Evidence of a Louse-Borne Outbreak Involving Typhus in Douai, 1710-1712 during the War of Spanish Succession

Background: The new field of paleomicrobiology allows past outbreaks to be identified by testing dental pulp of human remains with PCR. Methods: We identified a mass grave in Douai, France dating from the early XVIII th century. This city was besieged during the European war of Spanish succession. We tested dental pulp from 1192 teeth (including 40 from Douai) by quantitative PCR (qPCR) for R. prowazekii and B. quintana. We also used ultra-sensitive suicide PCR to detect R. prowazekii and genotyped positive samples. Results and Discussion: In the Douai remains, we identified one case of B. quintana infection (by qPCR) and R. prowazekii (by suicide PCR) in 6/21 individuals (29%). The R. prowazekii was genotype B, a genotype previously found in a Spanish isolate obtained in the first part of the XX th century. Conclusion: Louse-borne outbreaks were raging during the XVIII th century; our results support the hypothesis that typhus was imported into Europe by Spanish soldiers from America

Eschar and neck lymphadenopathy caused by Francisella tularensis after a tick bite: a case report

<p>Abstract</p> <p>Introduction</p> <p>In 25 to 35% of cases, the aetiological agent of scalp eschar and neck lymphadenopathy after a tick bite remains undetermined. To date, <it>Rickettsia slovaca</it>, <it>Rickettsia raoultii </it>and more recently <it>Bartonella henselae </it>have been associated with this syndrome.</p> <p>Case presentation</p> <p>A four-year-old Caucasian boy was admitted to hospital with fever, vomiting and abdominal pain. On physical examination, an inflammatory and suppurating eschar was seen on the scalp, with multiple enlarged cervical lymph nodes on both sides. Although no tick was found in this scalp lesion, a diagnosis of tick-borne lymphadenopathy was suggested, and explored by serology testing and polymerase chain reaction of a biopsy from the eschar. <it>Francisella tularensis </it>DNA was found in the skin biopsy and the serology showed titres consistent with tularaemia.</p> <p>Conclusion</p> <p>This is, to the best of our knowledge, the first reported case of scalp eschar and neck lymphadenopathy after tick bite infection caused by <it>F. tularensis.</it></p

Predictive factors of clinical assays on hydroxychloroquine for COVID-19 mortality during the first year of the pandemic: A meta-synthesis

Background: The COVID-19 pandemic led to a violent debate about the efficacy of a repurposed drug hydroxychloroquine (HCQ) and a new broad-spectrum antiviral (remdesivir) and about randomized controlled trials (RCTs) and observational studies. To understand conflicting results in the literature, we performed a metasynthesis to determine whether intrinsic qualitative criteria within studies may predict apparent efficacy or ineffectiveness of HCQ and remdesivir. Methodology: Predictive criteria were identified through critical review of studies assessing HCQ and remdesivir for COVID-19 mortality from March to November 2020. Multiple correspondence analysis, comparative metaanalysis, and predictive value were used to explore and identify criteria associated with study outcomes. Results: Among the 61 included studies, potential conflict of interest, detailed therapeutic protocol, toxic treatment (overdose or use in contraindicated patients), known centers and doctors, and private data computing company were the most predictive criteria of the direction of effect of the studies. All 18 observational studies evaluating HCQ and reporting detailed therapeutic protocol without conflict of interest were Pro. Potential conflict of interest was a perfect predictor for remdesivir efficacy. RCTs were associated with HCQ inefficacy and potential conflict of interest. The most predictive criteria were validated and allowed perfect classification of 10 additional studies.Conclusion: In therapeutic trials on COVID-19, the major biases predicting the conclusions are not methodology nor data analysis, but conflict of interest and absence of medical expertise. The thorough search for declared or undeclared and direct or indirect conflict of interest, and medical expertise should be included in the quality criteria for the evaluation of future therapeutic studies in COVID-19 and beyond. A new checklist evaluating not only methodology but also conflict of interest and medical expertise is proposed

Acute Tick-borne Rickettsiosis Caused by Rickettsia sibirica in the Russian Far East

An acute tick-borne rickettsiosis caused by Rickettsia heilongjiangensis was diagnosed in 13 patients from the Russian Far East in 2002. We amplified and sequenced four portions of three rickettsial genes from the patients’ skin biopsy results and blood samples and showed that the amplified rickettsial genes belong to R. heilongjiangensis, which was recently isolated from Dermacentor sylvarum ticks in nearby regions of China. This rickettsia, belonging to subgroup of R. japonica, was previously suggested to be pathogenic for humans on the basis of serologic findings. We tested serum samples with different rickettsial antigens from 11 patients and confirmed increasing titers of immunoglobulin (Ig) G and IgM to spotted fever group rickettsiae, including R. heilongjiangensis. Clinical and epidemiologic data on these patients shows that this disease is similar to other tick-borne 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 β-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

Candidatus Bartonella mayotimonensis and Endocarditis

We describe a new Bartonella species for which we propose the name Candidatus Bartonella mayotimonensis. It was isolated from native aortic valve tissue of a person with infective endocarditis. The new species was identified by using PCR amplification and sequencing of 5 genes (16S rRNA gene, ftsZ, rpoB, gltA, and internal transcribed spacer region)

Mediterranean spotted fever: clinical and laboratory characteristics of 415 Sicilian children

BACKGROUND: Mediterranean spotted fever (MSF) is an acute febrile, zoonotic disease caused by Rickettsia conorii and transmitted to humans by the brown dogtick Rhipicephalus sanguineus. Nearly four hundred cases are reported every year (mainly from June to September) on the Italian island of Sicily. The aim of the study was to analyze the clinical and laboratory characteristics of patients with MSF and the efficacy of the drugs administered. METHODS: Our study was carried out on 415 children with MSF, during the period January 1997 – December 2004, at the "G. Di Cristina" Children's hospital in Palermo, Sicily, Italy. On admission patients' clinical history, physical and laboratory examination and indirect immunofluorescence antibody test (IFAT) for Rickettsia conorii were performed. Diagnosis was considered confirmed if the patients had an MSF diagnostic score greater than or equal to 25 according to the Raoult's scoring system. All patients were treated with chloramphenicol or with macrolides (clarithromycin or azithromycin). RESULTS: Fever, rash and tache noire were present in 386 (93%), 392 (94.5%) and 263 (63.4%) cases respectively. Eighteen (4.6%) children showed atypical exanthema. Chloramphenicol and newer macrolides all appeared to be effective and safe therapies. CONCLUSION: Clinical features of 415 children with MSF were similar to those reported by other authors except for a lower incidence of headache, arthralgia and myalgia and a higher frequency of epato-splenomegaly. Concerning therapy, clarithromycin can be considered a valid alternative therapy to tetracyclines or chloramphenicol especially for children aged < eight years

Q fever endocarditis masquerading as Mixed cryoglobulinemia type II. A case report and review of the literature

BACKGROUND: The clinical manifestations of Q fever endocarditis are protean in nature. Mixed cryoglobulinemia type II is rarely a facet of the presenting clinical manifestations of Q fever endocarditis. CASE PRESENTATION: We report a case of a 65-year-old pensioner with such an association and review the literature. As transesophageal echocardiograms are usually normal and blood cultures are usually negative in Q fever endocarditis, many of the manifestations (fever, rash, glomerulonephritis/evidence of renal disease, low serum C4 complement component, presence of mixed type II cryoglobulin, constitutional symptoms as arthralgias and fatigue) can be attributed to Mixed cryoglobulinemia type II per se. The use of Classic Duke Endocarditis Service criteria does not always suffice for the diagnosis of Q fever. CONCLUSION: The application of the modified criteria proposed by Fournier et al for the improvement of the diagnosis of Q fever endocarditis will help to reach the diagnosis earlier and thus reduce the high mortality of the disease. We would like to stress the importance of ruling out the diagnosis of Q fever endocarditis in cases of mixed type II cryoglobulinemia