ABO Blood Group Incompatibility Protects Against SARS-CoV-2 Transmission.

ABO blood groups appear to be associated with the risk of SARS-CoV-2 infection, but the underlying mechanisms and their real importance remain unclear. Two hypotheses have been proposed: ABO compatibility-dependence (neutralization by anti-ABO antibodies) and ABO-dependent intrinsic susceptibility (spike protein attachment to histo-blood group glycans). We tested the first hypothesis through an anonymous questionnaire addressed to hospital staff members. We estimated symptomatic secondary attack rates (SAR) for 333 index cases according to spouse ABO blood group compatibility. Incompatibility was associated with a lower SAR (28% vs. 47%; OR 0.43, 95% CI 0.27-0.69), but no ABO dependence was detected in compatible situations. For the second hypothesis, we detected no binding of recombinant SARS-CoV-2 RBD to blood group-containing glycans. Thus, although no intrinsic differences in susceptibility according to ABO blood type were detected, ABO incompatibility strongly decreased the risk of COVID-19 transmission, suggesting that anti-ABO antibodies contribute to virus neutralization.

Utility of PCR in Patients with Strongyloides stercoralis and HTLV-1 Coinfection in French Guiana.

Strongyloides stercoralis and human T-lymphotropic virus 1 (HTLV-1) coinfections have been extensively reported in the literature, but the diagnosis and treatment of strongyloidiasis remains a challenge, particularly in HTLV-1 carriers. Our objectives were to evaluate the efficacy of a new PCR method for the detection of S. stercoralis in HTLV-1-positive patients. Stools were collected over a 1-year period across the endemic region of French Guiana, including remote forest areas. Two systems of real-time PCR were then used comparatively, with small subunit and specific repeat as respective targets, and compared with the results of microscopic examinations. One-hundred and twelve stool samples were included. Twenty-seven patients (24.1%) presented a positive HTLV-1 serology. The overall prevalence of strongyloidiasis among the 112 patients was 30% with small-subunit PCR and 11.6% with microscopic examinations. In the seropositive population, all tested stools were negative, whereas 51.2% were positive using small-subunit PCR. Thus, PCR allowed a much-improved sensitivity, particularly in HTLV-1 carriers. Among the two systems investigated, small subunit yielded better results than specific repeat PCR, with prevalence rates in HTLV-1 carriers of 51.2% and 22.2%, respectively. Therefore, PCR should be considered as a useful tool for the diagnosis of strongyloidiasis, particularly in HTLV-1 carriers who often present a light parasitic load due to erratic administration of anthelmintic drugs.

A prospective matched study on symptomatic dengue in pregnancy.

Dengue fever is an increasing problem worldwide, but consequences during pregnancy remain unclear. Much of the available literature suffers from methodological biases that compromise the validity of clinical recommendations. We conducted a matched cohort study during an epidemic in French Guiana to compare events and pregnancy outcomes between two paired groups of pregnant women: women having presented with symptomatic dengue during pregnancy (n = 73) and women having had neither fever nor dengue during pregnancy (n = 219). Women in each arm were matched by place of follow up, gestation weeks at inclusion, and place of residence. Dengue infection was considered to be confirmed if viral RNA, N S1 antigen, the seroconversion of IgM antibodies or the presence of IgM was detected in collected samples. According to the 2009 WHO classification, 27% of the women with symptomatic dengue had at least one clinical or biological warning sign. These complications occurred after the 28th week of gestation in 55% of cases. The medical history, socioeconomic status and demographic characteristics were included in multivariate analysis. Exposure to dengue during pregnancy was not significantly associated with prematurity, small for gestational age infants, hypertension or emergency caesarian section. Maternal dengue with warning signs was a risk factor for peripartum hemorrhage with adjusted relative risk = 8.6(95% CI = 1.2-62). There was a near significant association between dengue and in utero death (p = 0.09). This prospective comparative study underlined the importance of taking into account potential confounders between exposure to dengue and the occurrence of obstetrical events. It also confirms the need for increased vigilance for pregnant women with dengue, particularly for women who present with severe dengue.

Incidence of infantile Pompe disease in the Maroon population of French Guiana.

OBJECTIVES: The aim of this study was to describe the epidemiology of infantile Pompe disease (IPD) in French Guiana, a French overseas territory, by combining a retrospective case records study and a prospective anonymous genotyping in a sample of mothers followed in the two major maternity units of French Guiana. METHODS: We identified 19 newborns with IPD born within a 13-year-period in French Guiana, corresponding to 1/4528 births. All children were born within the African-American Maroon (Bushinengue) community originating from slaves who settled along the Maroni river in the 19th century. We also performed an anonymised screening for all women in postpartum, in the two main maternity units of French Guiana. RESULTS: Genetic investigations revealed that all patients with IPD were homozygotes or compound heterozygotes for two known pathogenic variations: c.2560C>T p.(Arg854*) that has already been reported in African-Americans and c.1942G>A p.(Gly648Ser), a rare previously considered to be variant. We identified no heterozygotes among 453 mothers of various ethnicities in Cayenne, but 15 heterozygotes among 425 mothers (1/27) in Saint-Laurent-du-Maroni (95% CI 1/45 to 1/17), all from the Maroon community, which corresponds to an expected IPD incidence in Maroons of 1/1727 (95% CI 1/1156 to 1/8100). CONCLUSION: The incidence of IPD in the Maroon community is roughly 50 times higher than elsewhere in the world. The presence of only two different variants in all affected patients is compatible with a double founder effect in a relatively small population that has seldom mixed with other regional populations in the past and therefore has a reduced pool of genotypes.

Estimating the Risk of Vertical Transmission of Dengue: A Prospective Study.

The incidence of dengue worldwide is increasing rapidly. A better understanding of dengue transmission may help improve interventions against this major public health problem. The virus is mostly transmitted by vectors. There are, however, other modes of transmission, notably mother-to-child transmission or vertical transmission. We studied a prospective cohort of 54 women who had dengue while pregnant during the 2012-2013 epidemic in French Guiana to estimate the mother-to-child transmission rate and assess the clinical and biological presentation of neonatal dengue. The rate of vertical transmission was between 18.5% (95% confidence interval [CI]: 9.25-31.4) and 22.7% (95% CI: 11.5-37.8), depending on the calculation method used. Mother-to-child transmission occurred both in early and late pregnancy. There were 52 births, including three newborns who presented neonatal dengue with warning signs requiring platelet transfusion. This quantification of the mother-to-child transmission of dengue highlights three points: first, vertical transmission of dengue is not negligible; second, it is more frequent when maternal dengue occurs late during pregnancy near delivery; and third, reliable diagnostic tests must be used to allow the diagnosis of vertical transmission. Our findings indicate that if there is a known history of maternal dengue during pregnancy, or if there is fever during the 15 days before term, cord blood and placenta should be sampled after delivery and tested for the virus, and the newborn should be closely monitored during the postpartum period.

Blood lead levels and risk factors for lead exposure among pregnant women in western French Guiana: the role of manioc consumption.

Concerns regarding lead (Pb) poisoning in French Guiana first arose in 2011 following the discovery of excessively high levels of the metal amongst children in a small neighborhood without any apparent source of Pb. Since 2012, blood lead level (BLL) measurement has been proposed for all pregnant women in western French Guiana. The aim of this study was to determine BLL in pregnant women in this region and identify factors associated with elevated BLL. An observational study of a consecutive sample of women who delivered in the maternity ward of the hospital was conducted. Risk factors were investigated using a questionnaire administered postdelivery by midwives (N = 531). Approximately 25 and 5% of women displayed BLL of ≥50 µg/L and ≥100 µg/L, respectively. The geometric mean was 32.6 µg/L. Factors that were significantly associated with an elevated BLL after modeling (multivariate linear regression) included place of residence along the Maroni river, low level of education, daily consumption of manioc derivatives, weekly and daily consumption or personal preparation of manioc flour during pregnancy, and weekly consumption of wild game. This study provides insight into the regional and social disparities in BLL in French Guiana and potential sources of exposure. Evidence indicates that foods that are primarily produced and consumed in the Guiana Shield significantly affect BLL levels. Taken together with existing data, our results demonstrate that specific actions in terms of prevention, screening, and care are required to be adapted and put into place in order to reduce exposure.

Population movements and the HIV cascade in recently diagnosed patients at the French Guiana -Suriname border.

Border areas are particular "hot spots" generating high levels of HIV vulnerability and facing great challenges to control epidemics. The objective of this study is to describe the sociodemographic, clinical and biological profiles of newly HIV diagnosed people at the French Guiana - Suriname border, to construct an HIV care cascade and compare it with the Surinamese one. HIV-patients aged over 15 years newly diagnosed in western French Guiana in 2011 and 2012 were included in a retrospective cohort study. Patients were identified using different sources (n = 121). The male-to-female ratio was 0.8, 85% of the patients were of foreign origin, 72% were undocumented migrants, 21% were living in Suriname and 48% had baseline CD4 cell counts <200 cells/mm3. After one year, 34% were lost to follow-up, 54% received treatment, 34% had controlled viremia and 6% died. We observed a disappointing HIV cascade, like that of Suriname, requiring to develop a coordinated healthcare offer on both sides of the border. Targeted efforts through a bi-national collaboration are needed to address the specific issues of cross-border patients to reach the 90*3 UNAIDS's diagnosis, link to care and treatment targets and better control the local epidemic.

Epidemiological assessment of the severity of dengue epidemics in French Guiana.

BACKGROUND: Dengue fever is the most important arboviral infection that affects humans, particularly in tropical and subtropical regions. Here, we provide the first comprehensive overview of the severity of dengue epidemics in French Guiana. METHODOLOGY/PRINCIPAL FINDINGS: We monitored hospitalized cases between 2008 and 2013. Detailed clinical features and biological parameters were collected on a daily basis from all cases. Among the 1,356 cases, 216 (16%) were classified according to the WHO 2009 classification as dengue without warning signs (WS), 926 (68%) were classified as dengue with WS and 214 (16%) were classified as severe dengue. The severity rates were similar between the three major epidemics that occurred during the study period, whereas the hospitalization rate was highest in 2013. Fluid accumulation, aspartate aminotransferase (ASAT) counts>193 IU/L and platelet counts<75,000 cells/mm3 were associated with dengue severity. CONCLUSIONS/SIGNIFICANCE: Our findings provide a recent epidemiological description of the severity of dengue epidemics in French Guiana. These results highlight the potential impacts and consequences of implementing the WHO 2009 classification on hospital activity. Future studies should include virological and immunological investigations of well-documented serum samples.

Performance Testing of PCR Assay in Blood Samples for the Diagnosis of Toxoplasmic Encephalitis in AIDS Patients from the French Departments of America and Genetic Diversity of Toxoplasma gondii: A Prospective and Multicentric Study.

BACKGROUND: Toxoplasmic encephalitis in patients with AIDS is a life-threatening disease mostly due to reactivation of Toxoplasma gondii cysts in the brain. The main objective of this study was to evaluate the performance of real-time PCR assay in peripheral blood samples for the diagnosis of toxoplasmic encephalitis in AIDS patients in the French West Indies and Guiana. METHODOLOGY/PRINCIPAL FINDINGS: Adult patients with HIV and suspicion of toxoplasmic encephalitis with start of specific antitoxoplasmic therapy were included in this study during 40 months. The real-time PCR assay targeting the 529 bp repeat region of T. gondii was performed in two different centers for all blood samples. A Neighbor-Joining tree was reconstructed from microsatellite data to examine the relationships between strains from human cases of toxoplasmosis in South America and the Caribbean. A total of 44 cases were validated by a committee of experts, including 36 cases with toxoplasmic encephalitis. The specificity of the PCR assay in blood samples was 100% but the sensitivity was only 25% with moderate agreement between the two centers. Altered level of consciousness and being born in the French West Indies and Guiana were the only two variables that were associated with significantly decreased risk of false negative results with the PCR assay. CONCLUSION/SIGNIFICANCE: Our results showed that PCR sensitivity in blood samples increased with severity of toxoplasmic encephalitis in AIDS patients. Geographic origin of patients was likely to influence PCR sensitivity but there was little evidence that it was caused by differences in T. gondii strains. TRIAL REGISTRATION: ClinicalTrials.gov NCT00803621.

Shigellosis and Pregnancy in French Guiana: Obstetric and Neonatal Complications.

Shigella is a major cause of dysentery worldwide. Only a few cases of shigellosis during pregnancy have been reported. However, the neonatal and obstetric complications are potentially severe. The objective of this study was to describe the obstetric and neonatal complications of shigellosis during pregnancy. We carried out a retrospective study of 37 cases of shigellosis diagnosed in pregnant women at the maternity unit of Saint-Laurent du Maroni Hospital in west French Guiana between 2000 and 2014. Shigellosis diagnosis was based on the detection of Shigella in stool cultures from pregnant women (34 patients) or in a neonatal sample collected immediately after delivery (three neonates). In addition to the classic symptoms of shigellosis-an association of diarrhea, fever, and abdominal pain-we observed uterine contractions before the completion of 37 weeks of gestation in 61% of patients (N = 17/28). Cervical changes were associated with uterine contractions in 82% of cases (N = 14/17); 25% of the patients at risk of preterm birth went on to give birth prematurely (N = 3/12). Three cases of mother-to-child transmission were observed. Episodes of shigellosis in pregnant women may trigger uterine contractions and changes to the cervix, potentially resulting in miscarriage or preterm birth.

HIV-1 Pol Gene Polymorphism and Antiretroviral Resistance Mutations in Treatment-Naive Adult Patients in French Guiana Between 2006 and 2012.

Little information is available on the molecular epidemiologic profile of HIV-1 in French Guiana, the French department with the highest HIV/AIDS incidence. To follow the evolution of HIV-1 diversity, we carried out a molecular analysis of HIV-1 isolates from 305 treatment-naive patients between 2006 and 2012. Protease and reverse-transcriptase sequences were obtained for subtype characterization, polymorphism analysis, and identification of drug resistance mutations. Of 305 HIV-1 strains, 95.1% were subtype B viruses. The overall prevalence of transmitted drug-resistance mutations (TDRMs) was 4.6% (14/305), ranging from 1.9% to 7.1% depending on the year. This study shows a low level of HIV-1 genetic diversity and a moderate prevalence of TDRMs with no evidence of an increasing trend over the study period. Nevertheless, the strong genetic polymorphism observed on both genes may be of concern for long-term treatment of people living with HIV-1 and thus deserves continuous monitoring.

HIV-associated histoplasmosis early mortality and incidence trends: from neglect to priority.

BACKGROUND: Histoplasmosis is an endemic fungal infection in French Guiana. It is the most common AIDS-defining illness and the leading cause of AIDS-related deaths. Diagnosis is difficult, but in the past 2 decades, it has improved in this French overseas territory which offers an interesting model of Amazonian pathogen ecology. The objectives of the present study were to describe the temporal trends of incidence and mortality indicators for HIV-associated histoplasmosis in French Guiana. METHODS: A retrospective study was conducted to describe early mortality rates observed in persons diagnosed with incident cases of HIV-associated Histoplasma capsulatum var. capsulatum histoplasmosis admitted in one of the three main hospitals in French Guiana between 1992 and 2011. Early mortality was defined by death occurring within 30 days after antifungal treatment initiation. Data were collected on standardized case report forms and analysed using standard statistical methods. RESULTS: There were 124 deaths (45.3%) and 46 early deaths (16.8%) among 274 patients. Three time periods of particular interest were identified: 1992-1997, 1998-2004 and 2005-2011. The two main temporal trends were: the proportion of early deaths among annual incident histoplasmosis cases significantly declined four fold (χ2, p<0.0001) and the number of annual incident histoplasmosis cases increased three fold between 1992-1997 and 1998-2004, and subsequently stabilized. CONCLUSION: From an occasional exotic diagnosis, AIDS-related histoplasmosis became the top AIDS-defining event in French Guiana. This was accompanied by a spectacular decrease of early mortality related to histoplasmosis, consistent with North American reference center mortality rates. The present example testifies that rapid progress could be at reach if awareness increases and leads to clinical and laboratory capacity building in order to diagnose and treat this curable disease.

Fever in hospitalized HIV-infected patients in Western French Guiana: first think histoplasmosis.

In Western French Guiana, there was a dramatic increase in HIV prevalence between 1990 and 2000. The present study describes the causes of fever among HIV patients hospitalized in the medical ward of the only hospital in the western part of French Guiana. A retrospective descriptive study was conducted between 1 January 2008 and 30 June 2010 in the department of medicine of Saint Laurent du Maroni Hospital. The main characteristics of 67 patients having presented with fever in the first 48 hours of hospitalization were described. Among patients with CD4 <200/mm(3)the main febrile opportunistic infection was disseminated histoplasmosis (41.1%). Among patients with CD4 counts <50/mm(3)and fever without focal points 85.7% had disseminated histoplasmosis. Three patients died and all had disseminated histoplasmosis. Disseminated histoplasmosis is the most common febrile opportunistic infection in western French Guiana. Primary prophylaxis with itraconazole among immunocompromised patients seems warranted.

Characteristics and specificities of Cryptococcus infections in French Guiana, 1998-2008.

Cryptococcosis is a common opportunistic systemic mycosis caused by members of the encapsulated yeast genus Cryptococcus. The aetiological agents of the disease are classified into two species, i.e., Cryptococcus neoformans (serotypes A, D, and AD) affecting mainly immunocompromised patients and Cryptococcus gattii (serotypes B and C) usually found in immunocompetent individuals. Limited data exist on Cryptococcus infections in French Guiana, the department with the highest HIV incidence in the French territories. A retrospective study between January 1998 and December 2008 was performed on all patients with cryptococcosis, admitted to hospitals in French Guiana. Epidemiological data, clinical forms and diagnosis methods were studied. Of the 43 patients with cryptococcosis, 29 (67.4%) had HIV infections. Among the HIV-negative patients, two (4.7%) presented identified risk factors for cryptococcosis. This study has shown a high frequency of patients with HTLV-1 positive serology (12.1%). C. neoformans var. grubii was recovered with a frequency of 77.3% and was mainly isolated from patients with AIDS (13/17), whereas C. gattii (22.7%) was strictly isolated from HIV-negative patients with no apparent risk factors. Despite a socio-economic environment closer to western countries, the overall epidemiology of cryptococcosis in French Guiana is more similar to that found in South America, particularly with reference to the serotypes of the causative yeasts. Indeed, French Guiana presents an especially high proportion of cases caused by C. gattii, which may explain the significant incidence of this disease, particularly in HIV-negative and immunocompetent patients.

Plasma and urinary aluminum concentrations in severely anemic geophagous pregnant women in the Bas Maroni region of French Guiana: a case-control study.

The clays consumed by geophagous individuals contain large quantities of aluminum, a known neurological and hematological toxin. This is the first study to evaluate the risk of aluminum poisoning in geophagous individuals. Blind determinations of plasma and urinary aluminum concentrations were carried out in 98 anemic geophagous pregnant women and 85 non-anemic non-geophagous pregnant women. Aluminum concentrations were significantly higher (P < 0.0001) in the geophagous anemic women than in the controls, with odds ratios of 6.83 (95% confidence interval [CI] = 2.72-19.31) for plasma concentrations (13.92 ± 14.09 µg/L versus 4.95 ± 7.11 µg/L) and 5.44 (95% CI = 2.17-14.8) for urinary concentrations (92.83 ± 251.21 µg/L versus 12.11 ± 23 µg/L). The ingested clay is the most likely source of this overexposure to aluminum. If confirmed, the clinical consequences of this absorption for pregnant women and their offspring should be explored.

Detection of Histoplasma capsulatum DNA in human samples by real-time polymerase chain reaction.

The main aim of our study was to determine the added value of real-time polymerase chain reaction (PCR) for the diagnosis of Histoplasma capsulatum in routine biologic practice. No amplification signal was observed with the 18 non-H. capsulatum strains used to test the specificity of the protocol. The sensitivity threshold of the real-time PCR assay was about 10 fg of H. capsulatum DNA per microliter, tested with a 10-fold serial dilution of the positive control. We analyzed 348 human samples submitted for the routine diagnosis of systemic mycosis. Real-time PCR using the TaqMan system was evaluated against direct microscopic examination and culture. Among the 341 samples without PCR inhibition (n = 7), 66 tested positive by culture, whereas 74 tested positive by real-time PCR. Sensitivity of the real-time PCR assay was estimated at 95.4% and specificity at 96.0% with respect to culture, widely considered to be the gold standard method; however, the molecular approach in fact produced better sensitivity and specificity results. Moreover, for the 38 samples that tested negative by direct examination but positive by culture, the culture method took a mean of 31 days longer than the PCR method to generate results. The protocol presented here may be very useful for improving routine histoplasmosis diagnosis.

Standardization and comparison of endogenous erythroid colony assays performed with bone marrow or blood progenitors for the diagnosis of polycythemia vera.

The reliability of the assay of endogenous erythroid colony (EEC) formation in serum-free, cytokine-free collagen-based media was investigated in a multicentric study including 140 patients with polyglobuly (80 polycythemia vera (PV), 54 secondary erythrocytosis (SE), six idiopathic erythrocytosis (IE)) and 10 healthy donors. In each center, EEC assays were performed in parallel with progenitor cells from bone marrow (BM) and peripheral blood (PB); two commercialized media and 'low' and 'high' cell plating densities were tested. Negativity of EEC assays was considered certain only when sufficient BFU-E growth was obtained in control cultures with cytokines. In the two media, EEC formation was specific - never observed in cultures of healthy donors or SE patients - and comparable. BM EEC assays were positive (presence of eythroid colonies) for 75% ('low' plating) to 100% ('high' plating) of PV patients; PB EEC assays were positive for 83.3% ('low' plating) to 93.7% ('high' plating) of PV patients (differences not significant). Depending on the medium, 86.2-93.7% of patients with a positive BM EEC assay had a positive PB EEC assay. Hence, a standardized collagen-based EEC assay can be performed with either BM or PB progenitors; the EEC assay described here is positive for at least 75% of PV patients when a single EEC assay is performed, and for at least 94% of PV patients when both BM and PB EEC assays are performed.