Treatment of persistent focalized Q fever: time has come for an international randomized controlled trial.

Q fever is a worldwide zoonosis due to Coxiella burnetii, responsible for endocarditis and endovascular infections. Since the 1990s, the combination hydroxychloroquine + doxycycline has constituted the curative and prophylactic treatment in persistent focalized Q fever. This combination appears to have significantly reduced the treatment's duration (from 60 to 26 months), yet substantial evidence of effectiveness remains lacking. Data are mostly based on in vitro and observational studies. We conducted a literature review to assess the effectiveness of this therapy, along with potential alternatives. The proposed in vitro mechanism of action describes the inhibition of Coxiella replication by doxycycline through the restoration of its bactericidal activity (inhibited in acidic environment) by alkalinization of phagolysosome-like vacuoles with hydroxychloroquine. So far, the rarity and heterogeneous presentation of cases have made it challenging to design prospective studies with statistical power. The main studies supporting this treatment are retrospective cohorts, dating back to the 1990s-2000s. Retrospective studies from the large Dutch outbreak of Q fever (>4000 cases between 2007 and 2010) did not corroborate a clear benefit of this combination, notably in comparison with other regimens. Thus, there is still no consensus among the medical community on this issue. However insufficient the evidence, today the doxycycline + hydroxychloroquine combination remains the regimen with the largest clinical experience in the treatment of 'chronic' Q fever. Reinforcing the guidelines' level of evidence is critical. We herein propose the creation of an extensive international registry, followed by a prospective cohort or ideally a randomized controlled trial.

Erythema Migrans Caused by Borrelia spielmanii, France.

We describe a rare case of early Lyme borreliosis in France caused by Borrelia spielmanii, which manifested as a large erythema chronicum migrans rash. The patient completely recovered after a 15-day course of amoxicillin. Absence of pathognomonic signs prevented distinguishing B. spielmanii from other etiologies as cause in this case-patient.

Clinical patterns of somatic symptoms in patients suffering from post-acute long COVID: a systematic review.

BACKGROUND: Long COVID-19 may affect patients after hospital discharge. AIMS: This study aims to describe the burden of the long-term persistence of clinical symptoms in COVID-19 patients. METHODS: We conducted a systematic review by using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guideline. The PubMed and Google Scholar databases were searched for studies that included information on the prevalence of somatic clinical symptoms lasting at least 4 weeks after the onset of a PCR- or serology-confirmed diagnosis of COVID-19. The prevalence of persisting clinical symptoms was assessed and risk factors were described when investigated. Psychological symptoms and cognitive disorders were not evaluated in this study. RESULTS: Thirty-seven articles met the inclusion criteria. Eighteen studies involved in-patients only with a duration of follow-up of either less than 12 weeks, 12 weeks to 6 months, or more. In these studies, fatigue (16-64%), dyspnea (15-61%), cough (2-59%), arthralgia (8-55%), and thoracic pain (5-62%) were the most frequent persisting symptoms. In nineteen studies conducted in a majority of out-patients, the persistence of these symptoms was lower and 3% to 74% of patients reported prolonged smell and taste disorders. The main risk factors for persisting symptoms were being female, older, having comorbidities and severity at the acute phase of the disease. CONCLUSION: COVID-19 patients should have access to dedicated multidisciplinary healthcare allowing a holistic approach. Effective outpatient care for patients with long-COVID-19 requires coordination across multiple sub-specialties, which can be proposed in specialized post-COVID units.

When the patient is making the (wrong?) diagnosis: a biographical approach to patients consulting for presumed Lyme disease.

BACKGROUND: Media coverage of Lyme disease (LD) has led to an increase in consultations for presumed LD in Europe. However, LD is confirmed in only 10%-20% of patients, with a significant number remaining in a diagnostic dead-end. OBJECTIVES: To reach a deeper understanding of how patients themselves contribute to the diagnostic process. To describe the genesis of the LD hypothesis in care pathways. METHODS: In 2019, 30 patients from a prospective cohort consulting in the infectious diseases department at University Hospital in Marseille for presumed LD were recruited for semistructured interviews. The inclusion criteria were: suffering from subjective symptoms for 6 months, no clinical or paraclinical argument suggesting current LD. The patients' medical trajectories were collected using a biographical approach. RESULTS: The diagnosis of LD was primarily triggered by identification with personal testimonies found on the Internet. Most of patients were leading their own diagnostic investigation. The majority of participants were convinced they had LD despite the lack of medical evidence and the scepticism of their referring GP. CONCLUSION: GPs should first systematically explore patients' aetiologic representations in order to improve adherence to the diagnosis especially in the management of medically unexplained symptoms. Long COVID-19 syndrome challenge offers an opportunity to promote active patient involvement in diagnosis.

Polymicrobial Infections Among Patients with Vascular Q Fever, France, 2004-2020.

We report 5 cases of vascular Q fever complicated by polymicrobial superinfection in patients who had no risk factors for acute Q fever. Q fever was diagnosed by serologic and molecular assays for Coxiella burnetii. We confirmed additional infections using conventional graft cultures.

Routine Culture-Resistant Mycobacterium tuberculosis Rescue and Shell-Vial Assay, France.

We used shell-vial assay with a medium that buffered rifampin to isolate routine culture-resistant Mycobacterium tuberculosis bacteria from cerebrospinal fluid and rifampin-containing intervertebral disc and vertebral corpus of a patient in treatment for Pott's disease and disseminated tuberculosis. Whole-genome sequencing confirmed M. tuberculosis lineage 4 (Euro-American) strain.

Increased risk of chikungunya infection in travellers to Thailand during ongoing outbreak in tourist areas: cases imported to Europe and the Middle East, early 2019.

We report nine travellers with confirmed chikungunya virus infection, returning from tourist areas of Thailand to Sweden, Switzerland, the United Kingdom, Romania, Israel and France, diagnosed in January and February 2019. These sentinel tourists support the intensification of chikungunya virus circulation in Thailand and highlight the potential for importation to areas at risk of local transmission.

From Q Fever to Coxiella burnetii Infection: a Paradigm Change.

Coxiella burnetii is the agent of Q fever, or "query fever," a zoonosis first described in Australia in 1937. Since this first description, knowledge about this pathogen and its associated infections has increased dramatically. We review here all the progress made over the last 20 years on this topic. C. burnetii is classically a strict intracellular, Gram-negative bacterium. However, a major step in the characterization of this pathogen was achieved by the establishment of its axenic culture. C. burnetii infects a wide range of animals, from arthropods to humans. The genetic determinants of virulence are now better known, thanks to the achievement of determining the genome sequences of several strains of this species and comparative genomic analyses. Q fever can be found worldwide, but the epidemiological features of this disease vary according to the geographic area considered, including situations where it is endemic or hyperendemic, and the occurrence of large epidemic outbreaks. In recent years, a major breakthrough in the understanding of the natural history of human infection with C. burnetii was the breaking of the old dichotomy between "acute" and "chronic" Q fever. The clinical presentation of C. burnetii infection depends on both the virulence of the infecting C. burnetii strain and specific risks factors in the infected patient. Moreover, no persistent infection can exist without a focus of infection. This paradigm change should allow better diagnosis and management of primary infection and long-term complications in patients with C. burnetii infection.

Early Fecal Microbiota Transplantation Improves Survival in Severe Clostridium difficile Infections.

Background: Severe Clostridium difficile infections (CDIs) are associated with a high mortality rate despite medical and/or surgical treatment. Fecal microbiota transplantation (FMT) prevents recurrences, but its effect on survival has been shown only in patients with O27 ribotype CDI. Here, we investigated whether early FMT could improve survival in hospitalized CDI patients, particularly those with severe infection. Methods: We performed a retrospective cohort study between May 2013 and April 2016 at the infectious diseases department of the North University Hospital of Marseille, France. Patients received either medical treatment alone or treatment with early FMT. The primary outcome was the 3-month mortality rate. Results: A total of 111 patients were included: 66 in the FMT group and 45 in the non-FMT group. No patient underwent surgery. The O27 ribotype (odds ratio [OR], 3.64 [95% confidence interval {CI}, 1.05- 12.6], P = .04), severe CDI (OR, 9.62 [95% CI, 2.16-42.8], P = .003), and FMT (OR, 0.13 [95% CI, .04-.44], P = .001) were independent predictors of 3-month mortality. FMT improved survival in severe cases (OR, 0.08 [95% CI, .016-.34], P = .001) but not in nonsevere cases (OR, 1.07 [95% CI, .02-56.3], P = .97), independent of age, sex, comorbidities (Charlson score), and ribotype. The number of severe patients who needed to be treated to save 1 life at 3 months was 2. Conclusions: Early FMT dramatically reduces mortality and should be proposed as a first-line treatment for severe CDI. Further studies are needed to clarify complications and contraindications. Surgery should be reassessed in this context.

Identification of dengue type 2 virus in febrile travellers returning from Burkina Faso to France, related to an ongoing outbreak, October to November 2016.

Dengue fever is rarely reported in travellers returning from Africa. We report two cases of dengue fever in travellers returning from Burkina Faso to France. One of them presented a severe dengue fever with ALT > 1,000 IU/L and pericarditis. Serotype 2 was identified. The cases reflect a large ongoing outbreak with over 1,000 reported cases between August and November in the capital city. Clinicians should consider dengue fever in malaria-negative febrile travellers returning from Africa.

[Management of febrile illness in the traveler returning from the tropics]. / Conduite à tenir devant une fièvre au retour de voyage en zone tropicale.

Fever in the traveler returning from the tropics is a common clinical situation in primary care or emergency. The first priority of clinicians should be to eliminate severe infectious diseases whose treatment is urgent, the first of which is still malaria due to P. falciparum. In a second step, after the emergency diagnosis eliminated, geographic updated epidemiological context must be taken into account to consider some other diagnosis. Finally, risk factors and patient's clinical characteristics should be analyzed. The diagnostic approach that we propose should enable any clinician to perform the first steps of the management of fever in the traveler returning from the tropics.

Is there Lyme borreliosis in French Guiana? Descriptive study among patients referred for a suspected Lyme borreliosis in an Amazonian hospital between 2010 and 2022.

Lyme borreliosis (LB) existence in South America is debated, especially in the Amazon region. The infection with Lyme borreliae has never been reported in French Guiana where Borrelia burgdorferi sensu lato is not found in ticks. We describe the final diagnosis and presumed place of acquisition in patients consulting for suspicion of LB. We retrospectively collected data from all consecutive patients consulting for a suspicion of LB between 2010 and 2021 at Cayenne Hospital, French Guiana. Patients were classified by an adjudication committee as confirmed LB if they met the criteria of the French consensus, as possible LB if they had compatible symptoms and a good outcome after appropriate treatment, or excluded when a differential diagnosis was found. The place of acquisition was discussed in case of possible or confirmed case. Twenty-six patients were included. Rheumatologic symptoms were the most reported (88 %) followed by neurological symptoms (61 %). Twenty-four (92 %) of these patients were born out of French Guiana. Diagnosis of LB was considered as confirmed in 2 patients (8 %), for whom the place of acquisition was likely mainland France, and as possible in 3 patients (11 %) with early localized LB presumably acquired in French Guiana. Functional somatic disorders were diagnosed in 13 (50 %) patients whereas 9 (35 %) were found with another disease. This study did not confirm the acquisition of LB in French Guiana. However, three possible autochthonous cases encourage clinicians working in the Amazon area to stay aware of LB.

Enhancing sexual health and empowerment among migrant women sex workers: a community health worker-led intervention in Marseille, France.

Introduction: Given the high infection rate of sexually transmitted infections (STI) among migrant women sex workers (WSWs), it is necessary to understand how to improve prevention, information and care for this vulnerable population. Community health workers (CHWs), by linking community to health services, are positioned to improve health outcomes in migrant communities. This article aims to describe a pilot innovative intervention performed by CHWs to improve sexual health in migrant WSWs. Methods: This one-year intervention study used a respondent-driven sampling (RDS) to recruit a representative cohort of migrant WSWs in Marseille, France. Four CHWs were recruited from different communities and participated in all stages of the research. They performed individual and group interventions of prevention, support in care and empowerment. Data on participant characteristics, type of intervention and adherence to the intervention were reported via questionnaires given to participants. Simultaneously, semi-structured interviews and informal interviews of migrant WSW, CHWs and care providers were carried out. Results: A total of 132 migrant WSWs were included in the cohort. Very few of them knew about PrEP (12%) or already used HIV post-exposure treatment (9%). Migrant WSWs were often victims of rape or racism, 15 and 21%, respectively. In two-thirds of cases the level of health literacy was low. Participants suffered from a combination of vulnerability factors: difficulties with access to social rights, food or housing. Only 13% reported having benefited from medical follow-up or assistance by an NGO in the 3 months prior to the program. By 3 months, more than one third of the participants had been tested for HIV (35%) and 63% knew about PrEP. A total retention rate of 70% was reported in the cohort after 6 months. Conclusion: CHWs enabled to improve care access for migrant WSWs by improving the collaboration between care and social actors at a local level. Through these "bring-back-to" interventions for this hard-to-reach population, CHWs enabled an optimization of the care pathway. Our results also highlight the importance of a population-based approach for individual and group support of empowerment interventions in order to strengthen their capacity for action.

Yellow fever vaccine-associated neurologic and viscerotropic disease: a 10-year case series of the French National Reference Center for Arboviruses with clinical and immunological insights.

BACKGROUND: Immunization against the Yellow fever virus (YFV) with the 17D live-attenuated vaccine is the most effective way to prevent the disease. However, unexpected severe adverse events can occur. They consist in a neurological impairment - neurological disease (YEL-AND), a YF-like illness - viscerotropic disease (YEL-AVD) or anaphylaxis. In this article, we describe the epidemiology, clinical and biological features of YEL-AND and YEL-AVD cases reported to the French National Reference Center for Arboviruses (NRCA) in the past 10 years. METHODS: We conducted a national, retrospective study using the database of the NRCA from June 2012 to June 2022. All patients whose biological samples were sent to the NRCA for detection of YFV by serology and/or RT-qPCR for a suspected vaccine-associated adverse event were included. We collected data by reading medical records and conducted complementary neuro-immunological analysis, followed by a search for autoimmunity against type-1-interferon when samples were available at the NRCA. RESULTS: There were 10 cases of YEL-AND and 2 cases of YEL-AVD reported to the NRCA in the past 10 years, which represented an overall incidence of 0.6 for 100 000 doses. A total of 6/12 cases were previously healthy patients (50%, mean age 31 years), and 4/12 cases had cardiovascular co-morbidities (42%, mean age 56 years). The majority of YEL-AND had a favourable outcome at 6 months of follow up. One YEL-AVD patient passed. In secondary analyses, we evidenced a significant blood cerebrospinal fluid (CSF) barrier dysfunction, without intrathecal synthesis of immunoglobulin and without argument for a neuron damage. We further detected a significant rate of anti-type-1alpha interferon antibodies in 3/10 tested patients (2 YEL-AND and 1 YEL-AVD). CONCLUSION: YEL-AND and YEL-AVD are rare events that can underlie defect in the innate immunity of apparently healthy or mild co-morbid subjects. Outcome was generally favourable in the YEL-AND cases of our series, but still life-threatening or even fatal in the YEL-AVD cases.

Cell extract-containing medium for culture of intracellular fastidious bacteria.

The culture of fastidious microorganisms is a critical step in infectious disease studies. As a proof-of-concept experiment, we evaluated an empirical medium containing eukaryotic cell extracts for its ability to support the growth of Coxiella burnetii. Here, we demonstrate the exponential growth of several bacterial strains, including the C. burnetii Nine Mile phase I and phase II strains, and C. burnetii isolates from humans and animals. Low-oxygen-tension conditions and the presence of small hydrophilic molecules and short peptides were critical for facilitating growth. Moreover, bacterial antigenicity was conserved, revealing the potential for this culture medium to be used in diagnostic tests and in the elaboration of vaccines against C. burnetii. We were also able to grow the majority of previously tested intracellular and fastidious bacterial species, including Tropheryma whipplei, Mycobacterium bovis, Leptospira spp., Borrelia spp., and most putative bioterrorism agents. However, we were unable to culture Rickettsia africae and Legionella spp. in this medium. The versatility of this medium should encourage its use as a replacement for the cell-based culture systems currently used for growing several facultative and putative intracellular bacterial species.

Clinical and Epidemiological Aspects of Acute Q Fever in Reunion Island over Fourteen Years: A Retrospective Cohort Study.

The clinical characteristics and epidemiology of Q fever in the Tropics are poorly described. We performed a retrospective cohort study of hospitalized cases between 2004 and 2017 in Reunion Island. Acute Q fever was defined in presence of a positive serology (phase II IgG ≥ 200 and phase II IgM ≥ 50), or a seroconversion (4-fold increase in phase II IgG between paired samples), or a positive PCR (blood or serum). Forty-two cases matched the diagnostic criteria. The most common clinical manifestations were fever (85.7%) and pulmonary symptoms (61.9%), including pneumonia (45.2%). Ninety percent of the patients were living in a farming area. Cumulative incidence was estimated at 9.3 per 100,000 inhabitants (95%CI: 6.4-12.1) with cases diagnosed yearly all throughout the study period except in 2006. Together with the seroprevalence figures, these data suggest that Q fever reaches low to moderate endemic levels on Reunion Island. As previously reported, pulmonary symptoms are in the foreground.

Effectiveness of a Community Empowerment Intervention to Improve Access to Pre-exposure Prophylaxis in Migrant Women Sex Workers: Protocol for a Mixed Methods Implementation Study.

BACKGROUND: The World Health Organization recommends pre-exposure prophylaxis (PrEP) for all populations at substantial risk of HIV infection. However, at-risk women very rarely use PrEP in France-this represents a critical issue among migrant women sex workers (MWSWs). Previous studies on PrEP use among women sex workers or migrants focused on individual or social determinants of motivation. However, operational studies in real-word settings using a holistic population approach to maximize PrEP adherence among MWSWs are lacking. OBJECTIVE: FASSETS (ie, "Favoriser l'Accès à la Santé Sexuelle des Travailleuses du Sexe"; English: "facilitate the access to Sexual Health in women sex workers") is a participative, multilevel, mixed methods study aiming to improve global knowledge of and access to sexual health care and PrEP among MWSWs through targeted empowerment strategies. METHODS: This study comprises several phases: (1) phase 1: an initial qualitative study combining semistructured interviews, informal interviews, and participative observations will be performed among MWSWs, local community nongovernmental organizations, and institutions providing sexual reproductive health services to identify the determinants of PrEP access among MWSWs and for respondent-driven sampling (RDS); (2) phase 2: the size of the hidden MWSW population is estimated in Marseille through capture-recapture (the RDS survey will serve as "recapture"); (3) phase 3: a longitudinal cohort will be formed through RDS to represent the MWSW population with a goal of 150 inclusions-this cohort will be followed up for 12 months, and sequential questionnaires exploring medical history; knowledge of sexual health, HIV, and sexually transmitted infections; migration route; and current living conditions will be administered at inclusion (month 0) and months 3, 6, and 12 to measure the following interventional phase's outcomes; and (4) phase 4: an interventional study with community empowerment actions about sexual health and PrEP will be conducted with community health workers; standardized questionnaires and semistructured interviews, observations, and focus groups will highlight MWSWs' experiences with empowerment resources, concerns about sexual health, and especially PrEP use or uptake, and we will evaluate whether and how community-adapted empowerment actions conducted by community health workers are effective in increasing access to sexual health, prevention and screening of sexually transmitted infections, and PrEP knowledge and access among MWSWs. RESULTS: Recruitment commenced on March 1, 2022. We estimate the follow-up period to end on September 30, 2023. CONCLUSIONS: This multiphase study will provide robust evidence about the magnitude of the MWSW population in Marseille (the second largest town in France) and their current conditions of living, access to and knowledge of sexual health, and PrEP access. Using a mixed methods analysis, we will investigate whether individual and collective community health empowerment approaches can facilitate access to PrEP and its initiation, use, and adherence in this vulnerable population. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/42844.

Scedosporium apiospermum catheter-related soft-tissue infection: a case report and review of the literature.

We report a case of catheter-related Scedosporium apiospermum soft-tissue infection. This ubiquitous filamentous fungus can cause human infection after traumatic subcutaneous implantation of its conidia or their inhalation in near-drowning cases. It has also been reported as an etiological agent in a growing number of hospital-acquired infections.