Observational Cohort Study of Evolving Epidemiologic, Clinical, and Virologic Features of Monkeypox in Southern France.

We enrolled 136 patients with laboratory-confirmed monkeypox during June 4-August 31, 2022, at the University Hospital Institute Méditerranée Infection in Marseille, France. The median patient age was 36 years (interquartile range 31-42 years). Of 136 patients, 125 (92%) were men who have sex with men, 15 (11%) reported previous smallpox vaccinations, and 21 (15.5%) were HIV-positive. The most frequent lesion locations were the genitals (68 patients, 53%), perianal region (65 patients, 49%), and oral/perioral area (22 patients, 17%). Lesion locations largely corresponded with the route of contamination. Most (68%) patients had isolated anal, genital, or oral lesions when they were first seen, including 56 (61%) who had >1 positive site without a visible lesion. Concurrent sexually transmitted infections were diagnosed in 19 (15%) patients, and 7 patients (5%) were asymptomatic. We recommend vaccination campaigns, intensified testing for sexually transmitted infections, and increased contact tracing to control the ongoing monkeypox outbreak.

Early combination therapy with hydroxychloroquine and azithromycin reduces mortality in 10,429 COVID-19 outpatients.

We evaluated the age-specific mortality of unselected adult outpatients infected with SARS-CoV-2 treated early in a dedicated COVID-19 day hospital and we assessed whether the use of hydroxychloroquine (HCQ) + azithromycin (AZ) was associated with improved survival in this cohort. A retrospective monocentric cohort study was conducted in the day hospital of our center from March to December 2020 in adults with PCR-proven infection who were treated as outpatients with a standardized protocol. The primary endpoint was 6-week mortality, and secondary endpoints were transfer to the intensive care unit and hospitalization rate. Among 10,429 patients (median age, 45 [IQR 32-57] years; 5597 [53.7%] women), 16 died (0.15%). The infection fatality rate was 0.06% among the 8315 patients treated with HCQ+AZ. No deaths occurred among the 8414 patients younger than 60 years. Older age and male sex were associated with a higher risk of death, ICU transfer, and hospitalization. Treatment with HCQ+AZ (0.17 [0.06-0.48]) was associated with a lower risk of death, independently of age, sex and epidemic period. Meta-analysis evidenced consistency with 4 previous outpatient studies (32,124 patients-Odds ratio 0.31 [0.20-0.47], I2 = 0%). Early ambulatory treatment of COVID-19 with HCQ+AZ as a standard of care is associated with very low mortality, and HCQ+AZ improve COVID-19 survival compared to other regimens.

Fatal outcome of autochthonous hepatitis E in a patient with B cell lymphoma in Southeastern France.

We describe a case of fatal fulminant hepatitis E concomitant to malignant B cell lymphoma in a 73-year-old French woman. Infection was with an autochthonous hepatitis E virus of genotype 3f. Frequent consumption of uncooked pig liver sausage (figatellu) was the only risk factor found.

Fatal fulminant hepatitis E associated with autoimmune hepatitis and excessive paracetamol intake in Southeastern France.

We present, to our knowledge, the first case of fatal fulminant liver failure associated with hepatitis E virus infection, autoimmune hepatitis, and excessive paracetamol intake, which occurred in a 77-year-old woman. Hepatitis E testing should be performed in severe acute liver failure cases, even when another cause has been identified.

Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial.

BACKGROUND: Chloroquine and hydroxychloroquine have been found to be efficient on SARS-CoV-2, and reported to be efficient in Chinese COV-19 patients. We evaluate the effect of hydroxychloroquine on respiratory viral loads. PATIENTS AND METHODS: French Confirmed COVID-19 patients were included in a single arm protocol from early March to March 16th, to receive 600mg of hydroxychloroquine daily and their viral load in nasopharyngeal swabs was tested daily in a hospital setting. Depending on their clinical presentation, azithromycin was added to the treatment. Untreated patients from another center and cases refusing the protocol were included as negative controls. Presence and absence of virus at Day6-post inclusion was considered the end point. RESULTS: Six patients were asymptomatic, 22 had upper respiratory tract infection symptoms and eight had lower respiratory tract infection symptoms. Twenty cases were treated in this study and showed a significant reduction of the viral carriage at D6-post inclusion compared to controls, and much lower average carrying duration than reported in the litterature for untreated patients. Azithromycin added to hydroxychloroquine was significantly more efficient for virus elimination. CONCLUSION: Despite its small sample size, our survey shows that hydroxychloroquine treatment is significantly associated with viral load reduction/disappearance in COVID-19 patients and its effect is reinforced by azithromycin.

Testing the repatriated for SARS-Cov2: Should laboratory-based quarantine replace traditional quarantine?

BACKGROUND: An ongoing epidemic of respiratory diseases caused by a novel coronavirus (COVID 2019, SARS-CoV2) started in Wuhan, Hubei, in China at the end of December 2019. The French government decided to repatriate the 337 French nationals living in Wuhan and place them in quarantine in their home country. We decided to test them all for SARS-Cov2 twice in order to reduce anxiety among the population and decision-makers. METHODS: We investigated the presence of SARS-CoV-19 in asymptomatic carriers by testing all repatriated patients within the first 24 h of their arrival in France and at day 5. Viral RNA was extracted from pooled nasal and oropharyngeal swab fluids or sputum in the absence of nasal/oropharyngeal swabs. Detection of SARS-CoV-2 RNA was then carried out using several real-time reverse transcription (RT)-PCR assays. RESULTS: We tested 337 passengers at day 0 and day 5. All the tests for SARS-CoV2 were negative. By optimising the sampling process, sending samples sequentially and reducing the time-scale for biological analysis, we were able to test the samples within 5 h (including sampling, shipment and biological tests). CONCLUSION: Optimising our procedures reduces anxiety and reassures the population and decision makers.

Rapid viral diagnosis and ambulatory management of suspected COVID-19 cases presenting at the infectious diseases referral hospital in Marseille, France, - January 31st to March 1st, 2020: A respiratory virus snapshot.

BACKGROUND: Rapid virological diagnosis is needed to limit the length of isolation for suspected COVID-19 cases. METHOD: We managed the first 280 patients suspected to have COVID-19 through a rapid care circuit and virological diagnosis in our infectious disease reference hospital in Marseille, France. Rapid viral detection was performed on sputum and nasopharyngeal samples. RESULTS: Over our study period, no SARS-CoV-2 was detected. Results were obtained within approximately 3 h of the arrival of patient samples at the laboratory. Other viral infections were identified in 49% of the patients, with most common pathogens being influenza A and B viruses, rhinovirus, metapneumovirus and common coronaviruses, notably HKU1 and NL63. CONCLUSION: Early recognition of COVID-19 is critical to isolate confirmed cases and prevent further transmission. Early rule-out of COVID-19 allows public health containment measures to be adjusted by reducing the time spent in isolation.

Early treatment of COVID-19 patients with hydroxychloroquine and azithromycin: A retrospective analysis of 1061 cases in Marseille, France.

BACKGROUND: In France, the combination hydroxychloroquine (HCQ) and azithromycin (AZ) is used in the treatment of COVID-19. METHODS: We retrospectively report on 1061 SARS-CoV-2 positive tested patients treated for at least three days with the following regimen: HCQ (200 mg three times daily for ten days) + AZ (500 mg on day 1 followed by 250 mg daily for the next four days). Outcomes were death, clinical worsening (transfer to ICU, and >10 day hospitalization) and viral shedding persistence (>10 days). RESULTS: A total of 1061 patients were included in this analysis (46.4% male, mean age 43.6 years - range 14-95 years). Good clinical outcome and virological cure were obtained in 973 patients within 10 days (91.7%). Prolonged viral carriage was observed in 47 patients (4.4%) and was associated to a higher viral load at diagnosis (p < .001) but viral culture was negative at day 10. All but one, were PCR-cleared at day 15. A poor clinical outcome (PClinO) was observed for 46 patients (4.3%) and 8 died (0.75%) (74-95 years old). All deaths resulted from respiratory failure and not from cardiac toxicity. Five patients are still hospitalized (98.7% of patients cured so far). PClinO was associated with older age (OR 1.11), severity of illness at admission (OR 10.05) and low HCQ serum concentration. PClinO was independently associated with the use of selective beta-blocking agents and angiotensin II receptor blockers (p < .05). A total of 2.3% of patients reported mild adverse events (gastrointestinal or skin symptoms, headache, insomnia and transient blurred vision). CONCLUSION: Administration of the HCQ+AZ combination before COVID-19 complications occur is safe and associated with a very low fatality rate in patients.

Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: A pilot observational study.

BACKGROUND: We need an effective treatment to cure COVID-19 patients and to decrease virus carriage duration. METHODS: We conducted an uncontrolled, non-comparative, observational study in a cohort of 80 relatively mildly infected inpatients treated with a combination of hydroxychloroquine and azithromycin over a period of at least three days, with three main measurements: clinical outcome, contagiousness as assessed by PCR and culture, and length of stay in infectious disease unit (IDU). RESULTS: All patients improved clinically except one 86 year-old patient who died, and one 74 year-old patient still in intensive care. A rapid fall of nasopharyngeal viral load was noted, with 83% negative at Day7, and 93% at Day8. Virus cultures from patient respiratory samples were negative in 97.5% of patients at Day5. Consequently patients were able to be rapidly discharged from IDU with a mean length of stay of five days. CONCLUSION: We believe there is urgency to evaluate the effectiveness of this potentially-life saving therapeutic strategy at a larger scale, both to treat and cure patients at an early stage before irreversible severe respiratory complications take hold and to decrease duration of carriage and avoid the spread of the disease. Furthermore, the cost of treatment is negligible.

The effect of a single dose of oral ivermectin on pruritus in the homeless.

BACKGROUND: Homeless people commonly present with ectoparasite-based pruritus. We evaluated the efficacy of a single dose of ivermectin to reduce the pruritus prevalence in a homeless population. METHODS: We conducted a randomized, double-blind, placebo-controlled trial from January 2006 to April 2006 in two homeless shelters in the city of Marseille, France. Homeless people complaining of pruritus were randomized to receive either ivermectin (24 mg) or placebo. Follow-up visits were planned at day 14 and day 28 after the inclusion to assess the outcome of pruritus. RESULTS: Forty-two subjects with pruritus were randomized to the ivermectin group and 40 to the placebo group. On day 14, pruritus was reported by significantly more subjects in the placebo group than those in the ivermectin group for both the per-protocol (PP) population (91.42% versus 68.57%, P = 0.014) and the intention-to-treat (ITT) population (92.5% versus 73.80%, P = 0.038). No significant effect was observed at day 28. Ivermectin was the only independent factor associated with the absence of pruritus at day 14 in both PP population [OR: 4.60 (95% CI:1.13; 18.73), P = 0.033] and ITT population [OR: 4.38 (95% CI: 1.07; 17.77), P = 0.039]. CONCLUSIONS: A single dose of oral ivermectin has a transient beneficial effect on the reduction of the prevalence of pruritus in the homeless population. More studies are required to assess the efficacy of multiple repeated treatments with ivermectin to reduce scabies and body lice endemic among homeless people with pruritus and the impact of such treatment on this population.

Congenital tuberculosis after in vitro fertilization.

Genital tuberculosis (TB) is a major cause of infertility in the world, notably in developing countries, but its incidence is increasing in the western continents. In vitro fertilization (IVF) represents a useful treatment of infertility after TB. We report the first case of congenital TB after IVF and suggest improvement of usual screening before and after IVF.

Fatal fulminant primary hepatitis B virus infections with G1896A precore viral mutants in southeastern France.

Fulminant hepatitis has been shown to occur in about 1% of acute hepatitis B virus (HBV) infections, and its mortality rate is nearly 70%. Specific HBV genotypic features have been pointed out in fulminant acute hepatitis B worldwide, but these associations remain controversial. We describe all four primary HBV infections diagnosed in 2008 in our institution in Marseille, southeastern France, including two fatal cases. HBV genotypes were D or E. Precore G1896A HBV mutants were detected in both fatal fulminant primary HBV infections. Hepatitis B surface antigen and hepatitis B e antigen (HBeAg) were negative in two and three cases, respectively, despite HBV DNA detection. Primary HBV infection remains a cause of death in France. The impact of the precore G1896A mutation on the severity of AHB deserves to be assessed in larger studies in this country.

Leptospirosis diagnosed by molecular DNA detection on skin biopsy.

Leptospirosis is one of the most common anthropozoonoses in the world. Humans are accidental hosts who get infected through damaged skin or conjunctiva from environmental sources such as soil and water contaminated by urine or tissues from infected animals. We report the case of a young man for whom the diagnosis was obtained by polymerase chain reaction (PCR) detection from a skin biopsy.

Molecular identification of Borrelia crocidurae in a patient returning from Senegal.

Borrelia spp. are pathogens responsible for worldwide tickborne relapsing fever (TBRF). In West Africa, TBRF is due to a single species, Borrelia crocidurae, transmitted by the soft-body tick Ornithodoros sonrai. We report a case of B crocidurae infection in a French tourist in Senegal, diagnosed by molecular biology using 16S rDNA, flaB, and the 16S-23S intergenic spacer. We found six imported cases reported in travellers (since 1999). We review here clinical and molecular aspects and pathophysiology, and discuss diagnostic methods and therapeutic regimens. In the coming years, this emerging disease will be of concern to more and more travellers returning from disease-endemic regions. Thus, physicians must be aware of its presentation and diagnosis, since the spontaneous outcome can be severe, and a simple treatment is effective.

Possible autochthonous malaria from Marseille to Minneapolis.

We report 2 cases of Plasmodium falciparum malaria in southern France in a French woman and an American man of Togolese origin who reported no recent travel to malaria-endemic countries. Both infections occurred after a stay near Marseille, which raises the possibility of autochthonous transmission. Entomologic and genotypic investigations are described.