Dynamics of American tegumentary leishmaniasis in a highly endemic region for Leishmania (Viannia) braziliensis infection in northeast Brazil.

BACKGROUND: American Tegumentary Leishmaniasis (ATL) caused by Leishmania braziliensis is endemic in Corte de Pedra, Northeast Brazil. Most L. braziliensis infections manifest as localized cutaneous leishmaniasis (CL). Disseminated manifestations include mucosal leishmaniasis (ML), present at a low constant level for several decades, and newly emerging disseminated leishmaniasis (DL). Surprisingly, DL has recently surpassed ML in its spatial distribution. This led us to hypothesize that distinct forms of ATL might spread in different patterns through affected regions. METHODOLOGY/PRINCIPAL FINDINGS: We explored the incidence and geographic dispersion of the three clinical types of ATL over a span of nearly two decades in Corte de Pedra. We obtained the geographic coordinates of the homes of patients with ATL during 1992-1996, 1999-2003 and 2008-2011. The progressive dispersion of ML or DL in each time period was compared to that of CL in 2008-2011 with the Cusick and Edward's geostatistical test. To evaluate whether ATL occurred as clusters, we compared each new case in 2008-2011 with the frequency of and distance from cases in the previous 3 to 12 months. The study revealed that DL, ML and CL actively spread within that region, but in distinct patterns. Whereas CL and DL propagated in clusters, ML occurred as sporadic cases. DL had a wider distribution than ML until 2003, but by 2011 both forms were distributed equally in Corte de Pedra. The incidence of ML fluctuated over time at a rate that was distinct from those of CL and DL. CONCLUSIONS/SIGNIFICANCE: These findings suggest that CL and DL maintain endemic levels through successive outbreaks of cases. The sporadic pattern of ML cases may reflect the long and variable latency before infected patients develop clinically detectable mucosal involvement. Intimate knowledge of the geographic distribution of leishmaniasis and how it propagates within foci of active transmission may guide approaches to disease control.

An assessment of the genetic diversity of Leishmania infantum isolates from infected dogs in Brazil.

Correlations between the genetic diversity of Leishmania infantum (syn. L. chagasi) isolates and their respective geographic origins support the theoretic assumption that visceral leishmaniasis probably originated in the Old World. Because dogs are widely considered to be the main reservoir of this disease, the present study aimed to investigate the degree of genetic divergence among 44 leishmanial canine isolates from two Brazilian cities, Jequié and Campo Grande, located approximately 2,028 km from each other. We hypothesized that a low degree of genetic divergence would be observed among these isolates. In fact, statistical analyses found no significant differences between the isolates using both random amplified polymorphic DNA and multilocus microsatellite typing genotyping techniques with three and seven markers, respectively. These findings provide support for the recent introduction of L. infantum into the New World.

Miltefosine in the treatment of cutaneous leishmaniasis caused by Leishmania braziliensis in Brazil: a randomized and controlled trial.

BACKGROUND: Cutaneous leishmaniasis (CL) is treated with parenteral drugs for decades with decreasing rate cures. Miltefosine is an oral medication with anti-leishmania activity and may increase the cure rates and improve compliance. METHODOLOGY/PRINCIPAL FINDINGS: This study is a randomized, open-label, controlled clinical trial aimed to evaluate the efficacy and safety of miltefosine versus pentavalent antimony (Sb(v)) in the treatment of patients with CL caused by Leishmania braziliensis in Bahia, Brazil. A total of 90 patients were enrolled in the trial; 60 were assigned to receive miltefosine and 30 to receive Sb(v). Six months after treatment, in the intention-to-treat analyses, the definitive cure rate was 53.3% in the Sb(v) group and 75% in the miltefosine group (difference of 21.7%, 95% CI 0.08% to 42.7%, p = 0.04). Miltefosine was more effective than Sb(v) in the age group of 13-65 years-old compared to 2-12 years-old group (78.9% versus 45% p = 0.02; 68.2% versus 70% p = 1.0, respectively). The incidence of adverse events was similar in the Sb(v) and miltefosine groups (76.7% vs. 78.3%). Vomiting (41.7%), nausea (40%), and abdominal pain (23.3%) were significantly more frequent in the miltefosine group while arthralgias (20.7%), mialgias (20.7%) and fever (23.3%) were significantly more frequent in the Sb(v) group. CONCLUSIONS: This study demonstrates that miltefosine therapy is more effective than standard Sb(v) and safe for the treatment of CL caused by Leishmania braziliensis in Bahia, Brazil. TRIAL REGISTRATION: Clinicaltrials.gov Identifier NCT00600548.