Increased Prevalence of Alloimmunization in Sickle Cell Disease? Should We Restore Blood Donation in French Guiana?

Patients with sickle cell disease often undergo frequent blood transfusions. This increases their exposure to red blood cell alloantigens of donor units, thus making it more likely that they produce alloantibodies. This cross-sectional study aimed to describe the prevalence of allo-immunization in patients with sickle cell disease who were monitored at Cayenne Hospital in 2016. Of the 451 patients recruited during the study period, 238 (52.8%) were female. There were 262 (58.1%) homozygous sickle cell and 151 (33.5%) compound heterozygous sickle cell patients. The median age of the participants was 23.09 years (range, 0.5-68). We noted different red blood cell extended phenotypes: -in the Duffy system, the Fya- Fyb-profile was found in 299 patients (66%);-for the Kidd system, the most represented profile was Jka+ Jkb-, with 213 patients (47%). The Jka antigen was present in 355 patients;-in the MNS system, the S-s+ profile was found in 297 patients (66%);-the Lea antigen of the Lewis system was absent in 319 patients. The most frequent Rh phenotype in our patients was D+ C- E- c+ e+ K-, representing 51% of the patients. A total of 6,834 transfused packed red blood cell units were recorded. Sixty-eight patients (23%; 95% confidence interval, 20-25%) had detectable RBC alloantibodies. In multivariate logistic regression, only the mean number of single transfusions was statistically higher for the alloimmunized patients (p < 0.04). Thirteen (19%) of the patients with alloimmunization developed a delayed hemolytic transfusion reaction, thus representing 4.4% of the total number of transfused patients. Whether differences between donors from France vs. recipients from French Guiana could explain this high prevalence of alloimmunization to be examined. In conclusion, careful transfusion strategies for patients with RBC alloantibodies should allow further reduction of the rate of alloimmunization.

High prevalence of human papillomavirus infection in HIV-infected women living in French Antilles and French Guiana.

An association between HIV infection and cervical cancer, a major public health issue worldwide, has been reported. The aim of this study was to estimate the prevalence of human papillomavirus (HPV) infection and the distribution of HPV genotypes in HIV-infected women living in French Antilles and Guiana and to determine HIV-related characteristics associated with HPV infection. This cross-sectional study included 439 HIV-infected women who were followed between January 2011 and May 2014. Variables related to HIV infections were collected, and cervical samples were analysed to determine HPV genotypes. The median age of the population was 46 years. Estimated prevalence of HPV and high-risk (HR)-HPV infection were 50.1% IC95 [45.4-54.7] and 42% IC95 [37.3-46.6], respectively. HR-HPV 16, 52, 53 or intermediate risk-HPV-68 were found in 25% to 30% of the HPV-infected patients. Gynaecological screening revealed abnormal cervical smear in 24% and 42% of HR-HPV-negative and HPV-positive women, respectively (p = 0.003). Approximately 90% of women were on antiretroviral therapy (ART). Demographic characteristics associated with a higher prevalence of HPV infection included alcohol consumption. Regarding HIV-related characteristics, current therapy on ART, its duration, and undetectable plasma concentrations of RNA-HIV1 were associated with a lower risk of HPV infection. Infection rate with HR-HPV was higher than what is commonly reported in HIV-negative women worldwide and was more likely in women with incomplete HIV suppression. These results highlight the need for supporting adherence to ART, cervical cytology, HPV testing and HPV vaccination.

Modeling of the HIV epidemic and continuum of care in French Guiana.

BACKGROUND: In order to compute the continuum of care for French Guiana, it is necessary to estimate the total number of persons living with HIV. The main objective was to determine how many persons were infected with HIV and how many were unaware of it. METHODS: We used 2 different models to calculate the total number of persons infected with HIV: Spectrum's AIM module using CSAVR to compute incidence from case registration and vital statistics; and the ECDC model from the French Guiana HIV cohort data. RESULT: The present results show that both models led to similar results regarding the incident number of cases (i.e. for 2016 174 versus 161) and the total HIV population (in 2016 3206 versus 3539) respectively. The ECDC modeling tool showed that the proportion of undiagnosed HIV infections declined from 50% in 1990 to 15% in 2015. This amounted to a stable or slightly increasing total number of undiagnosed patients of 520. CONCLUSIONS: The estimations of the total HIV population by both models show that the HIV population is still growing. The incidence rate declined in 2000 and the decline of the number of newly acquired HIV infections, after a decline after 2003 is offset by population growth. The proportion of undiagnosed infections has declined to 15% but the number of undiagnosed infections remains stable. The HIV cascade shows that despite good results for treatment in care, reaching the 90*90*90 UNAIDS target may be difficult because a significant proportion of patients are lost to follow-up.

Unraveling the genetic diversity and phylogeny of Leishmania RNA virus 1 strains of infected Leishmania isolates circulating in French Guiana.

INTRODUCTION: Leishmania RNA virus type 1 (LRV1) is an endosymbiont of some Leishmania (Vianna) species in South America. Presence of LRV1 in parasites exacerbates disease severity in animal models and humans, related to a disproportioned innate immune response, and is correlated with drug treatment failures in humans. Although the virus was identified decades ago, its genomic diversity has been overlooked until now. METHODOLOGY/PRINCIPLES FINDINGS: We subjected LRV1 strains from 19 L. (V.) guyanensis and one L. (V.) braziliensis isolates obtained from cutaneous leishmaniasis samples identified throughout French Guiana with next-generation sequencing and de novo sequence assembly. We generated and analyzed 24 unique LRV1 sequences over their full-length coding regions. Multiple alignment of these new sequences revealed variability (0.5%-23.5%) across the entire sequence except for highly conserved motifs within the 5' untranslated region. Phylogenetic analyses showed that viral genomes of L. (V.) guyanensis grouped into five distinct clusters. They further showed a species-dependent clustering between viral genomes of L. (V.) guyanensis and L. (V.) braziliensis, confirming a long-term co-evolutionary history. Noteworthy, we identified cases of multiple LRV1 infections in three of the 20 Leishmania isolates. CONCLUSIONS/SIGNIFICANCE: Here, we present the first-ever estimate of LRV1 genomic diversity that exists in Leishmania (V.) guyanensis parasites. Genetic characterization and phylogenetic analyses of these viruses has shed light on their evolutionary relationships. To our knowledge, this study is also the first to report cases of multiple LRV1 infections in some parasites. Finally, this work has made it possible to develop molecular tools for adequate identification and genotyping of LRV1 strains for diagnostic purposes. Given the suspected worsening role of LRV1 infection in the pathogenesis of human leishmaniasis, these data have a major impact from a clinical viewpoint and for the management of Leishmania-infected patients.

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.

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.

Risk factors for disseminated histoplasmosis in a cohort of HIV-infected patients in French Guiana.

Disseminated histoplasmosis is the first AIDS-defining infection in French Guiana. A retrospective cohort study studied predictive factors of disseminated histoplasmosis in HIV-infected patients between 1996 and 2008. Cox proportional hazards models were used. The variables studied were age, sex, last CD4/CD8 count, CD4 nadir, herpes or pneumocystosis, cotrimoxazole and fluconazole use, antiretroviral treatment and the notion of recent initiation of HAART. A total of 1404 patients were followed for 6833 person-years. The variables independently associated with increased incidence of disseminated histoplasmosis were CD4 count<50 per mm3, CD4 count between 50 and 200 per mm3, a CD4 nadir <50 per mm3, CD8 count in the lowest quartile, herpes infection, and recent antiretroviral treatment initiation (less than 6 months). The variables associated with decreased incidence of histoplasmosis were antiretroviral treatment for more than 6 months, fluconazole treatment, and pneumocystosis. There were 13.5% of deaths at 1 month, 17.5% at 3 months, and 22.5% at 6 months after the date of diagnosis of histoplasmosis. The most important predictive factors for death within 6 months of diagnosis were CD4 counts and antiretroviral treatment. The present study did not study environmental/occupational factors but provides predictive factors for disseminated histoplasmosis and its outcome in HIV patients in an Amazonian environment during the HAART era.

How many have died from undiagnosed human immunodeficiency virus-associated histoplasmosis, a treatable disease? Time to act.

Human immunodeficiency virus (HIV)-associated disseminated Histoplasma capsulatum capsulatum infection often mimics tuberculosis. This disease is well know in the United States but is dramatically underdiagnosed in Central and South America. In the Amazon region, given the available incidence data and the regional HIV prevalence, it is expected that, every year, 1,500 cases of histoplasmosis affect HIV patients in that region alone. Given the mortality in undiagnosed patients, at least 600 patients would be expected to die from an undiagnosed but treatable disease. The lack of a simple diagnostic tool and the lack of awareness by clinicians spiral in a vicious cycle and made a major problem invisible for 30 years. The HIV/acquired immunodeficiency syndrome community should tackle this problem now to prevent numerous avoidable deaths from HIV-associated histoplasmosis in the region and elsewhere.

Primary prophylaxis of disseminated histoplasmosis in HIV patients in French Guiana: arguments for cost effectiveness.

Histoplasmosis is the first cause of acquired immunodeficiency syndrome (AIDS) and AIDS-related deaths in French Guiana. Cohort data were used to determine whether primary prophylaxis with 100 mg itraconazole for patients with CD4 counts < 150/mm(3) was cost-effective with different scenarios. For a scenario where 12% of patients died, 60% were aware of their human immunodeficiency virus (HIV) infection and adherence was only 50%, primary prophylaxis would prevent 1 death and 9 cases of histoplasmosis for a cost of 36,792 Euros per averted death, 1,533 per life-year saved, 4,415 Euros per averted case, when only counting the costs of itraconazole prophylaxis. Taking into account the total costs of hospitalization showed that primary prophylaxis would allow a savings of 185,178 Euros per year. Even in a scenario of low adherence, primary prophylaxis would be cost-effective in French Guiana, and presumably in the rest of the Guianas and the Amazon.

Risk factors for delayed access to specialized care in French Guiana.

The variables influencing the interval between diagnosis and effective access to specialized care were studied in a cohort of 2,661 human immunodeficiency virus (HIV)-positive patients in French Guiana between 1992 and 2008. Patients with a subsequent follow-up interruption were significantly more likely to have a delayed first consultation after the HIV diagnosis. Ordinal logistic regression showed that younger persons, women, and French citizens were independently associated with greater delays between the HIV diagnosis and the first specialized consultation. However, persons with acquired immunodeficiency syndrome (AIDS) were less likely to have a delay between the HIV diagnosis and the first specialized consultation. Focusing on the link between the private sector and specialized health care may shorten delays and improve care and follow-up.

What is AIDS in the Amazon and the Guianas? Establishing the burden of disseminated histoplasmosis.

The pathogen ecology of Amazonian regions may lead to specific differences in the most frequent clinical presentations of acquired immunodeficiency syndrome (AIDS). A retrospective cohort study was thus conducted to describe the main AIDS-defining events in French Guiana. Disseminated histoplasmosis was the most frequent opportunistic infection (15.4/1000 person years).

Predictive factors and incidence of anxiety and depression in a cohort of HIV-positive patients in French Guiana.

A retrospective cohort study was conducted to determine the predictive factors and the incidence of anxiety and depression in a cohort of patients followed in French Guiana. A total of 2315 patients were followed for a total of 9116 years of follow-up. The incidence rate of first observed depression was 1.89 per 100 person years. The incidence rate of first observed generalized anxiety was 1.27 per 100 person years. A single failure Cox proportional hazards model showed that patients diagnosed <1 year (Hazard ratio (HR)=4.15; 95% CI=1.15-14.9; P=0.029), patients treated

Crack cocaine use increases the incidence of AIDS-defining events in French Guiana.

We conducted a retrospective cohort study to determine the influence of crack cocaine use on the outcomes of HIV infection. The use of crack cocaine was associated with an increased incidence of AIDS: 27.8 per 100 person-years versus 6.6 per 100 person-years for nonusers, adjusted hazard ratio = 3.8 (1.9-7.5), P < 0.001. More specifically, crack users had a greater incidence of disseminated histoplasmosis, pneumocystosis, pulmonary tuberculosis, bacterial pneumonia, oesophageal candidiasis, cerebral toxoplasmosis, salmonellosis, and genital herpes. The care of HIV-infected crack users is particularly challenging and requires additional efforts to reduce the high morbidity of these patients.

AIDS-related Histoplasma capsulatum var. capsulatum infection: 25 years experience of French Guiana.

OBJECTIVE: Histoplasma capsulatum var. capsulatum infection is a major AIDS-defining illness in French Guiana. Although it affects South and Central American countries, the number of published cases is low. We present the largest series of AIDS-related histoplasmosis. The aim of this work is to describe clinical features and to help optimize investigations in settings where antigen detection methods are not available. DESIGN: Two hundred cases of AIDS-related histoplasmosis, diagnosed in the hospitals of French Guiana, were included retrospectively between 1982 and 2007. RESULTS: At the time of diagnosis, 92% of patients did not receive highly active antiretroviral therapy. CD4 cell count was less than 100 cells/microl for 80% of them. Most patients had fever, lymphadenopathies, and pulmonary and digestive symptoms. Neurological signs and skin/mucosal locations were less common. Other opportunistic infections were associated in 36.6% of cases (mostly tuberculosis). In most of the patients, lactic dehydrogenase was at least four times the normal value, and there was a moderate increase of aspartate aminotransaminase but not alanine aminotransaminase levels. Bone marrow aspirations were useful, but cultures of liver and lymphadenopathy specimens were the most contributive. Following treatment initiation, 17.5% died within a month. Presumptive treatment was started before diagnostic confirmation in 14.3% of the cases. CONCLUSION: In high prevalence settings, histoplasmosis often revealed AIDS in severely immunodeficient and poorly followed patients. In the absence of a quick sensitive technique, skin smear and fungal tissue cultures are contributive. Nevertheless, given the diagnostic delays and the poor prognosis, presumptive treatment with amphotericin B-containing regimens should be recommended when clinical and epidemiological contexts are evocative.

Increased incidence of mucosal candidiasis after HAART initiation: a benign form of immune reconstitution disease?

Immune reconstitution after HAART initiation is often complicated by adverse clinical manifestations caused either by the unmasking of preexisting untreated opportunistic infections or the clinical deterioration of a known and treated opportunistic infection. The present study was conducted to determine whether the initiation of HAART was followed by an increase in the incidence of mucosal candidiases, a possible manifestation of immune reconstitution disease of the unmasking type.