Fatal Flea-Borne Typhus in Texas: A Retrospective Case Series, 1985-2015.

AbstractFlea-borne (murine) typhus is a global rickettsiosis caused by Rickettsia typhi. Although flea-borne typhus is no longer nationally notifiable, cases are reported for surveillance purposes in a few U.S. states. The infection is typically self-limiting, but may be severe or life-threatening in some patients. We performed a retrospective review of confirmed or probable cases of fatal flea-borne typhus reported to the Texas Department of State Health Services during 1985-2015. When available, medical charts were also examined. Eleven cases of fatal flea-borne typhus were identified. The median patient age was 62 years (range, 36-84 years) and 8 (73%) were male. Patients presented most commonly with fever (100%), nausea and vomiting (55%), and rash (55%). Respiratory (55%) and neurologic (45%) manifestations were also identified frequently. Laboratory abnormalities included thrombocytopenia (82%) and elevated hepatic transaminases (63%). Flea or animal contact before illness onset was frequently reported (55%). The median time from hospitalization to administration of a tetracycline-class drug was 4 days (range, 0-5 days). The median time from symptom onset to death was 14 days (range, 1-34 days). Flea-borne typhus can be a life-threatening disease if not treated in a timely manner with appropriate tetracycline-class antibiotics. Flea-borne typhus should be considered in febrile patients with animal or flea exposure and respiratory or neurologic symptoms of unknown etiology.

Brill-Zinsser disease in a patient following infection with sylvatic epidemic typhus associated with flying squirrels.

Recrudescent Rickettsia prowazekii infection, also known as Brill-Zinsser disease, can manifest decades after untreated primary infection but is rare in contemporary settings. We report the first known case of Brill-Zinsser disease in a patient originally infected with a zoonotic strain of R. prowazekii acquired from flying squirrels.

Diagnosis of Queensland tick typhus and African tick bite fever by PCR of lesion swabs.

We report 3 cases of Queensland tick typhus (QTT) and 1 case of African tick bite fever in which the causative rickettsiae were detected by PCR of eschar and skin lesions in all cases. An oral mucosal lesion in 1 QTT case was also positive.

William Henderson (1810-72) and homeopathy in Edinburgh.

William Henderson was appointed professor of general pathology at Edinburgh University and physician-in-ordinary to the ERI. He produced several papers on clinical and pathological aspects of aortic and heart disease and contributed to the differentiation of typhus and typhoid fevers. He became a homeopathist and was at the centre of a controversy surrounding the introduction of homeopathy to Edinburgh in the 1840s. This involved the Faculty of Medicine, the RCPE and medical societies as well as medical personalities, prominent among whom were Professor Sir James Y Simpson, Professor Sir Robert Christison and Professor James Syme. Many Scottish medical graduates were involved in the introduction of homeopathy to the British Isles. Glasgow is one of only four UK cities still to have a homeopathic hospital.

Establishment of a novel endothelial target mouse model of a typhus group rickettsiosis: evidence for critical roles for gamma interferon and CD8 T lymphocytes.

A mouse model of typhus rickettsiosis that reproduces the hematogenous dissemination to the critical target organs, including brain, lungs, heart, and kidneys, primary endothelial and, to a lesser degree, macrophage intracellular rickettsial infection, and typical vascular-based lesions of louse-borne typhus and murine typhus was established. Intravenous inoculation of C3H/HeN mice with Rickettsia typhi caused disease with a duration of the incubation period and mortality rate that were dependent on the infective dose of rickettsiae. Lethal infection was associated with high concentrations of R. typhi in the lungs and brain, despite a brisker humoral immune response to the rickettsiae than in the sublethal infection. Gamma interferon and CD8 T lymphocytes were demonstrated to be crucial to clearance of the rickettsiae and recovery from infection in experiments in which specific monoclonal antibodies were administered to deplete these components. Death of animals depleted of gamma interferon or CD8 T lymphocytes was associated with overwhelming rickettsial infection demonstrated by titers of infectious rickettsiae and by immunohistochemistry. An effective antirickettsial immune response was associated with elevated serum concentrations of IL-12 on Day 5 and increased secretion of IL-12 by concanavalin-A-stimulated spleen cells on Day 5. Evidence for transient suppression of the immune response consisted of marked reduction in the secretion of IL-2 and IL-12 by concanavalin-A-stimulated spleen cells on Days 10 and 15. This model offers excellent opportunities for study of attenuation and pathogenetic mechanisms of typhus rickettsiae, which are established biologic weapons of potential use in bioterrorism.

Rudolf Virchow, not just a pathologist: a re-examination of the report on the typhus epidemic in Upper Silesia.

Rudolf Virchow (1821-1902) is mainly remembered as the "father" of cellular pathology; however, he was not just a pathologist. His contributions to anthropology, archeology, ethnography, and history, as well as his involvement in epidemiology, public health, and politics, portray a man with multiple interests, deeply engaged in the controversies of his time. In his Report on the Typhus Epidemics of Upper Silesia of 1848, the young Virchow reveals himself to be a self-assured pathologist, although his postmortem examinations failed to shed much light on typhus. Despite of his shortcomings and biases, Virchow's genius is revealed in his deep appreciation of the importance of the total physical, socio-cultural, economic, and political background of epidemic diseases. One can discern in the Report the making of Virchow, the politician and statesman who will contribute to the modernization of Germany's public health, and of the physician-scholar and physician-citizen who, despite of his shortcomings and militancy, continues to inspire and challenge us today.

Epidemic typhus fever and hearing loss: a histological study (Hallpike collection of temporal bone sections).

Hearing loss as a frequent complication of louse-borne epidemic typhus fever has been well documented in the reports of ENT specialists serving in both the Allied and the German armies in the last war. The present paper describes the characteristic histopathological features as noted in sections of the temporal bones from five British soldiers who died in 1944 of typhus fever during the last war in Eastern Asia. The VIIIth nerve showed multiple 'typhus nodules' and there was extensive interstitial neuritis of the VIIIth nerve and demyelination of the nerve fibres. There were also widely scattered aggregations of mononuclear cells in the inner ear. This unique study was based on the Hallpike collection of temporal bone sections.

Typhus-induced facial necrosis.

A patient with open wounds on his hands developed a severe case of typhus following exposure to a wild rabbit. Typhus resulted in extensive necrosis of the mid-face, including the nasal alae, pinna, and lips. The patient also sustained extensive extremity necrosis. A brief review of the epidemiology, pathophysiology, and treatment of this cause of facial necrosis is presented, as well as a discussion of dopamine gangrene. While this uncommon entity probably played a large part in the necrosis of this patient's extremities, these peripheral lesions are also compatible with typhus.

Epidemic typhus infection in cynomolgus monkeys (Macaca fascicularis).

A nonhuman primate model of clinical Rickettsia prowazekii infections was developed in cynomolgus monkeys (Macaca fascicularis). Monkeys infected intravenously with 10(7) plaque-forming units developed clinical signs of illness and pathological changes characteristic of epidemic typhus infection in humans. Increases in total leukocyte counts, serum alkaline phosphatase, blood urea nitrogen, and serum glutamic pyruvate transaminase values were observed. Microscopic examination revealed typical typhus nodules in the brains of two monkeys that died. These data indicated that the cynomolgus monkey is a suitable model for study of the pathogenesis of epidemic typhus infection and may prove valuable in the evaluation of candidate R. prowazekii vaccines.

Infectious process in the lungs after intranasal challenge of white mice with Rickettsia prowazekii. A histologic immunoluminescent and electron microscopic study.

The lungs of white mice given intranasal injections of various amounts of Rickettsia prowazekii were studied. Agent parasitism, mainly in the alveolar epithelium and nonciliated cells of bronchiolar epithelium, underlies the infectious process developing in the lungs. Rickettsiae may lodge in these cells without inducing both local and general alterations or a leukocyte response. After being released from the cells they inhabit, rickettsiae evoke acute exudative inflammation. The inflammation is accompanied by marked circulatory disorders, necrosis of exudate cells and vascular thrombosis, which are induced by toxic products of the agent. Polymorphonuclear leukocytes and macrophages represent the main defense mechanism of a host. They ingest and destroy rickettsial organisms. If infection runs a favorable course, phagocytes destroy the rickettsiae, and the organisms are entirely cleared from the lungs.