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.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Sand flies include a group of insects that are of medical importance and that vary in geographic distribution, ecology, and pathogen transmission. Approximately 163 species of sand flies have been ...reported in Colombia. Surveillance of the presence of sand fly species and the actualization of species distribution are important for predicting risks for and monitoring the expansion of diseases which sand flies can transmit. Currently, the identification of phlebotomine sand flies is based on morphological characters. However, morphological identification requires considerable skills and taxonomic expertise. In addition, significant morphological similarity between some species, especially among females, may cause difficulties during the identification process. DNA-based approaches have become increasingly useful and promising tools for estimating sand fly diversity and for ensuring the rapid and accurate identification of species. A partial sequence of the mitochondrial cytochrome oxidase gene subunit I (COI) is currently being used to differentiate species in different animal taxa, including insects, and it is referred as a barcoding sequence. The present study explored the utility of the DNA barcode approach for the identification of phlebotomine sand flies in Colombia. We sequenced 700 bp of the COI gene from 36 species collected from different geographic localities. The COI barcode sequence divergence within a single species was <2% in most cases, whereas this divergence ranged from 9% to 26.6% among different species. These results indicated that the barcoding gene correctly discriminated among the previously morphologically identified species with an efficacy of nearly 100%. Analyses of the generated sequences indicated that the observed species groupings were consistent with the morphological identifications. In conclusion, the barcoding gene was useful for species discrimination in sand flies from Colombia.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Major depressive disorder (MDD) associated with chronic neglected tropical diseases (NTDs) has been identified as a significant and overlooked contributor to overall disease burden. Cutaneous ...leishmaniasis (CL) is one of the most prevalent and stigmatising NTDs, with an incidence of around 1 million new cases of active CL infection annually. However, the characteristic residual scarring (inactive CL) following almost all cases of active CL has only recently been recognised as part of the CL disease spectrum due to its lasting psychosocial impact.
We performed a multi-language systematic review of the psychosocial impact of active and inactive CL. We estimated inactive CL (iCL) prevalence for the first time using reported WHO active CL (aCL) incidence data that were adjusted for life expectancy and underreporting. We then quantified the disability (YLD) burden of co-morbid MDD in CL using MDD disability weights at three severity levels. Overall, we identified 29 studies of CL psychological impact from 5 WHO regions, representing 11 of the 50 highest burden countries for CL. We conservatively calculated the disability burden of co-morbid MDD in CL to be 1.9 million YLDs, which equalled the overall (DALY) disease burden (assuming no excess mortality in depressed CL patients). Thus, upon inclusion of co-morbid MDD alone in both active and inactive CL, the DALY burden was seven times higher than the latest 2016 Global Burden of Disease study estimates, which notably omitted both psychological impact and inactive CL.
Failure to include co-morbid MDD and the lasting sequelae of chronic NTDs, as exemplified by CL, leads to large underestimates of overall disease burden.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The S-containing heterocyclic compounds benzothiopyrans or thiochromones stand out as having promising biological activities due to their structural relationship with chromones (benzopyrans), which ...are widely known as privileged scaffolds in medicinal chemistry. In this work, we report the synthesis of 35 thiochromone derivatives and the in vitro antileishmanial and cytotoxic activities. Compounds were tested against intracellular amastigotes of
and cytotoxic activity against human monocytes (U-937 ATCC CRL-1593.2). Compounds bearing a vinyl sulfone moiety,
,
,
,
,
and
, displayed the highest antileishmanial activity, with EC
values lower than 10 μM and an index of selectivity over 100 for compounds
and
. When the double bond or the sulfone moiety was removed, the activity decreased. Our results show that thiochromones bearing a vinyl sulfone moiety are endowed with high antileishmanial activity and low cytotoxicity.
American visceral leishmaniasis (VL) is a vector-borne disease caused by
(syn.
) and transmitted by
and
phlebotomine sand flies. Dogs not only are the main host reservoirs of the parasite but also ...suffer the disease; therefore, canine VL (CVL) has assumed an important role in public health. In Colombia, human and CVL are restricted to two transmission foci: one in the north region (Caribbean coast) and other in the central south region (middle Magdalena River Valley). We present a CVL case involving a 2-year-old male dog with a history of lack of appetite, general weakness, and progressive loss of weight. A diagnosis of CVL was obtained using the direct parasitological examination in spleen and bone marrow samples stained with Giemsa and RT-qPCR. The infecting
species was identified as
by PCR-restriction fragment length polymorphism amplifying the
gene from bone marrow and spleen samples and confirming by sequencing. The patient responded favorably to treatment with intramuscular meglumine antimoniate at a dose of 100 mg/kg daily for 8 weeks and oral allopurinol at a dose of 10 mg/kg every 12 hours until new indication. This is the first report of urban CVL in the city of Cali, Colombia, highlighting the need for surveillance and control programs in the municipalities of the department of Valle del Cauca, a region where VL has not been informed before. The findings also indicate the need to reinforce the surveillance programs in other rural and urban regions of the country where favorable eco-epidemiological conditions exist.
A new series of N–substituted 2–pyrazolines 9a–f, 10a–f, 11a–f, 12a–f and 13a–f were obtained from the cyclocondensation reaction of (7–chloroquinolin–4–yl)aminochalcones 8a–f with hydrazine hydrate ...and its derivatives. Fourteen of the synthesized compounds including the starting chalcones were selected by US National Cancer Institute (NCI) for testing their anticancer activity against 60 different human cancer cell lines, with the most important GI50 values ranging from 0.28 to 11.7 μM (0.13–6.05 μg/mL) and LC50 values ranging from 2.6 to > 100 μM (1.2 to > 51.7 μg/mL), for chalcones 8a,d and pyrazolines 10c,d. All compounds were assessed for antibacterial activity against wild type and multidrug resistant gram negative and gram positive bacteria, with MIC values ranging from 31.25 to 500 μg/mL. Additionally, the novel compounds were tested for antifungal and antiparasitic properties. Although these compounds showed mild activity against Candida albicans, chalcones 8a and 8e showed high activity against Cryptococcus neoformans with MIC50 = 7.8 μg/mL. For anti–Plasmodium falciparum activity the 2–pyrazoline 11b was the most active with EC50 = 5.54 μg/mL. Regarding the activity against Trypanosoma cruzi, compound 10a was highly active with EC50 = 0.70 μg/mL. Chalcone 8a had good activity against Leishmania panamensis amastigotes with EC50 = 0.79 μg/mL.
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•New series of 4,5–dihydro–1H–pyrazoles were synthesized from quinoline–chalcones.•Compounds 8c,d and 10a,c showed important anticancer activity with GI50 0.28–11.7 μM.•Chalcones 8a and 8e showed excellent anti–C. neoformans activity with MIC50 = 7.8 μg/mL.•Pyrazoline 9d selectively inhibited N. gonorrhoeae growth.•Compounds 8a, 10a and 11b were active to Leishmania, Trypanosoma and Plasmodium, respectively.
Pentavalent antimonials (Sb5) and miltefosine are the first-line drugs for treating cutaneous leishmaniasis in Colombia; however, toxicity and treatment duration negatively impact compliance and ...cost, justifying an active search for better therapeutic options. We compared the efficacy and safety of thermotherapy and meglumine antimoniate for the treatment of cutaneous leishmaniasis in Colombia.
An open randomized Phase III clinical trial was performed in five military health centres. located in northwestern, central and southern Colombia. Volunteers with parasitological positive diagnosis (Giemsa-stained smears) of cutaneous leishmaniasis were included. A single thermotherapy session involving the application of 50°C at the center and active edge of each lesion. Meglumine antimoniate was administered intramuscularly at a dose of 20 mg Sb5/kg weight/day for 20 days.
Both groups were comparable. The efficacy of thermotherapy was 64% (86/134 patients) by protocol and 58% (86/149) by intention-to-treat. For the meglumine antimoniate group, efficacy by protocol was 85% (103/121 patients) and 72% (103/143) by intention-to-treat, The efficacy between the treatments was statistically significant (p 0.01 and < 0.001) for analysis by intention to treat and by protocol, respectively. There was no difference between the therapeutic response with either treatment regardless of the Leishmania species responsible for infection. The side effects of meglumine antimoniate included myalgia, arthralgia, headache and fever. Regarding thermotherapy, the only side effect was pain at the lesion area four days after the initiation of treatment.
Although the efficacy rate of meglumine antimoniate was greater than that of thermotherapy for the treatment of cutaneous leishmaniasis, the side effects were also greater. Those factors, added to the increased costs, the treatment adherence problems and the progressive lack of therapeutic response, make us consider thermotherapy as a first line treatment for cutaneous leishmaniasis.
•There is a strong association of DENV cases in Colombia with ENSO indices and with local temperature and rainfall.•El Niño (La Niña) phenomenon is related to the intensification (weakening) of ...dengue cases at the national level and in the regions with statistically significant results.•The influence of ENSO in dengue dynamics is not stationary and the influence of local climate variables varies in space and time.•The Pacific and Andes regions control the overall relationship between dengue dynamics and ENSO at the national scale.
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Dengue virus (DENV) is an endemic disease in the hot and humid low-lands of Colombia. We characterize the association of monthly series of dengue cases with indices of El Niño/Southern Oscillation (ENSO) at the tropical Pacific and local climatic variables in Colombia during the period 2007-2017 at different temporal and spatial scales. For estimation purposes, we use lagged cross-correlations (Pearson test), cross-wavelet analysis (wavelet cross spectrum, and wavelet coherence), as well as a novel nonlinear causality method, PCMCI, that allows identifying common causal drivers and links among high dimensional simultaneous and time-lagged variables. Our results evidence the strong association of DENV cases in Colombia with ENSO indices and with local temperature and rainfall. El Niño (La Niña) phenomenon is related to an increase (decrease) of dengue cases nationally and in most regions and departments, with maximum correlations occurring at shorter time lags in the Pacific and Andes regions, closer to the Pacific Ocean. This association is mainly explained by the ENSO-driven increase in temperature and decrease in rainfall, especially in the Andes and Pacific regions. The influence of ENSO is not stationary, given the reduction of DENV cases since 2005, and that local climate variables vary in space and time, which prevents to extrapolate results from one region to another. The association between DENV and ENSO varies at national and regional scales when data are disaggregated by seasons, being stronger in DJF and weaker in SON. Overall, the Pacific and Andes regions control the relationship between dengue dynamics and ENSO at national scale. Cross-wavelet analysis indicates that the ENSO-DENV relation in Colombia exhibits a strong coherence in the 12 to 16-months frequency band, which implies the frequency locking between the annual cycle and the interannual (ENSO) timescales. Results of nonlinear causality metrics reveal the complex concomitant effects of ENSO and local climate variables, while offering new insights to develop early warning systems for DENV in Colombia.
Cutaneous leishmaniasis and Chagas disease are vector-borne parasitic disease causing serious risks to million people living in poverty-stricken areas. Both diseases are a major health problem in ...Latin America, and currently drugs for the effective treatment of these diseases have important concerns related with efficacy or toxicity than need to be addressed.
We report herein the synthesis and biological activities (cytotoxicity, leishmanicidal and trypanocidal activities) of ten quinolone-hydrazone hybrids. The structure of the products was elucidated by spectrometric analyses. The synthesized compounds were evaluated against amastigotes forms of L. (V) panamensis which is the most prevalent Leishmania species in Colombia and Trypanosoma cruzi that is the major pathogenic species to humans; in turn, cytotoxicity was evaluated against human U-937 macrophages.
Compounds 6b, 6c and 8 showed activity against L. (V) panamensis with EC50 of 6.5 ± 0.8 μg/mL (21.2 μM), 0.8 ± 0.0 μg/mL (2.6 μM) and 3.4 ± 0.6 μg/mL (11.1 μM), respectively, while compounds 6a and 6c had activity against T. cruzi. with EC50 values of 1.4 ± 0.3 μg/mL (4.8 μM) and 6.6 ± 0.3 μg/mL (4.6 μM), respectively. Even compound 6a showed better activity against T. cruzi than the standard drug benznidazole with EC50 = 10.5 ± 1.8 μg/mL (40.3 μM).
Analysis of the results obtained against leishmaniasis indicates that antiparasite activity is related to the presence of 2-substituted quinoline (isoquinolinic core) and the hydroxyl group in positions 3 and 4 of the aromatic ring. Although the majority of these compounds were highly cytotoxic, the antiparasite activity was higher than cytotoxicity and therefore, they still have potential to be considered as hit molecules for leishmanicidal and trypanocidal drug development.
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•We synthesized ten quinoline hydrazones with good yields.•Five of the compounds obtained were active against L. (V) panamensis and three of them against Trypanosoma cruzi.•The presence of 2-substituted quinoline o isoquinolinic core increase the leishmanicidal activity.•Hydroxyl group in positions 3 and 4 of the aromatic ring is essential for activity.
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