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Reported are the results of a study to determine the efficacy and safety of liposomal amphotericin B (AmBisome) for treating visceral leishmaniasis (kala-azar) in several developing countries where the disease is endemic (Brazil, India, and Kenya). At each study site, sequential cohorts of 10 patients each were treated with AmBisome at a dose of 2 mg [multiplied by] [kg.sup.-1] [multiplied by] [day.sup.-1] (2 MKD). The first cohort received regimen 1:2 MKD on days 1-6 and day 10 (total dose: 14 mg/kg). If the efficacy with this regimen was satisfactory, a second cohort received regimen 2:2 MKD on days 1-4 and day 10 (total dose: 10 mg/kg); and a third cohort received regimen 3:2 MKD on days 1, 5, and 10 (total dose: 6 mg/kg). In India, regimens 1, 2, and 3 (which were studied concurrently) each cured 100% of 10 patients. In Kenya, regimen I cured all 10 patients, regimen 2 cured 90% of 10 patients, but regimen 3 cured only 20% of 5 patients. In Brazil, regimen 1 was only partially curative: 5 of 13 patients (62%). Therefore, 15 patients were administered regimen 4 (2 MKD for 10 consecutive days; total dose, 20 mg/kg) and 13 patients were cured (83%). These results suggest that for the treatment of kala-azar the following doses of AmBisome should be administered: in India and Kenya, 2 mg/kg on days 1-4 and day 10; and in Brazil, 2 mg/kg on days 1-10., Introduction Visceral leishmaniasis ("kala-azar") results from multiplication of Leishmania within the systemic reticuloendothelium. The disease is primarily caused by Leishmania donovani in the Indian subcontinent and Africa, by L. infantum [...]

Background. Pentavalent antimony (Sb(v)) is the mainstay therapy for mucosal leishmaniasis (ML), but it is toxic, and relapses are common. Immunotherapy using a mixture of killed parasites, with or without bacille Calmette-Guerin, is an alternative but is used sporadically because of inconsistent results. Methods. We developed a defined immunotherapeutic antigen preparation for use in an observational, open-label trial to treat 6 patients with ML with a history of Sb(v) therapy failure. All patients were treated with the antigens thiol-specific antioxidant, Leishmania major stress inducible protein 1, Leishmania elongation initiation factor, and Leishmania heat shock protein 83, plus granulocyte-macrophage colony-stimulating factor. Patients underwent clinical and pathological evaluations before the initiation of immunotherapy and at 3, 6, 9, 12, 18, 24, and 60 months after. Results. One month after the third injection, 1 patient showed complete clinical remission (CC) and remained disease free for the duration of the study. At the 9-month follow-up examination, 5 patients showed CC, and all patients were asymptomatic at a subsequent 5-year follow-up examination. Conclusions. These data support the concept that vaccine therapy with a defined antigen combination, used with standard chemotherapy, is a safe and effective approach to treat drug-refractory ML. Copyright © 2006 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]

The intracellular protozoan parasites of the genus Leishmania have been recognized as opportunistic pathogens in immunosuppressed individuals, including those infected with human immunodeficiency virus type-1 (HIV-1). Leishmaniasis and AIDS overlap in several sub-tropical and tropical regions around the world, including the Mediterranean area. In 1994, 3%-7% of HIV-1-infected individuals in southern Europe developed visceral leishmaniasis. In humans, interestingly, both HIV-1 and Leishmania interact with, invade, and multiply within cells of myeloid or lymphoid origin. The combined modulation of Leishmania - and HIV-1-related pathogenesis in the co-infected cases is therefore probably a realistic goal. In the light of the recent demonstration that L. donovani can up-regulate HIV-1 replication, both in monocytoid and lymphoid cells in vitro and in co-infected individuals, it is clear from the epidemiological data available that Leishmania can probably act as a powerful co-factor in the pathogenesis of HIV-1 infection. In those who are co-infected, complex mechanisms involving cytokine secretion and cellular-signalling events play pivotal roles in the Leishmania-mediated activation and pathogenesis of HIV-1. An overview of the recent findings concerning this Leishmania/HIV-1 interaction is presented here. [ABSTRACT FROM AUTHOR]

Describes a study to evaluate the treatment of visceral leishmaniasis with pentavalent antimony and interferon gamma. Study details; Results; Conclusion.

Introduction: L-carnitine (LC) has been associated with inflammatory mediator reduction and with downregulating the angiotensin-converting enzyme-2 (ACE2) receptor, which is the target of SARS-CoV-2 attachment., Methods: This pilot phase 2 randomized, double-blind placebo-controlled trial contained two cohorts. Cohort 1 comprised 101 individuals with negative RT-PCR SARS-CoV-2 test results who cohabitated with an individual diagnosed with SARS-CoV-2 infection. Cohort 2 comprised 122 individuals with positive SARS-CoV-2 RT-PCR test results who were asymptomatic or had mild COVID-19 pneumonia symptoms. Participants in each cohort were randomized 1:1 to receive either 2 g elemental oral LC supplementation or placebo daily for 21 days. Primary endpoints included adverse events, SARS-CoV-2 infection incidence in Cohort 1, and disease progressions in Cohort 2. Secondary endpoints included between-group laboratory profile comparisons and Cohort 2 ACE1/ACE2 plasma levels. Disease progression was compared between the Cohort 2 groups using chest computed tomography., Results: In Cohort 1, two SARS-CoV-2 infections occurred in each group. The common adverse events included headache, dyspnea, and tiredness. In Cohort 2, platelet counts were elevated, and fibrinogen levels reduced in the LC group compared with those of the placebo group., Conclusion: Our study showed that LC was well-tolerated and suggests it modulates coagulation pathways. Furthermore, chest computed tomography images of the Cohort 2 LC group showed significant lung lesion improvement, suggesting that LC may slow COVID-19 progression., Competing Interests: The authors from CIMATEC University Center, who were independent of Lonza Greenwood LLC., conducted the research and have no conflict of interest, which means they have not received shares of Lonza’s stock or participation in any other aspects of Lonza’s business. SD, RD, and ZS are employees of Lonza, while KJ is a consultant to Lonza. The authors declare that this study received funding from Lonza Greenwood LLC. The funder was involved in the study design and writing of the article. The funder was not involved in the data collection, analysis or data interpretation., (Copyright © 2023 Badaro, Barbosa, de Araujo Neto, Machado, Soares, de Senna, Taddeo, de Araújo, Durkee, Donninger, Judge and Saiyed.)

Diagnostic testing for M. tuberculosis infection has advanced with QuantiFERON and GeneXpert, but simple cost-effective alternatives for widespread TB screening has remained elusive and purified protein derivative (PPD)-based tuberculin skin testing (TST) remains the most widely used method. PPD-based tests have reduced performance, however, in BCG vaccinees and in individuals with immune deficiencies. We compared the performance of skin testing with the recombinant DPPD protein against that of a standard PPD-based skin test. Our data indicates similar performance of DPPD and PPD (r 2  = 0.7689) among HIV-negative, active TB patients, all of whom presented greater than 10 mm induration following administration. In contrast to results demonstrating that PPD induced indurations greater than 5 mm (i.e., the recommended threshold for positive results in this population) in only half (19 of 38) of the HIV positive TB patients, 89.5% (34 of 38) of these participants developed indurations greater than 5 mm when challenged with DPPD. Importantly, none of the patients that were positive following PPD administration were negative following DPPD administration, indicating markedly improved sensitivity of DPPD among HIV-infected individuals. Our data indicate that DPPD has superior performance in skin testing than the current TST standard.

Background: Mozambique is an emerging lower income country (LIC) on the southeast coast of Africa. There are significant workforce shortages in medical and health professions in the country. Mozambique was one of 12 countries in Africa that was awarded a grant through the Medical Education Partnership Initiative (MEPI) in 2010. The overarching goal of MEPI Mozambique was to enhance the capacity of medical schools to train the medical and scientific leadership corps that the country required to facilitate the training of doctors and other health professionals, and thus to strengthen the national health system., Objective: The aim of this article is to provide an overview of MEPI Mozambique activities, its outcomes and successes, lessons learned, and how these have sustainably strengthened the health sector in the country.What Was Done: The Eduardo Mondlane University (UEM) formed a partnership with the University of California, San Diego (UCSD) to implement MEPI Mozambique. A range of activities in medical education, research capacity development, electronic connectivity and information technology, and developing relationships among medical education stakeholders, were performed.Outcomes and Effects: The activities and innovations introduced under MEPI became part of the daily routine in medical education in Mozambique, dramatically influencing attitudes and perceptions. Joint research with partners leveraged research capabilities. The creation of a research support center offered a mechanism to sustainably build on MEPI achievements. Scientific knowledge generated through research has been translated into practice and policy, and has improved the working environment for health professionals. The use of interactive communication technologies enabled the scaling up of training and research in sustainable ways, and created communities of practice., Conclusion: MEPI Mozambique developed transformational long-term partnerships between UEM, UCSD and other partners. These are changing the trajectory of medical and health professions education in Mozambique and creating sustainable capacity for research., Competing Interests: The authors have no competing interests to declare., (© 2018 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC-BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See http://creativecommons.org/licenses/by/4.0/.)

Objective: To evaluate the incidence of medication errors due to dose omissions and the reasons for non-administration of medications., Design: A cohort study blinded to the nursing staff was conducted for 5 consecutive days to evaluate administration of prescribed medications to selected inpatients., Setting: A major academic teaching hospital in Brazil., Participants: Dispensed doses to patients in medical and surgical wards., Main Outcome Measures: Doses returned to pharmacy were evaluated to identify the rate of dose omission without a justification for omission., Results: Information was collected from 117 patients in 11 wards and 1119 doses of prescribed medications were monitored. Overall, 238/1119 (21%) dispensed doses were not administered to the patients. Among these 238 doses, 138 (58%) had no justification for not being administered. Failure in the administration of at least 1 dose occurred for 58/117 (49.6%) patients. Surgical wards had significantly more missed doses than that in medical wards (P = 0.048). The daily presence of a pharmacist in the wards was significantly correlated with lower frequency of omission errors (P = 0.019). Nervous system medications were missed more significantly than other medications (P < 0.001). No difference was noted in the omission doses in terms of route of administration., Conclusions: High incidence of omission errors occurs in our institution. Factors such as the deficit of nursing staff and clinical pharmacists and a weak medication dispensing system, probably contributed to incidence detected. Blinding nursing staff was essential to improve the sensibility of the method for detecting omission errors., (© The Author 2016. Published by Oxford University Press in association with the International Society for Quality in Health Care; all rights reserved.)

Background: The early diagnosis of asymptomatic, acute, and subclinical Leishmania infections remains a challenge for controlling visceral leishmaniasis (VL). Individuals with acute VL represent <1% of Leishmania infections occurring in active transmission endemic areas. In this cross-sectional study with a prospective follow-up, we explored the risk factors associated with acquisition of Leishmania infection in an area with newly identified endemic VL., Materials and Methods: Ninety-four households were randomly selected from the study area, which included a population of 213 individuals (10% of the total population of Pé de Areia, Bahia, Brazil). Clinical and epidemiological surveys were prospectively performed to detect cases of asymptomatic infections, acute VL, and subclinical VL, using the leishmanin skin test (LST), and serological response to two Leishmania-specific antigens: rK39 and rK26., Results: Within the 92 households included in the study, the prevalence of Leishmania infection in individuals detected by positive serology was 91/197 (46.2%; 95% CI: 0.3937-0.5316) and by LST was 29/114 (25.4%; 95% CI: 0.1834-0.3414). Reactivity to both antigens was detected in 64/197 individuals (32.5%; 95% CI: 0.2634-0.3931). Among 89 individuals diagnosed with leishmaniasis, we found acute VL in one (1%), subclinical VL in 20 (22.5%), and asymptomatic Leishmania infection in 68 (76.4%) subjects. Use of repellents and bed nets showed no significant protection (prevalence ratio [PR] = 1.01, p = 1.0). Interestingly, individuals residing in houses with a sand backyard had significant protection against Leishmania infection (PR = 1.24, p = 0.049) compared to those with a different type or no backyard. Moreover, the presence of cat or dog at home was also not a risk factor (dog: PR = 1.14, 95% CI: 0.80-1.64; and cat: PR = 1.19, 95% CI: 0.78-1.81). We conclude that in newly discovered areas of transmission of L. infantum infection with sylvatic reservoirs, periodic surveys may be helpful in identifying risk factors for infection and optimizing prevention guidelines.