Search

Abstract Anti-angiogenic agents elicit considerable immune modulatory effects within the tumor microenvironment, underscoring the rationale for synergistic clinical development of VEGF and immune checkpoint inhibitors in advanced gastric cancer (AGC). Early phase studies involving Asian patients demonstrated encouraging anti-tumor efficacies. We report the results of the REGOMUNE phase II study, in which Caucasian patients were administered regorafenib, a multi-tyrosine kinase inhibitor, in combination with avelumab, a PD-L1-targeting monoclonal antibody. This therapeutic regimen resulted in deep and durable responses in 19% of patients, with the median duration of response not yet reached. Notwithstanding, a significant proportion of AGC patients exhibited no therapeutic advantage, prompting investigations into mechanisms of inherent resistance. Comprehensive biomarker profiling elucidated that non-responders predominantly exhibited an augmented presence of M2 macrophages within the tumor microenvironment and a marked overexpression of S100A10 by neoplastic cells, a protein previously implicated in macrophage chemotaxis. Additionally, peripheral biomarker assessments identified elevated levels of cytokines, including CSF-1, IL-4, IL-8, and TWEAK, correlating with adverse clinical outcomes, thereby accentuating the role of macrophage infiltration in mediating resistance. These insights furnish an invaluable foundation for elucidating, and potentially circumventing, resistance mechanisms in current AGC therapeutic paradigms, emphasizing the integral role of tumor microenvironmental dynamics and immune modulation.

Abstract To eliminate malaria, all populations must be included. For those who are not reached by the health care system, specific interventions must be tailor-made. An innovative Malakit strategy, based on the distribution of self-diagnosis and self-treatment kits, has been evaluated in the Suriname-French Guiana- Amapá (Brazil) region. The results showed effectiveness and good acceptability. The Malakit intervention is complex and has many components. Its transferability requires adaptation to other populations and regions, while retaining the main features of the intervention. This article provides the keys to adapting, implementing and evaluating it in other contexts facing residual malaria in hard-to-reach and/or mobile populations. The process of transferring this intervention includes: diagnosis of the situation (malaria epidemiology, characteristics of the population affected) to define the relevance of the strategy; determination of the stakeholders and the framework of the intervention (research project or public health intervention); adaptation modalities (adaptation of the kit, training, distribution strategy); the role of community health workers and their need for training and supervision. Finally, evaluation needs are specified in relation to prospects for geographical or temporal extension. Malaria elimination is likely to increasingly involve marginalized people due to climate change and displacement of populations. Evaluation of the transferability and effectiveness of the Malakit strategy in new contexts will be essential to increase and refine the evidence of its value, and to decide whether it could be an additional tool in the arsenal recommended in future WHO guidelines.

ContextFrench Guiana is a French overseas department where very different linguistic, cultural and societal populations live together in a small area. Health issues and their specific epidemiological profiles call for research projects crossing several cultures. In this context, health mediators have a role to play in research. The aim of this study was to describe the perceptions, attitudes and opinions on research of mediators and researchers collaborating on research projects, and to describe the strengths and difficulties encountered during this cooperation.MethodsThe Inter-med project was conducted in French Guiana between February 2022 and April 2023 on the base of semi-directive interviews with mediators, or researchers, all working in health research in the intercultural context of French Guiana. The socio-demographic characteristics of the participants were described. An inductive thematic analysis was carried out on all the interviews, and word occurrence analysis on certain themes. The information was triangulated with field coordination notebooks from two epidemiological surveys conducted in French Guiana between 2021 and 2022.ResultsA total of 26 semi-structured interviews were conducted and 1,328 notebook pages analyzed. Mediation was described as an indispensable interface between the world of research and that of the population targeted by a survey. Mediators have a role to play at different stages of projects, in respect of good clinical practice, ethics and legislation. They act as interfaces between languages, concepts and representations. Their profession remains under-defined and under-dimensioned. The jobs offered are often precarious. Mediation work is emotionally costly, calls on soft skills and requires a combination of rigor and flexibility. All these aspects are implemented in the specific world of research, where there are common concepts and divergent perceptions. Researchers and mediators converge on a common goal: improving health.ConclusionThis study covers several aspects of the development and implementation of research projects. Respect for good clinical practice and people, transparency and data quality are redundant concerns, and this study touches on ethnocentrism, stigmatization and cultural representations. This study points out that the integration and recognition of mediators could be beneficial in research conducted in a cross-cultural context.

Background: Radiotherapy combined with fluorouracil (5FU) and cisplatin for locally advanced esophageal cancer is associated with a 20–25% pathologic complete response (pCR) rate. Cetuximab increases the efficacy of radiotherapy in patients with head and neck carcinomas. The aim of this phase I/II trial was to determine the optimal doses and the pCR rate with chemoradiotherapy (C-RT) plus cetuximab. Methods: A 45-Gy radiotherapy regimen was delivered over 5 weeks. The phase I study determined the dose-limiting toxicity and the maximum tolerated dose of 5FU-cisplatin plus cetuximab. The phase II trial aimed to exhibit a pCR rate > 20 % (25 % expected), requiring 33 patients (6 from phase I part plus 27 in phase II part). pCR was defined as ypT0Nx. Results: The phase I study established the following recommended doses: weekly cetuximab (400 mg/m2 one week before, and 250 mg/m2 during radiotherapy); 5FU (500 mg/m2/day, d1-d4) plus cisplatin (40 mg/m2, d1) during week 1 and 5. In the phase II part, 32 patients received C-RT before surgery, 31 patients underwent surgery, and resection was achieved in 27 patients. A pCR was achieved in five patients (18.5 %) out of 27. After a median follow-up of 19 months, the median progression-free survival was 13.7 months, and the median overall survival was not reached. Conclusions: Adding cetuximab to preoperative C-RT was toxic and did not achieve a pCR > 20 % as required. The recommended doses, determined during the phase I part, could explain these disappointing results due to a reduction in chemotherapy dose-intensity. Trial registration: This trial was registered with EudraCT number 2006-004770-27.

Abstract Background First‐line nivolumab plus chemotherapy and nivolumab plus ipilimumab both demonstrated significant overall survival (OS) benefit versus chemotherapy in previously untreated patients with advanced esophageal squamous cell carcinoma (ESCC) in the CheckMate 648 trial, leading to approvals of both nivolumab‐containing regimens in many countries. We report longer‐term follow‐up data. Methods This open‐label, phase III trial (NCT03143153) enrolled adults with previously untreated, unresectable, advanced, recurrent, or metastatic ESCC. Patients were randomized 1:1:1 to nivolumab plus chemotherapy, nivolumab plus ipilimumab, or chemotherapy. Primary endpoints were OS and progression‐free survival (PFS) by blinded independent central review. Hierarchical testing was performed first in patients with tumor cell programmed death ligand 1 (PD‐L1) expression of ≥1% and then in the overall population. Results A total of 970 patients were randomly assigned. After 29 months of minimum follow‐up, nivolumab plus chemotherapy continued to demonstrate improvement in OS versus chemotherapy (hazard ratio [HR] = 0.59 [95% CI: 0.46–0.76]) in patients with tumor cell PD‐L1 expression of ≥1% and in the overall population (HR = 0.78 [95% CI: 0.65–0.93]) and with nivolumab plus ipilimumab versus chemotherapy (HR = 0.62 [95% CI: 0.48–0.80]) in patients with tumor cell PD‐L1 expression of ≥1% and in the overall population (HR = 0.77 [95% CI: 0.65–0.92]). In patients with tumor cell PD‐L1 expression of ≥1%, nivolumab plus chemotherapy demonstrated PFS benefit versus chemotherapy (HR = 0.67 [95% CI: 0.51–0.89]); PFS benefit was not observed with nivolumab plus ipilimumab versus chemotherapy (HR = 1.04 [95% CI: 0.79–1.36]). Among all treated patients (n = 936), Grade 3–4 treatment‐related adverse events were reported in 151 (49%, nivolumab plus chemotherapy), 105 (32%, nivolumab plus ipilimumab), and 110 (36%, chemotherapy) patients. Conclusions Nivolumab plus chemotherapy and nivolumab plus ipilimumab continued to demonstrate clinically meaningful OS benefit versus chemotherapy with no new safety signals identified with longer follow‐up, further supporting use as first‐line standard treatment options for patients with advanced ESCC.

(1) Background: Only a few studies on histoplasmosis in immunocompetent patients have been reported in French Guiana. Therefore, we conducted a detailed clinical description of hospitalized patients suffering with histoplasmosis among non-HIV patients. (2) Methods: This is a single-center, retrospective study conducted at Cayenne Hospital Center between 2008 and 2022. (3) Results: Our cohort was composed of 31 (91%) adults (>18 years of age) and 3 (9%) children, with a sex ratio, M:F, of 1:2. The median age was higher among the women than among the men (70 versus 54 years). The collection of respiratory samples constituted the majority of the performed examinations (38%). Fever (>37 °C) was found in 56% of patients. Surprisingly, the histoplasmosis was disseminated in 82% of patients with an overall case fatality rate of 14.7%. However, immunosuppressive conditions were found in 52% (16/31) of the adult patients, including lymphoid hemopathies, diabetes and immunosuppressive drugs. Conclusions: This disease, though rare and usually considered a mostly benign disease in non-HIV patients, presented a relatively high mortality rate in our cohort. Thus, histoplasmosis should be suspected, screened and investigated as a first line of defense in highly endemic areas, even in immunocompetent and non-HIV patients, especially those with fever or chronic respiratory symptoms.

Abstract Scaling-up an experimental intervention is always a challenge. On the border between French Guiana, Brazil and Suriname, an interventional study demonstrated the effectiveness of distributing self-diagnosis and self-treatment kits (Malakits) to control malaria in mobile and hard-to-reach populations. Its integration into the Suriname’s National Malaria Elimination Plan after a 2-year experiment faced numerous challenges, including human resources to cope with the additional workload of coordinators and to maintain the motivation of community health workers. The economic recession in Suriname, the Covid pandemic, and logistical issues also hampered the scale-up. Finally, thanks to the commitment of stakeholders in Suriname and French Guiana, the integration of Malakit distribution into the Surinamese national programme was proved possible.

Abstract Background In French Guiana (population 294,000) the prevalence of type 2 diabetes (10%) and of HIV(1.1%) are very high. Our objective was to determine the prevalence of diabetes and its complications in a HIV cohort. Materials and methods We enrolled HIV-infected persons followed in Cayenne, Kourou, and Saint Laurent du Maroni hospitals between January 1, 1992 and December 31, 2021 in the French Hospital Database for HIV (FHDH) a national database compiling data from all French regions. Results There was no difference of diabetes prevalence between men (8.2%) and women (8.8%), P = 0.4. Patients with diabetes were older (56 years ± 13.4) than those without diabetes (44.7 years ± 13.6) and prevalence increased with age. The proportion of persons with diabetes was greater among virologically suppressed persons (10%) than those with a detectable viral load under antiretroviral treatment (5.8%). Persons with diabetes had substantially greater CD4 counts at diagnosis than persons without diabetes. The majority of macro and microvascular complications were observed in people with diabetes. Persons with diabetes and HIV were significantly less likely to have had AIDS (1.6 versus 2.2 per 100 person-years, respectively). Overall, 374 persons living with HIV of 4167 had died (9%) the proportion of persons with diabetes among the dead was greater than those who did not die 11.7% versus 8.1%, respectively, p = 0.017. However, persons with diabetes were older and hence died older, 62.3 years (SD = 1.9) for deceased persons with diabetes versus 50.4 years (SD = 0.8), P

Objectives: The burden of histoplasmosis is as great as that of tuberculosis in Latin America and the attributable mortality is even higher. A better assessment of severity could help reduce mortality. Methods: From the French Guiana HIV-histoplasmosis database, we attempted to identify factors associated with 30-day death after antifungal drug initiation and constructed a prognostic score. We evaluated its discrimination performance using several resampling methods. Results: Of the 415 patients included, 56 (13.5%) died within 30 days of treatment. The fatality-associated factors were performance status ≥3, altered mental status, dyspnea, C-reactive protein ≥75 mg/l, hemoglobin

In French Guiana, life expectancy is between 2 and 3 years below that of France, reflecting differences in mortality rates that are largely sensitive to primary healthcare and thus preventable. However, because poverty affects half of the population in French Guiana, global measurements of life expectancy presumably conflate at least two distinct situations: persons who have similar life expectancies as in mainland France and persons living in precariousness who have far greater mortality rates than their wealthier counterparts. We thus aimed to synthesize what is known about statistical regularities regarding exposures and sketch typical French Guiana exposomes in relation to health outcomes. We conducted a narrative review on common exposures in French Guiana and made comparisons between French Guiana and mainland France, between rich and poor in French Guiana, and between urban and rural areas within French Guiana. The most striking fact this panorama shows is that being a fetus or a young child in French Guiana is fraught with multiple threats. In French Guiana, poverty and poor pregnancy follow-up; renouncing healthcare; wide variety of infectious diseases; very high prevalence of food insecurity; psychosocial stress; micronutrient deficiencies; obesity and metabolic problems; and frequent exposure to lead and mercury in rural areas constitute a stunningly challenging exposome for a new human being to develop into. A substantial part of the population’s health is hence affected by poverty and its sources of nutrition.

IntroductionIn a context of high HIV prevalence, poor pregnancy follow-up, frequent poverty, preeclampsia, and preterm delivery, we aimed to describe the characteristics and outcomes of pregnancies among women living with HIV in French Guiana.MethodsA retrospective cohort study was conducted on HIV-infected pregnancies enrolled between January 1st 1992 to 31st July 2022. Overall, there were 1,774 pregnancies in 881 women living with HIV.ResultsFor 75.1% of pregnancies, the HIV diagnosis was already known before pregnancy and in 67.6% of women, HIV follow-up predated pregnancy. Nearly half of women, 49.6%, only had one pregnancy since having been diagnosed with HIV. Although most women received antiretroviral therapy during pregnancy, for those with the available information we found only 48.5% had an undetectable viral load at delivery. Overall, 15.3% of pregnancies ended with an abortion. There were a total of 110 newborns infected with HIV representing an overall transmission rate of 6.2% (110/1,771). Between 1993 and 2002, the transmission rate was 34%, between 2003 and 2012 it was 1.3%, and between 2013 and 2022 it was 0.7%. Overall, in Cayenne, since 2008, 106 of 581 HIV–infected pregnancies (18.2%) with available information were premature before 37 weeks of pregnancy; of these, 33 (5.7%) were very preterm deliveries and 73 (13.3%) were late preterm deliveries. Over time, in Cayenne, preterm delivery declined significantly.ConclusionsThe present study emphasizes that, despite spectacular progress in reducing mother to child transmission, pregnancy outcomes among women living with HIV are still preoccupying with high incidence of preterm delivery and low birth weight. Teasing out what fraction is linked to HIV and what fraction is linked to social precariousness and poor follow-up was not possible in this study. Despite the high incidence of very preterm delivery recent progress suggests that coordination efforts to improve follow-up may also have improved obstetrical outcomes.

In French Guiana, more than a third of the population, and nearly half of the adults, are of foreign origin. This immigration is explained by the French standard of living, which is attractive to nationals of surrounding countries. Infectious diseases remain in the top 10 causes of premature death, often in the most precarious populations. In this context we aimed to synthesize the state of the knowledge regarding immigration and infectious diseases in French Guiana and the general implications that follow this diagnosis.For HIV, although the majority of patients are of foreign origin, estimates of the presumed date of infection based on CD4 erosion modelling and from molecular analyses suggest that the majority of transmissions in foreign-born individuals occur in French Guiana and that the Guiana shield has been a crossroad between Latin America and the Caribbean. Among key populations bridging these regions illegal gold miners are very mobile and have the greatest proportion B Caribbean HIV viruses. Gold miners have been a key vulnerable population for falciparum malaria and other tropical diseases such as leishmaniasis, leprosy, or leptospirosis. The complex history of migrations in French Guiana and on the Guiana Shield is also reflected in the fingerprinting of mycobacterium tuberculosis and the high incidence of tuberculosis in French Guiana, notably in immigrants, reflects the incidences in the countries of origin of patients. The high burden of infectious diseases in immigrants in French Guiana is first and foremost a reflection of the precarious living conditions within French Guiana and suggests that community-based proactive interventions are crucial to reduce transmission, morbidity, and mortality from infectious diseases.

Introduction Social determinants of health, such as living and working conditions, economical and environmental context and access to care, combine to impact the health of individuals and communities. In French Guiana (FG), the persons working in informal artisanal and small-scale gold mining in the rainforest are a particularly vulnerable population which lives in precarious conditions and far from the health system. Previous studies have demonstrated their high morbidity due to infectious diseases. This study aims to describe the social determinants of health in this specific population.Methods This international multicentre cross-sectional survey included people working on the informal FG gold mines at the crossing points located at both borders with Suriname and Brazil. After collecting written informed consent, a structured questionnaire was administered.Results From September to December 2022, 539 gold miners were included. These poorly educated migrants, mainly from Brazil (99.1%) did not have access to drinkable water (95.4%), lived in close contact with wild fauna by hunting, eating bushmeat or being bitten and were exposed to mercury by inhalation (58.8%) or ingestion (80.5%). They report frequent accidents (13.5%) and chronic treatment interruptions (26.6% of the 11.9% reporting chronic treatment). Half of them considered themselves in good health (56.4%).Conclusion This study shows a singular combination of adverse exposures of gold miners working in FG such as zoonoses, heavy metal poisoning, aggression of wild fauna. For ethical as well as public health reasons, actions towards health equity must be considered at different levels: individual, community, environmental, systemic and global level. As end users of minerals, we must assume our responsibilities for the well-being of the extractors by including health in political decisions to engage together in global health.Trial registration number NCT05540470.

The drivers of the HIV epidemic, the viruses, the opportunistic infections, the attitudes and the resources allocated to the fight against HIV/AIDS, vary substantially across countries. French Guiana, at the crossroads between Amazonian South America and the Caribbean, constitutes a singular context with poor populations and rich country health funding, which has allowed researchers to gather lots of information on the particulars of our epidemic. We aimed to focus on the little known story of forty years of HIV research in French Guiana and emphasize how local research intertwined with public health action has yielded continuous progress, despite the difficult social conditions of the affected population. We searched Web of Science and associated local experts who worked through much of the epidemic in selecting the most meaningful products of local research for clinical and public health outcomes in French Guiana. Research tools and facilities included, from 1991 onwards, the HIV hospital cohort and the HIV-histoplasmosis cohort. Ad hoc studies funded by the ANRS or the European Regional Development fund shed light on vulnerable groups. The cumulative impact of prospective routine collection and focused efforts has yielded a breadth of knowledge, allowing for informed decisions and the adaptation of prevention, testing and care in French Guiana. After this overview, we emphasize that the close integration of research and public health was crucial in adapting interventions to the singular context of French Guiana.

IntroductionWith over half of the population living under the poverty threshold, the social and health context in French Guiana is more difficult than in mainland France. The prevalence of diabetes is twice as great and end-stage renal failure is 45% higher than in mainland France.ObjectiveOur objective was to describe the profile of diabetic patients with chronic kidney disease in French Guiana and search for possible risk factors.MethodWe conducted a multicenter cross-sectional observational study based on the CODIAM cohort (Cohort of Diabetes in French Amazonia). We analyzed 1,287 patients followed up between May 2019 and June 2021 at Cayenne Hospital, Saint Laurent Hospital, and delocalized health centers.ResultsIn our cohort, chronic kidney disease was present after an average of 12 years of diabetes. Compared with the French population, 41% of diabetic patients had chronic kidney disease (i.e., 12% more), and had an average age of 56 years (i.e., 10 years younger). Forty-eight per cent of these patients were obese (i.e., 7% more). Seventy-four per cent of patients were precarious and 45% were foreigners but neither was associated with chronic kidney disease, contrary to countries where the health system is not universal.ConclusionScreening of patients with chronic kidney disease among diabetics in French Guiana remains a real challenge. Patients were younger and more obese than in other French territories. In this cohort, precariousness and immigration were not associated with the presence of chronic kidney disease. However, particular attention should be paid to hypertensive patients and those over 65 years of age, which are, with diabetes itself, the two most obvious risk factors for developing chronic kidney disease among diabetic patients in our territory.

BackgroundAccess to health care is a major public health issue. The social determinants of health have a role in accessing health care and in meeting the health needs of populations. With 281 million international migrants around the world, population movements are another major issue. Migrants are particularly exposed to precariousness during their migratory journey and after their settlement. These vulnerabilities may have deleterious effects on their health status and on their social conditions. In French Guiana, 36% of the population is of foreign origin. The objective of this study is to explore the barriers and the facilitators to accessing health care for migrants in French Guiana in 2022, from the perspective of health care professionals, social workers and local NGO actors.MethodsThis research is an exploratory qualitative study based on the experiential knowledge of health care professionals, social workers and local NGO actors in French Guiana. 25 semi-structured interviews were conducted with these professionals and actors between April and June 2022, using an interview guide to explore their practices, representations and beliefs of access to health care and accompaniment of migrants in their patient journey. The interviews were transcribed and analyzed using the thematic analysis method.ResultsA total of 25 health care professionals, social workers and local NGO actors were included in the study. Participants highlighted that migrants are exposed to many factors hindering their access to health care in French Guiana (administrative complexity, language barriers, financial barriers, mobility issues, etc.). With the situations of great precariousness and the inadequacies of the public authorities, associative support (social, health and legal accompaniment process provided by NGOs and associations) has an important role in providing close support to migrants. Moreover, health mediation supports migrants in their social and health care journey to lead them toward empowerment. Health mediators contribute to promote a better understanding between professionals and migrants.ConclusionIn French Guiana, associative support and health mediation promote access to health care and social accompaniment for migrants. This article highlights the issues surrounding access to health care, associative support and health mediation in the Guianese context, which is marked by significant socio-cultural diversity and precariousness. Considering the benefits of associative support and health mediation, as well as social inequalities in health, is essential for health care professionals, social workers, local NGO actors, associations, public health authorities and political decision-makers to initiate concrete and suitable actions in favor of access to health care and social support for migrants in French Guiana.

Abstract Background Clandestine gold miners remain key hosts for malaria in French Guiana (FG) and contribute to imported malaria cases in Suriname and Brazil. The Malakit intervention, implemented in FG borders with Suriname and Brazil, provided gold miners with training on malaria and kits for self-diagnosis and self-treatment. Having shown a likely impact on malaria transmission, Suriname has now implemented it in routine care for cross-border moving populations. However, a decrease in malaria transmission is frequently associated with a decrease in risk perception, knowledge, and good practices regarding malaria. This study aims to describe the evolution of the perceptions, knowledge, attitudes, and practices (KAP) related to malaria among clandestine gold miners between 2015 and 2019, and to estimate the impact of Malakit on the FG/Suriname border. Methods The primary outcome was the overall KAP score over time and among participants and not participants in the Malakit intervention. A propensity score matching analysis and an inverse probability of treatment weighing analysis were used to estimate the Average Treatment effect on the Treated and the Average Treatment Effect of Malakit, respectively. Results Perception and knowledge scores were significantly lower in 2019 compared to 2015 (− 0.27 and − 0.23 points, respectively, p

Objectives: French Guiana, the least-vaccinated French territory, also has the lowest COVID-19 vaccination coverage in Latin America. We aimed to estimate how many deaths, hospitalizations and costs the vaccines had and could have avoided. Methods: We calculated the Number Needed to Vaccinate to prevent one death per year, 1 standard hospitalization, 1 Intensive Care Unit admission given the mean incidence numbers of the past 6 months, and divided the number of persons vaccinated to estimate how many deaths and hospitalizations had been avoided in French Guiana at that time. Results: The crude number needed to vaccinate to prevent one death per year, the crude number needed to vaccinate to prevent one hospitalization per 6 months were computed Based on our observed incidence and ICU admission rate, the crude number needed to vaccinate to prevent one ICU admission per 6 months.After 6 months with an incidence exceeding 400 per million inhabitants, and 148 observed deaths, we estimate that vaccination avoided 46 deaths (IC95%=43.5–48.7). If the number of vaccinated persons had reached the same proportion as mainland France, 141 deaths per year could have been prevented (IC95%=131.9–147.6).With 2085 hospitalization and 370 ICU admissions during the same period, we estimate that the current albeit low vaccination rate avoided 300 hospital (IC95%=280–313) and 77 (IC95%=72–81) ICU admissions. With the same vaccination rates as mainland France, we estimate that 900 hospitalizations and 231 ICU admissions would have been avoided.Similarly, there would have been 139 ICU admission (instead of 370). Conclusions: In sparsely populated French Guiana these numbers are quite substantial and framing the vaccine benefits and wasted opportunities using such concrete numbers may help convincing undecided persons to get vaccinated.

BackgroundIn Reunion Island, dengue outbreaks have been occurring since 2018. The healthcare facilities are facing the problem of managing a massive influx of patients and a growing care burden. The aim of this study was to evaluate the performance of the SD Bioline Dengue Duo rapid diagnostic test in adults consulting at an emergency department during the 2019 epidemic.Methodology/principal findingsThis retrospective study of diagnostic accuracy included patients over 18 years old, suspected of dengue, who were admitted to emergency units of the University Hospital of Reunion between the 1st of January and 30th of June, 2019, and were tested for dengue fever with the SD Bioline Dengue Duo rapid diagnostic test and reverse transcriptase polymerase chain reaction. Over the study period, 2099 patients were screened retrospectively. Of them, 671 patients matched the inclusion criteria. The overall rapid diagnostic test performance was 42% for sensitivity and 15% for specificity. The non-structural 1 antigen component had a good specificity of 82% but a low sensitivity of 12%. The immunoglobulin M component had a sensitivity of 28% and a specificity of 33%. Sensitivities were slightly improved beyond the 5th day of illness compared to the early stage for all components, but only the non-structural 1 antigen component had a better specificity of 91%. Furthermore, predictive values were low and post-test probabilities never improved pre-test probabilities in our setting.Conclusions/significanceThese results suggest that the SD Bioline Dengue Duo RDT did not achieve sufficient performance levels to rule in, or discard, an early point of care dengue diagnosis in the emergency department during the 2019 epidemic in Reunion.

Abstract Background A novel strategy to combat malaria was tested using a methodology adapted to a complex setting in the Amazon region and a hard-to-reach, mobile community. The intervention strategy tested was the distribution, after training, of malaria self-management kits to gold miners who cross the Surinamese and Brazilian borders with French Guiana to work illegally in the remote mining sites in the forest of this French overseas entity. Main text This article aims at presenting all process and implementation outcomes following the Conceptual Framework of Implementation Fidelity i.e. adherence, including content and exposure, and moderators, comprising participant responsiveness, quality of delivery, facilitation strategies, and context. The information sources are the post-intervention survey, data collected longitudinally during the intervention, a qualitative study, data collected during an outreach mission to a remote gold mining site, supervisory visit reports, in-depth feedback from the project implementers, and videos self-recorded by facilitators based on opened ended questions. As expected, being part of or close to the study community was an essential condition to enable deliverers, referred to as “facilitators”, to overcome the usual wariness of this gold mining population. Overall, the content of the intervention was in line with what was planned. With an estimated one third of the population reached, exposure was satisfactory considering the challenging context, but improvable by increasing ad hoc off-site distribution according to needs. Participant responsiveness was the main strength of the intervention, but could be enhanced by reducing the duration of the process to get a kit, which could be disincentive in some places. Regarding the quality of delivery, the main issue was the excess of information provided to participants rather than a lack of information, but this was corrected over time. The expected decrease in malaria incidence became a source of reduced interest in the kit. Expanding the scope of facilitators’ responsibilities could be a suitable response. Better articulation with existing malaria management services is recommended to ensure sustainability. Conclusions These findings supplement the evaluation outcomes for assessing the relevance of the strategy and provide useful information to perpetuate and transfer it in comparable contexts. Trial registration ClinicalTrials.gov. NCT03695770 . 10/02/2018 “Retrospectively registered”.

Background and Aims. In French Guiana, the prevalence of diabetes is around 10%, and cardio and neurovascular pathologies are the first medical cause of early mortality. Lipoprotein(a) (Lp(a)) is described in the literature as a risk factor independent of other cardiovascular risk factors, but there are important interindividual differences, especially according to ethnicity. The objective of this study was to investigate the association of Lp(a) and macrovascular complications in a multiethnic population of patients with diabetes in the French Amazon. Materials and Methods. Since May 2019, 1243 patients were screened 806 of whom had Lp(a) determination. We compared the prevalence of macrovascular complications in three groups according to Lp(a) concentration: between 0 and 75 mg/mL, between 76 and 300 mg/mL, and >300 mg/mL. Results. 712 patients in the study had type 2 diabetes (88.34% of the sample). A history of hypertension was significantly associated with greater Lp(a) levels. Lp(a) concentration was greater among Creole ethnic groups. No association was found between Lp(a) levels and macrovascular complications in the Lpa>300 mg/mL group. Conclusions. These results do not replicate findings in mostly Caucasian populations suggesting that the Lp(a) threshold for, or the link with, cardiovascular risk may be different given the predominantly African origin of the French Guianese population. Further studies should study genetic polymorphisms in our population.

PurposeThe border between the State of Amapa, Brazil, and French Guiana is mostly primary forest. In the Oyapock basin, socioeconomic circumstances have fueled sex work, gold mining and the circulation of sexually transmitted infections. Given the lack of comprehensive data on this border area, we describe the different sexually transmitted infections along the Brazil/French Guiana border and the testing and care activity.MethodsWe conducted a review of the available scientific and technical literature on sexually transmitted infections in this complex border area. Temporal trends were graphed and for Human Immunodeficiency Virus (HIV) we estimated incidence using the European Center for prevention and Disease Control modeling tool.ResultsUntil 2019, 26 of the 46 HIV-infected patients followed and treated in Saint Georges de l'Oyapock were residing on the Brazilian side in Oiapoque. Virological suppression was only achieved for 75% of treated patients; but dropped to 62% during the COVID-19 epidemic. In 2019, cooperation efforts allowed HIV care in Oiapoque, resulting in the transfer of Brazilian patients previously followed on the French side and a substantial increase in the number of patients followed in Oiapoque. The average yearly HIV serological testing activity at the health center in Saint Georges was 16 tests per 100 inhabitants per year; in Camopi it was 12.2 per 100 inhabitants. Modeling estimated the number of persons living with HIV around 170 persons, corresponding to a prevalence of 0.54% and about 40 undiagnosed infections. The model also suggested that there were about 12 new infections per year in Saint Georges and Oiapoque, representing an HIV incidence rate of 3.8 cases per 10,000 per year. HPV prevalence in Saint Georges ranges between 25 and 30% and between 35 and 40% in Camopi. Testing activity for other sexually transmitted infections markedly increased in the past 5 years; the introduction of PCR for chlamydiasis and gonorrhea also had a substantial impact on the number of diagnoses.ConclusionsThe ongoing cooperation between multiple partners on both sides of the border has led to remarkable progress in primary prevention, in testing efforts, in treatment and retention on both sides of the border. In a region with intense health professional turnover, nurturing cooperation and providing accurate assessments of the burden of sexually transmitted infections is essential to tackle a problem that is shared on both sides of the border.

Circulating cell‐free DNA (cfDNA) contains circulating tumor DNA (ctDNA), which can be obtained from serial liquid biopsies to enable tumor genome analysis throughout the course of treatment. We investigated cfDNA and mutant ctDNA as potential biomarkers to predict the best outcomes of regorafenib‐treated metastatic colorectal cancer (mCRC) patients. We analyzed longitudinally collected plasma cfDNA of 43 mCRC patients prospectively enrolled in the phase II TEXCAN trial by IntPlex qPCR. Qualitative (KRAS, NRAS, BRAFV600E mutations) and quantitative (total cfDNA concentration, mutant ctDNA concentration, mutant ctDNA fraction) parameters were correlated with overall survival (OS) and progression‐free survival (PFS). When examined as classes or continuous variables, the concentrations of total cfDNA, mutant ctDNA, and, partly, mutant ctDNA fraction prior to regorafenib treatment correlated with OS. Patients with baseline cfDNA > 26 ng·mL−1 had shorter OS than those with cfDNA value below this threshold (4.0 vs 6.9 months; log‐rank P = 0.0366). Patients with baseline mutant ctDNA > 2 ng·mL−1 had shorter OS than those with mutant ctDNA below this threshold (log‐rank P = 0.0154). We show that pretreatment cfDNA and mutant ctDNA levels may identify mCRC patients that may benefit from regorafenib treatment.

BackgroundProgressive disseminated histoplasmosis remains a major but neglected cause of death among patients with advanced HIV. Recently, aiming to reduce avoidable deaths, the Pan American Health Organization issued the first diagnosis and treatment guidelines for HIV-associated histoplasmosis. But what proportion of progressive disseminated histoplasmosis in HIV-infected patients is severe is currently not known. Because this proportion influences treatment needs, we aimed to estimate this in a cohort of 416 patients in French Guiana.MethodsWe used the definition in the recent PAHO/WHO guidelines for severity. We used regression modelling to predict the impact of CD4 count on the proportion of severe cases. In a territory where treatment cost is not a limiting factor and where histoplasmosis is well known, we assumed that clinicians' initial treatment reflected their perception about the severity of the case and therefore, the needs for different treatments.ResultsUsing these definitions, since the beginning, there were 274 (65.9%) severe/moderately severe cases and 142 (34.1%) mild cases. In practice 186 cases were treated with deoxycholate or liposomal amphotericin B (44.7%) and 230 (55.3%) cases treated with itraconazole as first line treatment. The Kappa concordance measure between the guideline definition and the actual treatment given was 0.22. There was a 9% risk difference for death within 30 days of antifungal treatment initiation between severe/moderately severe and mild cases. Over threequarters (77%) of early deaths were attributed to severe/moderately severe cases.ConclusionsThis is the only rigorous estimate of the proportion of severe/moderately severe cases of progressive disseminated histoplasmosis in symptomatic HIV patients on the largest published cohort. These numbers may help defend budget needs for rapid diagnostic tests and liposomal amphotericin B.

BackgroundFrench Guiana is a multicultural French territory in Amazonia with an old migration history and a high prevalence of HIV infection. The objective of this study was to evaluate situations of sexual vulnerability and their associated factors among migrant women in French Guiana.MethodsA cross-sectional epidemiological study was carried out in 2021 in the French Red Cross Prevention and Health Centers of the two main cities of French Guiana (Cayenne and Saint Laurent du Maroni). Analysis was performed with multivariate stepwise logistic regression using Stata 15.0 software.FindingsA total of 382 migrant women were included, with a median age of 31 years, mainly born in Haiti (80%), Suriname (9%), or Dominican Republic (6%), undocumented (71%), and with financial difficulties (77%). Among the 20% having casual partners, 57% reported unprotected sexual intercourse, more often the Haitian and Surinamese women. A history of rape was reported by 20% of women, most often in the country of origin (71%). Lifetime rape was associated with being threatened [aOR = 3.69 (1.96–6.96)] or being physically abused [aOR = 12.95 (6.51–25.75)] in the multivariate analysis. Among the women surveyed, 30% reported having ever exchanged sex for money, food, or shelter in their lifetime. Transactional sex is more common among Dominican women [aOR = 5.59 (1.84–16.95)] and women living in French Guiana for more than 2 years [aOR = 2.32 (1.38–3.92)]. Transactional sex is also associated with alcohol misuse [aOR = 2.57 (1.46–4.53)], history of threats [aOR = 2.03 (1.14–3.63)], history of rape [aOR = 1.92 (1.03–3.60)], and depressive disorders [aOR = 2.08 (1.21–3.60)].InterpretationMigrant women in French Guiana are in a situation of sexual vulnerability. An intervention focused on sexual education and the promotion of prevention tools among Haitian women is advisable. Better prevention and support for transactional sex are needed to prevent violence and its mental health and alcohol misuse consequences for all women, especially Dominican women.

BackgroundMost emerging pathogens are zoonoses and have a wildlife origin. Anthropization and disruption of ecosystems favor the crossing of inter-species barriers. We hypothesize that the marginalized population of undocumented goldminers in the Amazon is at risk of acquiring zoonoses.MethodA multicentric cross-sectional study included consenting gold-mining adult workers in 2019. A clinical examination recorded dermatological signs of leishmaniosis and past history of yellow fever vaccination. Biological tests were performed for yellow fever, Q fever and leptospirosis serologies. Additional blood samples from a previous study in 2015 were also tested for leptospirosis.ResultsIn 2019, 380 individuals were included in the study, along with 407 samples from the 2015 biological collection. The seroprevalence of leptospirosis was 31.0% [95%CI = 26.4-35.5] in 2015 and 28.1% [23.5-32.7] in 2019. The seroprevalence of Q fever was 2.9% [1.2-4.6]. The majority of participants reported being vaccinated against yellow fever (93.6%) and 97.9% had seroneutralizing antibodies. The prevalence of suspected active mucocutaneous leishmaniasis was 2.4% [0.8-3.9].DiscussionThese unique data shed new light on the transmission cycles of zoonoses still poorly understood in the region. They support the existence of a wild cycle of leptospirosis but not of Q fever. Leishmaniasis prevalence was high because of life conditions and tree felling. High yellow fever vaccine coverage was reassuring in this endemic area. In the era of global health, special attention must be paid to these vulnerable populations in direct contact with the tropical ecosystem and away from the health care system.

AimsThe social parameters of an individual impact the incidence of cardiovascular diseases. French Guiana, an overseas French territory with a lower standard of living than France, has a prevalence of diabetes mellitus that is twice that of mainland France. In this context we aimed to study the relation between precariousness, diabetes complications and glycemic control.MethodsA multicenter prospective cohort was initiated since May 2019. 1243 patients were included and their outcomes and history were compared between the precarious and non-precarious based on their EPICES score, a score that measures social isolation and precariousness.Results73.3% of the sample was considered precarious. Retinopathy was significantly more frequent among the deprived. There were no significant differences for other macro or microvascular complications.There was a significant difference in Glycated Haemoglobin between the precarious and non-precarious groups (8.3% (67 mmol/l) vs 8.8% (73mmol/l)). After adjusting for potential confounders, precariousness was no longer associated with poor glycemic control; the independent factors significantly associated with poor glycemic control were: not being fluent in French, having creole or portugese as mother language, and not having any insurance.ConclusionsPrecariousness is a risk factor for retinal complications in patients with diabetes mellitus in French Guiana. In this chronic disease, the universal healthcare system alleviates health inequalities for many, but not all, diabetic complications.Translation and cultural mediation may further reduce health inequalities in this multicultural territory where a substantial proportion of the population is not fluent in French.

One in every 227 babies born in French Guiana has sickle cell disease, which represents the greatest incidence in France. This study aimed to determine the incidence of stroke in children with sickle cell disease and its associated risk factors. This retrospective cohort study included all children with sickle cell disease diagnosed in the neonatal period who were born in French Guiana between 01/01/1992 and 12/31/2002. Of a total of 218 records, 122 patients were included. There were 70 HbSS/Sβ0 (58%), 40 HbSC (33%), and 11 Sβ + thalassemia (9%). The number of emergency admissions was significantly different between genotypes, with a higher number in SS/Sβ0 children (p = 0.004). There were significantly more acute chest syndromes (p = 0.006) and more elevated Lactate Dehydrogenase in SS/Sβ0 patients (p = 0.003). Three of these patients had ischemic strokes at a mean age of 6.9 years, and one had a hemorrhagic stroke at the age of 9,2 years. The incidence rate of ischemic stroke for SS/Sβ0 children was 3.1 (95% CI: 1.0–9.7) per 1,000 patient-years, and the clinically apparent stroke risk by the age of 15 years and 3 months was 6,4%. The incidence of hemorrhagic stroke was 1.1 (95% CI: 0.1–7.4) per 1,000 patients-years. No patient with SC or Sβ + thalassemia genotypes experienced any stroke.

Abstract Background The chemotherapy triplet FOLFOXIRI combined to the anti-VEGF antibody bevacizumab is an option in selected patients with metastatic colorectal cancer. In this setting, RAS-mutated metastatic colorectal cancer do not benefit the same from treatment than RAS-wildtype metastatic colorectal cancer do. Together with its antiangiogenic properties, the tyrosine-kinase inhibitor regorafenib has also anti-proliferative activities whatever the RAS status is. The present trial aims at studying the safety and the efficacy of regorafenib in combination with FOLFIRINOX – a chemotherapy triplet using a different dosing schedule than FOLFOXIRI - in patients with RAS-mutated metastatic colorectal cancer. Methods FOLFIRINOX-R is a prospective, multicentric, non-randomised, dose-finding phase 1–2 trial. The primary endpoints are the determination of the maximum tolerated dose, the recommended phase 2 dose, and the proportion of patients achieving disease control at 48-weeks. Phase 1 follows a 3 + 3 design (12 to 24 patients to be included). Sixty nine patients will be necessary in phase 2, including 5% non-evaluable ones, with the following assumptions, one-stage Fleming design, α = 5%, β = 20%, p0 = 35% and p1 = 50%. Key eligibility criteria include Eastern Cooperative Oncology Group Performance Status of ≤1 and RAS-mutated metastatic colorectal cancer not amenable to surgery with curative intent and not previously treated for metastatic disease. FOLFIRINOX (oxaliplatin 85 mg/m2, folinic acid 400 mg/m2, irinotecan 150–180 mg/m2, 5-fluorouracil: 400 mg/m2 then 2400 mg/m2 over 46 h) is administered every 14 days. Regorafenib (80 to 160 mg, as per dose-level) is administered orally, once daily on days 4 to 10 of each cycle. Discussion FOLFIRINOX-R is the first phase I/II study to evaluate the safety and efficacy of regorafenib in combination with FOLFIRINOX as frontline therapy for patients with RAS-mutated metastatic colorectal cancer. Trial registration EudraCT: 2018-003541-42 ; ClinicalTrials.gov: NCT03828799 .

There are great variations between population subgroups, notably in poorer countries, leading to substantial inconsistencies with those predicted by the classical epidemiologic transition theory. In this context, using public data, we aimed to determine how the singular case of French Guiana fit and transitioned in the epidemiologic transition framework. The data show a gradual decline in infant mortality to values above 8 per 1000 live births. Premature mortality rates were greater but declined more rapidly in French Guiana than in mainland France until 2017 when they reascended in a context of political turmoil followed by the COVID-19 pandemic and strong reluctance to get vaccinated. Although infections were a more frequent cause of death in French Guiana, there is a marked decline and circulatory and metabolic causes are major causes of premature death. Fertility rates remain high (>3 live births per woman), and the age structure of the population is still pyramid-shaped. The singularities of French Guiana (rich country, universal health system, widespread poverty) explain why its transition does not fit neatly within the usual stages of transition. Beyond gradual improvements in secular trends, the data also suggest that political turmoil and fake news may have detrimentally affected mortality in French Guiana and reversed improving trends.

Background: Involved in physical and brain development, immunity and metabolism, micronutrients have profound health effects. The nutritional status of pregnant women is a major determinant of foetal health. French Guiana has a rapid population growth. Social inequalities, cultural practices and gastrointestinal nematode infections in French Guiana could affect the prevalence of these deficiencies. The main objective of the present study was to estimate the prevalence of micronutrient deficiency among pregnant women in French Guiana. The secondary objective was to identify socio-demographic, dietary, obstetrical and neonatal risk factors associated with deficiencies. Methods: Pregnant women over 22 weeks of pregnancy hospitalized for delivery at the Obstetrical Emergency Department of the Hospital Center in Cayenne from May 2018 to March 2019 were included. A socio-demographic and food questionnaire was administered. Medical data were collected from the medical records. Blood and urine samples were taken. The descriptive analysis used Student and chi-squared tests. Results: A total of 341 women were included. The majority were born in Haiti (39%) and French Guiana (34%). At least one micronutrient deficiency was observed in 81% of women. Precarious women had a significantly greater risk of micronutrient deficiency during pregnancy compared to those with both normal and complementary health insurance. Conclusions: Micronutrient deficiencies in pregnant women in French Guiana are a public health problem, a fact that was previously overlooked in the context of rising obesity. With over half the women overweight or obese, and 81% with at least 1 micronutrient deficiency, balanced nutrition should be a major focus.

Abstract Objective Despite scaling-up testing and antiretroviral treatment in Latin America, advanced HIV remains a significant public health problem. The objective of the present study was look for historical risk factors for death in French Guiana’s HIV cohort taking into account the immunological status, the main opportunistic infections, and their treatment. A retrospective cohort study was conducted on data collected between 1992 and 2008 to identify factors associated with death in a cohort 2323 patients. Results There were 370 deaths for a total 9608 patient-years. Being on tuberculosis treatment was associated with a greater hazard of death. The diagnosis of confirmed tuberculosis, of histoplasmosis, of toxoplasmosis, and pneumocystosis were independently associated with death. Interactions terms between cotrimoxazole treatment and pneumocystosis, or between confirmed tuberculosis and tuberculosis treatment showed a protective treatment-effect. All patients having received anti-tuberculosis treatment (n = 347) did not have a final diagnosis of tuberculosis (n = 93). For histoplasmosis, 199 patients received antifungal treatment while 141 were diagnosed as having histoplasmosis. The number of patients on anti-tuberculosis drugs was far greater that the number of patients with confirmed tuberculosis, and these patients on treatment without confirmed tuberculosis had a twofold greater risk of dying.

BackgroundAlthough the simplification of antiretroviral (AVR) treatment regimens and follow-up has led to fewer constraints for patients with HIV, their follow-up remains of paramount importance to optimize AVR therapy, to detect and prevent HIV-related morbidity, and prevent secondary infections. The problem of follow-up interruption in French Guiana has been persistent and seemingly impervious to efforts to alleviate it.ObjectiveThe objective was to follow the trend of follow-up interruptions and to test the hypothesis that an increasing number of patients was, in fact, followed by private practitioners.MethodUsing the complementary lenses of the hospital HIV cohort and the health insurance information system, we looked at the incidence of follow-up interruption and the proportion of patients followed by private practitioners.ResultsWe tallied 803 persons that were not known to have died and who were lost to follow-up. Over time, hospital outpatients were lost to follow-up significantly sooner. By contrast, there was a significant trend with more and more patients exclusively followed by private practitioners.ConclusionWhile hospital outpatient care remains by far the most common mode of patient care, there seems to be a gradual erosion of this model in favor of private practice.

Summary: We postulate that a significant part of circulating DNA (cirDNA) originates in the degradation of neutrophil extracellular traps (NETs). In this study, we examined the plasma level of two markers of NETs (myeloperoxidase (MPO) and neutrophil elastase (NE)), as well as cirDNA levels in 219 patients with a metastatic colorectal cancer (mCRC), and in 114 healthy individuals (HI). We found that in patients with mCRC the content of these analytes was (i) highly correlated, and (ii) all statistically different (p < 0.0001) than in HI (N = 114). These three NETs markers may readily distinguish between patients with mCRC from HI, (0.88, 0.86, 0.84, and 0.95 AUC values for NE, MPO, cirDNA, and NE + MPO + cirDNA, respectively). Concomitant analysis of anti-phospholipid (anti-cardiolipin), NE, MPO, and cirDNA plasma concentrations in patients with mCRC might have value for thrombosis prevention, and suggested that NETosis may be a critical factor in the immunological response/phenomena linked to tumor progression.

Introduction. Over 75% of HIV patients in French Guiana are foreigners most of whom are actually infected locally. Objectives. We aimed to estimate the distribution of infections in time after arrival using a retrospective cohort. Methods. CD4 erosion modelling allowed to estimate the date of infection which was compared to the date of arrival in French Guiana in the subset of foreign patients that were estimated to have acquired HIV locally. Results. Among patients estimated to have been infected in French Guiana and having arrived after 1999, over half had been infected within 4 years and that a quarter of patients had acquired HIV within the 2 first years after arrival (median 3.9 years IQR=2.1-7.8 years). Conclusions. The added value of the present results is to show the rapid infection dynamics after arrival and emphasize the necessity of increasingly proactive combined prevention in recently arrived immigrants.

ObjectivesCommon representations of the world of gold mining-especially illegal-are usually negative: the activity conjures up images of drug trafficking, human exploitation, the sex trade, environmental destruction, and infectious diseases, in particular sexually transmitted infections (STIs). The aim of the present article is to describe the levels of risk behaviors such as transactional sex, multiple sexual partners, and the frequency of condom use, addictive substance consumption, and the prevalence of STIs among the population of illegal gold miners in French Guiana (FG), a French overseas entity in Amazonia, in order to guide potential interventions.MethodsAn observational multicenter cross-sectional study was carried out from October to December 2019 along the two borders of FG with Suriname and Brazil at rest sites used by the miners.ResultsAmong the 499 participants, transactional sex was very prevalent, declared by 33.5% of men and 8.4% of women. Condoms were more frequently used for transactional sex than with a non-commercial partner (93.4% versus 42.1%). More women were tested for HIV than men (91.1% versus 55.2%). Excessive alcohol consumption (57.3%%) and tobacco use (41.2%) were very frequent, but cocaine or crack consumption was low (1.2%), which refuted our initial assumption. Consumers of alcohol had more sexual partners and reported condom use more frequently. Prevalence of HIV, HCV, HBV, and syphilis was respectively 0.5% (95% CI: 0.1-2.1), 2.1% (95% CI: 0.7-3.6), 1.6% (95% CI: 0.3-2.8), and 12.4% (95% CI: 9.0-15.7), which was higher than in the local population, especially for syphilis.ConclusionThis study documents for the first time the risk behaviors of gold miners in FG. Although the level of condom use was high, the prevalence of STIs combined with the high rate of transactional sex should encourage an increase in prevention and screening, in particular through rapid tests, given the mobility of the population concerned.

Background: Illegal gold miners are currently key hosts for malaria in French Guiana (FG), with a risk of emergence of resistance linked to improper use of artemisinin-based combination therapy (ACT). The remoteness of the mines and regulatory issues hinder their access to health care. Methods: A quasi-experimental researched project (Malakit) implemented in FG borders with Brazil and Suriname aimed at determining the effectiveness of distributed kits for self-diagnosis and self-treatment to illegal gold miners, after training, at strategic border staging areas. Evaluation relied on questionnaires at inclusion and follow-up visits, and pre/post intervention surveys. The primary outcome was the proportion of persons reporting a use of certified ACT after a positive malaria diagnosis. The secondary outcomes assessed antimalarial adherence, kit use and impact on malaria epidemiology. Findings: The proportion of patients reporting a use of certified ACT after a positive diagnosis increased after the intervention (OR 1.8, 95%CI [1.1-3.0]). From April 2018 to March 2020, 3,733 persons participated in the intervention. The kit was used correctly by 71.7% [65.8-77.7] of the 223 persons reporting having used a malakit during the follow-up visits. No serious adverse events related to the misuse of malakit have been reported. The intervention appears to have accelerated the decline in malaria incidence in the region by 42.9%. Interpretation: This innovative international project showed that people with low education can correctly self-manage their malaria symptoms. This strategy could be integrated in the malaria control programs of the countries involved and considered in other regions with residual malaria in remote areas. Funding: This project was funded by the European Union, the Global Fund, Brazil MoH, Cayenne Hospital and FG Health Regional Agency. Editor's note: This translation in French was submitted by the authors and we reproduce it as supplied. It has not been peer reviewed. Our editorial processes have only been applied to the original abstract in English, which should serve as reference for this manuscript. The Lancet Group takes a neutral position with respect to territorial claims in published maps and institutional affiliations. Contexte: Les chercheurs d'or illégaux sont actuellement un réservoir clé du paludisme en Guyane, avec un risque d'émergence de résistance lié à une mauvaise utilisation des combinaisons thérapeutiques à base d'artémisinine (ACT). L'isolement de ces sites miniers clandestins et des contraintes règlementaires entravent leur accès aux soins. Méthodes: Un projet de recherche opérationnelle quasi-expérimental (Malakit) a été mis en œuvre aux frontières de la Guyane avec le Brésil et le Suriname. Il visait à déterminer l'efficacité de la distribution de kits d'autodiagnostic et d'autotraitement à des orpailleurs illégaux, après une formation adaptée, dans des zones stratégiques transfrontalières. L'évaluation s'est appuyée sur des questionnaires lors des visites d'inclusion et de suivi, et sur des enquêtes pré/post intervention. L'indicateur principal était la proportion de personnes déclarant avoir utilisé une ACT certifiée après un diagnostic positif de paludisme. Les indicateurs secondaires reposaient sur l'adhérence aux traitements antipaludiques, l'utilisation des kits et l'impact sur l'épidémiologie du paludisme. Résultats: La proportion de patients déclarant une utilisation d'ACT certifiée après un diagnostic positif a augmenté après l'intervention (OR 1,8, 95%CI [1,1-3,0]). D'avril 2018 à mars 2020, 3 733 personnes ont participé à l'intervention. Le kit a été utilisé correctement par 71,7% [65,8-77,7] des 223 personnes revues en visites de suivi ayant déclaré avoir utilisé un malakit. Aucun événement indésirable grave lié à une mauvaise utilisation du malakit n'a été signalé. L'intervention semble avoir accéléré la diminution de l'incidence du paludisme dans la région de 42,9%. Interprétation: Ce projet international innovant a montré que les personnes ayant un faible niveau d'éducation peuvent se prendre en charge par eux-mêmes pour des symptômes de paludisme. Cette stratégie pourrait être intégrée dans les programmes de lutte contre le paludisme des pays impliqués et envisagée dans d'autres régions où du paludisme résiduel persiste dans des zones isolées. Financement: Ce projet a été financé par l'Union Européenne, le Fonds Mondial, le Ministère de la santé du Brésil, le Centre Hospitalier de Cayenne et l'Agence Régionale de Santé de Guyane.

Objectives: Cervical cancer is the second most frequent cancer among women in French Guiana. The objective was to review a decade of cervical cancer data, and to study spatial and temporal trends. Study design: The design was retrospective and descriptive. Methods: The cancer registry of French Guiana compiled exhaustive data on cervical cancer throughout French Guiana between 2005 and 2015. Age-standardized incidence and mortality were computed and mapped to identify priority areas. Results: With 232 new cases recorded in French Guiana between 2005 and 2014 (23 annual cases), cervical cancer ranked 5th among all incident cancers (11%) and was the 2nd most frequent cancer in women (12% of cancers among women). The standardized incidence rate over the period 2005–2014 was 23.8 cases of cervical cancer per 100 000 woman-years. Between 2005-2009 and 2010–2014 the incidence of cervical cancer decreased from 26.26 cases per 100 000 to 22.66 cases per 100 000 and the mortality rate from cervical cancer decreased from 6 deaths per 100 000 to 3.2 deaths per 100 000.Within French Guiana, the standardized incidence rates were very heterogenous with the highest rates in remote areas. The standardized death rate from cervical cancer over the 2005–2014 decade was 4.4 cases per 100 000 woman-years. Conclusions: The present results suggest there has been progress in French Guiana, but there are still areas where screening is challenging and should be expanded. The recent authorization of HPV testing is an opportunity that could help health professionals achieve this goal. HPV vaccination –with a nonavalent vaccine—is also an important public health endeavor that could alleviate the burden of cervical cancer among the cohorts of women benefitting from it.

Certain patients who recover from severe pneumonia due to coronavirus disease 2019 (COVID-19) remain symptomatic in the post-infectious period, either clinically, radiologically, or respiratory. The post-COVID-19 period is characterized by clinical symptoms of varying duration from one subject to another and does not seem to depend on the severity of initial pneumonia. The persisting inflammatory and/or immune reactions in the post-COVID-19 period may play a role in the development of pulmonary lesions. Here, we report the case of a 61-year-old man with severe COVID-19 pneumonia, complicated by acute respiratory distress syndrome and pulmonary embolism, which required the patient's admission to the intensive care unit and high-flow oxygen therapy. The patient was hospitalized for 23 days for the management of his severe COVID-19 pneumonia. Afterwards, he was discharged home following a negative SARS-CoV-2 PCR test. The post-COVID-19 period was characterized by a complex respiratory symptomatology associating cough, resting dyspnea, and exertional dyspnea requiring oxygen therapy for several weeks. Surprisingly, the follow-up chest CT scan performed 4 weeks after discharge revealed bilateral interstitial lung lesions. After ruling out pulmonary superinfection, the patient was treated with oral corticosteroid for 3 months at a digressive dose. In our case, the use of corticosteroid therapy in the post-COVID19 phase had improved the outcome of the lung disease. These benefits are characterized by a rapid symptomatic improvement, accelerated repair of pulmonary images, rapid oxygen withdrawal, and rapid return to daily activities.

Background: The COVID 19 epidemic submerged many health systems in the Amazon. The objective of the present study was to focus on the epidemic curves of the COVID 19 epidemic in different centers, and to look at testing and mortality data.Methods: Publicly available datasets were used. The log10 of the daily cumulated number of cases starting from the day the territory reached 100 cumulated cases was plotted to compare the magnitude, shape and slope of the different curves. The maximum daily testing efforts were plotted for each territory in relation to the maximum daily number of diagnoses. The case fatality rate was computed by dividing the number of COVID 19 deaths by the number of confirmed cases.Results: In the Amazonian regions in general the speed of growth was generally lower than in Europe or the USA, or Southern Brazil. Whereas, countries like South Korea or New Zealand “broke” the curve relatively rapidly the log linear trajectory seemed much longer with signs of a decline in growth rate as of early July 2020. After a very slow start, French Guiana had the lowest slope when compared to other Amazonian territories with significant epidemics. The Amazonian states of Roraima, Amazonas, Parà, and Amapà had among the highest number of cases and deaths per million inhabitants in the world. French Guiana had significantly fewer deaths relative to its number of confirmed cases than other Amazonian territories. French Guiana had a late epidemic surge with intense testing scale-up often exceeding 4,000 persons tested daily per million inhabitants. Brazil was an outlier with low daily testing levels in relation to the number of daily diagnoses.Conclusions: There were marked heterogeneities mortality rates suggesting that socioeconomic, political factors, and perhaps ethnic vulnerability led to striking outcome differences in this Amazonian context.

Adrenal histoplasmosis and primary adrenal insufficiency are mostly described in immunocompetent patients. This particular tropism is attributed to the presence of cortisol within the adrenal gland, a privileged niche for Histoplasma growth. In French Guiana, disseminated histoplasmosis is the main opportunistic infection in HIV patients. Our objective was to search in our HIV-histoplasmosis cohorts to determine how frequent adrenal insufficiency was among these patients. Between January 1, 1981 and October 1, 2014, a multicentric retrospective, observational study of histoplasmosis was conducted. Patients co-infected by HIV and histoplasmosis were enrolled in French Guiana’s histoplasmosis and HIV database. Among 349 cases of disseminated histoplasmosis between 1981 and 2014, only 3 had adrenal insufficiency (0.85%). Their respective CD4 counts were 10, 14 and 43 per mm3. All patients had regular electrolyte measurements and 234/349 (67%) had abdominal ultrasonography and 98/349 (28%) had abdominopelvic CT scans. None of these explorations reported adrenal enlargement. Overall, these numbers are far from the 10% reports among living patients and 80-90% among histoplasmosis autopsy series. This suggests 2 conflicting hypotheses: First, apart from acute adrenal failure with high potassium and low sodium, less advanced functional deficiencies, which require specific explorations, may have remained undiagnosed. The second hypothesis is that immunosuppression leads to different tissular responses that are less likely to incapacitate the adrenal function. Furthermore, given the general immunosuppression, the adrenal glands no longer represent a particular niche for Histoplasma proliferation.

BackgroundDisseminated histoplasmosis is a major killer of patients with advanced HIV. It is proteiform and often hard to diagnose in the absence of diagnostic tests. We aimed to describe disseminated histoplasmosis with lymphadenopathies in French Guiana and to compare survival and severity of those patients to patients without lymphadenopathies.MethodsA retrospective cohort study was performed on data records collected between January 1, 1981 and October 1, 2014.ResultsAmong 349 cases of disseminated histoplasmosis 168 (48.3%) had superficial lymphadenopathies and 133(38.1%) had deep lymphadenopathies. The median LDH concentration, ferritin concentration, TGO concentration, and WHO performance status were lower among patients with deep lymphadenopathies than those without deep lymphadenopathies. There was a significant decrease in the risk of early death (

Disseminated histoplasmosis is one the main AIDS-defining opportunistic infections in HIV-infected patients, notably in Latin America. The non-specific and proteiform clinical presentation leads to diagnostic delays that may lead to fatal outcomes. This retrospective multicentric study aimed to describe the frequency and manifestations of gastrointestinal histoplasmosis in French Guiana, and to compare patients with disseminated histoplasmosis with or without gastrointestinal involvement. Between January 1, 1981 and October 1, 2014 co-infections with HIV and histoplasmosis were enrolled. Inclusion criteria were: age >18 years, confirmed HIV infection; first proven episode of histoplasmosis. Among 349 cases of disseminated histoplasmosis, 245 (70%) had a gastrointestinal presentation. Half of patients with gastrointestinal signs had abdominal pain or diarrhea, mostly watery. Half of patients with abdominal pain had diarrhea (63/124) and half of those with diarrhea (63/123) had abdominal pain. A significant proportion of patients also had hepatomegaly and, to a lesser degree, splenomegaly. After adjusting for potential confounding, the presence of lymphadenopathies >2cm (AOR = 0.2, IC95 = 0.04-0.7, P = 0.01), Haitian origin (AOR = 0.04, IC95 = 0.004-0.4, P = 0.006) were associated with a lower prevalence of gastrointestinal signs and positive gastrointestinal presence of H. capsulatum. Persons with a gastrointestinal H. capsulatum were more likely to have a decreased prothrombin time, lower ferritin, lower liver enzymes, and lower concentrations of LDH than those without gastrointestinal signs and symptoms. They also had a shorter interval between symptoms onset and diagnosis. Patients with a positive gastrointestinal identification of H. capsulatum were less likely to die at 1 month than those without a gastrointestinal presentation (respectively, 4.6% vs 18.5%, P = 0.01). Subacute or chronic gastrointestinal presentations are very frequent during disseminated histoplasmosis, they seem less severe, and should lead to suspect the diagnosis in endemic areas. There were populational or geographic differences in the frequency of gastrointestinal manifestations that could not be explained.

Histoplasmosis is the most frequent opportunistic infection and the first cause of mortality in HIV-infected patients in French Guiana and presumably in much of Latin America. Mucocutaneous lesions of histoplasmosis are considered as rare and late manifestations of the disease. It has been debated whether the greater proportion of cutaneo-mucous presentations in South America relative to the USA was the reflection of Histoplasma strains with increased dermotropism or simply delayed diagnosis and advanced immunosuppression. The objective of this study was to describe the clinical presentation, frequency, prognosis and temporal trends of cutaneomucous histoplasmosis in French Guiana. A retrospective study of patients with AIDS-related disseminated histoplasmosis followed in the three hospitals of French Guiana was performed between 1981 and 2014. Incident cases of histoplasmosis, proved by pathology and/or mycological examinations, were studied. Mucocutaneous histoplasmosis was confirmed by a positive cutaneous or mucosal biopsy. Mucocutaneous lesions were polymorphic. Ninety percent of patients were profoundly immunocompromised patients (CD4

BackgroundDisseminated histoplasmosis remains a major killer of immunocompromised patients in Latin America. Cytological and histological methods are usually present in most hospitals and may represent a precious diagnostic method. We report 15 years of experience of the department of pathology of the Centre Hospitalier de Cayenne Andrée Rosemon in French Guiana.MethodsSpecimens from live patients from January 2005 to June 2020 with the presence of H. capsulatum on cytological and/or histological analysis were analyzed. All specimens were examined by an experienced pathologist. The analysis was descriptive.ResultsTwo hundred two cytological and histological samples were diagnosed with histoplasmosis between January 2005 and June 2020. The 202 samples included 153 (75.7%) histopathological formalin-fixed and paraffin-embedded tissues (biopsy or surgical specimens) and 49 (24.3%) cytological analysis from all organs. One hundred thirty-four patients (82.7%) were HIV-positive, 15 patients (9.3%) had immunosuppressant treatment, and 13 patients (8%) were immunocompetent. Seventy-eight of 202 (38.5%) were samples from the digestive tract, mostly the colon (53/78 cases, 70%) and small intestine (14/78 cases, 18%). Microorganisms were more numerous in digestive samples (notably the colon) than in other organs. Lymphocyte and histiocyte inflammation of moderate to marked intensity were observed in all positive specimens. Tuberculoid epithelioid granuloma were present in 16/78 (20,5%) specimens including 14 colon and 2 small intestine specimens. There were 11/202 cases of liver histoplasmosis, 26/202 (12,8%) cases of pulmonary histoplasmosis. Bone marrow involvement was diagnosed in 14 (2%) specimens (8 aspiration and 6 biopsies). Lymph nodes were positive in 42 specimens (31 histology and 11 cytology). Histopathological analysis of the 31 lymph nodes showed a variable histological appearance. Tuberculoid forms were most frequent (24/31, 77,4%).ConclusionsFrom the pathologist perspective, this is the largest series to date showing that digestive involvement was the most frequent, usually with a tuberculoid form and a greater load of Histoplasma. With awareness and expertise, cytology and pathology are widely available methods that can give life-saving results in a short time to help orient clinicians facing a potentially fatal infection requiring prompt treatment.

Introduction: Haemophagocytic Lymphohistiocytosis (HLH), during HIV infection is a rare complication with a poor prognosis. There are few data on HLH within the Amazon region. The objective was to describe epidemiological, clinical and therapeutic features of HIV-related HLH in French Guiana.Methods: A retrospective analysis of adult HIV patients at Cayenne hospital with HLH between 2012 and 2015. A diagnosis of HLH was given if the patient presented at least 3 of 8 criteria of the HLH-2004 classification.Results: Fourteen cases of HLH were tallied during the study period. The mean age was 46 years with a sex ratio of 1.8. The most frequent etiology of HLH was an associated infection (12/14). Confirmed disseminated histoplasmosis, was found in 10 of 14 cases, and it was suspected in 2 other cases. The CD4 count was below 200/mm3 in 13/14 cases. An HIV viral load >100,000 copies/ml was observed in 13/14 cases. An early treatment with liposomal amphotericin B was initiated in 12/14 cases. The outcome was favorable in 12/14 of all cases and in 10/12 cases involving histoplasmosis. Case fatality was 2/14 among all cases (14.3%) et 1/10 among confirmed disseminated histoplasmosis with HLH (10%). During the study period 1 in 5 cases of known HIV-associated disseminated histoplasmosis in French Guiana was HLH.Conclusion: Histoplasmosis was the most frequent etiology associated with HLH in HIV-infected patients in French Guiana. The prognosis of HLH remains severe. However, a probabilistic empirical first line treatment with liposomal amphotericin B seemed to have a favorable impact on patient survival.

Abstract While the utility of circulating cell‐free DNA (cfDNA) in cancer screening and early detection have recently been investigated by testing genetic and epigenetic alterations, here, an original approach by examining cfDNA quantitative and structural features is developed. First, the potential of cfDNA quantitative and structural parameters is independently demonstrated in cell culture, murine, and human plasma models. Subsequently, these variables are evaluated in a large retrospective cohort of 289 healthy individuals and 983 patients with various cancer types; after age resampling, this evaluation is done independently and the variables are combined using a machine learning approach. Implementation of a decision tree prediction model for the detection and classification of healthy and cancer patients shows unprecedented performance for 0, I, and II colorectal cancer stages (specificity, 0.89 and sensitivity, 0.72). Consequently, the methodological proof of concept of using both quantitative and structural biomarkers, and classification with a machine learning method are highlighted, as an efficient strategy for cancer screening. It is foreseen that the classification rate may even be improved by the addition of such biomarkers to fragmentomics, methylation, or the detection of genetic alterations. The optimization of such a multianalyte strategy with this machine learning method is therefore warranted.