Background American Cutaneous Leishmaniasis (ACL), a vector borne disease, is caused by various species of Leishmania and in the Amazonas, Leishmania guyanensis is predominant. The recommended drugs for treatment of cutaneous leishmaniasis (CL) in Brazil are pentavalent antimonials, pentamidine isethionate (PI) and amphotericin B. Pentamidine was initially used as metanolsulfonate or mesylate (Lomidine) at a dose of 4 mg/kg/daily, containing 2.3mg of base. This drug was withdrawn from the market in the eighties, and currently is available as PI. The PI dose required to achieve an equivalent dose of pentamidine base is 7 mg/kg, rather than the 4 mg/kg that is currently recommended in Brazil. Objectives The aim of this study was to evaluate the efficacy and safety of PI in a single dose, two or three doses of 7 mg/kg body weight, intramuscularly, with an interval of seven days between each dose. Materials and methods This study was conducted as a controlled, randomized, open–label clinical trial for a total number of 159 patients with CL. Individuals aged 16–64 years with one to six lesions of confirmed CL based on amastigotes visualization in direct examination of Giemsa stained of dermal scraping from the border of the lesion with no previous treatment for CL and no abnormal values for liver enzymes were eligible to participate in the study. Patients with history of diabetes, cardiac, renal, and hepatic disease as well as pregnant women were excluded. Cure was defined as complete healing in the diameters of the ulcers and lesions skin six months after the end of the treatment. Results From November 2013 to December 2015, 159 patients were screened and allocated in three groups for treatment with PI: i) 53 patients were treated with a single dose intramuscularly injection of 7 mg/kg body weight; ii) 53 received two doses of 7 mg/kg within an interval of seven days; and iii) 53 were treated with three doses of 7mg/kg with an interval of seven days between each dose. In 120 patients, L. guyanensis was identified. A cure rate of 45%, 81.1% and 96.2% were observed in the first, second and third group, respectively. The cure in the three PI dose group was higher compared to the single-dose (p<0.0001) and two-dose groups (p = 0.03). No serious adverse events occurred. Conclusion The present study shows that PI is a safe drug and its efficacy varied with the number of doses. The administration of PI in patients with ACL, predominantly caused by L. guyanensis, was mostly efficient in three or two doses of 7 mg/kg. Trial registration ClinicalTrials.gov NCT02919605
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 (Sbv) 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 Sbv. Six months after treatment, in the intention-to-treat analyses, the definitive cure rate was 53.3% in the Sbv 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 Sbv 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 Sbv 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 Sbv group. Conclusions This study demonstrates that miltefosine therapy is more effective than standard Sbv and safe for the treatment of CL caused by Leishmania braziliensis in Bahia, Brazil. Trial Registration Clinicaltrials.gov Identifier NCT00600548
Fundamentals: American tegumentary leishmaniasis (ATL) treatment remains a challenge, since most available drugs are injectable and only a small number of comparative, randomized clinical trials have been performed to support their use. Moreover, treatment outcome may depend on the causative species of Leishmania. O BJECTIVES: To evaluate and compare the efficacy and tolerability of meglumine antimoniate, pentamidine isethionate, and amphotericin B in the treatment of ATL caused by Leishmania (Viannia) guyanensis. M ETHODS: 185 patients were selected according to the eligibility criteria and randomly allocated into three groups - two groups with 74 patients each, and one group with 37 patients, which underwent meglumine, pentamidine and amphotericin B treatment, respectively. Doses, mode of administration and time periods of treatment followed the current recommendations for each drug. Patients were re-exam- ined one, two and six months after completion of treatment. R ESULTS: No differences were observed among the therapeutic groups in relation to gender, age, number or site of lesions. Intention-to-treat (ITT) analysis showed efficacy of 58.1% for pentamidine and 55.5% for meglumine (p=0.857). The amphotericin B group was analyzed separately, since 28 patients (75.7%) in this group refused to continue participating in the study. Mild or moderate adverse effects were reported by 74 (40%) patients, especially arthralgia (20.3%) in the meglumine group, and pain (35.1%) or induration (10.8%) at the site of injection in the pentamidine group. C
American tegumentary leishmaniasis (ATL) treatment remains a challenge, since most available drugs are injectable and only a small number of comparative, randomized clinical trials have been performed to support their use. Moreover, treatment outcome may depend on the causative species of Leishmania.To evaluate and compare the efficacy and tolerability of meglumine antimoniate, pentamidine isethionate, and amphotericin B in the treatment of ATL caused by Leishmania (Viannia) guyanensis.185 patients were selected according to the eligibility criteria and randomly allocated into three groups - two groups with 74 patients each, and one group with 37 patients, which underwent meglumine, pentamidine and amphotericin B treatment, respectively. Doses, mode of administration and time periods of treatment followed the current recommendations for each drug. Patients were re-examined one, two and six months after completion of treatment.No differences were observed among the therapeutic groups in relation to gender, age, number or site of lesions. Intention-to-treat (ITT) analysis showed efficacy of 58.1% for pentamidine and 55.5% for meglumine (p=0.857). The amphotericin B group was analyzed separately, since 28 patients (75.7%) in this group refused to continue participating in the study. Mild or moderate adverse effects were reported by 74 (40%) patients, especially arthralgia (20.3%) in the meglumine group, and pain (35.1%) or induration (10.8%) at the site of injection in the pentamidine group.Pentamidine and meglumine show similar efficacy in the treatment of ATL caused by L. guyanensis. Given the low efficacy of both drugs, there is an urgent need for new therapeutical approaches.
The occurrence of tuberculosis with first-line multidrug resistance leads to the use of alternative medications, often at higher costs, longer treatment periods, and greater clinical complexity. Here, we report 3 patients with multidrug-resistant tuberculosis. One patient with human immunodeficiency virus died before the sensitivity test was performed. The early diagnosis of multidrug-resistant tuberculosis and appropriate treatment should be priorities of the National Tuberculosis Control Program in order to break the chain of transmission. In addition, the possibility of substituting the proportion method with more modern and faster techniques should be urgently evaluated.
It would be expected that AIDS had a major impact on the incidence and clinical course of leprosy in countries where both diseases are public health problems. However, epidemiological changes such as those seen in tuberculosis have not been observed in leprosy and HIV coinfection. Although a slight increase in HIV seroprevalence among leprosy patients has been observed in a few cohort and case control studies, – 5 there have been no changes in the leprosy incidence in the majority of leprosy endemic areas. – 9 Currently, there are few reports of HIV-positive patients on HAART presenting with multibacillary leprosy. In a recent review there were only two cases (borderline-lepromatous and borderline-borderline leprosy). The large majority were classified as borderlinetuberculoid leprosy. – 14 It is well known that there is an important CD4 count increase during the first few months of HAART. During this phase, a subgroup of patients may present with clinical deterioration despite the CD4 count improvement. This immunopathological inflammatory response to a wide range of pre-existing infectious agents has been called immune reconstitution inflammatory syndrome
BACKGROUND: The Amazon region corresponds to approximately 40% of the cases of leishmaniasis in Brazil. We report a prospective study with 180 patients conducted in a health care unit that diagnoses 10% of the cases of leishmaniasis in the Brazilian Amazon. The study addresses how a combination of procedures improves diagnosis in areas with high prevalence of Leishmania guyanensis. OBJECTIVES: to evaluate diagnostic methods in areas with high prevalence of Leishmania guyanensis. METHODS: All subjects were amastigote-positive by direct microscopic examination of lesion scarifications. We conducted skin biopsy and histopathology, polymerase chain reaction and parasite cultivation. RESULTS: Polymerase chain reaction detected almost ninety percent of infections when two amplification protocols were used (mini-exon and HSP-70). HSP-70 specific polymerase chain reaction matched the sensitivity of parasite cultivation plus histopathology. CONCLUSION: The best combination was polymerase chain reaction plus histopathology, which increased diagnostic sensitivity to 94%. Species discrimination by polymerase chain reaction disclosed prevalence of human infections with Leishmania guyanensis of 94% and with Leishmania braziliensis of 6% for this region
Multidrug-resistant tuberculosis (MDR-TB) is the main indicator of previous treatment in tuberculosis (TB) patients. MDR-TB among treatment-naïve patients indicates infection with drug-resistant Mycobacterium tuberculosis strains, and such cases are considered primary drug-resistant cases.To estimate the prevalence of drug resistance in pulmonary TB (PTB) treatment-naïve patients and to identify the socio-demographic and clinical characteristics of the resistant population.A total of 205 treatment-naïve PTB patients from Manaus, Amazonas State, Brazil, were enrolled. Drug susceptibility testing (DST) was performed on all positive mycobacterial cultures using the 1% proportion method.Positive M. tuberculosis cultures were obtained from only 175 patients for DST. The prevalence of primary MDR-TB was 1.7% (3/175); 14.3% (25/175) of the cultures presented resistance to at least one of the drugs. Resistance to streptomycin, isoniazid, rifampicin and ethambutol was respectively 8.6%, 6.9%, 3.4% and 2.3%. An association between TB patients with resistance to more than one drug and known previous household contact with a TB patient was observed (P= 0.008, OR 6.7, 95%CI 1.2-67.3).Although the prevalence of primary MDR-TB currently is relatively low, it may become a major public health problem if tailored treatment is not provided, as resistance to more than one drug is significantly associated with household contact.
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