Levers and Barriers to Vaccinate against COVID-19 in the Multicultural Context of French Guiana: A Qualitative Cross-Sectional Survey among Health Care Workers.

In French Guiana, a French overseas territory in South America facing a fourth wave of COVID-19, vaccination coverage is very low, both in the population and among health care workers (HCWs). Vaccine hesitancy concerned 35.7% of the latter in early 2021. The objective of this complementary study is to understand barriers and levers and to adapt messages to increase vaccination coverage among HCWs. We conducted a regional cross-sectional survey of HCWs with a questionnaire containing open-ended questions exploring factors associated with vaccine hesitancy and the needs to adapt the vaccination campaign in French Guiana. The discourses were analyzed using a qualitative approach based on grounded theory, with open coding of data by themes and construction of abstract categories. The analysis of the 357 responses collected from January to March 2021 reveals several trends. The ethical aspect of the HCWs' role emphasizes the importance of getting vaccinated themselves (to protect patients, to set an example...) and of vaccinating as many people as possible, including the most geographically or socially distant, such as undocumented migrants. However, some HCWs remain suspicious of the vaccine with concerns over the efficacy and side effects, of health institutions, and of the pharmaceutical industry. The role of fake news circulating on social networks has been widely discussed. Efforts to explain and convince HCWs must be continued in French Guiana using the identified levers to improve the acceptability of vaccination.

Attitudes towards the COVID-19 Vaccine and Willingness to Get Vaccinated among Healthcare Workers in French Guiana: The Influence of Geographical Origin.

Background: In the context of the global COVID-19 pandemic and the expansion of the more transmissible 20J/501Y.V3 (Gamma) variant of concern (VOC), mRNA vaccines have been made available in French Guiana, an overseas French territory in South America, from mid-January 2021. This study aimed to estimate the willingness to be vaccinated and the socio-demographic and motivational correlates among Health Care Workers (HCWs) in French Guiana. Methods: A cross-sectional survey was conducted from January 22 to March 26, 2021 among a sample of HCWs in French Guiana. They were asked about their willingness to get vaccinated against COVID-19 and vaccine hesitancy, vaccine uptake and vaccines attitudes. Factors associated with willingness to get vaccinated have been analyzed with ordinal logistic regression, using Stata software. Results: A total of 579 HCWs were interviewed, including 220 physicians and 200 nurses most often working in hospital (54%) or in the liberal sector (22%). Overall, 65.6% of respondents reported that they were willing or had already been vaccinated against COVID-19, while 24.3% of respondents reported that they did not want to get vaccinated against COVID-19 and 11.2% were unsure. HCWs were more willing to get vaccine if they were older, were worried about COVID-19 and were confident in the management of epidemic. Conversely, participants were less likely to have been vaccinated or willing to if they were nurses or of another non-medical profession, born in French Guiana, feared adverse effects, or if they did not trust pharmaceutical companies and management of the epidemic by authorities. Conclusion: Negative attitudes towards vaccines are a major public health concern among HCWs in French Guiana when considering the current active epidemic with Gamma VOC. General vaccine hesitancy and concerns about future side effects in particular represent important barriers. Low confidence in government and science are significant in COVID-19 vaccine refusal among non-medical staffs. Public health messaging with information on vaccine safety should be tailored to address these concerns. The specific challenges of HCWs from French Guiana must be taken into account.

Review of diagnostic methods and results for HIV-associated disseminated histoplasmosis: Pathologists are not sufficiently involved.

OBJECTIVES: Disseminated histoplasmosis is a major killer of HIV-infected persons in Latin America. Antigen detection, fungal culture and Polymerase Chain Reaction are often not available, but cytology and histology are present in most hospitals and may offer a diagnostic alternative. In this study, we review 34 years of clinical experience to describe the roles of cytology and histology in diagnosing disseminated histoplasmosis. METHODS: Retrospective multicentric study of 349 patients between 1 January 1981 and 1 October 2014 with confirmed disseminated histoplasmosis. RESULTS: Around 32/214 (14.9%) of samples were screened using cytopathology, as were 10/101 (9.9%) bronchoalveolar lavage samples and 5/61 (8.2%) of spinal fluid samples. The samples most commonly sent to pathology were liver biopsies, lower digestive tract and lymphnode biopsies; the greatest proportion of positive results were found in lower digestive tract (43/59 (72.9%) positives), lymph node (39/63 (66.1%)), and liver (38/75 (50.7%)) samples. Overall, 97.2% of bone marrow and 97% of bronchoalveolar lavage samples were directly examined by a mycologist. Positive direct examination was independently associated with death (aHR = 1.5 (95%CI = 1-2.2)). CONCLUSIONS: Opportunities for a rapid diagnosis were regularly missed, notably for bone marrow samples, which could have been examined using staining methods complementary to those of the mycologist.

HIV-Associated Disseminated Histoplasmosis and Rare Adrenal Involvement: Evidence of Absence or Absence of Evidence.

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.

Gastrointestinal disseminated histoplasmosis in HIV-infected patients: A descriptive and comparative study.

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.

Risk Factors for Mortality among HIV-Infected Patients with Disseminated Histoplasmosis.

Identifying prognostic factors is important in order to guide the choice of first-line therapy for disseminated histoplasmosis. Our objective was to identify factors associated with death among a cohort of 330 patients compiled over 34 years of clinical practice in French Guiana. Survival analysis was performed with death as the failure event and date of symptom onset as the origin event. Incidence rates were and Cox proportional hazards models were computed. Overall, 330 HIV-infected patients with disseminated histoplasmosis were included in the analysis, with 126 deaths occurring. One-quarter of all patients died within 6 months of the first symptoms. Patients with dyspnea, renal failure, arterial blood pressure < 90 mmHG, and a WHO performance score > 2 had a greater incidence of death. Bivariate analyses showed that patients with increased LDH, low hemoglobin, low serum protein, low CD4 counts, and low platelets tended to have a greater incidence of death. After adjusting for potential confounders, patients with dyspnea, a WHO performance score > 2, serum protein < 60 g/L, and hemoglobin < 8.9 g/dL had an increased risk of dying. The interaction terms showed that patients treated with liposomal amphotericin B had a marked reduction in death among patients with renal failure; among renal failure patients, the elevation of LDH was associated with a significant risk of death.

Heterogeneity of Clinical Presentations and Paraclinical Explorations to Diagnose Disseminated Histoplasmosis in Patients with Advanced HIV: 34 Years of Experience in French Guiana.

We aimed to describe the ways patients with disseminated histoplasmosis-a multifaceted and often lethal disease-present themselves and are explored. A retrospective, observational, multicentric study spanned the period between 1 January 1981 and 1 October 2014. Principal component analysis was performed for the sampling sites and for the clinical signs and symptoms. The factor loadings of the principal components were selected for eigenvalues > 1. The most frequent signs and symptoms were an alteration of the WHO general performance status, fever, digestive tract, respiratory signs and symptoms and lymphadenopathies. The most common sites sampled were bone marrow, respiratory tract, blood, lymph node and liver biopsies, with significant variations in the number of sites from which samples were taken to try to identify the pathogen. The principal component analysis clinical signs and symptoms leading to the diagnosis showed four main lines of variation. The factor loadings of the four main components were compatible with four broad types of clinical presentations and four types of exploration strategies. Extracting simple algorithms was difficult, emphasizing the importance of clinical expertise when diagnosis depends on obtaining a sample where Histoplasma can be seen or grown. Histoplasma antigen detection tests will help simplifying the algorithms.

Disseminated Histoplasmosis in HIV-Infected Patients: A Description of 34 Years of Clinical and Therapeutic Practice.

Disseminated histoplasmosis is the main AIDS-defining infection of French Guiana. We aim to describe our therapeutic experience for 349 patients with disseminated histoplasmosis between 1 January 1981 and 10 January 2014 in French Guiana. Survival, delays for treatment initiation, duration of induction therapy, and associated initial treatments are described. The death rate was 14.9 per 100 person-years, with an early drop in survival. Among those who died, >1/3 died within a year of HIV diagnosis, and ¾ of all patients with histoplasmosis had been diagnosed for HIV within a year. As induction treatment, 29% received liposomal amphotericin B, 12.9% received deoxycholate amphotericin B, 54% received itraconazole alone, and 21.8% received liposomal amphotericin B and itraconazole. The median delay between symptoms-onset and hospitalization was 19.5 days (IQR = 5-105). Liposomal amphotericin B or itraconazole was initiated shortly after admission. Treatment initiation was often presumptive for liposomal amphotericin B (27%) and itraconazole (20%). The median duration of liposomal amphotericin B treatment was 7 days (IQR = 5-11 days). The present study shows that ¾ of the patients were profoundly immunocompromised and had been diagnosed for HIV within the past year. Antifungal treatment was often initiated presumptively on admission. Over time there was a significant gradual decline in early death.

Reduced Severity in Patients With HIV-Associated Disseminated Histoplasmosis With Deep Lymphadenopathies: A Trench War Remains Within the Lymph Nodes?

Background: Disseminated 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. Methods: A retrospective cohort study was performed on data records collected between January 1, 1981 and October 1, 2014. Results: Among 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 (<1 month) among those with deep lymphadenopathies relative to those without (OR=0.26 (95%CI=0.10-0.60), P=0.0006) and in the overall risk of death (OR=0.33 (95%CI=0.20-0.55), P<0.0001). These associations remained strongly significant after adjusting for time period, CD4 counts, age, delay between beginning of symptoms and hospital admission, antifungal and antiretroviral treatment. Conclusions: The present data show that in patients with advanced HIV and disseminated histoplasmosis, the presence of deep lymphadenopathies is associated with fewer markers of severity and a lower risk of death. To our knowledge it is the first study to show this. The presence of deep lymphadenopathies is hypothesized to reflect the patient's partially effective defense against H. capsulatum.

Histoplasmosis and Tuberculosis Co-Occurrence in People with Advanced HIV.

Distinguishing between histoplasmosis, tuberculosis (TB), and co-occurrence of disease is a frequent dilemma for clinical staff treating people with advanced Human Immunodeficiency Virus (HIV) infection. This problem is most frequently observed in clinical settings in countries where both diseases are endemic. It is also a challenge outside these endemic countries in HIV clinics that take care of patients coming from countries with endemic histoplasmosis and TB. The gold standard for diagnosis of both of these diseases is based on conventional laboratory tests (culture, histopathology and special stains). These tests have several limitations, such as lack of laboratory infrastructure for handling isolates (biosafety level 3), shortage of laboratory staff who have appropriate training and experience, variable analytical performance of tests and long turn-around time. Recently, novel rapid assays for the diagnosis of histoplasmosis and TB became available. However, this technology is not yet widely used. Mortality in immunocompromised patients, such as people with advanced HIV, is directly linked with the ability to rapidly diagnose opportunistic diseases. The aim of this review is to synthesize the main aspects of epidemiology, clinical characteristics, diagnosis and treatment of histoplasmosis/TB co-occurrence in people with advanced HIV.

Burden of HIV-associated histoplasmosis compared with tuberculosis in Latin America: a modelling study.

BACKGROUND: Fungal infections remain a major contributor to the opportunistic infections that affect people living with HIV. Among them, histoplasmosis is considered neglected, often being misdiagnosed as tuberculosis, and is responsible for numerous deaths in Latin America. The objective of this study was to estimate the burden of HIV-associated histoplasmosis compared with tuberculosis in Latin American countries. METHODS: For this modelling study, we estimated prevalence of previous exposure to Histoplasma capsulatum, HIV-associated histoplasmosis annual incidence, and number of deaths in 2012 in Latin American countries based on historical histoplasmin skin test studies in the general population, with an antigen dilution level of more than 1/10. Studies were identified in a literature search. Data on HIV-associated tuberculosis were extracted from the WHO notifications and outcomes tables and data on people living with HIV were extracted from the UNAIDS report for the year 2012. We systematically propagated uncertainty throughout all the steps of the estimation process. FINDINGS: Among 1310 articles identified as of June 1, 2015, 24 articles were included in the study, representing 129 histoplasmin skin test studies led in the general population of Latin American countries. For the year 2012, we estimated a range of 6710 (95% CI 5680-7867) to 15 657 (13 254-18 357) cases of symptomatic HIV-associated histoplasmosis in Latin America. Hotspot areas for histoplasmosis prevalence (>30%) and incidence (>1·5 cases per 100 people living with HIV) were Central America, the northernmost part of South America, and Argentina. According to realistic scenarios, we estimated a range of 671 (95% CI 568-787) to 9394 (7952-11 014) deaths related to histoplasmosis, compared with 5062 (3777-6405) deaths related to tuberculosis reported in Latin America. INTERPRETATION: Our estimates of histoplasmosis incidence and deaths are high and consistent with published data. For the first time, the burden of histoplasmosis is estimated to be equivalent in incidence and even higher in deaths when compared with tuberculosis among people living with HIV in Latin America. FUNDING: None.

Primaquine 30 mg/day versus 15 mg/day during 14 days for the prevention of Plasmodium vivax relapses in adults in French Guiana: a historical comparison.

BACKGROUND: The preventive treatment of Plasmodium vivax relapse recommended by the World Health Organization is primaquine at a dose of 15 mg/day for 14 days, except for malaria cases from Asia and Oceania. Since 2006, CDC recommends the use of primaquine at 30 mg/day for 14 days. In France, all cases of malaria due to P. vivax are treated with 30 mg of primaquine. This systematically increased dosage needs to be evaluated according to epidemiological context. The aim of the study was to compare relapses after 14 days of primaquine at 15 or 30 mg/day. METHODS: All patients treated with primaquine after a vivax malaria episode in French Guiana, between 1 January, 2007 and 1 August, 2016, were studied. Based on the compulsory hospital pharmacy forms for primaquine delivery, adult patients who received 15 or 30 mg of primaquine during 14 days for hypnozoite eradication were included. The recommended dose was initially 15 mg and was changed to 30 mg in 2011. Vivax malaria recurrences within 2 months after primaquine treatment, and vivax malaria recurrences 2-6 months after primaquine in each treatment group were analysed using survival analysis at 2, 3 and 6 months. RESULTS: Out of 544 patients included, 283 received 15 mg/day and 261 received 30 mg/day of primaquine. At 2 and 3 months after primaquine treatment, the number of recurrences was 7 (2.5%) and 19 (7.3%), and 9 (3.4%) and 15 (5.3%), in the 15 and 30 mg groups (p = 0.51 respectively 0.35), respectively. Within 3 months, the median time to recurrence was 2.05 months in the 15 and 30 mg groups. At 6 months after primaquine treatment, the number of recurrences was 25 (8.8%) and 31 (11.9%) at 15 and 30 mg, respectively (p = 0.24). The median time to recurrence was 2.38 months at 15 mg/day and of 2.64 months at 30 mg/day. CONCLUSIONS: There were no significant differences between primaquine at 15 or 30 mg/day for 14 days in the prevention of P. vivax relapses at 2, 3 and 6 months after primaquine treatment in French Guiana.