Burden of leishmaniasis in Brazil and federated units, 1990-2016: Findings from Global Burden of Disease Study 2016.

BACKGROUND: The study presents estimates for the burden of visceral leishmaniasis (VL) and cutaneous and mucocutaneous leishmaniasis (CML) in Brazil and its 27 federated units using data from the Global Burden of Disease Study (GBD) 2016. METHODOLOGY: We report the incidence, years of life lost (YLL), years lived with disability (YLD), and disability-adjusted life years (DALY) for leishmaniasis in Brazil from 1990 to 2016. The metrics are presented as age-standardized rates per 100,000 inhabitants with their respective uncertainty intervals (95%UI) and relative percentages of change. PRINCIPAL FINDINGS: The age-standardized incidence rate of leishmaniasis decreased 48.5% from 1990 (71.0, 95%UI 24.3-150.7) to 2016 (36.5, 95%UI 24.7-50.9), whereas the age-standardized DALY increased 83.6% over the studied period from 12.2 (95%UI 7.9-18.8) to 22.4 (95%UI 13.3-36.2). The age-standardized incidence rate and YLL for VL increased by 52.9% and 108% from 1990 to 2016, respectively. Considering CML, the age-standardized incidence rate and YLD decreased by 51% and 31.8% respectively for the same period. For VL, similar profiles for male and female were observed, with YLL and DALY increasing over time; with males presenting slightly higher values. The highest YLL rates were among "under 1-year old" children, which increased 131.2% from 1990 to 2016. Regarding CML, the highest values of YLD and DALY were verified among males, and YLD values showed a similar profile, with rates increasing with age. The VL burden increased in some states in the Northeast and Southeast regions and decreased for CML in some Northern states. CONCLUSION: The increase of VL burden over the study period might be associated with the difficulties in controlling the disease spread. Information regarding the weight of VL and CML, including the death and disability tolls that they cause, highlights the impact of these neglected diseases on public health and the importance of effective prevention and treatment.

Mortality Trends for Neglected Tropical Diseases in the State of Sergipe, Brazil, 1980-2013.

BACKGROUND: Neglected Tropical Diseases are a set of communicable diseases that affect the population so low socioeconomic status, particularly 1.4 billion people who are living below the poverty level. This study has investigated the magnitude and mortality time trends for these diseases in the state of Sergipe, Northeast Region of Brazil. METHODS: We conducted an ecological study of time series, based on secondary data derived from the Mortality Information System of the Ministry of Health. The mortality rates (crude, age-standardized rates and proportional ratio) were calculated from the deaths due to Neglected Tropical Diseases in the state of Sergipe, from 1980 to 2013. The time trends were obtained using the Joinpoint regression model. RESULTS: Three hundred six thousand and eight hundred seventy-two deaths were certified in the state and Neglected Tropical Diseases were mentioned as the underlying cause in 1,203 certificates (0.39%). Mean number of deaths was 35.38 per year, and crude and age-standardized mortality rates were, respectively: 2.16 per 100 000 inhabitants (95% CI: 1.45-2.87) and 2.87 per 100 000 inhabitants (95% CI: 1.93-3.82); the proportional mortality ratio was 0.41% (95% CI: 0.27-0.54). In that period, Schistosomiasis caused 654 deaths (54.36%), followed by Chagas disease, with 211 (17.54%), and by Leishmaniases, with 142 (11.80%) deaths. The other diseases totalized 196 deaths (16.30%). There were increasing mortality trends for Neglected Tropical Diseases, Schistosomiasis and Chagas disease in the last 15 years, according to the age-standardized rates, and stability of the mortality trends for Leishmaniases. CONCLUSIONS: The Neglected Tropical Diseases show increasing trends and are a real public health problem in the state of Sergipe, since they are responsible for significant mortality rates. The following diseases call attention for showing greater number of deaths in the period of study: Schistosomiasis, Chagas disease and Leishmaniases. We finally suggest that public managers take appropriate actions to develop new strategies in epidemiological and therapeutic surveillance, and in the follow-up of these patients.

Avaliação do 17-AAG como agente leishmanicida e seu mecanismo de ação na indução da morte de parasitos do gênero leishmania spp / 17-AAG assessment as leishmanicidal agent and its mechanism of action for induction of parasites of the Leishmania genus death spp

A leishmaniose é uma doença endêmica no Brasil causada por parasitos protozoários do gênero Leishmania. A quimioterapia continua sendo a forma mais efetiva de tratamento com os antimoniais pentavalentes sendo usados há mais de 70 anos como a primeira linha de tratamento. O uso deste e de outros fármacos apresenta efeitos adversos graves, os esquemas terapêuticos empregados são desconfortáveis, além de relatos do aumento de casos de resistência. A proteína de choque térmico 90 (HSP90) é um membro da família das chaperonas presente em células eucarióticas e bactérias. Essa proteína é fundamental para o dobramento e estabilização de diferentes proteínas, chamadas genericamente de proteínas cliente. Essa chaperona vem sendo considerada um importante alvo molecular para o tratamento de diferentes doenças parasitárias. Nessa tese, o inibidor específico da atividade ATPásica da HSP90, o 17-allilamino-17-demethoxigeldanamicina (17- AAG) foi testado em parasitos do gênero Leishmania. Inicialmente, avaliamos o efeito em cultura axênica e observamos que o 17-AAG causa a morte desses parasitos em concentrações inferiores às necessárias para causar a morte de macrófagos. Observamos também que o tratamento com 17-AAG promove a morte intracelular dos parasitos em concentrações que variam de 25 a 500 nM nos tempos de 24 e 48 h...

Leishmaniases are endemic disease in Brazil caused by protozoan parasites from the genus Leishmania. Chemotherapy remains the most effective way of treatment and pentavalent antimonials, used for more than 70 years, remaining as first choice drugs for leishmaniasis treatment. The use of this and other drugs causes severe side effects, therapeutic regimens employed for leishmaniasis treatment are unpleasant, besides an increase number of resistance cases. The Heat Shock Protein 90 (HSP90) is a member of the chaperone family present in bacteria and eukaryotic cells. This protein is essential for the folding and stabilization of different proteins, known as client proteins. This chaperone has been considered an important molecular target for the treatment of different parasitic diseases. In this thesis, the specific inhibitors of the ATPase activity from the HSP90, 17-allylamino- 17-demethoxygeldanamycin (17-AAG), were tested against parasites from the genus Leishmania. First we evaluated its effect on axenic culture and observed that 17- AAG induces parasite cell death in lowerconcentrations than those needed to induce macrophage cell death. We also observed that 17-AAG intracellular parasite death in concentrations ranging from 25 to 500 nM after 24 or 48 h...

Iron status and C-reactive protein in canine leishmaniasis.

OBJECTIVE: To investigate the iron status, its relationship with C-reactive protein and the prognostic value of both in canine leishmaniasis. METHOD: Eighty-six dogs with leishmaniasis and two control groups (healthy dogs and dogs with diseases other than leishmaniasis) were selected. Iron status indicators and C-reactive protein were compared between the three groups. Correlations between C-reactive protein and iron, ferritin and total iron-binding capacity were evaluated in dogs with leishmaniasis. Iron, total iron-binding capacity and ferritin were compared between dogs stratified according to similar C-reactive protein concentrations. The mortality rate at 30 days post-diagnosis was compared between groups. Iron status indicators and C-reactive protein were compared between survivors and non-survivors. RESULTS: Dogs with leishmaniasis had lower iron and total iron-binding capacity and higher ferritin and C-reactive protein. There was a significant but low correlation of C-reactive protein with iron, ferritin and total iron-binding capacity. Dogs with leishmaniasis had decreased iron and total iron-binding capacity and increased ferritin compared to other ill patients with similar C-reactive protein concentrations. Mortality was not significantly different between groups but non-survivor dogs with leishmaniasis had higher C-reactive protein and lower total iron-binding capacity. CLINICAL SIGNIFICANCE: Inflammation contributes to the iron status alterations found in canine leishmaniasis but other mechanisms are likely involved. Low total iron-binding capacity and increased C-reactive protein are risk factors for outcome in canine leishmaniasis.

Leishmaniasis worldwide and global estimates of its incidence.

As part of a World Health Organization-led effort to update the empirical evidence base for the leishmaniases, national experts provided leishmaniasis case data for the last 5 years and information regarding treatment and control in their respective countries and a comprehensive literature review was conducted covering publications on leishmaniasis in 98 countries and three territories (see 'Leishmaniasis Country Profiles Text S1, S2, S3, S4, S5, S6, S7, S8, S9, S10, S11, S12, S13, S14, S15, S16, S17, S18, S19, S20, S21, S22, S23, S24, S25, S26, S27, S28, S29, S30, S31, S32, S33, S34, S35, S36, S37, S38, S39, S40, S41, S42, S43, S44, S45, S46, S47, S48, S49, S50, S51, S52, S53, S54, S55, S56, S57, S58, S59, S60, S61, S62, S63, S64, S65, S66, S67, S68, S69, S70, S71, S72, S73, S74, S75, S76, S77, S78, S79, S80, S81, S82, S83, S84, S85, S86, S87, S88, S89, S90, S91, S92, S93, S94, S95, S96, S97, S98, S99, S100, S101'). Additional information was collated during meetings conducted at WHO regional level between 2007 and 2011. Two questionnaires regarding epidemiology and drug access were completed by experts and national program managers. Visceral and cutaneous leishmaniasis incidence ranges were estimated by country and epidemiological region based on reported incidence, underreporting rates if available, and the judgment of national and international experts. Based on these estimates, approximately 0.2 to 0.4 cases and 0.7 to 1.2 million VL and CL cases, respectively, occur each year. More than 90% of global VL cases occur in six countries: India, Bangladesh, Sudan, South Sudan, Ethiopia and Brazil. Cutaneous leishmaniasis is more widely distributed, with about one-third of cases occurring in each of three epidemiological regions, the Americas, the Mediterranean basin, and western Asia from the Middle East to Central Asia. The ten countries with the highest estimated case counts, Afghanistan, Algeria, Colombia, Brazil, Iran, Syria, Ethiopia, North Sudan, Costa Rica and Peru, together account for 70 to 75% of global estimated CL incidence. Mortality data were extremely sparse and generally represent hospital-based deaths only. Using an overall case-fatality rate of 10%, we reach a tentative estimate of 20,000 to 40,000 leishmaniasis deaths per year. Although the information is very poor in a number of countries, this is the first in-depth exercise to better estimate the real impact of leishmaniasis. These data should help to define control strategies and reinforce leishmaniasis advocacy.

Epidemiology and direct medical costs of human leishmaniasis in Italy.

INTRODUCTION: In the last decades, visceral Leishmaniasis infection rate has increased in Western Mediterranean areas. Epidemiological data show that in Italy, especially in some regions, the prevalence of canine form is high. The aim of this study is to evaluate the epidemiological setting of Leishmaniasis in Italy, according to age groups and geographical areas, and to estimate the associated direct medical costs. METHODS: The study examined the ordinary and day-hospital discharges and the respective mean of hospital length of stay for Leishmaniasis and visceral Leishmaniasis in Italy, during the period 1999-2003. Moreover, we collected data about notifications of Leishmaniasis, from 1993 to 2004, and mortality due to this infectious disease, from 1993 to 1998. We evaluated the prevalence rates of discharges, the visceral and cutaneous Leishmaniasis notifications incidence rates and the mortality rates from disease, per 1,000,000 residents. Costs analysis was performed getting DRG number 423 rate, which corresponds to "other diagnosis related to infectious and parasitary diseases". RESULTS: Ordinary discharges decreased in the study period, while day-hospital discharges increased. Sicilia, Campania and Lazio regions showed the highest number of ordinary hospital discharges for Leishmaniasis (prevalence rates were respectively 16.29, 15.02 and 12.83 per 1,000,000 residents, in 2003). Campania and Sicilia showed also the highest prevalence rates of day-hospital discharges (respectively 17.29 and 35.39 per 1,000,000 residents in 2003). The analysis of incidence rates of notifications showed a cyclic trend of the visceral form of the disease, with the highest rates observed in the group aged 0-14 years (incidence rates per 1,000,000: 7.46 in 1996 and 8.59 in 2000). The highest mortality rates were observed in the group aged over 65 years; low but constant mortality rates for Leishmaniasis were seen in the age group 25-64 years. Direct costs for both ordinary and day-hospital admissions were: 1,561,218.46 Euro in 1999; 1,637,256.44 Euro in 2000; 1,459,892.92 Euro in 2001, 1,468,983.58 Euro in 2002 and 1,370,227.80 Euro in 2003. DISCUSSION: Discharges for Leishmaniasis showed non-homogeneous trend in Italy, especially in coastal Regions. Leishmaniasis notifications have slowly increased after 1993 and a high number of notifications was observed in the 0-14 years old group. The highest mortality rates were reported in the extreme age-groups: mortality was relevant for patients over 65 years. Moreover, cost analysis showed that health care of human Leishmaniasis requires long time of hospitalization with consequent high costs. Conclusion. Preventive measures have to be turned to extreme age groups. For future studies issues such as high costs of treating disease, cost-effectiveness evaluation of the 'current therapeutic approach compared to preventive interventions on dogs and vector insects would be of interest.

Aging and infectious diseases in the developing world.

Although demographic aging does not remain restricted to industrialized countries, the medical challenge arising from the aging population will be distinct in the developing world. This is particularly true with respect to infectious diseases, which have a distinct spectrum in the elderly population, as well as a greater overall relevance in the developing world. Tropical diseases have a specific presentation and epidemiology in elderly patients. Infectious diseases with a worldwide distribution impact elderly patients in the developing world in a specific manner, which is most obvious with respect to human immunodeficiency virus and tuberculosis but is also true with respect to "trivial" manifestations of infection, such as diarrhea and pneumonia. Malnutrition contributes in a major way to the immunodeficiency of elderly patients in the developing world. Poorly controlled use of antimicrobial drugs leads to multidrug-resistant microorganisms, which, together with the limited resources available for drug treatment, makes appropriate treatment of infections in elderly patients in developing countries very difficult. Infections in elderly patients will have an increasing impact on the public health and economy of developing countries.

SOCS1 is a critical inhibitor of interferon gamma signaling and prevents the potentially fatal neonatal actions of this cytokine.

Mice lacking suppressor of cytokine signaling-1 (SOCS1) develop a complex fatal neonatal disease. In this study, SOCS1-/- mice were shown to exhibit excessive responses typical of those induced by interferon gamma (IFNgamma), were hyperresponsive to viral infection, and yielded macrophages with an enhanced IFNgamma-dependent capacity to kill L. major parasites. The complex disease in SOCS1-/- mice was prevented by administration of anti-IFNgamma antibodies and did not occur in SOCS1-/- mice also lacking the IFNgamma gene. Although IFNgamma is essential for resistance to a variety of infections, the potential toxic action of IFNgamma, particularly in neonatal mice, appears to require regulation. Our data indicate that SOCS1 is a key modulator of IFNgamma action, allowing the protective effects of this cytokine to occur without the risk of associated pathological responses.

Determinaciòn in vitro del porcentaje de mortalidad de Leishmania amazonensis por compuestos puros utilizado el Mètodo de MTT / Annual reports 1993 / In vitro mortality of Leishmania amazonensis whith pure compounds by using MTT Method

Tres alcaloides isoquinòlicos, curine isochondodendrine e isotetrandrine fueron probados contra la forma Leishmania amazonensis in vitro usando el mètodo MTT sal de bromuro de 3-(4,5 dimetil tiazol -2 il)- 2,5- difenil tetrazolio, mètodo calorimètrico ràpido, ùtil para evaluar la supervivencia parasitaria ante la acciòn de compuestos puros seleccionados de acciòn antileishmaniàsica. El cambio de transmitancia fue leìdo utilizando el Lector de Elisa Bio-Rad EIA reader a 570 nm. El porcentaje de mortalidad fue calculado usando el log-probita a diferentes concentraciones de los compuestos puros a 100 ug/ml y 25 ug/ml. Curine demostrò mayor porcentaje de mortalidad a todas las diluciones, lo mismo que isotetrandrine resultò con un mayor porcentaje de mortalidad a todas las diluciones. A la concentraciòn de 100 ug/ml curine e isotetrandrine presentaron 100 por ciento de mortalidad, mientras que isochondendrine 90 por ciento de mortalidad. Tambièn a 50 ug/ml curine e isotetrandrine presentaron 100 por ciento de mortalidad e isochondendrine 50 por ciento de mortalidad. A la concentraciòn de 25 ug/ml curine, isotetrandrine e isochondondendrine presentaron 80 por ciento, 50 por ciento y 10 de mortalidad. Los resultados sugeren que el mètodo MTT podrìa ser ùtil para probar la actividad de compuestos puros contra Leishmania amazonensis

A mortalidade por doenças infecciosas e endemias em Minas Gerais / Endemic and infectious diseases mortality in Minas Gerais

O trabalho apresenta dados estatísticos sôbre a mortalidade por doenças infecciosas e endemias no Estado de Minas Gerais, no período de 1975 a 1981. O perfil de mortalidade por doenças transmissíveis näo se modificou significativamente no período, com exceçäo da poliomielite que sofreu impacto das campanhas de vacinaçäo. Foram também analisadas as ocorrências de óbitos por causas mal definidas, e se o paciente recebeu ou näo assistência médica, concluindo que ainda existe insuficiência de açöes preventivas, falta de acesso a cuidados médicos, e precariedade de recursos de diagnóstico e tratamento

Epidemiological, clinical and therapeutic features of Bihar kala-azar (including post kala-azar dermal leishmaniasis).

This epidemic of kala-azar in Bihar, India, started from a small block and gradually spread to almost all of North Bihar. Vaishali was the district most affected, with the highest incidence rate of 5.9 per thousand in 1978. The epidemic spread more to the east than to the west. In 1977 there were 100,000 cases of kala-azar in Bihar and in Vaishali district the death rate was 28.7% of affected cases. It took five years to control the epidemic. 750 parasitologically confirmed cases of kala-azar were studied. The male:female ratio was 5.5:1. 63.4% of cases were aged 10 to 29 years. Clinical features were classical. Sodium stibogluconate, used as a first line drug, was effective in 92.6% of cases. By increasing the course of antimonial therapy from 10 to 20 days the relapse rate was reduced to 0.5% compared with 15% in the previous epidemic. Kala-azar patients who also had tuberculosis were treated with the antimonial and antituberculosis drugs concurrently and all cases recovered. 86 cases unresponsive to sodium stibogluconate were given pentamidine, which was effective in 93.4%. Side effects with sodium stibogluconate were minimal, but were common and serious with pentamidine. The need for a safer drug effective in cases which do not respond to antimony was very evident. 20 cases of post kala-azar dermal leishmaniasis (PKDL) were reviewed: two had no previous previous history of kala-azar. The relapse rate was higher in PKDL than in kala-azar.