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Data on Kaposi sarcoma in French Guiana are scarce and out of date.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.

Presence of Leishmania RNA Virus 1 in Leishmania guyanensis Increases the Risk of First-Line Treatment Failure and Symptomatic Relapse.

Treatment failure and symptomatic relapse are major concerns in American tegumentary leishmaniasis (TL). Such complications are seen frequently in Leishmania guyanensis infections, in which patients respond variously to first-line antileishmanials and are more prone to develop chronic cutaneous leishmaniasis. The factors underlying this pathology, however, are unknown. Recently, we reported that a double-stranded RNA virus, Leishmania RNA virus 1 (LRV1), nested within L. guyanensis parasites is able to exacerbate experimental murine leishmaniasis by inducing a hyperinflammatory response. This report investigates the prevalence of LRV1 in human L. guyanensis infection and its effect on treatment efficacy, as well as its correlation to symptomatic relapses after the completion of first-line treatment. In our cohort of 75 patients with a diagnosis of primary localized American TL, the prevalence of LRV1-positive L. guyanensis infection was elevated to 58%. All patients infected with LRV1-negative L. guyanensis were cured after 1 dose (22 of 31 [71%]) or 2 doses (31 of 31 [100%]) of pentamidine. In contrast, 12 of 44 LRV1-positive patients (27%) presented with persistent infection and symptomatic relapse that required extended therapy and the use of second-line drugs. Finally, LRV1 presence was associated with a significant increase in levels of intra-lesional inflammatory markers. In conclusion, LRV1 status in L. guyanensis infection is significantly predictive (P = .0009) of first-line treatment failure and symptomatic relapse and has the potential to guide therapeutic choices in American TL.

IL-10 producing CD8+ T cells in human infection with Leishmania guyanensis.

Cytokines are increasingly recognized as important components of the cellular immune responses to intracellular pathogens. In this study, we analyzed the production of TGF-beta, IL-10 and IFN-gamma by PBMC of unexposed naïve subjects and LCL patients after stimulation with live Leishmania guyanensis (L.g.). We demonstrated that IFN-gamma is produced in controls and LCL patients, IL-10 only in LCL patients and TGF-beta only in naïve subjects. Furthermore, in naive subjects, neutralization of TGF-beta induced IL-10 production. IL-10 produced in naïve subjects when TGF-beta is neutralized or in LCL patients did not modify the IFN-gamma production but inhibit reactive nitrogen species production. Analysis of the phenotype of IL-10 producing cells in naive subjects when TGF-beta is neutralized clearly showed that they are memory CD45RA- CD8+ T cells. In LCL patients, IL-10 producing cells are both CD45RA- CD4 and CD8+ T cells. The role of these IL-10 producing CD8+ T cells in the development of the diseases should be carefully evaluated.

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.

Epidemiology and Characteristics of Kikuchi-Fujimoto Disease in the African-Descent Population of Martinique, French West Indies.

OBJECTIVE: To provide an epidemiologic description of Kikuchi-Fujimoto disease (KFD), and to describe its relationship with systemic lupus erythematosus (SLE) in a population of sub-Saharan origin. METHODS: Patients were retrospectively included on the basis of lymph node histology compatible with KFD reported in Martinique from 1991 until 2013. In order to describe the characteristics of the disease in a larger cohort, we subsequently included more patients of Afro-Caribbean origin from Guadeloupe and French Guiana. RESULTS: In Martinique, mean annual incidence between 1991 and 2013 was 2.78 cases for 1 million inhabitants (95% confidence interval 1.73-3.93). A total of 36 Afro-Caribbean patients from the 3 French American regions were included. Mean age was 30.5 years (range 5-59 years) and the female:male ratio was 3:1. The main characteristics were cervical adenopathies (88.8%), fever (83.3%), asthenia (73.0%), weight loss (64.4%), and recurrence in 33.3%. KFD was associated with lupus (n = 9 for SLE, n = 2 for cutaneous lupus) in 36.6% (11 of 30). CONCLUSION: We report the first epidemiologic description of KFD in a population of sub-Saharan origin. According to our data, this disease is present in the black African diaspora and is strongly associated with autoimmune diseases, particularly lupus.

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.

Immune reconstitution inflammatory syndrome associated with HIV and leprosy.

BACKGROUND: Immune reconstitution inflammatory syndrome (IRIS) is an unusual inflammatory reaction to an opportunistic infection that occurs in human immunodeficiency virus (HIV)-positive patients with profound immunosuppression during the reconstitution of the immune system in the initial months of highly active antiretroviral treatment. OBSERVATIONS: We describe 3 cases of leprosy occurring in patients treated with a combination of 3 antiretroviral drugs who fulfilled the criteria for IRIS. A reactional state occurred in all 3 cases. Two of the 3 patients presented an unusual ulcerous progression of the lesions not generally observed in cases of leprosy. The outcome was favorable in all 3 cases. The frequency of IRIS associated with leprosy in French Guiana and Martinique is estimated at 3 cases per 1000 HIV-positive patients receiving highly active antiretroviral treatment. CONCLUSION: Leprosy should be recognized as an IRIS-associated infection with possibility of atypical presentation.

Climate and leishmaniasis in French Guiana.

To study the link between climatic variables and the incidence of leishmaniasis a study was conducted in Cayenne, French Guiana. Patients infected between January 1994 and December 2010. Meteorological data were studied in relation to the incidence of leishmaniasis using an ARIMA model. In the final model, the infections were negatively correlated with rainfall (with a 2-month lag) and with the number of days with rainfall > 50 mm (lags of 4 and 7 months). The variables that were positively correlated were temperature and the Multivariate El Niño Southern Oscillation Index with lags of 8 and 4 months, respectively. Significantly greater correlations were observed in March for rainfall and in November for the Multivariate El Niño/Southern Oscillation Index. Climate thus seems to be a non-negligible explanatory variable for the fluctuations of leishmaniasis. A decrease in rainfall is linked to increased cases 2 months later. This easily perceptible point could lead to an interesting prevention message.

Staphylococcal Panton-Valentine leucocidin as a major virulence factor associated to furuncles.

Panton-Valentine Leucocidin (PVL), one of the ß-barrel pore-forming staphylococcal leucotoxins, is known to be associated to furuncles and some severe community pneumonia. However, it is still uncertain how many other virulence factors are also associated to furuncles and what the risk factors of furuncles are in immuno-compromised status of patients, especially the HIV (+) patients. In this paper, we use antigen immunoprecipitation and multiplex PCR approach to determine the presence of 19 toxins, 8 adhesion factors and the PFGE profiles associated to furuncles in three independent patient study groups of S. aureus (SA) isolates collected from the Cayenne General Hospital (French Guiana). The patient groups were made of: 16 isolates from HIV (-) patients, 9 from HIV (+) patients suffering from furuncles, and 30 control isolates from patients with diverse secondary infected dermatitis. Our data reveals that the majority (96%) of SA strains isolated from HIV patient-derived furuncles significantly produced PVL (p<10(-7)), whereas only 10% of SA strains produced this toxin in secondary infected dermatosis. A high prevalence of LukE-LukD-producing isolates (56 to 78%) was recorded in patient groups. Genes encoding clumping factor B, collagen- and laminin-binding proteins (clfB, cna, lbp, respectively) were markedly frequent (30 to 55%), without being associated to a specific group. Pulse field gel electrophoresis evidenced 24 overall pulsotypes, whereas the 25 PVL-producing isolates were distributed into 15 non clonal fingerprints. These pulsotypes were not specific PVL-producing isolates. PVL appears to be the major virulence factor associated to furuncles in Europe and in South America regardless of the immune status of the HIV patients.

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.

Increased incidence of leprosy following HAART initiation: a manifestation of the immune reconstitution disease.

A retrospective cohort study was conducted to determine whether the incidence of leprosy varied with the duration of antiretroviral therapy (ART). Between 1992 and 2006, seven cases of leprosy were observed. The incidence of leprosy in untreated patients was 0.7 per 1000 person-years, 13 per 1000 person-years in persons receiving HAART for more than 3 months and 0.9 per 1000 person-years for persons receiving HAART for more than 3 months. The adjusted hazard ratio was 18.5 (95% confidence interval, 1.6-217) with P = 0.02. In tropical areas where HAART is increasingly available, physicians should be aware of the possibility of incident leprosy shortly after HAART initiation.

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.

Selective expression of the V beta 14 T cell receptor on Leishmania guyanensis--specific CD8+ T cells during human infection.

Peripheral blood mononuclear cells from subjects never exposed to Leishmania were stimulated with Leishmania guyanensis. We demonstrated that L. guyanensis-stimulated CD8(+) T cells produced interferon (IFN)- gamma and preferentially expressed the V beta 14 T cell receptor (TCR) gene family. In addition, these cells expressed cutaneous lymphocyte antigen and CCR4 surface molecules, suggesting that they could migrate to the skin. Results obtained from the lesions of patients with localized cutaneous leishmaniaisis (LCL) showed that V beta 14 TCR expression was increased in most lesions (63.5%) and that expression of only a small number of V beta gene families (V beta 1, V beta 6, V beta 9, V beta 14, and V beta 24) was increased. The presence of V beta 14 T cells in tissue confirmed the migration of these cells to the lesion site. Thus, we propose the following sequence of events during infection with L. guyanensis. After initial exposure to L. guyanensis, CD8(+) T cells preferentially expressing the V beta 14 TCR and secreting IFN- gamma develop and circulate in the periphery. During the infection, these cells migrate to the skin at the site of the parasitic infection. The role of these V beta 14 CD8(+) T cells in resistance to infection remains to be determined conclusively.

Evidence for a multiclonal origin of multicentric advanced lesions of Kaposi sarcoma.

BACKGROUND: Kaposi sarcoma (KS) is a complex tumor of uncertain clonality. Studying the viral clonality of the human herpesvirus 8 (HHV-8) in KS to determine clonality of the tumors, a strategy that has been used previously with Epstein-Barr virus and its associated tumors, may elucidate whether multicentric (disseminated) KS lesions correspond to metastatic lesions or to expansions of independent clones. METHODS: A series of 139 KS biopsies (from skin, lymph node, or tonsil) was obtained from 98 patients, with 59 biopsies from 18 patients with disseminated multicentric KS skin lesions. The degree of spindle cell infiltration in biopsies was established by direct observation of hematoxylin-eosin-stained sections, and HHV-8 viral load was quantified by real-time polymerase chain reaction. To determine cellular clonality, the size heterogeneity of the HHV-8-fused terminal repeat (TR) region was determined by probing of electrophoresed restricted genomic DNA from KS biopsies for the HHV-8 TR sequence. RESULTS: HHV-8 clonality analysis was performed on the 62 samples for which sufficient DNA was obtained. Most samples corresponded to histologically nodular lesions with high spindle cell infiltration and high viral load. A clonal HHV-8 pattern was determined for 59 samples; 11 were found to be monoclonal and 48 to be oligoclonal. The informative samples that were from disseminated KS skin lesions (n = 26, from six patients) were either monoclonal or oligoclonal, and the size of HHV-8 episomes varied between these samples. CONCLUSION: Although some tumor KS lesions were monoclonal expansions of HHV-8-infected spindle cells, most advanced lesions were oligoclonal proliferations. Furthermore, individual KS disseminated tumor skin lesions were found to represent distinct expansions of HHV-8-infected spindle cells. Thus, our results suggest that KS lesions, especially in patients with advanced skin tumors, are reactive proliferations rather than true malignancies with metastatic dissemination.

Nosocomial nasal myiasis owing to Cochliomyia hominivorax: a case in French Guiana.

Abstract The larval stages of the fly Cochliomyia hominivorax are responsible for myiasis, which primarily affects wounds. We report the case of a bed-ridden patient with dementia who developed right nasal myiasis during his stay at Cayenne Hospital. Progression was favorable, but the nasal pyramid was partially destroyed. In zones where this fly is endemic, particular attention should be given to hospitalized patients with wounds and consciousness problems.

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.

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.

Adult T-cell leukaemia/lymphoma-like human T-cell leukaemia virus-1 replication in infective dermatitis.

Adult T-cell leukaemia/lymphoma (ATLL) is a malignant T-cell proliferation that occurs in 3-5% of individuals infected with human T-cell leukaemia virus-1 (HTLV-1). HTLV-1 infection is also linked to the development of infective dermatitis (ID), an exudative dermatitis of children that has been proposed as a cofactor of ATLL. Here, HTLV-1 replication was investigated over time in a girl with ID and multiparasitic infestation including strongyloidiasis, a disease also known to predispose HTLV-1 carriers to ATLL. Quantitative polymerase chain reaction (PCR) revealed extremely high proviral loads. During the 2-year period of the present study, the proportion of circulating infected cells ranged between 12% and 36%. Quadruplicate linker-mediated PCR amplification of HTLV-1 flanking sequences identified a pattern of extensive and persistent oligoclonal expansion of infected lymphocytes. As viral loads, both the number and the degree of infected T-cell expansion were independent of treatment or clinical signs. However, the temporal fluctuation of proviral loads correlated significantly with the degree of infected T-cell expansion, but not with the overall number of detected clones. This pattern of HTLV-1 replication over time is very different from that observed in asymptomatic carriers and reminiscent of that observed in ATLL, a result consistent with the proposal of ID as an ATLL cofactor.

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