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.

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.

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.

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 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.

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.

Q Fever as a Cause of Community-Acquired Pneumonia in French Guiana.

In French Guiana, community-acquired pneumonia (CAP) represents over 90% of Coxiella burnetii acute infections. Between 2004 and 2007, we reported that C. burnetii was responsible for 24.4% of the 131 CAP hospitalized in Cayenne. The main objective of the present study was to determine whether the prevalence of Q fever pneumonia remained at such high levels. The secondary objectives were to identify new clinical characteristics and risk factors for C. burnetii pneumonia. A retrospective case-control study was conducted on patients admitted in Cayenne Hospital, between 2009 and 2012. All patients with CAP were included. The diagnosis of acute Q fever relied on titers of phase II IgG ≥ 200 and/or IgM ≥ 50 or seroconversion between two serum samples. Patients with Q fever were compared with patients with non-C. burnetii CAP in bivariate and multivariate analyses. During the 5-year study, 275 patients with CAP were included. The etiology of CAP was identified in 54% of the patients. C. burnetii represented 38.5% (106/275; 95% CI: 31.2-45.9%). In multivariate analysis, living in Cayenne area, being aged 30-60 years, C-reactive protein (CRP) > 185 mg/L, and leukocyte count < 10 G/L were independently associated with Q fever. The prevalence of Q fever among CAP increased to 38.5%. This is the highest prevalence ever reported in the world. This high prevalence justifies the systematic use of doxycycline in addition to antipneumococcal antibiotic regimens.

High endemicity of Q fever in French Guiana: A cross sectional study (2007-2017).

Q fever (QF) is a zoonosis caused by Coxiella burnetii (Cb). French Guiana (FG) had a high incidence but no data have been published since 2006. The objective of this study was to update the incidence and epidemiological data on QF in FG. A retrospective study of all FG Q fever serodiagnosis between 2007 and 2017 was carried out. Among the 695 patients included, the M/F sex-ratio was 2.0 and the median age of 45.3 years (IQR 33.7-56.3). The annual QF incidence rate was 27.4 cases (95%CI: 7.1-47.7) per 100,000 inhabitants ranging from 5.2 in 2007 to 40.4 in 2010. Risk factors associated with Q fever compared to general population were male gender, being born in mainland France, an age between 30 to 59 years-old and a residence in Cayenne and surroundings. The incidence of QF in FG remains high and stable and the highest in the world.

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.

Exploring convolutional neural networks with transfer learning for diagnosing Lyme disease from skin lesion images.

BACKGROUND AND OBJECTIVE: Lyme disease which is one of the most common infectious vector-borne diseases manifests itself in most cases with erythema migrans (EM) skin lesions. Recent studies show that convolutional neural networks (CNNs) perform well to identify skin lesions from images. Lightweight CNN based pre-scanner applications for resource-constrained mobile devices can help users with early diagnosis of Lyme disease and prevent the transition to a severe late form thanks to appropriate antibiotic therapy. Also, resource-intensive CNN based robust computer applications can assist non-expert practitioners with an accurate diagnosis. The main objective of this study is to extensively analyze the effectiveness of CNNs for diagnosing Lyme disease from images and to find out the best CNN architectures considering resource constraints. METHODS: First, we created an EM dataset with the help of expert dermatologists from Clermont-Ferrand University Hospital Center of France. Second, we benchmarked this dataset for twenty-three CNN architectures customized from VGG, ResNet, DenseNet, MobileNet, Xception, NASNet, and EfficientNet architectures in terms of predictive performance, computational complexity, and statistical significance. Third, to improve the performance of the CNNs, we used custom transfer learning from ImageNet pre-trained models as well as pre-trained the CNNs with the skin lesion dataset HAM10000. Fourth, for model explainability, we utilized Gradient-weighted Class Activation Mapping to visualize the regions of input that are significant to the CNNs for making predictions. Fifth, we provided guidelines for model selection based on predictive performance and computational complexity. RESULTS: Customized ResNet50 architecture gave the best classification accuracy of 84.42% ±1.36, AUC of 0.9189±0.0115, precision of 83.1%±2.49, sensitivity of 87.93%±1.47, and specificity of 80.65%±3.59. A lightweight model customized from EfficientNetB0 also performed well with an accuracy of 83.13%±1.2, AUC of 0.9094±0.0129, precision of 82.83%±1.75, sensitivity of 85.21% ±3.91, and specificity of 80.89%±2.95. All the trained models are publicly available at https://dappem.limos.fr/download.html, which can be used by others for transfer learning and building pre-scanners for Lyme disease. CONCLUSION: Our study confirmed the effectiveness of even some lightweight CNNs for building Lyme disease pre-scanner mobile applications to assist people with an initial self-assessment and referring them to expert dermatologist for further diagnosis.

"Chiclero's Ulcer" Due to Leishmania mexicana in Travelers Returning from Central America: A Case Report and Review of the Literature.

Cutaneous leishmaniasis (CL) due to a New World species of Leishmania is increasingly seen among returning international travelers, and most cases arise from travel to Mexico, Central and South America. We described a case of CL in a women presenting a nonhealing ulceration under her right ear with slight increase of size of the left parotid gland under the skin lesion, evolving for 4 months. In her history of travel, she reported a ten-day stay in Mexico during the Christmas vacation in the Yucatan region with only half a day walking in the tropical forest. Diagnosis of CL due to Leishmania mexicana was done via PCR detection and sequencing from swab sampling of the lesion. The patient recovered without antiparasitic treatment. Clinicians should consider diagnosing Chiclero's ulcer in patients returning from endemic areas such as Central America and Texas who present with chronic ulceration. A noninvasive sampling is sufficient for the PCR-based diagnosis of this disease.

Evaluation of pain susceptibility by taking blood pressure in patients with infections: A prospective comparative study.

ABSTRACT: Pain sensitization leading to polyalgia can be observed during infectious diseases. The blood pressure cuff-evoked pain threshold (BPCEPT) has been used in previous studies as a screening tool for fibromyalgia.We aimed to use the BPCEPT as a screening test for detecting pain sensitization in patients suffering from infectious diseases. We also investigated whether specific factors were associated with pain sensitization.We performed a prospective comparative study including all patients of our infectious diseases center in a 1-year period. We created a positive control group of patients suffering from fibromyalgia and a negative control group of "apparently healthy" patients consulting for vaccination.The blood pressure (BP) cuff was inflated until the patient signaled that they experienced pain, and this pressure value was noted.A total of 2355 patients were included. The positive control group had significantly lower values of the BPCEPT than all other groups. Among hospitalized patients with infectious diseases, a low BPCEPT was significantly associated with high temperature (P < .0001), older age (P = .002), being a woman (P = .004), high serum glutamic-oxaloacetic transaminase (P = .007), and high C reactive protein levels (P = .02). Moreover, in multivariate analysis, respiratory infection, meningitis, urinary tract infection, febrile neutropenia, and Q fever were independently associated with a low BPCEPT. A significant negative dynamic correlation between the BPCEPT and temperature was also observed (P < .001).We demonstrated for the first time in a large sample of patients that the BPCEPT method can be used to detect pain susceptibility. We observed a significant dynamic correlation between pain sensitization and temperature. Additionally, pain sensitization was associated with some diseases, suggesting that they trigger pain sensitivity.

Methodological Quality Assessment with the AGREE II Scale and a Comparison of European and American Guidelines for the Treatment of Lyme Borreliosis: A Systematic Review.

BACKGROUND: Most European and American countries recently updated their guidelines on Lyme borreliosis (LB). The aim of this study was to provide a comparative overview of existing guidelines on the treatment of LB in Europe and America and to assess the methodological quality of their elaboration. METHODS: A systematic search was carried out in MEDLINE, Google Scholar, and the national databases of scientific societies from 2014 to 2020. Quality was assessed by two independent reviewers using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool. RESULTS: Twelve guidelines were included. The scores for the AGREE II domains (median ± IQR) were: overall assessment 100 ± 22, scope and purpose 85 ± 46, stakeholder involvement 88 ± 48, rigour of development 67 ± 35, clarity of presentation 81 ± 36, applicability 73 ± 52 and editorial independence 79% ± 54%. Cohen's weighted kappa showed a high agreement (K = 0.90, 95%CI 0.84-0.96). Guidelines were quite homogeneous regarding the recommended molecules (mostly doxycycline in the first intention and ceftriaxone in the second intention), their duration (10 to 28 days), and their dosage. The differences were due to the lack of well-conducted comparative trials. The International Lyme and Associated Diseases Society (ILADS) guidelines were the only ones to suggest longer antibiotics based on an expert consensus. CONCLUSION: European and American guidelines for the treatment of LB were quite homogeneous but based on moderate- to low-evidence studies. Well-conducted comparative trials are needed to assess the best molecules, the optimal duration and the most effective doses.

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.

Human Q Fever on the Guiana Shield and Brazil: Recent Findings and Remaining Questions.

PURPOSE OF REVIEW: In this review, we report on the state of knowledge about human Q fever in Brazil and on the Guiana Shield, an Amazonian region located in northeastern South America. There is a contrast between French Guiana, where the incidence of this disease is the highest in the world, and other countries where this disease is practically non-existent. RECENT FINDINGS: Recent findings are essentially in French Guiana where a unique strain MST17 has been identified; it is probably more virulent than those usually found with a particularly marked pulmonary tropism, a mysterious animal reservoir, a geographical distribution that raises questions. SUMMARY: Q fever is a bacterial zoonosis due to Coxiella burnetii that has been reported worldwide. On the Guiana Shield, a region mostly covered by Amazonian forest, which encompasses the Venezuelan State of Bolivar, Guyana, Suriname, French Guiana, and the Brazilian State of Amapá, the situation is very heterogeneous. While French Guiana is the region reporting the highest incidence of this disease in the world, with a single infecting clone (MST 117) and a unique epidemiological cycle, it has hardly ever been reported in other countries in the region. This absence of cases raises many questions and is probably due to massive under-diagnosis. Studies should estimate comprehensively the true burden of this disease in the region.