DHR-ICMR Guidelines for diagnosis & management of Rickettsial diseases in India.

Rickettsial diseases, caused by a variety of obligate intracellular, gram-negative bacteria from the genera Rickettsia, Orientia, Ehrlichia, Neorickettsia, Neoehrlichia, and Anaplasma, belonging to the Alphaproteobacteria, are considered some of the most covert emerging and re-emerging diseases and are being increasingly recognized. Among the major groups of rickettsioses, commonly reported diseases in India are scrub typhus, murine flea-borne typhus, Indian tick typhus and Q fever. Rickettsial infections are generally incapacitating and difficult to diagnose; untreated cases have case fatality rates as high as 30-45 per cent with multiple organ dysfunction, if not promptly diagnosed and appropriately treated. The vast variability and non-specific presentation of this infection have often made it difficult to diagnose clinically. Prompt antibiotic therapy shortens the course of the disease, lowers the risk of complications and in turn reduces morbidity and mortality due to rickettsial diseases. There is a distinct need for physicians and health care workers at all levels of care in India to be aware of the clinical features, available diagnostic tests and their interpretation, and the therapy of these infections. Therefore, a Task Force was constituted by the Indian Council of Medical Research (ICMR) to formulate guidelines for diagnosis and management of rickettsial diseases. These guidelines include presenting manifestations, case definition, laboratory criteria (specific and supportive investigations) and treatment.

[Gastroenteritis with fever, headache and rash after travelling in India]. / Gastroenteritis mit Fieber, Zephalgie und Exanthem nach Indienreise.

A 63-year-old patient presented to our emergency unit two days after returning from India suffering from watery diarrhea, nausea, fever and headache. On admission we found a maculopapular rash on his trunk and forehead. Laboratory findings revealed a leuko-thrombopenia and elevated levels of CRP and procalcitonin. We started treatment with ciprofloxacin. After 48 hours of treatment the diarrhea subsided, whereas the rush on his trunk increased. Under the suspicion of rickettsial fever we started doxycycline 200 mg/d. Because of an incipient pneumonia we added ceftriaxon. The patient improved rapidly and the laboratory abnormalities resolved. Serological investigations revealed a significant increase of specific antibodies against Rickettsia typhi. In conclusion, headache with fever and maculopapular rash after traveling to endemic countries should rise suspicion for murine typhus.

A systematic review of the untreated mortality of murine typhus.

Murine typhus is an acute febrile, flea-borne disease caused by the bacteria Rickettsia typhi. The disease occurs worldwide but is likely underrecognized due to its non-specific symptoms, causing significant morbidity. A systematic review found disease complications in one-fourth of all patients and a long fever duration in those untreated. Although mortality in treated cases is estimated to be very low, some case series have shown a notably higher mortality in untreated patients. This study aimed to describe the outcomes and estimate the mortality of untreated murine typhus through a comprehensive systematic literature review. We systematically searched the literature for articles describing untreated murine typhus patients, excluding cases with no laboratory assay confirmed diagnosis, those who received efficacious treatment, had incomplete information on primary outcome and articles describing less than 10 patients and performed a narrative synthesis of the study findings. The study protocol followed the PRISMA guidelines and was part of a more extensive protocol registered at PROSPERO (CRD42018101991). Twelve studies including a total of 239 untreated patients matched the eligibility criteria. Only a single study reported one death in 28 patients, giving a patient series mortality of 3.6% and an overall mortality of 0.4% in 239 untreated patients. Complications were reported in 10 of the 12 studies and included involvement of the central nervous system, kidney and lung, with a hospitalisation rate of 70% and ICU admission rate of 27% in one study. The mean duration of fever in untreated patients was 15 days in two and 12.7 days in one study. Although the untreated mortality in this study was low, the sample size was small. Murine typhus caused significant morbidity when untreated, leading to high hospitalisation rates and highlighting the importance of early diagnosis and treatment of this neglected disease to reduce disease burden and health-care related costs.

Clinical and epidemiological observations regarding the 1998 Kauai murine typhus outbreak.

Five cases of murine typhus occurring on southwestern Kauai in 1998 are described, following an investigation by the Department of Health. Two cases also had concurrent leptospirosis. Recent habitat changes of peridomestic animals and their fleas may have increased the risk for developing murine typhus. Increased suspicion of typhus by island physicians and more aggressive rodent control activities are recommended.

Severe murine typhus with shock and acute respiratory failure in a Japanese traveler after returning from Thailand.

We treated a case of severe murine typhus in a Japanese traveler after returning from Thailand. Although the disease is typically self-limited or mild, the patient showed shock and multiple organ failure including acute respiratory distress syndrome. Then the patient fully recovered following intensive care and administration of antirickettsial medicines.

Imported rickettsioses: think of murine typhus.

Murine typhus is a disease still prevalent in many parts of the world. Because the incidence in the US and Europe has declined rapidly, physicians in these continents have become unfamiliar with the clinical picture. Murine typhus is associated with significant morbidity and fatalities do occur, especially in the elderly and when late recognized. We present a patient with murine typhus that illustrates the wide variety of symptoms in this disease, which makes diagnosis difficult. However, if one keeps the possibility of murine typhus in mind, it is easily diagnosed and treated.

Characteristics of lymphoid cells that adoptively transfer immunity to Rickettsia mooseri infection in mice.

The capacity of adoptively transferred immune lymphoid cells or passively transferred immune serum to alter the course of an established Rickettsia mooseri (R. typhi) infection in the spleen was evaluated in BALB/c mice. Immune cells, but not immune serum, controlled the established infection. An effective lymphocyte was a T-cell which had to possess a capacity to divide.

Imported rickettsioses in German travelers.

Twenty-two cases of rickettsiosis imported to Germany (13 men, nine women, average age 42 years) in a 5-year period were analyzed retrospectively regarding the travel histories, symptoms and clinical findings, laboratory features and course of the disease. The two primary rickettsial diseases were boutonneuse fever (18 patients) and scrub typhus (three patients). One patient had murine typhus. The main symptom was fever in 91% followed by headache (64%), myalgia (40%), arthralgia (50%) and diarrhea (36%). The most frequent clinical finding was lymphadenopathy in 65%. Eschar was detectable in 55% of patients with Rickettsia conori infection and in one patient with Rickettsia tsutsugamushi infection. All patients with R. tsutsugamushi infection as well as 33% of the patients with R. conori infection had a macular exanthema. One patient with scrub typhus had pleural and pericardial effusions. Seventy-three percent had an increased ESR. Three patients had leucocytosis, three increased transaminases and two normochromic anemia. The incubation period for R. conori infection was 5 to 28 days (average 14 days), for R. tsutsugamushi infection 7 to 21 days (average 16 days). Twenty-one patients were treated with tetracycline or doxycycline, one with erythromycin. All patients were cured. One patient had a relapse. Due to the fact that the symptoms are often not characteristic and that the routine laboratory findings are of only marginal help, the diagnosis of rickettsial diseases is often not easy. A detailed travel history sometimes gives an important hint for diagnosis.