BedBiopsy: Diagnostic performance of bedside ultrasound-guided bone biopsies for the management of diabetic foot infection.

OBJECTIVE: We aimed to assess the feasibility and diagnostic performance of ultrasound-guided bone biopsies at the bedside of diabetic patients admitted for suspected foot osteitis not requiring surgery. RESEARCH DESIGN AND METHODS: In this retrospective monocentric study, we compared the performance of ultrasound-guided (n = 29 consecutive patients, Dec.2020-Oct.2022) versus surgical (n = 24 consecutive patients, Jan.2018-Nov.2020) bone biopsies at confirming or ruling out diabetic foot osteitis (primary outcome). RESULTS: Patient characteristics were similar in the two intervention groups, including arteritis prevalence (62.3 %), SINBAD score, and wound location (phalanges 36 %, metatarsus 43 %, and calcaneus 21 %). However, the ultrasound-guided group was older (67 ± 11 versus 60 ± 13 years respectively, P = 0.047) and had more type 2 diabetes (97 % versus 75 %, P = 0.038). Diagnostic performance (i.e., capacity to confirm or rule out suspected osteitis) was similar for ultrasound-guided (28/29 cases: 25 confirmations, 3 invalidations) and surgical (24 confirmations/24) biopsies, P = 0.358. No biopsy-related side effect or complication was observed for either intervention, even for patients on antiaggregation and/or anticoagulation therapy. The mean (± standard deviation) time necessary to perform the biopsy was shorter in the ultrasound-guided group (2.6 ± 3.0 versus 7.2 ± 5.8 days, respectively, P < 0.001) and wound evolution at three months was more favorable (83.3 versus 41.2 %, P = 0.005) (94.4 % versus 66.7 %, respectively, patients with new surgical procedure within six months excluded; P = 0.055). Even though not statistically significant, healing rates in terms of wound and osteitis at six months were also better in the ultrasound-guided group (wound: 40.9 % versus 36.8 %; P = 0.790, and osteitis: 81.8 vs 55.6 % P = 0.071). CONCLUSION: In diabetic patients with suspected foot osteitis not requiring surgery, bedside ultrasound-guided bone biopsies may constitute a promising alternative to surgical biopsies. This intervention provided excellent tolerance and microbiological documentation, short lead-times, and more favorable wound prognosis.

Respective roles of social deprivation, health literacy, and clinical factors for COVID-19: a case-control study in hospitalized patients.

Introduction: To investigate the association between social deprivation and COVID-19 among hospitalized patients in an underprivileged department of the greater Paris area. Methods: Individuals hospitalized for COVID-19 between March 1st and October 31, 2020, were included, matched on age and sex, and compared with patients hospitalized for any other reason with negative RT-PCR for SARS-CoV-2, through a case-control study. Clinical, socio-demographic characteristics, health literacy, and social deprivation, assessed by the EPICES score, were collected. Factors associated with COVID-19 in hospitalized patients were assessed using univariate and multivariate logistic regression models. Results: 69 cases and 180 controls were included. Participants were mostly men (N = 148: 59.4%) aged 65 or older (N = 109: 44.1%). Median EPICES score was 43.2 (IQR 29.4-62.9). EPICES score > 30.17 (precariousness threshold) was not significantly associated with COVID-19 in hospitalized patients (adjusted odds ratio (aOR) = 0.46; 95% Confidence Interval (CI) [0.21-1.01]). Advanced age, higher BMI, professional activity, home area of less than 25 m2 per person, and low health literacy, were significantly associated with COVID-19 in hospitalized patients. Discussion: This study highlights probable risk factors for specific exposition in disadvantaged area: maintenance of professional activity, smaller home area, and low health literacy.

Favorable outcome without corticosteroids during post-artesunate delayed hemolysis with positive direct antiglobulin test in severe imported Plasmodium falciparum malaria, France.

OBJECTIVES: Positive direct antiglobulin tests (DATs) have been reported in cases of post-artesunate delayed hemolysis (PADH), but the causal role of auto-immune hemolysis remains unclear. We aimed to analyze a cohort of patients with PADH and DAT during severe malaria. METHODS: We describe PADH and DAT results in a 7-year multi-center retrospective cohort of patients receiving artesunate for severe imported malaria. RESULTS: Of 337 patients treated with artesunate, 46 (13.6%) had at least one DAT result within 30 days of treatment initiation, and 25/46 (54.3%) had at least one positive DAT. Among 40 patients with available data, 17 (42.5%) experienced PADH. Patient characteristics were similar for patients with a positive or negative DAT, and DAT positivity was not associated with PADH occurrence (P = 0.36). Among patients, 5/13 (38.5%) with a positive DAT after day 7 experienced PADH, compared to 10/13 (76.9%) of those with a negative DAT after day 7 (P = 0.11). Overall, 41% of patients required blood transfusions, and outcome was favorable without corticosteroids, even in cases of PADH. CONCLUSIONS: DAT does not appear to be a marker of PADH, but rather an indirect marker of an immune-mediated mechanism. DAT positivity should not lead to the administration of systemic corticosteroids during PADH.

Chronic schistosomiasis imported in France: A retrospective multicentre analysis of 532 patients, calling for international recommendations.

BACKGROUND: Schistosomiasis is a major public health issue for migrants. This study aims to describe the clinical presentation and management of imported schistosomiasis in France. METHODS: We included all new cases of schistosomiasis in patients aged ≥18 years, defined by a positive specific Western blot and/or a positive parasitological analysis of urine, stool or biopsy, between January 1, 2016, and December 31, 2019, in 4 laboratories in Paris and Western France. RESULTS: Over the study period, 532 patients were included. Mean age was 37 years (18-91), and 461/532 (87 %) were men. Among 476/532 (89 %) patients born in an endemic area, 433 (91 %) were born in sub-Saharan Africa. Most of the patients (405/532, 76 %) had only a positive serology, and 127/532 (24 %) had ova on microscopic examination. Among 361/532 (68 %) who had at least one urine, stool or biopsy analysis, microscopic analysis was positive in 127 (35 %). Imaging showed lesions compatible with schistosomiasis in 88/164 (54 %) patients with clinical symptoms and 13/29 (45 %) patients without (p = 0.5). Patients who arrived in France less than one year before diagnosis were more likely to have clinical symptoms than those who arrived in France 1-5 years and >5 years prior to diagnosis (52 %, 41 % and 43 %, respectively, p = 0.03). Two-hundred and seventeen patients (40.8 %) were left untreated. CONCLUSION: Approximately 50 % of patients with imported chronic schistosomiasis have radiological abnormalities, whether they are symptomatic or not, and management is heterogeneous. Multidisciplinary international guidelines are requested to clarify the management of this neglected disease.

Updated mortality and causes of death in 2020-2021 in people with HIV: a multicenter study in France.

OBJECTIVE: The aim of this study was to assess updated mortality and causes of death in people with HIV (PWH) in France. DESIGN AND METHODS: We analyzed all deaths in PWH followed up between January 1, 2020, and December 31, 2021, in 11 hospitals in the Paris region. We described the characteristics and causes of death among deceased PWH, and evaluated the incidence of mortality and associated risk factors using a multivariate logistic regression. RESULTS: Of the 12 942 patients followed in 2020--2021, 202 deaths occurred. Mean annual incidence of death [95% confidence interval (95% CI)] was 7.8 per 1000 PWH (6.3-9.5). Forty-seven patients (23%) died from non-AIDS nonviral hepatitis (NANH)-related malignancies, 38 (19%) from non-AIDS infections (including 21 cases of COVID-19), 20 (10%) from AIDS, 19 (9%) from cardiovascular diseases (CVD), 17 (8.4%) from other causes, six (3%) from liver diseases, and five (2.5%) from suicides/violent deaths. The cause of death was unknown in 50 (24.7%) patients. Risks factors for death were age [adjusted odds ratio (aOR) 1.93; 1.66-2.25 by additional decade), AIDS history (2.23; 1.61-3.09), low CD4 + cell count (1.95; 1.36-2.78 for 200-500 cells/µl and 5.76; 3.65-9.08 for ≤200 versus > 500 cells/µl), and viral load more than 50 copies/ml (2.03; 1.33-3.08), both at last visit. CONCLUSION: NANH malignancies remained in 2020-2021 the first cause of death. COVID-19 accounted for more than half of the mortality related to non-AIDS infections over the period. Aging, AIDS history, and a poorer viro-immunological control were associated with death.

Severe Scabies: A French Multi-centre Study Involving 95 Patients with Crusted and Profuse Disease and Review of the Literature.

The aim of this multi-centre French retrospective study was to identify severe, i.e. crusted and profuse, scabies patients. Records were retrieved from 22 Dermatology or Infectious Diseases departments in the Ile-de-France from January 2009 to January 2015 to characterize epidemiology, demography, diagnosis, contributing factors, treatment features, and outcomes in severe scabies. A total of 95 inpatients (57 crusted and 38 profuse) were included. A higher number of cases was observed among elderly patients (>75 years), mostly living in institutions. Thirteen patients (13.6%) reported a history of previously treated scabies. Sixty-three patients (66.3%) had been seen by a previous practitioner for the current episode (up to 8 previous visits). Initial misdiagnosis (e.g. eczema, prurigo, drug-related eruptions, psoriasis) was documented in 41 patients (43.1%). Fifty-eight patients (61%) had already received 1 or more previous treatments for their current episode. Forty percent received corticosteroids or acitretin for an initial diagnosis of eczema or psoriasis. Median time from the onset of symptoms to the diagnosis of severe scabies was 3 months (range 0.3-22). Itch was present in all patients at diagnosis. Most patients (n=84, 88.4%) had comorbidities. Diagnostic and therapeutic approaches varied. Complications occurred in 11.5% of cases. To date, there is no consensus for diagnosis and treatment, and future standardization of is required for optimal management.

Updates on the worldwide burden of amoebiasis: A case series and literature review.

BACKGROUND: Amoebiasis is an intestinal and tissue parasitic infection caused by the protozoan Entamoeba histolytica. Despite significant medical importance and worldwide dispersion, little is known about the epidemiology and distinct geographical distribution of various clinical forms of amoebiasis in the world. In this study, we present an amoebiasis case series referred to Avicenne Hospital (Bobigny, France) from 2010 to 2022 followed by an overview of the released literature to explore diverse clinico-pathology of amoebiasis and to update the actual epidemiological situation of this parasitosis worldwide. METHODS: The referred patients underwent a combination of clinical and parasitological examinations and imaging. The study was followed by an overview of released literature performed based on PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guideline. RESULTS: A total of 15 patients with amoebiasis were diagnosed with an average age of 48.5 years old at the occurrence time of infection. Men (78%) were the most affected patients. Most of the cases were reported following a trip to endemic regions, such as Mali, India, Nepal, Algeria, Cameroon or Congo. All of the processed patients exhibited a hepatic amoebiasis. Amoebic abscess was observed in all cases with an average size of 6.3 cm. Of these patients, seven cases (46.7%) benefited from drainage following a risk of rupture or superinfection of the abscess. A compilation of findings extracted from 390 scientific publications via seven major medical databases, allowed us to update the main epidemiological and clinical events that has led to the current worldwide expansion of amoebiasis. We presented a clinical and epidemiological overview of the amoebiasis accompanied with a worldwide illustrative map displaying the current distribution of known amoebiasis foci in each geographical ecozone of Asia, Europe, Africa, Americas, and Australia. CONCLUSIONS: Although Metropolitan France is not known as an endemic region of amoebiasis, amoebic liver abscess was the most frequent clinical form observed among our 15 patients processed. Most of infected patients had a history of travel to or lived-in endemic areas before arriving in France.

Invasive Rhinosinusitis Caused by Alternaria infectoria in a Patient with Autosomal Recessive CARD9 Deficiency and a Review of the Literature.

Phaeohyphomycoses comprise a heterogeneous group of fungal infections caused by dematiaceous fungi and have primarily been reported in patients with underlying acquired immunodeficiencies, such as hematological malignancies or solid-organ transplants. Over the past decade, a growing number of patients with phaeohyphomycosis but otherwise healthy were reported with autosomal recessive (AR) CARD9 deficiency. We report a 28-year-old woman who presented with invasive rhinosinusitis caused by Alternaria infectoria. Following a candidate gene sequencing approach, we identified a biallelic loss-of-function mutation of CARD9, thereby further broadening the spectrum of invasive fungal diseases found in patients with inherited CARD9 deficiency. In addition, we reviewed 17 other cases of phaeohyphomycosis associated with AR CARD9 deficiency. Physicians should maintain a high degree of suspicion for inborn errors of immunity, namely CARD9 deficiency, when caring for previously healthy patients with phaeohyphomycosis, regardless of age at first presentation.

Immunogenicity and reactogenicity of heterologous and homologous mRNA-1273 and BNT162b2 vaccination: A multicenter non-inferiority randomized trial.

Background: Although effective mRNA vaccines for SARS-CoV-2 infection have been deployed worldwide, their interchangeability could facilitate the scale-up of vaccination programs. The objective of the trial was to assess whether the immune response induced by a heterologous SARS-CoV-2 mRNA primo vaccination is non-inferior to that of a homologous mRNA vaccination. Methods: We conducted a multicenter, randomized, open-label trial in adults 18 years of age and older who received a first dose of SARS-CoV-2 mRNA vaccine. Participants were randomly assigned in a 1:1 ratio to receive a second dose of BNT162b2 or mRNA-1273, 28 to 49 days after the first dose. Randomization was stratified on the vaccine received at the first vaccination. The primary endpoint was the anti-spike IgG antibodies titer measured 28 days after the second vaccine dose. This study is registered with ClinicalTrials.gov, Trial, NCT04900467. Findings: Of the 414 randomized participants recruited from May 28 to July 2, 2021, 390 were included in the per protocol analysis: 94 participants in group 1 (BNT162b2/BNT162b2), 96 in group 2 (BNT162b2/mRNA-1273), 97 in group 3 (mRNA-1273/mRNA-1273), and 103 in group 4 (mRNA-1273/BNT162b2). The geometric mean titers ratios of anti-spike IgG antibodies for each heterologous regimen relative to the corresponding homologous regimen were 1·37 (two-sided 95% CI, 1·10 to 1·72) in the groups 1 and 2 and 0·67 (two-sided 95% CI, 0·55 to 0·82) in the groups 3 and 4. Levels of neutralizing antibodies to the main circulating SARS-Cov-2 viral strains were higher with the vaccine regimen containing mRNA-1273. Participants who received mRNA-1273 as a second dose experienced a higher rate of local adverse reactions and general symptoms than those who received BNT162b2 (p < 0·0001). Interpretation: The two SARS-CoV-2 mRNA vaccines could be used with flexibility for the second dose of COVID-19 primo vaccination. Tolerance remains good regardless of vaccine sequence although mRNA-1273 was more reactogenic. Funding: French Ministries of Solidarity and Health and Research. BNT162b2 was provided by Pfizer/BioNTech. mRNA-1273 was provided by Moderna.

Impaired antibody response to COVID-19 vaccination in advanced HIV infection.

OBJECTIVES: Coronavirus disease 2019 (COVID-19) vaccination is reportedly efficient in people with HIV (PWH) but vaccine trials included participants with normal CD4+ T-cell counts. We analyzed seroconversion rates and antibody titers following two-dose vaccination in PWH with impaired CD4+ T-cell counts. METHODS: We collected retrospective postvaccination SARS-COV-2 serology results available in a university hospital for PWH vaccinated between March and September, 2021 who were tested for antispike antibodies from 8 to 150 days following dose 2. Antibody titers were compared in PWH with CD4+ T-cell count less than 200 cells/µl, 200 < CD4+ T-cell counts < 500 cells/µl and CD4+ T-cell count greater than 500 cells/µl at vaccination. RESULTS: One hundred and five PWH were included: n = 54 in the CD4+ T-cell count less than 500 cells/µl group (n = 18 with CD4+ <200 cells/µl, n = 36 with 200 < CD4+ < 500 cells/µl) and 51 in the CD4+ T-cell count greater than 500 cells/µl group. They received two doses of BNT162b2 (75%), mRNA-1273 (8.5%), or ChAdOx1 nCoV-19 (16.5%). The median time from vaccine dose 2 to serology was consistent across all groups (73 days, interquartile range [29-97], P = 0.14). Seroconversion rates were 100% in the CD4+ T-cell count greater than 500 cells/µl group but 89% in participants with CD4+ T-cell counts less than 500 cells/µl (22 and 5.5% seronegative in the CD4+ T-cell counts <200 cells/µl and 200 < CD4+ < 500 cells/µl groups, respectively). Median antibody titers were 623.8 BAU/ml [262.2-2288] in the CD4+ greater than 500 cells/µl group versus 334.3 BAU/ml [69.9-933.9] in the CD4+ less than 500 cells/µl group (P = 0.003). They were lowest in the CD4+ less than 200 cells/µl group: 247.9 BAU/ml [5.88-434.9] (P = 0.0017) with only 44% achieving antibody titers above the putative protection threshold of 260 BAU/ml. CONCLUSION: PWH with CD4+ T-cell counts less than 500 cells/µl and notably less than 200 cells/µl had significantly lower seroconversion rates and antispike antibody titers compared with PWH with CD4+ T-cell counts greater than 500 cells/µl, warranting the consideration of targeted vaccine strategies in this fragile population.

Spatial determinants of excess all-cause mortality during the first wave of the COVID-19 epidemic in France.

BACKGROUND: The first wave of the COVID-19 pandemic in France was associated with high excess mortality, and anecdotal evidence pointed to differing excess mortality patterns depending on social and environmental determinants. In this study we aimed to investigate the spatial distribution of excess mortality during the first wave of the COVID-19 pandemic in France and relate it at the subnational level to contextual determinants from various dimensions (socioeconomic, population density, overall health status, healthcare access etc.). We also explored whether the determinants identified at the national level varied depending on geographical location. METHODS: We used available national data on deaths in France to calculate excess mortality by department for three age groups: 0-49, 50-74 and > 74 yrs. between March 1st and April 27th, 2020. We selected 15 variables at the department level that represent four dimensions that may be related to overall mortality at the ecological level, two representing population-level vulnerabilities (morbidity, social deprivation) and two representing environmental-level vulnerabilities (primary healthcare supply, urbanization). We modelled excess mortality by age group for our contextual variables at the department level. We conducted both a global (i.e., country-wide) analysis and a multiscale geographically weighted regression (MGWR) model to account for the spatial variations in excess mortality. RESULTS: In both age groups, excess all-cause mortality was significantly higher in departments where urbanization was higher (50-74 yrs.: ß = 15.33, p < 0.001; > 74 yrs.: ß = 18.24, p < 0.001) and the supply of primary healthcare providers lower (50-74 yrs.: ß = - 8.10, p < 0.001; > 74 yrs.: ß = - 8.27, p < 0.001). In the 50-74 yrs. age group, excess mortality was negatively associated with the supply of pharmacists (ß = - 3.70, p < 0.02) and positively associated with work-related mobility (ß = 4.62, p < 0.003); in the > 74 yrs. age group our measures of deprivation (ß = 15.46, p < 0.05) and morbidity (ß = 0.79, p < 0.008) were associated with excess mortality. Associations between excess mortality and contextual variables varied significantly across departments for both age groups. CONCLUSIONS: Public health strategies aiming at mitigating the effects of future epidemics should consider all dimensions involved to develop efficient and locally tailored policies within the context of an evolving, socially and spatially complex situation.

The association of metabolic syndrome and COVID-19 deterioration.

BACKGROUND AND AIMS: To evaluate the prevalence and prognostic value of metabolic syndrome (MetS) in patients admitted for coronavirus disease 2019 (COVID-19). METHODS AND RESULTS: In this monocentric cohort retrospective study, we consecutively included all adult patients admitted to COVID-19 units between April 9 and May 29, 2020 and between February 1 and March 26, 2021. MetS was defined when at least three of the following components were met: android obesity, high HbA1c, hypertension, hypertriglyceridemia, and low HDL cholesterol. COVID-19 deterioration was defined as the need for nasal oxygen flow ≥6 L/min within 28 days after admission. We included 155 patients (55.5% men, mean age 61.7 years old, mean body mass index 29.8 kg/m2). Fifty-six patients (36.1%) had COVID-19 deterioration. MetS was present in 126 patients (81.3%) and was associated with COVID-19 deterioration (no-MetS vs MetS: 13.7% and 41.2%, respectively, p < 0.01). Logistic regression taking into account MetS, age, gender, ethnicity, period of inclusion, and Charlson Index showed that COVID-19 deterioration was 5.3 times more likely in MetS patients (95% confidence interval 1.3-20.2) than no-MetS patients. CONCLUSIONS: Over 81.3% of patients hospitalized in COVID-19 units had MetS. This syndrome appears to be an independent risk factor of COVID-19 deterioration.

Severe long-delayed malaria caused by Plasmodium malariae in an elderly French patient.

BACKGROUND: Plasmodium malariae is the cause of the rare but severe form of malaria that sometimes affects individuals travelling to malaria-endemic regions. This report presents the unique case of a patient exhibiting severe malaria symptoms caused by P. malariae with no record of recent travel to any malaria-endemic areas. CASE PRESENTATION: An 81-year-old French woman was admitted to the emergency department with sustained fever and severe weakness for the past 5 days. She suffered from anaemia, thrombocytopenia, confusion, somnolence, pulmonary complications, and hypoxaemia. In the absence of any concrete aetiology that could explain the fever together with thrombocytopenia, physicians suspected malaria as a probable diagnosis. The LAMP-PCR and lateral flow test confirmed the presence of malaria parasite, Plasmodium sp. Microscopic examination (May-Grünwald Giemsa-stained thin blood smear) revealed the presence of trophozoites, schizonts, and gametocytes with 0.93 % parasitaemia. Conventional PCR amplification targeting 510 bp DNA fragment of small subunit ribosomal RNA (ssrRNA) and bidirectional sequencing identified the parasite as Plasmodium malariae. The travel history of this patient revealed her visits to several countries in Europe (Greece), North Africa (Tunisia and Morocco), and the West Indies (Dominican Republic). Of these, the latter was the only country known to be endemic for malaria at the time (three malaria parasite species were prevalent: Plasmodium falciparum, Plasmodium vivax, and P. malariae). The patient had most likely got infected when she visited the Dominican Republic in the summer of 2002. This time interval between the initial parasite infection (2002) till the onset of symptoms and its subsequent diagnosis (2020) is a reminder of the ability of P. malariae to persist in the human host for many years. CONCLUSIONS: This report highlights the persistent nature and ability of P. malariae to cause severe infection in the host even after a prolonged time interval.

Immunization Catch-Up for Newly Arrived Migrants in France: A Cross-Sectional Study among French General Practitioners.

BACKGROUND: Migrants often undergo an incomplete vaccination program in regards to the French recommendations. The aim of this study was to evaluate the practices of French General Practitioners' (GPs) in terms of catch-up vaccination. METHODS: A cross-sectional study was carried-out in 2017-2018 in France. An online questionnaire was disseminated by email through scholarly societies to GPs involved in the care and the vaccination of migrants. Analyses included univariate and multivariate analysis with a logistic regression model. RESULTS: A total of 216 GPs completed the survey. A majority identified themselves with an average level regarding the prevention of infectious diseases among migrant populations (56.7%) and confirmed this is part of their daily practice (83.3%). The majority of respondents do not perform more than two injections on the same day. When compared to GPs working in health centres, those with a private practice are more likely to report returning to a full primary vaccination schedule (adjusted OR = 2.90, 95% CI [1.29-6.53]). Aside from the serology for hepatitis B and to a lesser extent for measles, other pre-vaccination serologies were not frequently used by GPs. When a migrant declares to be up-to-date with his immunisations, only 56.5% of doctors consider this information reliable. CONCLUSIONS: This study clarified the vaccination practices of GPs receiving migrant patients in consultation and showed its heterogeneity. An important need for benchmarks has been identified and these results were used for the elaboration of the French guidelines on vaccines catch-up.

Longitudinal study based on a safety registry for malaria patients treated with artenimol-piperaquine in six European countries.

BACKGROUND: European travellers to endemic countries are at risk of malaria and may be affected by a different range of co-morbidities than natives of endemic regions. The safety profile, especially cardiac issues, of artenimol (previously dihydroartemisinin)-piperaquine (APQ) Eurartesim® during treatment of uncomplicated imported falciparum malaria is not adequately described due to the lack of longitudinal studies in this population. The present study was conducted to partially fill this gap. METHODS: Participants were recruited through Health Care Provider's safety registry in 15 centres across 6 European countries in the period 2013-2016. Adverse events (AE) were collected, with a special focus on cardiovascular safety by including electrocardiogram QT intervals evaluated after correction with either Bazett's (QTcB) or Fridericia's (QTcF) methods, at baseline and after treatment. QTcB and/or QTcF prolongation were defined by a value > 450 ms for males and children and > 470 ms for females. RESULTS: Among 294 participants, 30.3% were women, 13.7% of Caucasian origin, 13.5% were current smoker, 13.6% current alcohol consumer and 42.2% declared at least one illness history. The mean (SD) age and body mass index were 39.8 years old (13.2) and 25.9 kg/m2 (4.7). Among them, 75 reported a total of 129 AE (27 serious), 46 being suspected to be related to APQ (11 serious) and mostly labelled as due to haematological, gastrointestinal, or infection. Women and Non-African participants had significantly (p < 0.05) more AEs. Among AEs, 21 were due to cardiotoxicity (7.1%), mostly QT prolongation, while 6 were due to neurotoxicity (2.0%), mostly dizziness. Using QTcF correction, QT prolongation was observed in 17/143 participants (11.9%), only 2 of them reporting QTcF > 500 ms (milliseconds) but no clinical symptoms. Using QTcB correction increases of > 60 ms were present in 9 participants (6.3%). A trend towards increased prolongation was observed in those over 65 years of age but only a few subjects were in this group. No new safety signal was reported. The overall efficacy rate was 255/257 (99.2%). CONCLUSIONS: APQ appears as an effective and well-tolerated drug for treatment of malaria in patients recruited in European countries. AEs and QT prolongation were in the range of those obtained in larger cohorts from endemic countries. Trial registration This study has been registered in EU Post-Authorization Studies Register as EUPAS6942.

Unintentional artenimol/piperaquine overdose in two children occurring without evidence of subsequent cardiotoxicity.

At the emergency department of the Robert-Debré children's hospital in Paris, France, artenimol/piperaquine (AP) has been the first-line antimalarial treatment since September 2012. Most children receive the first dose at the hospital and return home if, after 1 hour's observation, there have been no episodes of vomiting. Here we report the case of two children, aged 11 years and 5 years, respectively, in whom the entire cumulative 3 days' treatment course combined was accidentally administered instead of just the first-day treatment dose. Serum piperaquine levels were measured between Hour 40 (H40) and Day 29 (D29) post-ingestion for the first patient, and between H17 and D7 for the second patient. Corrected QT (QTc) values were measured between H12 and D20 for the first patient and between H17 and H64 for the second patient. Despite reports of adverse electrophysiological events, AP overdose occurred without consequence on the QTc interval or clinical cardiac state in these two children.