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Epidemic typhus is transmitted to human beings by the body louse Pediculus humanus corporis. The disease is still considered a major threat by public-health authorities, despite the efficacy of antibiotics, because poor sanitary conditions are conducive to louse proliferation. Until recently, Rickettsia prowazekii, the causal agent, was thought to be confined to human beings and their body lice. Since 1975, R prowazekii infection in human beings has been related to contact with the flying squirrel Glaucomys volans in the USA. Moreover, Brill-Zinsser disease, a relapsed form of epidemic typhus that appears as sporadic cases many years after the initial infection, is unrelated to louse infestation. Stress or a waning immune system are likely to reactivate this earlier persistent infection, which could be the source of new epidemics when conditions facilitate louse infestation. Finally, R prowazekii is a potential category B bioterrorism agent, because it is stable in dried louse faeces and can be transmitted through aerosols. An increased understanding of the pathogenesis of epidemic typhus may be useful for protection against this bacterial threat.

Background Rickettsiae are obligate intracellular bacteria responsible for many febrile syndromes around the world, including in sub-Saharan Africa. Vectors of these pathogens include ticks, lice, mites and fleas. In order to assess exposure to flea-associated Rickettsia species in Madagascar, human and small mammal samples from an urban and a rural area, and their associated fleas were tested. Results Anti-typhus group (TGR)- and anti-spotted fever group rickettsiae (SFGR)-specific IgG were detected in 24 (39%) and 21 (34%) of 62 human serum samples, respectively, using indirect ELISAs, with six individuals seropositive for both. Only two (2%) Rattus rattus out of 86 small mammals presented antibodies against TGR. Out of 117 fleas collected from small mammals, Rickettsia typhi , a TGR, was detected in 26 Xenopsylla cheopis (24%) collected from rodents of an urban area ( n  = 107), while two of these urban X. cheopis (2%) were positive for Rickettsia felis , a SFGR . R. felis DNA was also detected in eight (31%) out of 26 Pulex irritans fleas. Conclusions The general population in Madagascar are exposed to rickettsiae, and two flea-associated Rickettsia pathogens, R. typhi and R. felis , are present near or in homes. Although our results are from a single district, they demonstrate that rickettsiae should be considered as potential agents of undifferentiated fever in Madagascar.

The body louse, Pediculus humanus humanus, is a strict human parasite, living and multiplying in clothing. Louse infestation is associated with cold weather and a lack of hygiene. Three pathogenic bacteria are transmitted by the body louse. Borrelia recurrentis is a spirochete, the agent of relapsing fever, recently cultured on axenic medium. Historically, massive outbreaks have occurred in Eurasia and Africa, but currently the disease is found only in Ethiopia and neighboring countries. Bartonella quintana is now recognized as an agent of bacillary angiomatosis bacteremia, trench fever, endocarditis, and chronic lymphadenopathy among the homeless. Rickettsia prowazekii is the agent of epidemic typhus. The most recent outbreak (and the largest since World War II) was observed in Burundi. A small outbreak was also reported in Russia in 1997. Louse infestation appears to become more prevalent worldwide, associated with a decline in social and hygienic conditions provoked by civil unrest and economic instability.

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.

Typhus is an acute febrile disease caused by a series of bacteria called Rickettsia that is transmitted by insects such as lice, fleas, and ticks. This disease has appeared several times in Iran and caused many casualties. There were some therapeutic measures taken by European physicians in Tehran and medical graduates of the Dar al-Fonun school or expatriates who had studied medical courses in Western countries, even though the taken steps were not enough. Due to the lack of sanitation and cleaning products after the outbreak of World War I in March 1917 and its synchronization with the swift outbreak of Typhus in 1918, heavy casualties followed. In this study, we first examine the prevalence of Typhus in the Qajar dynasty in Iran, and will then focus on the pathological importance of this disease history in Iran. After that, we will study the role of Typhus prevalence and World War I in the Persian famine, malnutrition, and food poverty. Moreover, we investigated the role that this great war had in strengthening the spread of this disease and its role in the death of many Iranian people.

Depending on the availability of the sample volume, the ELISA positive samples were further subjected to molecular testing using a Rickettsia genus-specific 17 kDa gene semi-nested polymerase chain reaction (PCR) assay [9]. [...]there is a need for expanded epidemiological studies to confirm the presence of TGR, not only in humans but also in small mammals and their ectoparasites. [...]very low number of samples could be attempted for PCR.

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.

BackgroundMany soldiers in Napoleon’s Grand Army died of infectious diseases during its retreat from Russia. Because soldiers were commonly infested with body lice, it has been speculated that louse-borne infectious diseases, such as epidemic typhus (caused by Rickettsia prowazekii), were common MethodsWe investigated this possibility during recent excavations of a mass grave of Napoleon’s soldiers in Vilnius, Lithuania. Segments of 5 body lice, identified morphologically and by polymerase chain reaction (PCR) amplification and sequencing, were found in earth from the grave that also contained fragments of soldiers’ uniforms ResultsDNA of Bartonella quintana (the agent of trench fever) was identified by PCR and sequencing in 3 of the lice. Similarly, PCR and sequencing of dental pulp from the remains of 35 soldiers revealed DNA of B. quintana in 7 soldiers and DNA of R. prowazekii in 3 other soldiers ConclusionsOur results show that louse-borne infectious diseases affected nearly one-third of Napoleon’s soldiers buried in Vilnius and indicate that these diseases might have been a major factor in the French retreat from Russia

Louse borne typhus (also called epidemic typhus) was one of man's major scourges, and epidemics of the disease can be reignited when social, economic, or political systems are disrupted. The fear of a bioterrorist attack using the etiologic agent of typhus, Rickettsia prowazekii, was a reality. An attenuated typhus vaccine, R. prowazekii Madrid E strain, was observed to revert to virulence as demonstrated by isolation of the virulent revertant Evir strain from animals which were inoculated with Madrid E strain. The mechanism of the mutation in R. prowazekii that affects the virulence of the vaccine was not known. We sequenced the genome of the virulent revertant Evir strain and compared its genome sequence with the genome sequences of its parental strain, Madrid E. We found that only a single nucleotide in the entire genome was different between the vaccine strain Madrid E and its virulent revertant strain Evir. The mutation is a single nucleotide insertion in the methyltransferase gene (also known as PR028) in the vaccine strain that inactivated the gene. We also confirmed that the vaccine strain E did not cause fever in guinea pigs and the virulent revertant strain Evir caused fever in guinea pigs. We concluded that a single nucleotide insertion in the methyltransferase gene of R. prowazekii attenuated the R. prowazekii vaccine strain E. This suggested that an irreversible insertion or deletion mutation in the methyl transferase gene of R. prowazekii is required for Madrid E to be considered a safe vaccine.

Whether increases in typhus group rickettsiosis in Galveston County, Texas, USA, are caused by increased recognition or true reemergence is unclear. We conducted a serosurvey that demonstrated Rickettsia typhi antibodies increased from 1.2% in 2013 to 7.8% in 2021 (p<0.001). These findings support pathogen reemergence rather than enhanced recognition alone.