. leachi, Hyalomma rufipes, R. appendiculatus and R. evertsi have been found to be infected. In Ethiopa, R. conorii infects another three species of Amblyomma^. The propensity of R. conorii to infect various species of Amblyomma is of some relevance as the tick that most commonly bites humans in the Perth region of Western Australia is Amblyomma triguttatum^. Although the susceptibility of this tick to R. conorii has not yet been proven, it is conceivable that the infection could become endemic if it were introduced. The illness now recognised as being due to this organism was first described by Conor and Bruch in Tunis in 1910 (cited in'). The incidence of infection appears to have been rising in the Mediterranean region over the past decade. Three large series of approximately 200 patients have been described recently from Spain\ France"* and Portugal*. All patients had a fever and this was marked in almost all of them. More than 90% of patients had a generalised maculopapular rash which usually erupted around the third day of fever and affected the trunk, limbs and face. In a few patients, the rash was predominantly macular in nature. Petechiae were present in a small proportion of cases. An eschar (tache noire) was observed in three-quarters of patients and consisted of a small ulcer with a black centre surrounded by a red halo. Eschars were seen on all parts of the body but were most common on the lower limbs in adults. Myalgias and headache were prominent symptoms, being seen in more than half of the patients while a lesser number complained of other systemic symptoms. Haematological studies revealed a normal ESR and white cell count in most patients; 20% of patients had either a leucopenia or leucocytosis. Half of the patients had a mild elevation in liver enymes. Thus, the two patients described here had clinical

DAVID I. GROVE and laboratory features similar to those described in large series. A diagnosis of tick typhus is most frequently confirmed serologically.

4 DAVID I. GROVE and laboratory features similar to those described in large series. A diagnosis of tick typhus is most frequently confirmed serologically. Glassically, antibodies appear against the OX19 and OX2 strains of Proteus vulgaris but not the OXK strain of P. mirabilis in R. conorii infections'. Rising titres to these antigens were not seen in either of my patients but this is not exceptional as a positive Weil-Felix reaction was seen in only 78% of patients in one series'. Recently, an immunofluorescent antibody assay for rickettsial infections which is both more sensitive and specific has become available ". In the assay employed in Perth, sero-reactivity can distinguish between but not within two groups of species of Rickettsia". The spotted fever group antigen test can be used to diagnose infections with R. rickettsii, R. conorii, R. australis, R. siberica and R. akari while infections with R. typhi (= mooseri) and R. prowazekii are diagnosed with typhus group antigens. No specific assay is yet available for the diagnosis of scrub typhus due to R. tsutsugamushi. Rickettsial antibodies were sought in the second patient and a diagnostic rise in titre was found. An alternative method of diagnosis is to perform immunofluorescent staining of R. conorii in cryostat sections of skin biopsy specimens of either the eschar or papular lesions'^". This has the advantage of permitting prompt diagnosis but requires the availability of appropriate antisera and was not used in these cases. Font- Creus et al.' have reviewed the histological appearances. Studies of the eschar have shown epidermal ulceration covered by necroinflammatory material, endothelial hyperplasia of the small dermal arterioles and a mixed perivascular Ieucocytic infiltrate. Examination of the maculopapular lesions revealed a dermal perivascular lymphohistiocytic infiltrate and diffuse vasculitis with partial or complete thrombosis of the vascular lumen with microinfarction and extravasation. Mediterranean spotted fever has generally been considered to be a benign condition. Untreated, the natural duration of the illness is days'\ However, deaths have occurred in 2.5% of 199 patients in France'' and 2.4% of 247 patients in Portugal*. The majority of patients in reported series have been treated with tetracycline although a few have received either chloramphenicol, cotrimoxazole or erythromycin'"". In vitro studies have indicated that the minimum inhibitory concentrations for a Moroccan strain of R.conorii were less than or equal to 0.25 fig/xnl for doxycycline, tetracycline, chloramphenicol, ciprofloxacin and rifampicin but that it was relatively resistant to erythromycin (4 ^g/ml) and co-trimoxazole (10 ;Ug/ml)". A recent randomised trial has shown that two oral doses of doxycyline 200 mg twelve hours apart was as effective as 500 mg tetracycline given four times daily for ten days". REFERENCES ' Schlaeffer F, Lederer K, Mates SM. Mediterranean spotted fever in an American woman. Arch Int Med 1985; 145: ' Harris RL, Kaplan SL, Bradshaw MW, Williams TW. Boutonneuse fever in American travelers. J Infect Dis 1986; 153: ' Font-Creus B, Bella-Cueto F, Espejo-Arenas E et al. Mediterranean spotted fever: a cooperative study of 227 cases. Rev Infect Dis 1985; 7: ' Raolut D, Weiller PJ, Chagnon A, Chaudet H, Gallais H, Casanova P. Mediterranean spotted fever: clinical, laboratory and epidemiological features of 199 cases. Am J Trop Med Hyg 1986; 35: ' Ormsbee RA. Related spotted fevers and rickettsioses. In: Hunter GW, Swartzwelder JC, Clyde DF, eds. Tropical Medicine. Fifth ed. Philadelphia: WB Saunders and Company, 1976; ' Pearce RL, Grove DI, Tick infestation in soldiers who were bivouacked in the Perth region. Med J Aust 1987; 146: ' Olmer D, Olmer J. Fievre boutonneuse: fievre exanthematique du littoral mediterranean. Paris: Masson, 1933 ' Proenca R, Morgado A, Codinho A, Pachecho F, Ferreira N, Barreros T. Boutonneuse fever (febre escaro-nodular): an analysis of 247 cases during the period Proceedings of the International Congress for Infectious Diseases, Rio de Janiero, Brazil, Abstract No. 397, April, 1988; 397 ' Mansueto S, Vitale G, Tringali G, Pintagro C, Occhino C, Miceli MD. Studi sieroimmunologici nella febbre bottonosa. 1. Valutazione di un kit del commercio per micro-immunofluorescenza nella diagnostica sierologica della febbre bottonosa. Quad Sclavo Diagn 1983; 19: ' Mansueto S, Vitale G, Tringali G et al. Studi sieroimmunologici nella febbre bottonosa. II. Ampiezza, cinetica, durata e dislocazione immunoglobulinica (lga, IgG e IgM) olella risposta anticorpale anti-/?. conorii (metodo di microimmunofluorescenza indiretta). G Mai Inf Paras 1983; 35: " Hechemy KE, Raoult D, Eismann C, Yangsook Han, Fox JA. Detection of antibodies to Rickettsia conorii with a latex agglutination test in patients with Mediterranean spotted fever. J Infect Dis 1986; 153: " Raoult D, de Micco C, Gallais H, Toga M. Laboratory diagnosis of Mediterranean spotted fever by immunofluorescent demonstration of Rickettsia conorii in cutaneous lesions. J Infect Dis 1984; 150:

5 AFRICAN TICK TYPHUS IN TRAVELLERS Herrero-Herrero JI, Walker DH, Ruiz-Beltran R. " Raoult D, Roussellier P, Vestris G, Tamalet J. In vitro Immunohistochemical evaluation of the cellular immune antibiotic susceptibility of Rickettsai rickettsii and response to Rickettsia conorii in taches noires. J Infect Rickettsia conorii: plaque assay and microcolorimetric Dis 1987; 155: assay. J Infect Dis 1987; 155: Pedro Pons. A Rickettsiosis frecuente y poco conocida " Bella-Cueto F, Font-Creus B, Segura-Porta F, Espejoentre nosotros: fiebre exantematica mediterranea (fiebre Arenas E, Lopez-Pares P, Munoz-Espin T. Comparative, botonosa). Enfermedad de Conor y Bruch. Med Clin randomized trial of one-day doxycyline versus 10-day (Barcelona) 1945; 5:1-6 tetracycline therapy for Mediterranean spotted fever. J Infect Dis 1987; 155:

African tick typhus. David Mabey

African tick typhus. David Mabey African tick typhus David Mabey 25 year old English man Holiday in Zimbabwe for 3 months Became unwell on plane home Fever Rash Generalised lymphadenopathy This photo was taken 2 days after onset of symptoms