What Is the Part of Tropical Diseases Among Infectious Complications in Renal Transplant Recipients in the Amazon? A 12-Year Multicenter Retrospective Analysis in French Guiana.

BACKGROUND: Infectious complications in kidney transplant recipients (KTRs) are well studied in temperate countries but remain barely known in tropical ones. The main objective of this study was to describe infection-related hospitalizations in patients living in the Amazon, where it has never been described. METHODS: All KTRs residing in French Guiana between 2007 and 2018 were included retrospectively. Infection-related hospitalizations were collected in the main medical centers of the territory. RESULTS: Eighty-two patients were included, and 42 were infected during the study period (51%). Eighty-seven infections were identified. The main sites of infection were urinary, in 29% of cases (25/87), and pulmonary, in 22% of cases (19/87). When documented (48/87), bacterial infections were predominant (35/48), followed by viral (8/48), fungal (4/48), and parasitic infections (1/48). Endemic so-called tropical infections accounted for 6% of infections (5/87). Histoplasma capsulatum was the most commonly isolated fungus (2/4). CONCLUSIONS: This study suggests that the spectrum of infections in KTRs in French Guiana differs little from that of temperate countries. Nevertheless, some tropical infections are described. More studies on fungal infections in KTRs should be undertaken to clarify the weight of histoplasmosis in these patients.

Invasive Fungal Infections in Persons Living with HIV in an Amazonian Context: French Guiana, 2009-2019.

Although the burden of histoplasmosis in patients with advanced HIV has been the focus of detailed estimations, knowledge about invasive fungal infections in patients living with HIV in an Amazonian context is somewhat scattered. Our goal was thus to adopt a broader view integrating all invasive fungal infections diagnosed over a decade in French Guiana. All patients hospitalized at Cayenne hospital from 1 January 2009 to 31 December 2018 with a proven diagnosis of invasive fungal infection were included (N = 227). Histoplasmosis was the most common (48.2%), followed by Cryptococcus infection (26.3%), and pneumocystosis (12.5%). For cryptococcal infection, there was a discordance between the actual diagnosis of cryptococcal meningitis n = (26) and the isolated presence of antigen in the serum (n = 46). Among the latter when the information was available (n = 34), 21(65.6%) were treated with antifungals but not coded as cryptococcocosis. Most fungal infections were simultaneous to the discovery of HIV (38%) and were the AIDS-defining event (66%). The proportion of major invasive fungal infections appeared to remain stable over the course of the study, with a clear predominance of documented H. capsulatum infections. Until now, the focus of attention has been histoplasmosis, but such attention should not overshadow other less-studied invasive fungal infections.

What is AIDS in the Amazon and the Guianas in the 90-90-90 era?

INTRODUCTION: In the past decade, new diagnostic methods and strategies have appeared, HIV testing efforts and the generalization of antiretroviral therapy may have influenced the number of opportunistic diagnoses and mortality of HIV-infected patients. To test this hypothesis we compiled data on the top opportunistic infections and causes of early death in the HIV cohort of French Guiana. METHODS: HIV-infected persons followed in Cayenne, Kourou, and Saint Laurent du Maroni hospitals from 2010 to 2019 were studied. Annual incidence of different opportunistic infections and annual deaths are compiled. For patients with opportunistic infections we calculated the proportion of early deaths. RESULTS: At the time of analysis, among 2 459 patients, (treated and untreated) 90% had a viral load <400 copies, 91% of the patients in the cohort were on antiretroviral treatment, and 94.2% of patients on treatment for over 6 months had undetectable viral loads. Only 9% of patients had CD4 counts under 200 per mm3. Histoplasmosis clearly remained the most frequent (128 cases) opportunistic infection among HIV-infected persons followed by cerebral toxoplasmosis (63 cases) and esophageal candidiasis (41 cases). Cryptococcal meningitis was ranked 5th most frequent opportunistic infection as was tuberculosis (31 cases). The trend for a sharp decline in early deaths continued (3.9% of patients). CONCLUSIONS: Despite the successes of antiretrovirals, patients presenting with advanced HIV are still common and they are still at risk of dying. Improved diagnosis, and notably systematic screening with appropriate tools are still important areas of potential progress.

Contributing to Elimination of Cross-Border Malaria Through a Standardized Solution for Case Surveillance, Data Sharing, and Data Interpretation: Development of a Cross-Border Monitoring System.

BACKGROUND: Cross-border malaria is a significant obstacle to achieving malaria control and elimination worldwide. OBJECTIVE: This study aimed to build a cross-border surveillance system that can make comparable and qualified data available to all parties involved in malaria control between French Guiana and Brazil. METHODS: Data reconciliation rules based on expert knowledge were defined and applied to the heterogeneous data provided by the existing malaria surveillance systems of both countries. Visualization dashboards were designed to facilitate progressive data exploration, analysis, and interpretation. Dedicated advanced open source and robust software solutions were chosen to facilitate solution sharing and reuse. RESULTS: A database gathering the harmonized data on cross-border malaria epidemiology is updated monthly with new individual malaria cases from both countries. Online dashboards permit a progressive and user-friendly visualization of raw data and epidemiological indicators, in the form of time series, maps, and data quality indexes. The monitoring system was shown to be able to identify changes in time series that are related to control actions, as well as differentiated changes according to space and to population subgroups. CONCLUSIONS: This cross-border monitoring tool could help produce new scientific evidence on cross-border malaria dynamics, implementing cross-border cooperation for malaria control and elimination, and can be quickly adapted to other cross-border contexts.

Spectrum of skin diseases in Amerindian villages of the Upper Oyapock, French Guiana.

BACKGROUND: Due to their genetic characteristics, their isolation in rainforest areas, and their traditional way of life, Amerindian populations are likely to suffer from a specific spectrum of dermatoses. However, there are few available data on such skin disorders. Our aims were to describe all skin disorders in two Amerindian villages of French Guiana. METHODS: This retrospective study concerned all patients who consulted in the Health Centres of Camopi and Trois-Sauts between July 1, 2017, and December 31, 2018. We included all patients classified with an ICD code linked to a skin disorder. All medical records were cross-checked by two dermatologists to correct misclassifications. RESULTS: A total of 639 patients formed the study population, for 866 different skin disorders. Non-sexually transmitted infections represented 57.6% of all skin disorders, followed by eczema (11.5%) and bites/envenomations (9.1%). Bacteria were responsible for 238 skin infections, followed by fungi (141 cases) and parasites (69 cases, including 43 scabies, nine cutaneous leishmaniasis, and two tungiasis). We reported a low prevalence of sexually transmitted infections (10 cases) and an absence of skin cancers. CONCLUSIONS: This study revealed the absence of skin cancer in the Amerindian population of the Upper Oyapock and the important burden of infectious and animal-related diseases. Future studies should assess a possible underestimation of sexually transmitted diseases in this area. Public health policies should target neglected diseases such as cutaneous leishmaniasis, tungiasis, scabies, and envenomations. Atopic dermatitis was a significant and unexpected cause of consultations.

Spatial dynamics and epidemiology for AIDS in remote areas in French Guiana.

Although AIDS care is generally improving in French Guiana, disparities among regions and certain key populations remain significant. The purpose of this study was to describe the spatial and clinical characteristics of people living with HIV (PLHIV) in remote areas in comparison to those followed in hospitals on the urban coast of French Guiana. The data presented were obtained from outpatient on primary care centers located in rural regions away from the urban coast. Data were compared with that from medical records of PLHIV treated in French Guiana's urban care. The evolution of the annual rate of discovery of HIV seropositivity indicates a lag in remote areas as compared to urban and coastal areas. In recent years, the epidemic appeared as particularly active in rural areas among Brazilian patients. The median age of PLHIV in remote areas was 43.8 years, the sex ratio (M/F) was 0.93. Nearly 37% of PLHIV were discovered with advanced disease (<200 CD4/mm3). The percentage of virological success after six months of HAART was 80% and 88% in remote areas and urban area, respectively. Efforts must be made to control and halt the spread of the HIV epidemic, as these remote sites represent strategic points.

Descriptive epidemiology of suicide attempts and suicide in the remote villages of French Guiana.

OBJECTIVE: The overall rate of suicide in French Guiana is estimated at 6 per 100,000, a rate that is lower than in mainland France. Given the frequent reports of suicide in Amerindian communities, our hypothesis was that this figure fails to capture a more contrasted reality. Our objective was to refine estimates and determine suicide rates in remote villages of French Guiana. METHODS: We included patients for whom a suicide attempt or suicide was mentioned in medical records. The Health centers were grouped into two zones according to geographical remoteness. RESULTS: The highest suicide rates observed in the remote Amerindian villages of Camopi and Trois Sauts were, respectively, 118 and 78/100,000. The median age at the time of suicide was significantly younger in remote zones [23 years (95% CI 21.59-25.06)] than in non-remote zones-[27 years (95% CI 24.47-29.31)]. The most frequent methods were hanging (78%) and intoxication (22%). CONCLUSIONS: The suicide rate in remote areas in French Guiana was eight times higher than in France. The suicide of young people in remote areas in French Guiana and specifically in Amerindian villages must be better understood and prevented with contextualized and adapted care.

Cryptosporidiosis Outbreak in Immunocompetent Children from a Remote Area of French Guiana.

In September 2014, an increase in the number of Cryptosporidium spp. gastrointestinal tract infections was reported over a 6-month period among children living in a remote area along the Maroni River in French Guiana. Children presented gastroenteritis symptoms with Cryptosporidium-positive stools. Questionnaires were administered and stool examinations were controlled 3 months after the onset of symptoms. Data collection included demographics, food consumption, river behavior, symptoms, and outcome. Stool specimens were tested using microscopy and polymerase chain reaction. Samples from the water systems were examined for turbidity and culture for bacteria. Data from the reference laboratory were analyzed to calculate the median cryptosporidiosis incidence among immunocompetent patients from 2008 to 2015. Data on gastroenteritis cases reported by the Delocalized Center for Prevention and Care in the area were also collected. We report a cluster of 14 cases. All cases were children, aged between 4.5 and 38 months. Seven reported moderate to severe dehydration and required hospitalization. Speciation and microbiological typing revealed the cluster strain was Cryptosporidium hominis subtype IbA10G2 but C. hominis IbA9G2 and IbA15G1 strains were also identified. The median incidence in French Guiana was 5.8 cases per year before the outbreak. The first cases of the cluster appeared in the dry season. We describe the clinical features, epidemiology, and state of current investigations for the largest documented outbreak of cryptosporidiosis in French Guiana.

A Large Outbreak of Thiamine Deficiency Among Illegal Gold Miners in French Guiana.

From September 2013 to July 2014, several gold miners working in the tropical forest consulted the Maripasoula Health Center in French Guiana for edema and findings consistent with right-sided cardiac failure. Of the 42 cases of beriberi that were diagnosed, one patient died. The laboratory and clinical investigation demonstrated vitamin B1 deficiency in most of the patients tested. Furthermore, 30 of 42 patients responded favorably to 500 mg of intravenous or intramuscular thiamine supplementation. In addition, dietary investigation showed insufficient thiamine intake in these patients. We concluded that patients had acquired beriberi because of diet restrictions, hard labor, and infectious diseases, notably malaria. In 2016, cases were still being reported. We recommend screening for compatible symptoms in gold miners, thiamine supplementation, and nutritional intervention.

TRP channel-associated factors are a novel protein family that regulates TRPM8 trafficking and activity.

TRPM8 is a cold sensor that is highly expressed in the prostate as well as in other non-temperature-sensing organs, and is regulated by downstream receptor-activated signaling pathways. However, little is known about the intracellular proteins necessary for channel function. Here, we identify two previously unknown proteins, which we have named "TRP channel-associated factors" (TCAFs), as new TRPM8 partner proteins, and we demonstrate that they are necessary for channel function. TCAF1 and TCAF2 both bind to the TRPM8 channel and promote its trafficking to the cell surface. However, they exert opposing effects on TRPM8 gating properties. Functional interaction of TCAF1/TRPM8 also leads to a reduction in both the speed and directionality of migration of prostate cancer cells, which is consistent with an observed loss of expression of TCAF1 in metastatic human specimens, whereas TCAF2 promotes migration. The identification of TCAFs introduces a novel mechanism for modulation of TRPM8 channel activity.

Remodeling of channel-forming ORAI proteins determines an oncogenic switch in prostate cancer.

ORAI family channels have emerged as important players in malignant transformation, yet the way in which they reprogram cancer cells remains elusive. Here we show that the relative expression levels of ORAI proteins in prostate cancer are different from that in noncancerous tissue. By mimicking ORAI protein remodeling observed in primary tumors, we demonstrate in in vitro models that enhanced ORAI3 expression favors heteromerization with ORAI1 to form a novel channel. These channels support store-independent Ca(2+) entry, thereby promoting cell proliferation and a smaller number of functional homomeric ORAI1-based store-operated channels, which are important in supporting susceptibility to apoptosis. Thus, our findings highlight disrupted dynamic equilibrium of channel-forming proteins as an oncogenic mechanism.

Identification of CAD as an androgen receptor interactant and an early marker of prostate tumor recurrence.

Markers of prostate tumor recurrence after radical prostatectomy are lacking and highly demanded. The androgen receptor (AR) is a nuclear receptor that plays a pivotal role in normal and cancerous prostate tissue. AR interacts with a number of proteins modulating its stability, localization, and activity. To test the hypothesis that an increased expression of AR partners might foster tumor development, we immunopurified AR partners in human tumors xenografted into mice. One of the identified AR partners was the multifunctional enzyme carbamoyl-phosphate synthetase II, aspartate transcarbamylase, and dihydroorotase (CAD), which catalyzes the 3 initial steps of pyrimidine biosynthesis. We combined experiments in C4-2, LNCaP, 22RV1, and PC3 human prostate cell lines and analysis of frozen radical prostatectomy samples to study the CAD-AR interaction. We show here that in prostate tumor cells, CAD fosters AR translocation into the nucleus and stimulates its transcriptional activity. Notably, in radical prostatectomy specimens, CAD expression was not correlated with proliferation markers, but a higher CAD mRNA level was associated with local tumor extension (P=0.049) and cancer relapse (P=0.017). These results demonstrate an unsuspected function for a key metabolic enzyme and identify CAD as a potential predictive marker of cancer relapse.

Thrombospondin-1 triggers cell migration and development of advanced prostate tumors.

The antitumor effects of pharmacologic inhibitors of angiogenesis are hampered in patients by the rapid development of tumor resistance, notably through increased invasiveness and accelerated metastasis. Here, we reevaluated the role of the endogenous antiangiogenic thrombospondin 1 (TSP1) in prostate carcinomas in which angiogenesis is an active process. In xenografted tumors, we observed that TSP1 altogether inhibited angiogenesis and fostered tumor development. Our results show that TSP1 is a potent stimulator of prostate tumor cell migration. This effect required CD36, which also mediates TSP1 antiangiogenic activity, and was mimicked by an antiangiogenic TSP1-derived peptide. As suspected for pharmacologic inhibitors of angiogenesis, the TSP1 capacities to increase hypoxia and to trigger cell migration are thus inherently linked. Importantly, although antiangiogenic TSP1 increases hypoxia in vivo, our data show that, in turn, hypoxia induced TSP1, thus generating a vicious circle in prostate tumors. In radical prostatectomy specimens, we found TSP1 expression significantly associated with invasive tumors and with tumors which eventually recurred. TSP1 may thus help select patients at risk of prostate-specific antigen relapse. Together, the data suggest that intratumor disruption of the hypoxic cycle through TSP1 silencing will limit tumor invasion.

Status of the executioner step of apoptosis in human with normal spermatogenesis and azoospermia.

OBJECTIVE: To localize the different proteins involved in the executioner step of apoptosis in the human testicular tissue: effector caspases (3, 6, and 7), caspase inhibitors called inhibitor of apoptosis proteins (IAPs, such as XIAP), and IAP inhibitors such as Smac/DIABLO and to investigate XIAP and Smac expression and activation of caspase-3 in azoospermia. DESIGN: Retrospective study. SETTING: The Biology of Reproduction Center of Poissy and Inserm U407, France. PATIENT(S): Twenty-five patients diagnosed as azoospermic and 4 patients with normal testicular histology. INTERVENTION(S): Testicular biopsies for histopathological assessment. MAIN OUTCOME MEASURE(S): Localization of proteins by immunohistochemistry. RESULT(S): Effector caspase-7 seemed to be absent from normal human testes, whereas procaspase-3 and procaspase-6 were detected in both somatic and germ cells. XIAP was mainly expressed in Sertoli cells, whereas its inhibitor Smac was detected in pachytene spermatocytes. On the other hand, although few apoptotic germ cells were detected in biopsies from patients with obstructive azoospermia, increased levels of apoptotic germ cells were detected in spermatogenetic arrest. This increase in apoptotic germ cells was associated with increased levels of active caspase-3 in patients with spermatogenetic arrest, whereas the expression of XIAP and Smac/DIABLO was at similar levels in all groups. CONCLUSION(S): Active caspase-3 might be important in the apoptotic process observed in spermatogenetic arrest.