Rickettsia honei Infection in a Traveler Returning From India

Abstract

We report a case of Rickettsia honei infection in a US tourist returning from India and the Himalayas. This case highlights a need for awareness of various Rickettsia species endemic to India and the importance for physicians to consider rickettsial diseases in returning travelers with eschar or rash-associated febrile illnesses.

CASE PRESENTATION

A previously healthy, 18-year-old man presented with a 6-day history of fevers, chills, rigors, headache, and rash on dorsum of left lower leg. Signs and symptoms started 3 days after return from a 3-month stay in India (primarily Northern India), which included camping and hiking in the Himalayas. He reported receiving occasional arthropod bites. Eight other travelers accompanied the patient but none reported similar illness. The patient did not take malaria prophylaxis. Initial physical examination revealed a warm, pink area at the ankle, with red streaks from ankle to knee and a fever of 102°F/38.9°C. Complete blood count with differential and a comprehensive metabolic panel showed mild elevation of monocytes (13.7%; range, 1.0%–12.5%), mild hyponatremia attributed at the time to high water intake without electrolyte replacement (sodium 134 mmol/L; range, 135–144 mmol/L), and a normal platelet count. He was diagnosed with cellulitis, administered a 1-gram intramuscular dose of ceftriaxone, prescribed oral cephalexin (500 mg, 4 times daily for 10 days), and instructed to take antipyretics. He returned for follow-up the next day and received a second 1-gram intramuscular dose of ceftriaxone. The patient was again seen the following day, reporting persistent fever and chills despite taking acetaminophen and ibuprofen. The streaks on his leg were sensitive to touch. Vasculitis and endocarditis were considered. A dermatologist was consulted, where erythematous macules and papules were noted on the lower extremities, torso, and arms (Figure 1A and B). A rickettsial illness was suspected, and punch-biopsy specimens were obtained from rash lesions on his left lateral malleolus (on this day described as deeply purpuric with a necrotic crust), left thigh, and abdomen. Cephalexin was discontinued in favor of oral doxycycline (100 mg twice daily for 10 days), with complete resolution of fever within approximately 12 hours. Histopathological evaluation of biopsy specimens demonstrated a dense, predominantly lymphocytic perivascular infiltrate involving small vessels of the dermis with occasional thrombi (Figure 2A, B, and C). No ulceration of the overlying epidermis was noted.

Figure 1.

Clinical images of Rickettsia honei eschar and spotted fever rash. (A) Purpuric eschar on left lateral malleolus. (B) Spotted fever rash on legs.

Figure 2.

Histopathologic and immunohistochemical evaluation of a skin punch biopsy specimen from the left lateral malleolus. (A) The biopsy demonstrates a superficial and deep dermal perivascular infiltrate (hematoxylin and eosin stain, magnification ×2.5). (B) Superficial portion of skin shows perivascular inflammation with vasculitis, vascular thrombi, and focal epidermal necrosis (hematoxylin and eosin stain, magnification ×10). (C) Inflammation surrounding a vessel comprises lymphocytes and histiocytes (hematoxylin and eosin stain, magnification ×20). (D) Immunohistochemical staining of spotted fever group Rickettsia species in the cytoplasm of mononuclear cells located in a perivascular distribution (immunoalkaline phosphatase with naphthol-fast red substrate, magnification ×63).

Formalin-fixed, paraffin-embedded (FFPE) biopsy specimens from the left lateral malleolus and left thigh were sent to the Centers for Disease Control and Prevention for immunohistochemical (IHC) and polymerase chain reaction (PCR) evaluation. An IHC assay detected no antigens of Orientia tsutsugamushi (the agent of scrub typhus) in either specimen; an IHC stain for spotted fever group Rickettsia [1] demonstrated intact coccobacilli and rickettsial antigens in perivascular inflammatory infiltrates and around endothelial cells of the left lateral malleolus biopsy (Figure 2D), but not in the thigh biopsy. Deoxyribonucleic acid extracted from each of the FFPE tissues was evaluated using a gltA real-time PCR assay to detect Rickettsia species [2], and a positive result was obtained for only the left lateral malleolus specimen. A conventional, nested PCR was used to amplify a segment of the outer membrane protein A (ompA) gene [2] from FFPE tissue of the left lateral malleolus biopsy specimen, and a 438-bp sequence revealed complete identity to the corresponding sequence of Thai tick typhus Rickettsia (GenBank accession number U43809.1), a strain of Rickettsia honei described in ticks in Thailand [3]. The sequence also revealed 99.77% identity to R honei subspecies marmionii (GenBank accession number DQ309096.1), the etiologic agent of Flinders Island spotted fever in Australia, [3–5] and to Rickettsia spp AL2003 (GenBank accession number AJ585044.1), also related to R honei, which was identified in a tick attached to a person in Queensland, Australia who subsequently developed spotted fever [5, 6]. Derivation of the Rickettsia ompB genetic sequence was attempted but, due to the fragmented nature of the FFPE specimen, could not be obtained.

Patient Consent Statement

The patient’s written consent was obtained.

CONCLUSIONS

The causative agents of rickettsial diseases in India have not been well studied, although evidence suggests that at least 2 spotted fever group Rickettsia species endemic to India cause illnesses in humans [7, 8]. Infection with R honei was described in a patient from Nepal in 2009 [9]; but to our knowledge has not been reported previously from India. This report emphasizes the need for considering rickettsioses in returning travelers with fever and rash or eschar [10]. Obtaining biopsies for subsequent IHC and/or PCR evaluation may also provide unique insight into the causative species.