Tuberculosis treatment outcomes among precarious patients in France.

OBJECTIVES: Patients lost to follow-up and treatment failure in tuberculosis disease (TB) are major public health issues. In the absence of appropriate treatment, approximately 70 % of smear-positive patients will die within 10 years of disease progression. This study, conducted in the French region with the highest incidence, aimed to assess tuberculosis treatment outcomes and its determinants. PATIENTS AND METHODS: A prospective, multicenter cohort study (CO1TB) of adults and children treated for TB was conducted in four hospitals in the North of Paris. Treatment outcome at 1 year and associated socioeconomic and clinical factors were studied by multivariate logistic regression. RESULTS: Among 145 TB cases included from May 2018 to January 2020, patients were mainly born abroad and most lived in difficult socioeconomic conditions. During treatment, 25/145 (17 %) patients experienced adverse effects, which were not significantly associated with discontinuation of treatment (p = 0.99). At 1 year, 114 (78 %) had completed treatments, 26 (19 %) were lost to follow-up, three (2.1 %) were still being treated and two (1.4 %) had died. In the multivariate analysis, a history of TB was significantly associated with unfavorable treatment outcome (aOR = 5.3, 95 %CI (1.5;18.6) and a trend towards significance (p < 0.2) was observed among patients aged under 24 years (aOR = 2.9, 95 %-CI 0.95;8.5). CONCLUSION: In this precarious population, socioeconomic conditions were not found to be associated with unfavorable treatment outcome, whereas history of tuberculosis and young age played a role. Increased monitoring is thus required for these patients.

About the need to address pediatric health inequalities in French Guiana : a scoping review.

INTRODUCTION: French Guiana is a French overseas territory in South America, marked by poverty and inequalities. Access to different services, including healthcare, is unequal depending on where people live. Several studies showed that among adults, the most precarious individuals had greater incidences of chronic and infectious diseases. Although the median age of the population living in this territory is 25, there is no specific focus on the pediatric population although it is documented that socioeconomic inequalities have an impact on child health. The objective of this scoping review is to shed light on health challenges concerning children living in French Guiana. METHODS: A literature search was performed on PubMed to identify relevant articles, and additional references were added if within the scope of this review. RESULTS: A total of 106 publications were reviewed. Perinatal health issues were linked to a high rate of teenage pregnancies with poor medical follow-up leading to complications such as preterm deliveries and congenital malformations and abnormalities. Infectious diseases were a significant burden with worrisome vaccination coverage figures for some bacterial infections, partly explaining a high mortality rate attributable to infectious diseases. Herbicide poisoning with paraquat was reported in children, and environment-related concerns such as wild animal attacks as well as lead and mercury exposure were reported. Some children living in remote Amerindian communities had a higher suicide rate than in mainland France, and chronic diseases such as sickle cell disease were reported to have more transfusion-related complications. CONCLUSION: Children living in French Guiana have worse pediatric health indicators in comparison with children from mainland France.

Public health issues and health rendezvous for migrants from conflict zones in Ukraine: A French practice guideline.

Given the number of people leaving the war zone in Ukraine and arriving in France, the French high council for public health (HCSP) has drawn up a number of recommendations. The experts have taken into account the vulnerability of migrant populations, which is exacerbated by (a) promiscuity that increases the risk of exposure to infectious agents; (b) the psychological consequences of conflict, family separation and exile; (c) prevalence in Ukraine of communicable diseases such as (possibly multi-resistant) tuberculosis, HIV and HCV; (d) low vaccination coverage (risk of circulation of poliovirus) and (e) the risk of spreading infectious diseases (Covid-19, measles…). Consequently, experts recommend that priority be given to: (i) Initial (immediate) reception, which will help to provide emergency care and to assess immediate needs (psychological disorders, risk of medication breakdown and risk of infection); (ii) Other priority measures (vaccination catch-up, including vaccination against SARS-CoV-2 and mandatory vaccination for children's entry into school, screening for post-traumatic stress disorder and tuberculosis) must be implemented as soon as feasible. At this stage, it is imperative: To ensure coordination and access to information throughout the country, by providing medico-social support (opening of social rights and access to care); To digitize medical data for the purposes of traceability; To use professional interpreting and/or health facilitators, or else, if necessary, digital translation tools. (iii) Finally, experts stress the need for vigilance in terms of management, conservation of social rights and continuity of care after the initial period, and organization of a "health rendezvous" within four months of a migrant's entering the country.

Screening for active and latent TB among migrants in France.

SETTING: Migrants to Europe face a disproportionate burden of infections, including TB, yet little is known about the approach taken by primary and secondary care providers to screening and treatment. We therefore explored policy and practice relating to screening of active TB and latent TB infection (LTBI) in France.METHODS: We conducted an online national survey of French primary and secondary care physicians regarding their practices in relation to TB/LTBI screening among migrants.RESULTS: 367 physicians responded to the questionnaire among which 195 (53.1%) were primary care physicians, 126 (34.3%) were TB specialists in secondary care, and 46 (12.5%) other physicians; 303 (85.5%) were involved daily in the care of migrants. Most respondents recommended systematic TB screening with chest X-ray for migrants from medium and high-incidence countries (71.9%). Primary care physicians were less likely to offer screening than physicians in other settings (aOR 0.21, 95% CI 0.09-0.48). 220 (61.8%) offered LTBI screening for children (<15 years) and 34.0% for all migrants from high incidence countries.CONCLUSION: Improving awareness on TB screening is a critical next step to improve health outcomes in migrant groups and meet regional targets for tackling TB.

COVID-19 vaccine hesitancy among persons living in homeless shelters in France.

COVID-19 vaccine hesitancy is frequent and can constitute a barrier to the dissemination of vaccines once they are available. Unequal access to vaccines may also contribute to socioeconomic inequalities with regard to COVID-19. We studied vaccine hesitancy among persons living in homeless shelters in France between May and June 2020 (n = 235). Overall, 40.9% of study participants reported vaccine hesitancy, which is comparable to general population trends in France. In multivariate regression models, factors associated with vaccine hesitancy are: being a woman (OR = 2.55; 95% CI 1.40-4.74), living with a partner (OR = 2.48, 95% CI 1.17-5.41), no legal residence in France (OR = 0.51, 95% CI 0.27-0.92), and health literacy (OR = 0.38, 95% CI 0.21, 0.68). Our results suggest that trends in vaccine hesitancy and associated factors are similar among homeless persons as in the general population. Dissemination of information on vaccine risks and benefits needs to be adapted to persons who experience severe disadvantage.

COVID-19 vaccines: Frequently asked questions and updated answers.

At the end of December 2019, China notified the World Health Organization about a viral pneumonia epidemic soon to be named COVID-19, of which the infectious agent, SARS-CoV-2, was rapidly identified. Less than one year later, published phase 3 clinical trials underlined the effectiveness of vaccines utilizing hitherto unusual technology consisting in injection of the messenger RNA (m-RNA) of a viral protein. In the meantime, numerous clinical trials had failed to identify a maximally effective antiviral treatment, and mass vaccination came to be considered as the strategy most likely to put an end to the pandemic. The objective of this text is to address and hopefully answer the questions being put forward by healthcare professionals on the different anti-SARS-CoV-2 vaccines as regards their development, their modes of action, their effectiveness, their limits, and their utilization in different situations; we are proposing a report on both today's state of knowledge, and the 14 February 2021 recommendations of the French health authorities.

[Vaccination Uptake in Newly-Arrived Migrants in France]. / Le rattrapage vaccinal des personnes migrantes arrivant sur le territoire français.

The issue of catching up vaccines among children and adult migrants is of concern in France. Migrants do not represent a homogeneous population, but a majority of them are insufficiently vaccinated on the basis of the French vaccination schedule that includes more vaccine than those of their countries of origin. Among migrants, people in precarious situations or belonging to certain social groups have poorer immunization coverage, are exposed to a delay in the implementation of their catch-up and are at higher risk of vaccine-preventable infectious diseases. Epidemic situations of vaccine-preventable diseases have been observed in France, accelerating the awareness of the need to implement catch-up vaccination programs and highlighting the difficulties to implement this catch-up in people who have, for the most, already received vaccinations in their countries of origin but have no vaccine proof. Different catch-up strategies are possible with or without pre- or post-vaccination serologies and were the subject of recommendations co-developed by the French High Authority in Health (HAS) and the French Infectious Disease Society (SPILF).

La problématique du rattrapage vaccinal chez les enfants et adultes migrants s'installant en France est un enjeu de santé publique. Les migrants ne représentent pas une population homogène, mais une majorité d'entre eux sont insuffisamment vaccinés au regard du calendrier vaccinal français qui est plus exigeant que ceux des pays d'origine. Au sein des populations migrantes, les personnes en situation de précarité ou appartenant à certains groupes sociaux sont plus souvent insuffisamment vaccinées, sont exposées à un retard de la mise en œuvre de son rattrapage, alors qu'elles sont surexposées au risque de maladies infectieuses à prévention vaccinale comme la rougeole ou la varicelle. Des situations épidémiques de maladies à prévention vaccinale ont été observées en France, accélérant la prise de conscience de la nécessité de mettre en place des programmes de rattrapage vaccinal. Leur mise en œuvre est confrontée à la problématique des modalités pratiques de ce rattrapage chez des personnes ayant pour la grande majorité déjà reçu des vaccinations dans leur pays d'origine, mais n'ayant pas de trace de ces dernières. Différentes stratégies de rattrapage sont possibles avec ou sans recours à des sérologies préou postvaccinales notamment et ont fait l'objet de discussions et de l'élaboration de recommandations sous l'égide de la Haute Autorité de santé (HAS) et de la Société de pathologie infectieuse de langue française (SPILF).

Urogenital schistosomiasis detected in sub-Saharan African migrants attending primary healthcare consultations in Paris, France: a 14-year retrospective cohort study (2004-2017).

Urogenital schistosomiasis (UGS) remains common in sub-Saharan African migrants. The aim of the study was to describe UGS cases detected among patients attending primary healthcare consultations in free outpatient clinics in Paris. This retrospective cohort study included all cases of active UGS from 2004 to 2017. Cases were defined by the presence of Schistosoma haematobium typical ova at urine microscopy. Primary care physicians prescribed it on the basis of epidemiological or clinical criteria. Demographic, clinical, biological, and imaging data were retrieved. Active UGS was diagnosed in 105 cases. The sex ratio (F/M) was 3/102 with a median age of 25. Most cases came from West Africa and recently arrived in Europe (median delay, 1 year). Patients under 18 (23%) were more frequent after 2011. Compatible symptoms were reported in 63/104 patients (60%), hematuria being the most frequent (43/104). Urine dipstick detected micro-hematuria in 42/60 patients screened (70%). In 73 cases, urine microscopy was performed from either one, two, or three micturitions on separate days. The rate of positive urine microscopy increased from one (69.2%) to two micturitions (95.4%). All patients except three received praziquantel. Among those who underwent ultrasonography, 30/86 (35%) had abnormalities, 28/30 at the bladder. A step-by-step clinical assessment led to the detection of active UGS: questions on age, location in childhood and hematuria, physical examination, and urine dipstick. A prospective study in primary care is needed for protocol-based management of active UGS to be part of a socio-medical program for migrants.

Active pulmonary tuberculosis: Role for amikacin in early treatment.

OBJECTIVE: To evaluate the efficacy of amikacin on sputum conversion during initial sputum smear positive tuberculosis treatment. MATERIAL AND METHODS: Single-center observational cohort study (2012-2013) evaluating time to sputum smear conversion with standard treatment (ST) versus standard treatment+amikacin (IV 15mg/kg/day) for seven days (STamK). RESULTS: Forty-five patients were included. Median time to smear negative samples was 26.5 days (14-56) for the 30 (66.7%) patients included in the ST group and 48 days (19.5-69.5) for the 15 patients (33.3%) included in the STamK group (P=0.76). Time to negative culture was only known for 27 patients (61.4%): 47.5 days (26-58) for 18 patients in the ST group and 40 days (14-77) for nine patients in the STamK group. CONCLUSION: Despite our small sample size, the addition of amikacin in active tuberculosis treatment did not seem to impact time to smear conversion or period of contagiousness.

Reproducibility of liver stiffness measurements in hepatitis C virus (HCV)-infected patients in Egypt.

Elastometry has demonstrated good accuracy, but little is known about its reproducibility. The aim of this study was to assess the intra- and inter-operator reproducibility of liver stiffness measurement among hepatitis C virus (HCV)-infected patients in Egypt. The study was conducted among HCV-infected patients referred for treatment evaluation in two hepatitis treatment centres of Cairo. Two operators took liver stiffness measurement two times per patient the same day. Intra- and inter-reproducibility were estimated by different methods: Bland and Altman graphics, variation coefficient, intraclass correlation coefficient and Kappa coefficient; 7.1 kPa was used as the threshold of significant (≥F2) fibrosis whenever needed. Fifty-eight patients were included in the study, and 216 measurements were taken. Failure rate was 7% and associated with overweight. For a value of 7.1 kPa, the inter-operator 95% limits of agreement were estimated at ±2.88 kPa. Intra- and inter-operator coefficients of variation ranged between 11% and 15%, intraclass correlation coefficients [95% confidence interval] between 0.94 [0.86-0.97] and 0.97 [0.95-0.99], and Kappa coefficients between 0.65 [0.44-0.88] and 0.92 [0.81-1.00]. The reliability of liver stiffness measurement is questionable when considering the decision to initiate antiviral therapy because of the percentage of discordance between measurements is notable, especially in the intermediate fibrosis stages.

Altered myocardial gene expression reveals possible maladaptive processes in heterozygous and homozygous cardiac myosin-binding protein C knockout mice.

Familial hypertrophic cardiomyopathy (FHC) is an autosomal dominant disease characterized by left ventricular hypertrophy (LVH) predominantly affecting the interventricular septum. Cardiac myosin-binding protein C (cMyBP-C) mutations are common causes of FHC. Gene expression profiling was performed in left ventricles of 9-week-old wild-type mice, heterozygous cMyBP-C KO mice displaying asymmetric septal hypertrophy, and homozygous mice developing eccentric LVH. Knocking out one or two cMyBP-C genes leads primarily to gene expression changes indicating an increased energy demand, activation of the JNK and p38 parts of the MAPK pathway and deactivation of the ERK part, and induction of apoptosis. Altered gene expression for processes related to cardiac structure, contractile proteins, and protein turnover was also identified. Many of the changes were more pronounced in the homozygous KO mice. These alterations point to physiological and pathological adaptations in the prehypertrophic heterozygous KO mice and the hypertrophic homozygous mice.

Congenital muscular dystrophy with primary partial laminin alpha2 chain deficiency: molecular study.

The authors report a case of congenital muscular dystrophy with mild nonprogressive muscle weakness, white matter hypodensity, and absence of the laminin alpha2 chain in muscle fibers with two antibodies, but not with four others. They identified mutations in LAMA2, which explain the partial laminin alpha2 deficiency. Analysis of this case and two others allows us to refine the epitopes of two of the commercial antibodies, and illustrate the importance of using antibodies directed against different domains of the protein.

Merosin-deficient congenital muscular dystrophy with mental retardation and cerebellar cysts unlinked to the LAMA2, FCMD and MEB loci.

We report a case of congenital muscular dystrophy with secondary merosin deficiency, structural involvement of the central nervous system and mental retardation in an 8-year-old girl from a consanguineous family. She had early-onset hypotonia, generalized muscle wasting, with weakness especially of the neck muscles, joint contractures, mental retardation and high creatine kinase. Muscle biopsy showed dystrophic changes with partial deficiency of the laminin alpha(2) chain. Cranial magnetic resonance imaging revealed multiple small cysts in the cerebellum, without cerebral cortical dysplasia or white matter changes. The laminin alpha(2) chain (6q2), Fukuyama type congenital muscular dystrophy (9q31-q33) and muscle-eye-brain disease (1p32-p34) loci were all excluded by linkage analysis. We suggest that this case represents a new entity in the nosology of congenital muscular dystrophy.

Partial laminin alpha2 chain deficiency in a patient with myopathy resembling inclusion body myositis.

It is becoming evident that clinical phenotypes associated with partial laminin alpha2 chain deficiency are variable. We recently observed a 29-year-old man with leukoencephalopathy and vacuolar myopathy resembling inclusion body myositis. Laminin alpha2 immunohistochemical analysis showed reduction of the protein on muscle fiber surfaces. Molecular analysis revealed two novel compound heterozygous mutations in the LAMA2 gene. This is the first report linking a mutation in the LaMA2 gene with leukoencephalopathy and inclusion body-like myositis.

Identification of homozygous and heterozygous dy2J mice by PCR.

The dystrophia muscularis dy2J/dy2J mouse is an animal model for one form of human congenital muscular dystrophy. A point mutation in the gene coding for the laminin-2 alpha 2 chain leads to the expression of a truncated, partially functional protein. We developed a simple assay for the detection of the dy2J allele, which contains a new NdeI restriction site. Genomic DNA was prepared from animals of known status and amplified by PCR. The digestion of the PCR product with the restriction enzyme resulted in characteristic profiles. Then, this technique was used to identify heterozygous mice among unaffected animals of unknown status. Subsequently, the heterozygous genotype of these mice was confirmed by the birth of dystrophic offspring after mating. This technique allows the detection of the dy2J allele in heterozygous and homozygous animals at any age.

Structure, genetic localization, and identification of the cardiac and skeletal muscle transcripts of the human integrin alpha7 gene (ITGA7).

We have determined the structure and the exon size pattern of the human integrin alpha7 subunit gene (ITGA7), which has been shown to be affected in a form of congenital myopathy. The gene is composed of at least 27 exons spanning a region of about 22.5 kb. The sequence of all exon/intron boundaries was determined and conforms to the GT/AG splicing consensus. We investigated the different splicing forms previously described in human and rodents. The major cytoplasmic variants alpha7A and alpha7B, which are developmentally regulated and tissue specific, were identified in human tissues, as well as the extracellular isoforms X1 and X2. The recently described D variant was detected in adult tissues by RT-PCR but not the C variant. We localized ITGA7 on chromosome 12q13 by high-resolution radiation hybrid mapping between D12S312 and D12S90 and identified a new CA-repeat microsatellite in intron 1.

Genomic organization of the KCNQ1 K+ channel gene and identification of C-terminal mutations in the long-QT syndrome.

The voltage-gated K+ channel KVLQT1 is essential for the repolarization phase of the cardiac action potential and for K+ homeostasis in the inner ear. Mutations in the human KCNQ1 gene encoding the alpha subunit of the KVLQT1 channel cause the long-QT syndrome (LQTS). The autosomal dominant form of this cardiac disease, the Romano-Ward syndrome, is characterized by a prolongation of the QT interval, ventricular arrhythmias, and sudden death. The autosomal recessive form, the Jervell and Lange-Nielsen syndrome, also includes bilateral deafness. In the present study, we report the entire genomic structure of KCNQ1, which consists of 19 exons spanning 400 kb on chromosome 11p15.5. We describe the sequences of exon-intron boundaries and oligonucleotide primers that allow polymerase chain reaction (PCR) amplification of exons from genomic DNA. Two new (CA)n repeat microsatellites were found in introns 10 and 14. The present study provides helpful tools for the linkage analysis and mutation screening of the complete KCNQ1 gene. By use of these tools, five novel mutations were identified in LQTS patients by PCR-single-strand conformational polymorphism (SSCP) analysis in the C-terminal part of KCNQ1: two missense mutations, a 20-bp and 1-bp deletions, and a 1-bp insertion. Such mutations in the C-terminal domain of the gene may be more frequent than previously expected, because this region has not been analyzed so far. This could explain the low percentage of mutations found in large LQTS cohorts.

Merosin-deficient congenital muscular dystrophy with severe mental retardation and normal cranial MRI: a report of two siblings.

The evidence of severe structural brain abnormalities in association with severe mental retardation is characteristic in congenital muscular dystrophy (CMD) forms other than the 'classical' form. However, it seems that the nosology of CMD is not complete yet, as we have clinical, immunohistochemical and genetic data suggesting that there are other unclassified forms. Here we report two CMD siblings from a consanguineous family with partial merosin-deficiency in muscle biopsies, severe mental retardation and normal MRI of the brain. The disease was not linked to the LAMA2 gene (6q22-23) or to Fukuyama congenital muscular dystrophy (FCMD) (9q31-33). To our knowledge, such an association may constitute a new entity within the broad clinical spectrum of CMD.