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Objective: Murine typhus has been increasingly reported on Reunion island, Indian ocean, following documentation of eight autochthonous infections in 2012-2013. We conducted a serosurvey to assess the magnitude of the seroprevalence of rickettsioses in the population. Two hundred and forty-one stored frozen sera taken from the 2009 Copanflu-RUN cohort were analysed using an immunofluorescence assay allowing to distinguish typhus group (TGR) and spotted fever group Rickesttsiae (SFGR). Seropositivity was defined for a dilution titre of Rickettsia IgG antibodies ≥ 1:64. Seroprevalence was weighted to account for the discrepancy between the Copanflu-RUN subset and the general population, as to infer prevalence at community level. Prevalence proportion ratios (PPR) were measured using log-binomial models., Results: The weighted seroprevalences of typhus group rickettsioses and spotted fever group rickettsioses were of 12.71% (95% CI 8.84-16.58%) and 17.68% (95% CI 13.25-22.11%), respectively. Pooled together, data suggested that a fifth of the population had been exposed at least to one Rickettsia group. Youths (< 20 years) were less likely seropositive than adults (adjusted PPR 0.13, 95% CI 0.01-0.91). People living in the western dryer part of the island were more exposed (adjusted PPR 2.53, 95% CI 1.07-5.97). Rickettsioses are endemic on Reunion island and circulated before their first identification as murine typhus in year 2011. Surprisingly, since isolation of Rickettsia africae from Amblyomma variegatum in year 2004 or isolation of Rickettsia felis from Amblyomma loculosum, no autochthonous cases of African tick-bite fever or flea-borne spotted fever has yet been diagnosed.

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.

AbstractRickettsial infections are recognized as important causes of fever throughout southeast Asia. Herein, we determined the seroprevalence to rickettsioses within rural and urban populations of northern Vietnam. Prevalence of individuals with evidence of prior rickettsial infections (IgG positive) was surprisingly low, with 9.14% (83/908) testing positive to the three major rickettsial serogroups thought to circulate in the region. Prevalence of typhus group rickettsiae (TG)-specific antibodies (6.5%, 58/908) was significantly greater than scrub typhus group orientiae (STG)- or spotted fever group rickettsiae (SFG)-specific antibodies ( P < 0.05). The majority of TG seropositives were observed among urban rather than rural residents ( P < 0.05). In contrast, overall antibody prevalence to STG and SFG were both very low (1.1%, 10/908 for STG; 1.7%, 15/908 for SFG), with no significant differences between rural and urban residents. These results provide data on baseline population characteristics that may help inform development of Rickettsia serological testing criteria in future clinical studies.

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.

Tick typhus causes hemorrhagic lesions over the skin. Retina also shows hemorrhages and exudates. Many cases have been reported in western literature about this condition. To our best of knowledge, this is the first case report of tick typhus in India which was also associated with inflammatory choroidal neovascularization., Competing Interests: There are no conflicts of interest.

In August 2012, laboratory tests confirmed a mixed outbreak of epidemic typhus fever and trench fever in a male youth rehabilitation center in western Rwanda. Seventy-six suspected cases and 118 controls were enrolled into an unmatched case-control study to identify risk factors for symptomatic illness during the outbreak. A suspected case was fever or history of fever, from April 2012, in a resident of the rehabilitation center. In total, 199 suspected cases from a population of 1,910 male youth (attack rate = 10.4%) with seven deaths (case fatality rate = 3.5%) were reported. After multivariate analysis, history of seeing lice in clothing (adjusted odds ratio [aOR] = 2.6, 95% confidence interval [CI] = 1.1-5.8), delayed (≥ 2 days) washing of clothing (aOR = 4.0, 95% CI = 1.6-9.6), and delayed (≥ 1 month) washing of beddings (aOR = 4.6, 95% CI = 2.0-11) were associated with illness, whereas having stayed in the rehabilitation camp for ≥ 6 months was protective (aOR = 0.20, 95% CI = 0.10-0.40). Stronger surveillance and improvements in hygiene could prevent future outbreaks., (© The American Society of Tropical Medicine and Hygiene.)

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., (© 2013 The Authors; Internal Medicine Journal © 2013 Royal Australasian College of Physicians.)

This article is an update and literature review of the clinical and neuroimaging findings of the commonly known rickettsial, spirochetal, and eukaryotic parasitic infections. Being familiar with clinical presentation and imaging findings of these infections is crucial for early diagnosis and treatment especially in patients who live in or have a travel history to endemic regions or are immunocompromised., (Copyright © 2012 Elsevier Inc. All rights reserved.)

In 1825 Dr. Thomas Miner wrote about an epidemic that occurred in Middletown, Connecticut in 1823. He called this disease "Typhus syncopalis," sinking typhus, or New England spotted fever. Differences in the understanding of disease processes in the early 19th century preclude a definitive modern equivalent fortyphus syncopalis. In addition, there are disagreements among Dr. Miners' contemporaries with regard to fever classification systems. Examination of the symptoms and physical findings as described by Dr. Miner suggest the presence of encephalitis or meningitis as well as a syndrome resembling a shock-like state. Based on symptom comparisons, this paper suggests that typhus syncopalis was likely meningococcemia caused by Neisseria meningiditis.

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.

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.

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.

This selection reviews several topics in the news: - in internal medicine, the cardiovascular and pulmonary risk factors in progressive systemic sclerosis (circulating lupus anticoagulant, smoking, NT-pro BNP marker); the relations between lupus erythematous and polymorphic light eruption, or Jessner-Kanof syndrome; the diagnostic score of autoinflammatory syndromes; and the dysmetabolism syndrome of psoriasis; - in infectious diseases, the return of epidemic typhus; the emergence of TIBOLA rickettsiosis; the development of methicillin-resistant Staphylococcus aureus strains in both the nosocomial and community settings; and finally news on herpes group viral infections.

Recently in the field of rickettsiology, an explosion of new isolates of pathogens have received species designation and new disease names, all of which have been relatively neglected by primary care and infectious disease physicians. A broad group of other tick-associated rickettsial and ehrlichial agents of unknown pathogenicity exist (eg, R amblyommii) that may cause confusion in interpreting serologic surveys or a single elevated antibody titer. Rickettsial and ehrlichial diseases are remarkable for their uniform susceptibility to doxycycline but are clinically difficult to distinguish from many viral infections and each another, and therefore misdiagnosis and failure to treat have unfortunate and sometimes tragic outcomes. Globally, many of these bacteria have been named but the genetic differences among them are often small, and many of their clinical manifestations may not be distinguishable diagnostically.

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.

Enteric fever, typhus, leptospirosis, dengue, melioidosis, and tuberculous meningitis present urgent diagnostic problems that require experience and clinical judgment to make early evidence-based management decisions. Basic and applied research dealing with reliable antigen-based diagnostics has been published and confirmed for several of these infections. This should have initiated commercial production but has not. Established international firms see little profit in such diagnostic kits since they would be used in poor countries with little prospects for return of investment capital. We attempt to illustrate this issue, using common causes of acute febrile illnesses in the Southeast Asian region. We believe that rapid diagnostic technology could prevent significant delay in starting appropriate therapy, reduce hospital expenses, and even save lives.

Objective: To develop a quantitative real-time polymerase chain reaction (PCR) for detecting Rickettsia prowazekii., Methods: Primers and TaqMan-MGB probes designed based on ompB gene of R. prowazekii, were used to develop this method., Results: For the quantitative real-time PCR, the relationship between the values of threshold cycle (Ct) and the DNA copy number was linear (r = 0.999) and the sensitivity was about 100 times higher than that of the nested PCR for detecting the same DNA sample. The results of the genomic DNA samples of other rickettsial and bacterial agents detected by real-time PCR were all negative. DNAs extracted from blood samples of guinea pig infected with R. prowazekii were examined by real-time PCR and the positive results were obtained from some of these samples. However, the results of some samples in nested PCR assay were all negative., Conclusion: These results suggested that the real-time PCR was highly specific and sensitive for detection of R. prowazekii that was useful for the detection of tiny DNA of R. prowazekii in blood samples from patients suspected of having epidemic typhus.

The presence of R. prowazekii in lice using R. prowazekii-specific qPCR cassettes showed the changes of the rickettsial burden in the lice post-infection.

Certain arthropod-borne infections are common in tropical regions because of favorable climatic conditions. Water-borne infections like leptospirosis are common due to contamination of water especially during the monsoon floods. Infections like malaria, leptospirosis, dengue fever and typhus sometimes cause life threatening organ dysfunction and have several overlapping features. Most patients present with classicial clinical syndromes: fever and thrombocytopenia are common in dengue, malaria and leptospirosis; coagulopathy is frequent in leptospirosis and viral hepatitis. Hepatorenal syndrome is seen in leptospirosis, falciparum malaria and scrub typhus. The pulmonary renal syndrome is caused by falciparium malaria, leptospirosis, Hantavirus infection and scrub typhus. Fever with altered mental status is produced by bacterial meningitis, Japanese B encephalitis, cerebral malarial, typhoid encephalopathy and fulminant hepatic failure due to viral hepatitis. Subtle differences in features of the organ failure exist among these infections. The diagnosis in some of these diseases is made by demonstration of antibodies in serum, and these may be negative in the first week of the illness. Hence empiric therapy for more than one disorder may be justified in a small proportion of cases. In addition to specific anti-infective therapy, management of organ dysfunction includes use of mechanical ventilation, vasopressor drugs, continuous renal replacement therapy and blood products. Timely transfer of these patients to well-equipped ICUs with experience in managing these cases can considerably decrease mortality and morbidity.

The state of Nuevo Leon, Mexico has had outbreaks of typhus group rickettsiosis, most recently recognized in 1997. Evaluation of the sera of 345 patients with a dengue-like illness revealed that 25.5% had antibodies reactive with typhus group rickettsiae and 16% had antibodies to Rickettsia parkeri. Rickettsiae were detected by PCR and shell-vial isolations in the field-collected Amblyomma ticks. Molecular characterization by DNA sequence analysis of the gltA, ompB, and 17-kDa gene identified the organisms to be R. prowazekii.

Trench fever, a louse-borne disease caused by Bartonella quintana, is reemerging in homeless persons. Epidemic typhus is another life-threatening louse-borne disease caused by Rickettsia prowazekii and known to occur in conditions of war, famine, refugee camps, cold weather, poverty, or lapses in public health. We report the first case of seroconversion to R. prowazekii in a homeless person of Marseilles, France. This was associated with B. quintana bacteremia. Although no outbreaks of typhus have been notified yet in the homeless population, this disease is likely to reemerge in such situation.

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.

We report a case of epidemic typhus in a patient from the Batna region of Algeria, who presented with generalized febrile exanthema. The clinical diagnosis was confirmed by serological cross-adsorption followed by Western blotting. Our report emphasizes the threat of epidemic typhus in the highlands of Algeria.

Diagnosis of Rickettsia prowazekii forms at the final stage of its elimination. 30 cases of petechial typhus occurred in Russian Federation during the period from 1973 to 1996 were subjected to retrospective analysis. On the base of this analysis the false registration of disease "epidemic" form was revealed. Indeed it appeared to be the recurrences, i.e. the Brill's disease. The authors propose to use the table of differential diagnostic signs of both forms of Rickettsia prowazekii based on their clinical-and-epidemiological special features. It will help to avoid the false reports.

Early in the history of medicine, physician had a difficult time differentiating acute febrile illnesses without localizing signs. Typhoid fever and malaria share common features, which caused diagnostic problems during the 1800s. Physician even introduced a new term, typho-malaria, a testimony to their diagnostic confusion. Osler, consummate clinician and careful observer, had vast experience with typhoid fever and malaria. He was able to easily discern between the key features of both of these infections. He also relied on fever patterns to clearly differentiate typhoid fever from malaria. Osler is credited for debunking the term typho-malaria. His clinical description of typhoid fever remains unsurpassed. Clinicians still can benefit greatly from reading Osler's clinical description of typhoid fever.

The article presents epidemiological, clinical, laboratory and therapeutic characteristics of Brill-Zinsser disease (BZD). A total of 25 cases of BZD were retrospectively analyzed during the period from January 1, 1980 through December 31, 2000, and etiology was confirmed by rickettsial complement-fixation test (CFT). The majority of cases 15 (60%) quoted history of primary attack of epidemic typhus during or after the World War II. During the course of the disease in our patients different organic systems were involved. Aseptic meningitis was verified in 21 (84%) patients, rash in 17 (68%), liver lesion in 14 (56%), pneumonitis in 7 (28%), myopericarditis in 7 (28%) and 5 (20%) had renal lesion. Not a single clinical symptom or finding of disease has a diagnostic particularity. However, long term fever, headache, rash and aseptic meningitis, or information of infestation with lice in childhood, or a history of epidemic typhus should arouse a suspicion of this disease, which still occurs in Croatia.

The technology of preparing of a new ready for use diagnosticum for IHAT on the basis of polysaccharide of Rickettsia prowazekii cultivated by the Weight method has been developed. Technological conditions have been worked out, experimental series of the diagnosticum have been made and tested, high stability during the storage was confirmed which allows it to be recommended for the epidemic typhus laboratory diagnostics.

A patient residing in New Mexico had murine typhus diagnosed. A novel molecular assay was performed at the Centers for Disease Control and Prevention, and Rickettsia prowazekii, the agent of epidemic typhus, was found, rather than R. typhi. To our knowledge, this is the first reported case of epidemic typhus confirmed by means of polymerase chain reaction--based testing of cerebrospinal fluid, and it introduces a novel assay for the molecular diagnosis of both epidemic and murine typhus.

People in 5 Orang Ulu villages in Sarawak, Malaysia were tested for rickettsial infection by Weil-Felix reaction and by indirect immunoperoxidase reaction. Of those surveyed 9.6% were positive for typhus. Of the positives, 3.8% were positive for tick typhus (7/11), scrub typhus (4/11) or endemic typhus (1/11). The incidence of typhus was higher among semi-nomadic Penans compared with the settled Kayans.

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.