Time-window into the transcrustal plumbing system dynamics of Dominica (Lesser Antilles).

Dominica, one of the most magmatically active islands of the Lesser Antilles through its four active volcanoes, is likely host under its central part, below Morne Trois Pitons-Micotrin, to a well-established transcrustal mush system. Pre-eruptive spatiotemporal magma dynamics are examined for five, explosive, pumiceous eruptions of this volcano in the last 24 kyrs through a combined Crystal System Analysis and intracrystalline Fe-Mg interdiffusion timescales modelling approaches. Before all eruptions, two magmatic environments of close compositions have interacted. These interactions began ~ 10-30 years prior to the four smaller of these eruptions, with more sustained mixing in the last decade, accelerated in the last 2 years. This contrasts with the largest pumiceous eruption, involving deeper magmas, with magma interaction starting over roughly a century but with various patterns. This suggests a possibility that increasing reactivation signals could be registered at the surface some years before future eruptions, having significant implications for volcanic risk mitigation.

Antihelminthic therapy and antimony in cutaneous leishmaniasis: a randomized, double-blind, placebo-controlled trial in patients co-infected with helminths and Leishmania braziliensis.

Helminth infections influence the clinical response to certain diseases and are associated with delayed healing time of patients with cutaneous leishmaniasis (CL) caused by Leishmania braziliensis. We conducted a randomized, double-blind, placebo-controlled clinical trial to examine the role of early versus deferred treatment of intestinal helminth infection on the clinical course of patients with CL treated with pentavalent antimony. (Clinicaltrials.gov number NCT00469495). A total of 90 patients were enrolled, 51.1% (N = 23) of control patients had persistent lesions at Day 90, compared with 62.2% (N = 28) in the treatment group (difference 11.1%, 95% confidence interval = -9.1-30.0%). There was no statistically significant difference in overall time to cure between groups, although there was a tendency for shorter cure times in the control group. This study shows that early introduction of antihelminthic therapy does not improve clinical outcome in patients co-infected with helminths and L. braziliensis.

Association of treatment of American cutaneous leishmaniasis prior to ulcer development with high rate of failure in northeastern Brazil.

Cure rates for American cutaneous leishmaniasis (ACL) range between 60% and 90%. Early evidence suggests lower cure rates for early ACL before the development of the ulceration. We evaluated risk factors for treatment failure in patients with early and classic ulcerative ACL. Patients (n = 136) were 13-60 years of age and had lesions with a duration of 15-90-days. Patients were treated with antimony (20 mg/kg/day for 20 days). The primary outcome was lesion cure by 90 days without recurrence. Patients with early ACL (n = 16) had papules, nodules, plaques, or superficial ulcerations with less than 30 days of illness. Patients with classic ulcerative ACL (n = 120) had ulcerated classic lesions, longer duration, larger lesions, and higher levels of interferon-gamma and tumor necrosis factor-alpha (P < or = 0.01 for all comparisons). Ulcerated lesions were associated with a lower treatment failure rate compared with early ACL (25.8% versus 75.0%; P < 0.001). Early treatment of ACL does not prevent lesion ulceration and is associated with higher rates of treatment failure.

Influence of helminth infections on the clinical course of and immune response to Leishmania braziliensis cutaneous leishmaniasis.

BACKGROUND: Helminth infections influence the clinical outcome of and immune response to certain immune-mediated diseases. METHODS: We conducted a cohort study of 120 patients to examine the role that intestinal helminth infection plays in the clinical course of and immune response to cutaneous leishmaniasis (CL) treated with pentavalent antimony. RESULTS: Patients coinfected with Leishmania braziliensis and helminths took longer to heal (relative hazard for healing, 0.47 [95% confidence interval, 0.26-0.85]; P=.01) than patients with CL without helminths, with 70% of coinfected patients being cured at 90 days, compared with 92% of helminth-free patients. Coinfected patients had an immune response shifted toward the T helper 2 type, with increased total immunoglobulin E levels (P<.06) and a tendency toward increased interleukin-5 levels, compared with helminth-free patients with CL. CONCLUSIONS: Helminths influence both the clinical outcome and the immune response of patients with CL. These results may have clinical implications for the care of patients with CL caused by Leishmania braziliensis, because screening for and treatment of helminths may improve responses to treatment and possibly reduce the risk of progression to mucosal disease.

Modulation of T cell responses in HTLV-1 carriers and in patients with myelopathy associated with HTLV-1.

OBJECTIVE: Human T lymphotropic virus-type 1 (HTLV-1) activates the immune system leading to a persistent and exacerbated T-cell response with increased production of IFN-gamma and TNF-alpha. Overproduction of pro-inflammatory cytokines is correlated with the development of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), although some HTLV-1 carriers also show high levels of these cytokines. In this study, the ability of regulatory cytokines and cytokine antagonists to inhibit spontaneous IFN-gamma production was investigated. METHOD: IFN-gamma levels were measured by ELISA before and after addition of cytokines or anti-cytokines. RESULTS: Addition of IL-10 significantly reduced spontaneous IFN-gamma synthesis in cell cultures from HTLV-1 carriers, while no differences were observed in HAM/TSP patients. There was also a tendency to decreased IFN-gamma levels in cell cultures from HTLV-1 carriers with exogenous addition of TGF-beta. In paired analysis, neutralization of IL-2 significantly decreased IFN-gamma production in HTLV-1 carriers but not in HAM/TSP patients. Neutralization of IL-15 was less effective than neutralization of IL-2 in modulating IFN-gamma production. In HTLV-1 carriers, anti-IL-2 and simultaneous addition of anti-IL-2 and anti-IL-15 decreased IFN-gamma synthesis by 46 and 64%, respectively, whereas in patients with HAM/TSP simultaneous neutralization of both anti-cytokines only decrease IFN-gamma levels by 27%. CONCLUSIONS: Although a large proportion of HTLV-1 carriers produced high levels of pro-inflammatory cytokines similar to those observed in HAM/TSP patients, immune response can be downregulated by cytokines or cytokine antagonists in most HTLV-1 carriers. This modulation can be an important step in the prevention of tissue damage and progression from the HTLV-1 carrier state to HAM/TSP.

A large outbreak of histoplasmosis among American travelers associated with a hotel in Acapulco, Mexico, spring 2001.

During spring 2001, college students from Pennsylvania reported an acute febrile respiratory illness after returning from spring break vacation in Acapulco, Mexico. Acute pulmonary histoplasmosis was presumptively diagnosed and the cluster of illness was reported to the Centers of Disease Control and Prevention. A large investigation then ensued, which included finding student-travelers for interviews and requesting sera for histoplasmosis testing. We defined a clinical case by fever and at least one of the following: cough, shortness of breath, chest pain, or headache, in an Acapulco traveler during March-May 2001. A laboratory-confirmed case had positive serology. An initial study determined that the likely site of histoplasmosis exposure was Hotel H; we therefore performed a large cohort study among travelers who stayed at Hotel H. Of 757 contacted, 262 (36%) met the clinical case definition. Of 273 serum specimens tested, 148 (54%) were positive. Frequent use of Hotel H's stairwells, where construction was ongoing, was associated with increased risk of illness (relative risk = 10.5, 95% confidence interval = 3.7-30.5; P < 0.001). This is the first histoplasmosis outbreak associated with a hotel undergoing construction. Hotels in endemic areas should consider construction precaution measures to prevent histoplasmosis among their guests.