Etiology of fever of unknown origin in a selected group of Sri Lankan patients with prompt responses to Doxycycline

Abstract

BACKGROUND: Most patients with long duration of fever go undiagnosed in settings where diagnostic facilities are inadequate. Untreated rickettsial infections cause extended fevers; while both scrub typhus and tick typhus are re-emerging diseases in Sri Lanka, laboratory facilities to specifically diagnose rickettsial infections in Sri Lanka are not available. METHODS: We collected 2 ml venous blood from febrile patients who had no etiological diagnosis after 7 days of hospital admission, but who showed rapid clinical response to doxycycline, to verify whether they had experienced a rickettsial infection. Acute serum samples were analysed using IFA for rickettsial infections caused by Orientia tsutsugamushi, Rickettsia conorii and Rickettsia typhi. A positive IgG IFA titer >1:128 was used to define a probable case of rickettsial infection. RESULTS: 28 patients [15 males, mean age 32.5 (SD 9.2 yrs)] were studied. Mean duration of fever at admission was 6.1 days (SD 3.1). Two patients had features suggestive of encephalitis and two had erythema nodosum. Others had no specific clinical features. Routine investigations were inconclusive and blood cultures were negative. IgG-IFA titer of >128 was found in 10 for R. conorii, 6 for O. tsutsugamushi and 6 for both R. conorii and O. tsutsugamushi. None were positive for R. typhi. Six were negative for all tests. One patient with encephalitis and one with erythema nodosum had high titers for R. conorii. CONCLUSIONS: The majority of Sri Lankan patients with undiagnosed fever responding promptly to doxycycline had a rickettsial etiology. Patients with rickettsioses exhibit varied clinical presentations so greater use of doxycycline for patients with extended fevers in rickettsial-endemic settings with inadequate diagnostic facilities appears warranted. The high proportion of patients with tick typhus and antibodies against both spotted fever and scrub typhus rickettsiae was unexpected based on previous studies of patients from the same region who were confirmed to have scrub typhus by serology and by the presence of the classic eschar. It is unknown whether the etiology of tick typhus and vector(s) transmitting this agent on the Western lowland region of Sri Lanka are the same as those responsible for spotted fevers in the central hill country of Sri Lanka.