Case Report: Cardiovascular Manifestations due to Flea-Borne Typhus.

Flea-borne typhus is a vector-borne disease caused by Rickettsia typhi that occurs worldwide, except in Antarctica. In the United States, most cases are restricted to California, Hawaii, and Texas. The syndrome is characterized by nonspecific signs and symptoms: fever, headache, rash, arthralgia, cough, hepatosplenomegaly, diarrhea, and abdominal pain. Although flea-borne typhus can cause pulmonary, neurological, and renal complications, the cardiovascular system is rarely affected. We present a case of endocarditis resulting from flea-borne typhus diagnosed by blood microbial cell-free DNA testing that required valve replacement and antibiotic therapy for 6 months. In addition, we review 20 cases of presumed and confirmed cardiovascular manifestations resulting from flea-borne typhus in the literature.

The contributions of James Carmichael Smyth, Archibald Menzies and Robert Jackson to the treatment of typhus in royal naval vessels in the late 18th century.

In late 18th century Britain, typhus fever plagued the mass mobilisation of soldiers and posed a significant challenge to physicians of the time. Epidemic typhus was spread through highly infectious faeces of infected lice and carried a high mortality in patients and healthcare staff alike. Physicians James Carmichael Smyth (1741-1821) and Archibald Menzies (1754-1842) theorized that typhus fever was caused by infection of human exhalation. They trialled the use of vapourised nitrous acid to fumigate patients, their clothes and their bedspace, with apparent success. Despite this, typhus fever continued to ravage deployments of soldiers into the early 19th century, stimulating the continuing evolution of the understanding of typhus and its treatment.

Co-trimoxazole versus azithromycin for the treatment of undifferentiated febrile illness in Nepal: study protocol for a randomized controlled trial.

BACKGROUND: Undifferentiated febrile illness (UFI) includes typhoid and typhus fevers and generally designates fever without any localizing signs. UFI is a great therapeutic challenge in countries like Nepal because of the lack of available point-of-care, rapid diagnostic tests. Often patients are empirically treated as presumed enteric fever. Due to the development of high-level resistance to traditionally used fluoroquinolones against enteric fever, azithromycin is now commonly used to treat enteric fever/UFI. The re-emergence of susceptibility of Salmonella typhi to co-trimoxazole makes it a promising oral treatment for UFIs in general. We present a protocol of a randomized controlled trial of azithromycin versus co-trimoxazole for the treatment of UFI. METHODS/DESIGN: This is a parallel-group, double-blind, 1:1, randomized controlled trial of co-trimoxazole versus azithromycin for the treatment of UFI in Nepal. Participants will be patients aged 2 to 65 years, presenting with fever without clear focus for at least 4 days, complying with other study criteria and willing to provide written informed consent. Patients will be randomized either to azithromycin 20 mg/kg/day (maximum 1000 mg/day) in a single daily dose and an identical placebo or co-trimoxazole 60 mg/kg/day (maximum 3000 mg/day) in two divided doses for 7 days. Patients will be followed up with twice-daily telephone calls for 7 days or for at least 48 h after they become afebrile, whichever is later; by home visits on days 2 and 4 of treatment; and by hospital visits on days 7, 14, 28 and 63. The endpoints will be fever clearance time, treatment failure, time to treatment failure, and adverse events. The estimated sample size is 330. The primary analysis population will be all the randomized population and subanalysis will be repeated on patients with blood culture-confirmed enteric fever and culture-negative patients. DISCUSSION: Both azithromycin and co-trimoxazole are available in Nepal and are extensively used in the treatment of UFI. Therefore, it is important to know the better orally administered antimicrobial to treat enteric fever and other UFIs especially against the background of fluoroquinolone-resistant enteric fever. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02773407 . Registered on 5 May 2016.

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.

Dr Robert Robertson (1742-1829): Fever Specialist and Philosopher-Experimenter in the Treatment of Fevers with Peruvian Bark in the Latter Eighteenth-century Royal Navy.

The life and works of Dr Robert Robertson are reviewed set against the background of the extant British management of fevers during the latter 18th-century. Commencing in 1769, using the febrifuge Peruvian bark (cortex Peruvianus; Jesuit's Powder), he experimented and tested Peruvian bark mono-therapy protocols in the tropics in the cure and prevention of intermittent fever (predominantly malaria). His later work also showed the benefit of the bark in the acute care of developed continuous fevers (largely Ship Fever due to Epidemic Louse-borne Typhus Fever) in both the Temperate and Torrid Zones. In the realm of comparative statistics Robertson first demonstrated the safety and effectiveness of bark therapy against the dangerous depleting processes of the antiphlogistic regimen. He was the first to alert the Admiralty to the efficacy of bark in both the cure of acute fevers as well as a prophylactic in the tropics, and signalled the dangers of bloodletting in treating fevers of the tropics. He authored 13 books devoted to fevers outlining his theory of Febrile Infection and its treatment. The essay concludes with his role as the Physician-in-Charge of the Royal Hospital, Greenwich over a 28-year period, as an acknowledged expert in the small British group of 18th-century fever specialists.

Queensland tick typhus: three cases with unusual clinical features.

Queensland tick typhus (QTT), caused by Rickettsia australis, is usually a relatively mild illness but can occasionally be severe. We describe three cases of probable QTT with unusual clinical features, namely splenic infarction, fulminant myopericarditis and severe leukocytoclastic vasculitis. QTT may present with uncommon clinical features in addition to the more common manifestations. A high index of suspicion enables specific antibiotic therapy that may hasten recovery.

Treatment of Rickettsia spp. infections: a review.

Human rickettsioses caused by intracellular bacteria of the genus Rickettsia are distributed worldwide and are transmitted by arthropod vectors such as ticks, fleas, mites and lice. They have a wide range of manifestations from benign to life-threatening diseases. Mortality rates of up to 30% have been reported for some rickettsioses. Here, the authors will review in vitro and human studies of the various compounds that have been used for the treatment of Rickettsia spp. infections. The authors will also provide recommendations for the treatment of spotted fever and typhus group rickettsioses.

Adipose tissue serves as a reservoir for recrudescent Rickettsia prowazekii infection in a mouse model.

Brill-Zinsser disease, the relapsing form of epidemic typhus, typically occurs in a susceptible host years or decades after the primary infection; however, the mechanisms of reactivation and the cellular reservoir during latency are poorly understood. Herein we describe a murine model for Brill-Zinsser disease, and use PCR and cell culture to show transient rickettsemia in mice treated with dexamethasone >3 months after clinical recovery from the primary infection. Treatment of similarly infected mice with cyclosporine failed to produce recrudescent bacteremia. Therapy with doxycycline for the primary infection prevented recrudescent bacteremia in most of these mice following treatment with dexamethasone. Rickettsia prowazekii (the etiologic agent of epidemic typhus) was detected by PCR, cell culture, and immunostaining methods in murine adipose tissue, but not in liver, spleen, lung, or central nervous system tissues of mice 4 months after recovery from the primary infection. The lungs of dexamethasone-treated mice showed impaired expression of beta-defensin transcripts that may be involved in the pathogenesis of pulmonary lesions. In vitro, R. prowazekii rickettsiae infected and replicated in the murine adipocyte cell line 3T3-L1. Collectively these data suggest a role for adipose tissue as a potential reservoir for dormant infections with R. prowazekii.

Typhus fever: an overlooked diagnosis.

A case of typhus fever is presented. On admission, the clinical diagnosis was typhoid fever. Forty-eight hours after admission, the presence of subconjunctival haemorrhage, malena, and jaundice raised the possibility of a different aetiology, the two most likely differentials being dengue and typhus. Finally, a co-infection of typhoid and typhus was discovered. This uncommon clinical scenario should be taken into account in the management of patients with high fever on admission being treated as a case of typhoid fever.

[Lice and lice-borne diseases in humans]. / Les poux et les maladies transmises á l'homme.

Among the three lice which parasite the human being, the human body louse, Pediculus humanus humanus, is a vector of infectious diseases. It lives and multiplies in clothes and human infestation is associated with cold weather and a lack of hygiene. Three pathogenic bacteria are transmitted by the body louse: 1) Rickettsia prowazekii, the agent of epidemic typhus of which the most recent outbreak (and the largest since World War II) was observed during the civil war in Burundi; 2) Borrelia recurrentis, the agent of relapsing fever, historically responsible of massive outbreaks in Eurasia and Africa, which prevails currently in Ethiopia and neighboring countries; 3) Bartonella quintana, the agent of trench fever, bacillary angiomatosis, chronic bacteremia, endocarditis, and lymphadenopathy. Body louse infestation, associated with a decline in social and hygienic conditions provoked by civil unrest and economic instability, is reemergent worldwide. Recently, a forth human pathogen, Acinetobacter baumannii, has been associated to the body louse.

[Effect of fosfidomycin on development of various infections in mice]. / Deistvie fosmidomitsina na razvitie nekotorykh infektsii u myshei.

Antibiotic fosmidomycin will know as inhibitor of the nonmevalonate pathway of isoprenoid biosynthesis and as possible antimalarial drug, was shown to possess a certain protective effect on mice experimentally infected with tularemia, tiphus or coli-septicemia. Positive effect on mice with chronic form of tuberculosis was not observed when the animals were given 1 mg of fosmidomycin per capita twice a day. Under oxidative conditions an ESR signal of long living nitroxil free radicals were registered in the water solution of fosmidomycin. The radicals are supposed to be involved in the therapeutic effect of the antibiotic.

[Rickettsiosis: state of the art at the turn of the 21st century]. / Rikketsiozy: sovremennoe sostoianie problemy.

Information about changes in the modern taxonomy of intracellular bacteria conditionally united within the nomination of "Rickettsioses" is presented in the paper. Due to a total hobby related with keeping home animals (pets), cats and dogs, apart from the cattle, joined the natural ecological cycles of rickettsioses stimulation. The morbidity of rickettsioses of the acaroid group has been persistently growing; like in case with other pathologies (Lyme's disease) involving the acaroid transfer factor, its obvious "urbanization" is pronounced. Absolute and relative morbidity indices in respect to rickettsioses, which are epidemiologically important for Russia, are presented. The modern knowledge database concerning the rickettsioses makes it possible to control the epidemic process for this infection category. It is noteworthy, that Prowazek's rickettsiosis of its both forms (i.e. the epidemic and relapsing ones), which does not have an independent cycle of circulation of its stimulator in wild nature, and unlike the acaroid group rickettsioses, turned into a socially controllable infection. It will be totally eliminated, during 10-15 years, both in Russia and the CIS countries. The practitioners are well supplied with a variety of drugs of tetracycline and fluorine-quinol groups, which makes it possible to arrest the infection process in patients rapidly and effectively and to prevent the lethal cases. A low incidence rate of rickettsioses, including Q fever, within the general infection morbidity, and taking into consideration the availability of methods for effective therapy and prevention, makes one consider a comprehensive vaccination against the discussed group of infections to be irrational. Obviously, such vaccination must be still applied in respect to a limited number of persons from among high-risk groups and for two or three varieties of rickettsioses only (i.e. Prowazek's rickettsioses, Rocky Mountain spotted fever and Q fever). Live vaccines, obtained on the basis of attenuated and recombined strains (which have a full-scale set of specific antigens), are recommended.

Rickettsiosis transmitidas por piojos, pulgas y ácaros

Las rickettsiosis son un conjunto de enfermedades zoonóticas producidas por bacterias pleomorfas que necesitan, para su propagación, distintas especies de mamíferos como reservorio y diversas especies de artrópodos como vector. La lesión fundamental es una vasculitis y la clínica consiste en fiebre y exantema, así como en una lesión típica debida a la picadura del insecto, además de otras manifestaciones generales e inespecíficas. El diagnóstico se basa en cultivos celulares y en pruebas serológicas, especialmente la inmunofluorescencia indirecta. El tratamiento se realiza con tetraciclinas y cloranfenicol, aunque con ciertas precauciones en niños de corta edad. La profilaxis se basa en el control de los vectores y en evitar la exposición (AU)

Rickettsial phospholipase A2 as a pathogenic mechanism in a model of cell injury by typhus and spotted fever group rickettsiae.

Phospholipase A2 activity by typhus group rickettsiae causes hemolysis in vitro. Rickettsial phospholipase A2 has been proposed to mediate entry into the host cell, escape from the phagosome, and cause injury to host cells by both typhus and spotted fever group rickettsiae. In a rickettsial contact-associated cytotoxicity model, the interaction of Rickettsia prowazekii or R. conorii with Vero cells caused temperature-dependent release of 51Cr from the cells. Treatment of rickettsiae, but not the cells, with a phospholipase A2 inhibitor (bromophenacyl bromide) or with antibody to king cobra venom inhibited cell injury. Rickettsial treatment with bromophenacyl bromide inhibited the release of free fatty acids from the host cell. Neither the inhibitor nor antivenom impaired rickettsial active transport of L-lysine. Thus, host cell injury was mediated by a rickettsial phospholipase A2-dependent mechanism.

[Epidemic typhus in tropical Africa. A reemerging disease that is severe but curable]. / Le typhus épidémique en Afrique tropicale. Une maladie ré-émergente grave mais curable.

In tropical regions of Africa, frequently subject to social and political upheavals, there is an ever-present threat of typhus epidemics, as shown by the recent typhus outbreak in Burundi in 1997. Epidemic typhus should be systematically suspected in certain epidemiological conditions: famine, war, high-density populations (refugee camps, prisons), the presence of body louse in the clothing, and in the presence of certain clinical findings: severe infectious syndrome (temperature above 38 C), severe pain and muscle weakness, with coughing and severe neurological signs. The rapid diagnosis and treatment of typhus are essential. The prognosis has improved, thanks to the specific antibiotics that are currently available, particularly doxycycline, prescribed as a single oral dose of 200 mg for adults or of 100 mg for children. However, the prognosis still depends to a large extent on the speed of diagnosis. Typhus epidemics could be effectively predicted and limited if the measures for control of the body louse recommended by the World Health Organization were applied in the areas with the most favorable epidemiological conditions.