Person: Cruz, Israel
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First Name
Israel
Last Name
Cruz
Institution
ISCIII
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ISCIII::Escuela Nacional de Sanidad (ENS)
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Publication Training on standard operating procedure for Whole Blood stimulation Assay (WBA)(2022) Torres Garcia, Ana Maria; Sanchez Herrero, Carmen; Carrillo, Eugenia; Cruz, Israel; Moreno, JavierPurpose and scopes: To describe the procedure for Whole Blood stimulation Assay (WBA) using blood samples from VL patients. Learning objetives: by the end of this training you should be able to perform Whole Blood stimulation Assay (WBA) with VL blood samples: Understand the procedure; follow the steps in the correct order; correctly mark the samples through all the procedure to avoid mess of samples and register all material for subsequent shipment and correct indentification.Publication Estudio integral del brote comunitario de Leishmaniasis en la comunidad de Madrid. Una visión completa de 12 años de investigación en el Centro Colaborador de la OMS para Leishmaniasis del CNM - ISCIII(Instituto de Salud Carlos III (ISCIII). Centro Nacional de Microbiología (CNM), 2023) Fuster, Fernando; San Martín, Juan Víctor; Mongue, Begoña; Chicharro, Carmen; Moreno, Javier; Carrillo, Eugenia; Cruz, Israel; Nieto Martinez, Francisco Javier; Jimenez, Maribel; Molina, Ricardo; Martin-Martin, Ines; Bernardo, LorenaEstudio del brote de leishmaniasis en Fuenlabrada y otros municipios de la Comunidad de Madrid. Ha sido un trabajo de investigación realizado a lo largo de los últimos 12 años en el Centro Colaborador de la OMS para Leishmaniasis del ISCIII.Publication Endemic transmission of visceral leishmaniasis in Bhutan(American Society of Tropical Medicine and Hygiene (ASTMH), 2012-12) Yangzom, Thinley; Cruz, Israel; Bern, Caryn; Argaw, Daniel; den Boer, Margriet; Vélez, Iván Dario; Bhattacharya, Sujit K; Molina, Ricardo; Alvar, Jorge; Agencia Española de Cooperación Internacional para el DesarrolloVisceral leishmaniasis was first reported in Bhutan in 2006. We conducted studies of the parasite, possible vectors and reservoirs, and leishmanin skin test and risk factor surveys in three villages. Nineteen cases were reported from seven districts. Parasite typing yielded two novel microsatellite sequences, both related to Indian L. donovani. In one case village, 40 (18.5%) of 216 participants had positive leishmanin skin test results, compared with 3 (4.2%) of 72 in the other case village and 0 of 108 in the control village. Positive results were strongly associated with the village and increasing age. None of the tested dogs were infected. Eighteen sand flies were collected, 13 Phlebotomus species and 5 Sergentomyia species; polymerase chain reaction for leishmanial DNA was negative. This assessment suggests that endemic visceral leishmaniasis transmission has occurred in diverse locations in Bhutan. Surveillance, case investigations, and further parasite, vector, and reservoir studies are needed. The potential protective impact of bed nets should be evaluated.Publication Immunization with H1, HASPB1 and MML Leishmania proteins in a vaccine trial against experimental canine leishmaniasis(Elsevier, 2007-07-20) Moreno, Javier; Nieto Martinez, Francisco Javier; Masina, S; Cañavate, Carmen; Cruz, Israel; Chicharro, Carmen; Carrillo, Eugenia; Napp, S; Reymond, C; Kaye, P M; Smith, D F; Fasel, N; Alvar, Jorge; RMF Dictagene; Novartis; Fonds de la Recherche Scientifique (Belgique)The protective capabilities of three Leishmania recombinant proteins - histone 1 (H1) and hydrophilic acylated surface protein B1 (HASPB1) immunized singly, or together as a protein cocktail vaccine with Montanide, and the polyprotein MML immunized with MPL-SE adjuvant - were assessed in beagle dogs. Clinical examination of the dogs was carried out periodically under blinded conditions and the condition of the dogs defined as asymptomatic or symptomatic. At the end of the trial, we were able to confirm that following infection with L. infantum promastigotes, five out of eight dogs immunized with H1 Montanide, and four out of eight dogs immunized with either the combination of HASPB1 with Montanide or the combination of H1+HASPB1 with Montanidetrade mark, remained free of clinical signs, compared with two out of seven dogs immunized with the polyprotein MML and adjuvant MPL-SE, and two out of eight dogs in the control group. The results demonstrate that HASPB1 and H1 antigens in combination with Montanide were able to induce partial protection against canine leishmaniasis, even under extreme experimental challenge conditions.Publication Leishmania in discarded syringes from intravenous drug users(Elsevier, 2002-03-30) Cruz, Israel; Morales, Miguel Ángel; Noguer, I; Rodríguez, A; Alvar, Jorge; World Health Organization (WHO/OMS); Fundación para la Investigación y la Prevención del Sida en España; Instituto de Salud Carlos IIINeedle sharing by intravenous drug users (IVDUs) has been proposed as providing an alternative, artificial, and anthroponotic cycle for leishmania transmission. We looked for parasites in syringes discarded by IVDUs using two different PCR techniques. Leishmania spp were detected in 65 (52%) of 125 syringes collected in southern Madrid, Spain, in 1998, and in 52 (34%) of 154 collected in southwestern Madrid in 2000-01. We found shared restriction fragment length polymorphisms in 12 of 65 positive samples tested, suggesting that syringe sharing can indeed promote the spread of leishmania clones among IVDUs.Publication Implications of zoonotic and vector-borne parasites to free-roaming cats in central Spain(Elsevier, 2018-02-15) Montoya, A; García, M; Gálvez, Rosa; Checa, R; Marino, V; Sarquis, J; Barrera, JP; Rupérez, C; Caballero, L; Chicharro, Carmen; Cruz, Israel; Miró, GCats are definitive hosts and reservoirs for several parasites, some of which are responsible for serious zoonotic diseases. We conducted a case-control study of data from a trap-neuter-return (TNR) programme (years 2014-2017) designed to examine the prevalence of zoonotic parasites in free-roaming cats living in urban areas of central Spain. In the animal population tested (n = 263), we detected a 29.2% prevalence of endoparasites, including high rates of cestodes (12.9%) and Toxocara cati (11.7%). While faecal samples showed no Toxoplasma gondii oocysts, the seroprevalence of T. gondii infection was 24.2%. Antibodies to Leishmania infantum were detected in 4.8% of the animals, though all skin and blood samples analyzed were PCR negative for this parasite. Ectoparasites (ticks and fleas) were found in 4.6% of the cat population, and 10.6% of the cats were detected with Otodectes cynotis. Finally, 6.3% and 7.9% cats tested positive for feline leukaemia virus and feline immunodeficiency virus, respectively. Our study provides useful information for animal-welfare and public-health, as the parasites detected can affect native wild animals through predation, competition and disease transmission. Our detection of zoonotic parasites such as L. infantum, T. gondii, T. cati, Giardia duodenalis and several ectoparasites prompts an urgent need for health control measures in stray cats.Publication Leishmania Genome Dynamics during Environmental Adaptation Reveal Strain-Specific Differences in Gene Copy Number Variation, Karyotype Instability, and Telomeric Amplification(American Society for Microbiology (ASM), 2018) Bussotti, Giovanni; Gouzelou, Evi; Côrtes Boité, Mariana; Kherachi, Ihcen; Harrat, Zoubir; Eddaikra, Naouel; Mottram, Jeremy C; Antoniou, Maria; Christodoulou, Vasiliki; Bali, Aymen; Guerfali, Fatma Z; Laouini, Dhafer; Mukhtar, Maowia; Dumetz, Franck; Dujardin, Jean-Claude; Smirlis, Despina; Lechat, Pierre; Pescher, Pascale; El Hamouchi, Adil; Lemrani, Meryem; Chicharro, Carmen; Llanes-Acevedo, Ivonne Pamela; Botana, Laura; Cruz, Israel; Moreno, Javier; Jeddi, Fakhri; Aoun, Karim; Bouratbine, Aïda; Cupolillo, Elisa; Späth, Gerald F; Belgian Science Policy Office; Unión EuropeaProtozoan parasites of the genus Leishmania adapt to environmental change through chromosome and gene copy number variations. Only little is known about external or intrinsic factors that govern Leishmania genomic adaptation. Here, by conducting longitudinal genome analyses of 10 new Leishmania clinical isolates, we uncovered important differences in gene copy number among genetically highly related strains and revealed gain and loss of gene copies as potential drivers of long-term environmental adaptation in the field. In contrast, chromosome rather than gene amplification was associated with short-term environmental adaptation to in vitro culture. Karyotypic solutions were highly reproducible but unique for a given strain, suggesting that chromosome amplification is under positive selection and dependent on species- and strain-specific intrinsic factors. We revealed a progressive increase in read depth towards the chromosome ends for various Leishmania isolates, which may represent a nonclassical mechanism of telomere maintenance that can preserve integrity of chromosome ends during selection for fast in vitro growth. Together our data draw a complex picture of Leishmania genomic adaptation in the field and in culture, which is driven by a combination of intrinsic genetic factors that generate strain-specific phenotypic variations, which are under environmental selection and allow for fitness gain.IMPORTANCE Protozoan parasites of the genus Leishmania cause severe human and veterinary diseases worldwide, termed leishmaniases. A hallmark of Leishmania biology is its capacity to adapt to a variety of unpredictable fluctuations inside its human host, notably pharmacological interventions, thus, causing drug resistance. Here we investigated mechanisms of environmental adaptation using a comparative genomics approach by sequencing 10 new clinical isolates of the L. donovani, L. major, and L. tropica complexes that were sampled across eight distinct geographical regions. Our data provide new evidence that parasites adapt to environmental change in the field and in culture through a combination of chromosome and gene amplification that likely causes phenotypic variation and drives parasite fitness gains in response to environmental constraints. This novel form of gene expression regulation through genomic change compensates for the absence of classical transcriptional control in these early-branching eukaryotes and opens new venues for biomarker discovery.Publication What is responsible for a large and unusual outbreak of leishmaniasis in Madrid?(Elsevier, 2013-12) Carrillo, Eugenia; Cruz, Israel; Moreno, JavierSeveral towns in the southwest of Madrid, Spain, have been suffering from an outbreak of leishmaniasis since 2009 and, by December 2012, human infections had increased significantly. Although dogs are the main reservoir host, hares are suspected as a potential culprit for the surprising increase of cases.Publication Comparison of 8 weeks standard treatment (rifampicin plus clarithromycin) vs. 4 weeks standard plus amoxicillin/clavulanate treatment [RC8 vs. RCA4] to shorten Buruli ulcer disease therapy (the BLMs4BU trial): study protocol for a randomized controlled multi-centre trial in Benin(BioMed Central (BMC), 2022-07-08) Johnson, Roch Christian; Sáez-López, Emma; Anagonou, Esaï Sèdjro; Kpoton, Godwin Gérard; Ayelo, Adjimon Gilbert; Gnimavo, Ronald Sètondji; Mignanwande, Franck Zinsou; Houezo, Jean-Gabin; Sopoh, Ghislain Emmanuel; Addo, Juliet; Orford, Lindsay; Vlasakakis, Georgios; Biswas, Nandita; Calderon, Felix; Della Pasqua, Oscar; Gine-March, Anna; Herrador, Zaida; Mendoza-Losana, Alfonso; Díez, Gabriel; Cruz, Israel; Ramón-García, Santiago; Fundación ANESVAD; Tres Cantos Open Lab FoundationBackground: Buruli ulcer (BU) is a neglected tropical disease caused by Mycobacterium ulcerans that affects skin, soft tissues, and bones, causing long-term morbidity, stigma, and disability. The recommended treatment for BU requires 8 weeks of daily rifampicin and clarithromycin together with wound care, physiotherapy, and sometimes tissue grafting and surgery. Recovery can take up to 1 year, and it may pose an unbearable financial burden to the household. Recent in vitro studies demonstrated that beta-lactams combined with rifampicin and clarithromycin are synergistic against M. ulcerans. Consequently, inclusion of amoxicillin/clavulanate in a triple oral therapy may potentially improve and shorten the healing process. The BLMs4BU trial aims to assess whether co-administration of amoxicillin/clavulanate with rifampicin and clarithromycin could reduce BU treatment from 8 to 4 weeks. Methods: We propose a randomized, controlled, open-label, parallel-group, non-inferiority phase II, multi-centre trial in Benin with participants stratified according to BU category lesions and randomized to two oral regimens: (i) Standard: rifampicin plus clarithromycin therapy for 8 weeks; and (ii) Investigational: standard plus amoxicillin/clavulanate for 4 weeks. The primary efficacy outcome will be lesion healing without recurrence and without excision surgery 12 months after start of treatment (i.e. cure rate). Seventy clinically diagnosed BU patients will be recruited per arm. Patients will be followed up over 12 months and managed according to standard clinical care procedures. Decision for excision surgery will be delayed to 14 weeks after start of treatment. Two sub-studies will also be performed: a pharmacokinetic and a microbiology study. Discussion: If successful, this study will create a new paradigm for BU treatment, which could inform World Health Organization policy and practice. A shortened, highly effective, all-oral regimen will improve care of BU patients and will lead to a decrease in hospitalization-related expenses and indirect and social costs and improve treatment adherence. This trial may also provide information on treatment shortening strategies for other mycobacterial infections (tuberculosis, leprosy, or non-tuberculous mycobacteria infections).Publication Factors associated with Leishmania asymptomatic infection: results from a cross-sectional survey in highland northern Ethiopia(Public Library of Science (PLOS), 2012-09-27) Custodio, Estefania; Gadisa, Endalamaw; Sordo, Luis; Cruz, Israel; Moreno, Javier; Nieto Martinez, Francisco Javier; Chicharro, Carmen; Aseffa, Abraham; Abraham, Zelalem; Hailu, Tsegaye; Cañavate, Carmen; UBS Optimus Foundation; Instituto de Salud Carlos IIIBACKGROUND: In northern Ethiopia the prevalence of visceral leishmaniasis is steadily rising posing an increasing public health concern. In order to develop effective control strategies on the transmission of the disease it is important to generate knowledge on the epidemiological determinants of the infection. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a cross-sectional survey on children 4-15 years of age using a multi staged stratified cluster sampling on high incidence sub-districts of Amhara regional state, Ethiopia. The survey included a socio-demographic, health and dietary questionnaire, and anthropometric measurements. We performed rK39-ICT and DAT serological tests in order to detect anti-Leishmania antibodies and carried out Leishmanin Skin Test (LST) using L.major antigen. Logistic regression models were used. Of the 565 children surveyed 56 children were positive to infection (9.9%). The individual variables that showed a positive association with infection were increasing age, being male and sleeping outside [adjusted odds ratios (95% CI): 1.15 (1.03, 1.29), 2.56 (1.19, 5.48) and 2.21 (1.03, 4.71) respectively] and in relation to the household: past history of VL in the family, living in a straw roofed house and if the family owned sheep [adjusted OR (95% CI): 2.92 (1.25, 6.81), 2.71 (1.21, 6.07) and 4.16 (1.41, 12.31) respectively]. CONCLUSIONS/SIGNIFICANCE: A behavioural pattern like sleeping outside is determinant in the transmission of the infection in this area. Protective measures should be implemented against this identified risk activity. Results also suggest a geographical clustering and a household focalization of the infection. The behaviour of the vector in the area needs to be clarified in order to establish the role of domestic animals and house materials in the transmission of the infection.