Forty Years of HIV Research in French Guiana: Comprehend to Combat.

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.

Kaposi Sarcoma with Mucocutaneous Involvement in French Guiana: An Epidemiological Study between 1969 and 2019.

Data on Kaposi sarcoma in French Guiana are scarce and out of date. This territory presents unique epidemiological features. The objectives of this retrospective study were to analyse the clinical features, outcome and incidence of the different forms of Kaposi sarcoma in patients diagnosed between 1969 and 2019. The study population comprised a total of 52 patients. Clinical forms included epidemic Kaposi sarcoma (n=30), endemic (n=18), iatrogenic (n=2), classic (n=1) and unclassified Kaposi sarcoma (n=1). The mean annual incidence rate of epidemic Kaposi reached a peak in the 1990s (0.93/100,000) then decreased in the 2000s (0.33/100,000), while the incidence of endemic Kaposi sarcoma reached a peak in the 1980s (0.82/100,000) before decreasing in the 2000s (0.12/100,000). Factors associated with the epidemic form were: sexual intercourse between men (p=0.0054) and Haitian origin (p=0.035). The presence of nodules and/or tumour, lesions limited to the lower limbs, and age >65 years were associated with the endemic form. While Creole populations seem to be as affected by endemic Kaposi sarcoma as their African counterparts, the dynamics of Kaposi sarcoma in French Guiana are now dominated by the epidemic form.

The Fight against HIV-Associated Disseminated Histoplasmosis in the Americas: Unfolding the Different Stories of Four Centers.

Disseminated histoplasmosis is a major opportunistic infection of HIV-infected patients, killing thousands in Latin America each year. Yet, it remains a neglected disease that is often confused with tuberculosis, for lack of simple, affordable, and rapid diagnostic tools. There is great heterogeneity in the level of histoplasmosis awareness. The purpose of this report was to describe how the historical "awakening" to the threat of histoplasmosis came to be in four different centers that have actively described this disease: In Brazil, the Sao José hospital in Fortaleza; in Colombia, the Corporación para Investigaciones Biológicas in Medellin; in French Guiana, Cayenne Hospital; and in Guatemala, the Association de Salud Integral in Guatemala city. In Brazil and French Guiana, the search for leishmaniasis on the buffy coat or skin smears, respectively, led to the rapid realization that HIV patients were suffering from disseminated histoplasmosis. With time and progress in fungal culture, the magnitude of this problem turned it into a local priority. In Colombia and Guatemala, the story is different because for these mycology centers, it was no surprise to find histoplasmosis in HIV patients. In addition, collaborations with the CDC to evaluate antigen-detection tests resulted in researchers and clinicians developing the capacity to rapidly screen most patients and to demonstrate the very high burden of disease in these countries. While the lack of awareness is still a major problem, it is instructive to review the ways through which different centers became histoplasmosis-aware. Nevertheless, as new rapid diagnostic tools are becoming available, their implementation throughout Latin America should rapidly raise the level of awareness in order to reduce the burden of histoplasmosis deaths.

Mycobacterium ulcerans infection (Buruli ulcer) in French Guiana, South America, 1969-2013: an epidemiological study.

BACKGROUND: Mycobacterium ulcerans infection is the third most common mycobacterial disease in the world after tuberculosis and leprosy. To date, transmission pathways from its environmental reservoir to humans are still unknown. In South America, French Guiana has the highest reported number of M ulcerans infections across the continent. This empirical study aimed to characterise the epidemiology of M ulcerans infection in French Guiana between 1969 and 2013. METHODS: Data were collected prospectively mainly by two dermatologists at Cayenne Hospital's dermatology department between Jan 1, 1969, and Dec 31, 2013, for age, date of diagnosis, sex, residence, location of the lesion, type of lesion, associated symptoms, and diagnostic method (smear, culture, PCR, or histology) for all confirmed and suspected cases of M ulcerans. We obtained population data from censuses. We calculated mean M ulcerans infection incidences, presented as the number of cases per 100 000 person-years. FINDINGS: 245 patients with M ulcerans infections were reported at Cayenne Hospital's dermatology department during the study period. M ulcerans infection incidence decreased over time, from 6·07 infections per 100 000 person-years (95% CI 4·46-7·67) in 1969-83 to 4·77 infections per 100 000 person-years (3·75-5·79) in 1984-98 and to 3·49 infections per 100 000 person-years (2·83-4·16) in 1999-2013. The proportion of children with infections also declined with time, from 42 (76%) of 55 patients in 1969-83 to 26 (31%) of 84 in 1984-98 and to 22 (21%) of 106 in 1999-2013. Most cases occurred in coastal areas surrounded by marshy savannah (incidence of 21·08 per 100 000 person-years in Sinnamary and 21·18 per 100 000 person-years in Mana). Lesions mainly affected limbs (lower limbs 161 [66%] patients; upper limbs 60 [24%] patients). We diagnosed no bone infections. INTERPRETATION: The decrease of M ulcerans infection incidence and the proportion of children with infections over a 45 year period in this ultra-peripheral French territory might have been mostly driven by improving living conditions, prophylactic recommendations, and access to health care. FUNDING: Agence Nationale de la Recherche.

Incidence of chronic cutaneous lupus erythematosus in French Guiana: a retrospective population-based study.

OBJECTIVE: To retrospectively study the incidence of chronic cutaneous lupus erythematosus (CCLE) in French Guiana (FG), South America, during the period 1995-1999. METHODS: Private and public physicians specializing in dermatology, rheumatology, and internal medicine were asked during the year 2000 about lupus cases. We reviewed hospitals' files in data-processing departments. RESULTS: Twenty new cases of CCLE, mostly discoid form, were identified during this 5-year period in this population of predominantly African descent. The average annual incidence of the disease was 2.59 per 100,000 inhabitants (95% confidence interval 1.5-4). However, our methodology could introduce underestimation of the incidence of the disease. CONCLUSION: The average annual incidence of CCLE in FG appears to be low in this retrospective study, but is very similar to the only previously published data in the US.

An urban epidemic of human myiasis caused by Dermatobia hominis in French Guiana.

We report the onset of an urban epidemic of human myiasis caused by Dermatobia hominis. To our knowledge, this is the first urban epidemic described for D. hominis. The epidemic was most likely related to exceptional weather conditions and notably high rainfall in January 2000, which may have facilitated the maturation of the pupae.

External ophthalmomyiasis caused by Dermatobia hominis. A retrospective study of nine cases and a review of the literature.

PURPOSE: To report nine cases of external ophthalmomyiasis caused by Dermatobia hominis. METHODS: Retrospective, non-comparative, interventional case series. Participants consisted of patients (n = 9) presenting at Cayenne Hospital between 1968 and 2003. The location and number of larvae, the larval stage, and the medical and surgical procedures applied were studied in each case. RESULTS: Seven patients had palpebral myiasis (including one with three larvae) and two had conjunctival myiasis. Every patient had palpebral oedema. The larval respiratory pore was located on the palpebral skin or free margin or on the conjunctiva. Movements were present within the lesion in at least three patients. Petroleum ointment or ivermectine solution was used in at least four patients to smother or kill the larvae. Extraction under local anaesthesia was possible in six patients, while three required general anaesthesia. CONCLUSION: Several larvae may be present in a patient. Topical ivermectine may help to kill the larvae before extraction is attempted.

Differential production of systemic and intralesional gamma interferon and interleukin-10 in nodular and ulcerative forms of Buruli disease.

Buruli disease, caused by Mycobacterium ulcerans, is the third most important mycobacterial disease in humans besides tuberculosis and leprosy. We have compared systemic and intralesional cytokine production in patients presenting with a nodular form and a necrotizing, ulcerative form of the disease. Gamma interferon (IFN-gamma) levels in response to whole M. ulcerans and Mycobacterium bovis BCG bacilli and in response to purified Ag85 protein from BCG were lower in peripheral blood mononuclear cells (PBMC) cultures from Buruli disease patients than in PBMC from healthy purified protein derivative-positive contacts. Interleukin-4 (IL-4) and IL-13 content was below the detection threshold in these PBMC cultures. IFN-gamma production after stimulation with M. ulcerans was significantly lower (P < 0.05) in PBMC cultures from patients with ulcers than in those from patients with nodules. On the other hand, PBMC from Buruli disease patients produced significant levels of IL-10 in response to M. ulcerans (but not to M. bovis BCG) and production was highest in patients with the ulcerative form. Third, semiquantitative reverse transcription-PCR analysis demonstrated a similar difference in the local, intralesional cytokine profile for the two forms of the disease: high IFN-gamma but low IL-10 mRNA levels in nodular lesions and high IL-10 but low IFN-gamma mRNA levels in ulcerative lesions. Intralesional IL-4 and IL-13 mRNA levels were low and only detected in patients with the ulcerative form. Our results indicate, although they do not formally prove, that production of IL-10 rather than production of IL-4 or IL-13 by Th2-type T cells may be involved in the low M. ulcerans-specific IFN-gamma response in Buruli disease patients.

Histoplasmosis and acquired immunodeficiency syndrome: a study of prognostic factors.

We aimed to identify prognostic factors for AIDS-associated disseminated histoplasmosis. In a multivariate analysis, we found that dyspnea, a platelet count of <100,000 platelets/mm3, and lactate dehydrogenase levels of >2 times the upper limit of the normal range were significantly independently associated with the death of the patient during the first 30 days of antifungal treatment.

American cutaneous leishmaniasis, lepromatous leprosy, and pulmonary tuberculosis coinfection with downregulation of the T-helper 1 cell response.

Cutaneous leishmaniasis, leprosy, and tuberculosis are caused by intracellular pathogens whose development depends on impaired cell-mediated immunity. We report an exceptional triple association of American cutaneous leishmaniasis, lepromatous leprosy, and pulmonary tuberculosis in a man with no recognized immunodeficiency. Normal immunological assessment of the interferon-gamma pathway does not support the hypothesis of a genetic defect in any of the genes involved in the T helper (Th)-1 cytokine cascade in this patient. Unresponsiveness to interleukin (IL)-12 of his T cells after stimulation with Leishmania guyanensis, Mycobacterium bovis bacille Calmette-Guérin, and Mycobacterium leprae antigens suggested the inability to mount an appropriate Th cell response to upregulate the IL-12 receptor expression.

Th1 cell development induced by cysteine proteinases A and B in localized cutaneous leishmaniasis due to Leishmania guyanensis.

The cysteine proteinases CPA and CPB from Leishmania major induced Th1 responses in patients with leishmaniasis due to Leishmania guyanensis. Furthermore, cysteine proteinases induced neither interleukin 4 (IL-4) nor IL-13 and low levels of IL-10 in controls and patients. The results suggest that CPs would be quite good candidates for a vaccine against different Leishmania species.

Th2 responses predominate during the early phases of infection in patients with localized cutaneous leishmaniasis and precede the development of Th1 responses.

Intralesional Th2 responses preceded the development of Th1 responses in localized cutaneous leishmaniasis due to Leishmania guyanensis. Although the number of parasites increased in Th2 lesions, no correlation was found between the levels of cytokine expression and the number of parasites. In contrast, the decreased number of parasites in Th1 lesions is negatively correlated to gamma interferon expression.

Acquired immunodeficiency syndrome-related oral and/or cutaneous histoplasmosis: a descriptive and comparative study of 21 cases in French Guiana.

BACKGROUND: Oral or cutaneous acquired immunodeficiency syndrome (AIDS)-related histoplasmosis is a rare presentation of disseminated histoplasmosis. OBJECTIVE: To describe this clinical presentation and to compare it with other forms of AIDS-related disseminated histoplasmosis. METHODS: A cross-sectional study of patients with AIDS-related disseminated histoplasmosis was performed. CD4 counts and survival were compared between patients with oral or cutaneous histoplasmosis and patients with nonmucocutaneous disseminated histoplasmosis. RESULTS: The mean CD4 lymphocyte count was lower in patients with mucocutaneous lesions than in patients with nonmucocutaneous disseminated histoplasmosis (29 vs. 72/mm3, P = 0.002). The proportion of survivors 1 month after diagnosis did not differ significantly between the two groups (13/21 vs. 32/45, P = 0.4). At 6 months, the proportion of survivors was significantly lower for patients with mucocutaneous lesions (6/21 vs. 22/39, P = 0.03). CONCLUSIONS: These results suggest that mucocutaneous lesions occur at a later stage of human immunodeficiency virus infection, but are not, in themselves, associated with a higher level of mortality. The excess mortality at 6 months reflects deaths from other complications of severe immunodepression. This study confirms the polymorphism of mucocutaneous lesions, emphasizing the need for systematic testing for Histoplasma in all cases of mucocutaneous lesions in AIDS patients.

LACK-specific CD4(+) T cells that induce gamma interferon production in patients with localized cutaneous leishmaniasis during an early stage of infection.

The profile of cytokines induced by soluble leishmania antigen (SLA) and the Leishmania homologue of the mammalian receptor for activated C kinase (LACK), a candidate vaccine against leishmaniasis, and the cellular source of the cytokines produced in response to these antigens were analyzed in patients infected with Leishmania guyanensis. Gamma interferon (IFN-gamma) and interleukin-10 (IL-10) were produced in response to LACK. Although LACK-specific CD4(+) cells producing IFN-gamma were isolated only during the early phase of infection (less than 30 days following the onset of infection), cells producing IL-10 in response to LACK were detected in all patients. CD4(+) T cells producing IFN-gamma and IL-13 were produced in response to SLA in all patients. SLA- and LACK-specific T cells are effector memory cells, as they are CD45RA(-) CCR7(-) CD4(+) T cells. CD4(+) T cells producing IFN-gamma are CD62L(-), and CD4(+) T cells producing IL-10 are CD62L(+), indicating that these cells have different tissue-homing capacities. These findings show that SLA and LACK induce both type 1 (IFN-gamma) and type 2 (IL-10 or IL-13) cell responses.

A pentamidina: excelente terapêutica da leishmaniose cutânea; esquema de tratamento idealizado na Guiana Francesa em dose única / Pentamidine: excelent therapy of cutaneous leishmaniasis: treatment schedule used in French Guiany with single-dose

Apresenta-se a experiência no tratamento da leishmaniose cutânea com a pentamidina, em vários esquemas terapêuticos, assinalando os bons resultados e a regular tolerância ao medicamento. O esquema mais prático, parece ser o da administraçäo em infusäo venosa em dose única de três a quatro ampolas (360 a 480mg). Enfatiza-se a eficácia, tolerabilidade, baixo custo e facilidade de administraçäo em regiöes distantes, onde o paciente ou a equipe médica tem dificuldade de retornar em curto período de tempo