Person:
Nieto Martinez, Francisco Javier

First Name

Francisco Javier

Last Name

Nieto Martinez

Institution

ISCIII

Centrre

ISCIII::Centro Nacional de Microbiología (CNM)

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Now showing 1 - 10 of 22

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, Lorena
Estudio 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.
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.
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 III
BACKGROUND: 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.
Leishmania/HIV co-infections in the second decade.
(Medknow Publications, 2006-03) Cruz, Israel; Nieto Martinez, Francisco Javier; Moreno, Javier; Cañavate, Carmen; Desjeux, Philippe; Alvar, Jorge
Leishmania-HIV co-infection has been globally controlled in Southern Europe since 1997 because of highly active anti retroviral therapy (HAART), but it appears to be an increasing problem in other countries such as Ethopia, Sudan, Brazil or India where both infections are becoming more and more prevalent. Most of the scientific background on Leishmania/HIV co-infection has been dropped from the Mediterranean experience and although the situations among countries are not fully comparable, it is of high importance to take advantage of this knowledge. In this review several aspects of the Leishmania/HIV co-infection are emphasized viz., epidemiological features, new ways of transmission, pathogenesis, clinical outcome, diagnosis, treatment and secondary prohylaxis. An extensive review of the literature on Leishmania/HIV co-infection has allowed the inclusion of a comprehensive and updated list of bibliographical references.
Validation of rK39 immunochromatographic test and direct agglutination test for the diagnosis of Mediterranean visceral leishmaniasis in Spain
(Public Library of Science (PLOS), 2018-03-01) Bangert, Mathieu; Flores-Chavez, Maria; Llanes-Acevedo, Ivonne Pamela; Arcones, Carolina; Chicharro, Carmen; Garcia, Emilia; Ortega, Sheila; Nieto Martinez, Francisco Javier; Cruz, Israel; Instituto de Salud Carlos III
BACKGROUND: Visceral leishmaniasis (VL), the most severe form of leishmaniasis, is endemic in Europe with Mediterranean countries reporting endemic status alongside a worrying northward spread. Serological diagnosis, including immunochromatographic test based on the recombinant antigen rK39 (rK39-ICT) and a direct agglutination test (DAT) based on the whole parasite antigen, have been validated in regions with high VL burden, such as eastern Africa and the Indian subcontinent. To date, no studies using a large set of patients have performed an assessment of both methods within Europe. METHODOLOGY/PRINCIPAL FINDINGS: We selected a range of clinical serum samples from patients with confirmed VL (including HIV co-infection), Chagas disease, malaria, other parasitic infections and negative samples (n = 743; years 2009-2015) to test the performance of rK39-ICT rapid test (Kalazar Detect Rapid Test; InBios International, Inc., USA) and DAT (ITM-DAT/VLG; Institute of Tropical Medicine Antwerp, Belgium). An in-house immunofluorescence antibody test (IFAT), was included for comparison. Estimated sensitivities for rK39-ICT and DAT in HIV-negative VL patients were 83.1% [75.1-91.2] and 84.2% [76.3-92.1], respectively. Sensitivity was reduced to 67.3% [52.7-82.0] for rK39 and increased to 91.3% [82.1-100.0] for DAT in HIV/VL co-infected patients. The in-house IFAT was more sensitive in HIV-negative VL patients, 84.2% [76.3-92.1] than in HIV/VL patients, 79.4% [73.3-96.2]. DAT gave 32 false positives in sera from HIV-negative VL suspects, compared to 0 and 2 for rK39 and IFAT, respectively, but correctly detected more HIV/VL patients (42/46) than rK39 (31/46) and IFAT (39/46). CONCLUSIONS/SIGNIFICANCE: Though rK39-ICT and DAT exhibited acceptable sensitivity and specificity a combination with other tests is required for highly sensitive diagnosis of VL cases in Spain. Important variation in the performance of the tests were seen in patients co-infected with HIV or with other parasitic infections. This study can help inform the choice of serological test to be used when screening or diagnosing VL in a European Mediterranean setting.
Parasitemia Levels in Trypanosoma cruzi Infection in Spain, an Area Where the Disease Is Not Endemic: Trends by Different Molecular Approaches
(American Society for Microbiology (ASM), 2022-10-26) Flores-Chavez, Maria; Abras, Alba; Ballart, Cristina; Perez-Gordillo, Pilar; Gállego, Montserrat; Muñoz, Carmen; Moure, Zaira; Sulleiro, Elena; Nieto Martinez, Francisco Javier; Garcia, Emilia; Simon Mendez, Lorena; Cruz, Israel; Picado, Albert; Ibañez-Perez, Ismael; Foundation for Innovative New Diagnostics (Suiza); Instituto de Salud Carlos III; Fundación Mundo Sano; Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR)
Trypanosoma cruzi infection has expanded globally through human migration. In Spain, the mother-to-child route is the mode of transmission contributing to autochthonous Chagas disease (CD); however, most people acquired the infection in their country of origin and were diagnosed in the chronic phase (imported chronic CD). In this context, we assessed the quantitative potential of the Loopamp Trypanosoma cruzi detection kit (Sat-TcLAMP) based on satellite DNA (Sat-DNA) to determine parasitemia levels compared to those detected by real-time quantitative PCRs (qPCRs) targeting Sat-DNA (Sat-qPCR) and kinetoplast DNA minicircles (kDNA-qPCR). This study included 173 specimens from 39 autochthonous congenital and 116 imported chronic CD cases diagnosed in Spain. kDNA-qPCR showed higher sensitivity than Sat-qPCR and Sat-TcLAMP. According to all quantitative approaches, parasitemia levels were significantly higher in congenital infection than in chronic CD (1 × 10-1 to 5 × 105 versus >1 × 10-1 to 6 × 103 parasite equivalents/mL, respectively [P < 0.001]). Sat-TcLAMP, Sat-qPCR, and kDNA-qPCR results were equivalent at high levels of parasitemia (P = 0.381). Discrepancies were significant for low levels of parasitemia and older individuals. Differences between Sat-TcLAMP and Sat-qPCR were not qualitatively significant, but estimations of parasitemia using Sat-TcLAMP were closer to those by kDNA-qPCR. Parasitemia changes were assessed in 6 individual cases in follow-up, in which trends showed similar patterns by all quantitative approaches. At high levels of parasitemia, Sat-TcLAMP, Sat-qPCR, and kDNA-qPCR worked similarly, but significant differences were found for the low levels characteristic of late chronic CD. A suitable harmonization strategy needs to be developed for low-level parasitemia detection using Sat-DNA- and kDNA-based tests. IMPORTANCE: Currently, molecular equipment has been introduced into many health care centers, even in low-income countries. PCR, qPCR, and loop-mediated isothermal amplification (LAMP) are becoming more accessible for the diagnosis of neglected infectious diseases. Chagas disease (CD) is spreading worldwide, and in countries where the disease is not endemic, such as Spain, the parasite Trypanosoma cruzi is transmitted from mother to child (congenital CD). Here, we explore why LAMP, aimed at detecting T. cruzi parasite DNA, is a reliable option for the diagnosis of congenital CD and the early detection of reactivation in chronic infection. When the parasite load is high, LAMP is equivalent to any qPCR. In addition, the estimations of T. cruzi parasitemia in patients living in Spain, a country where the disease is not endemic, resemble natural evolution in areas of endemicity. If molecular tests are introduced into the diagnostic algorithm for congenital infection, early diagnosis and timely treatment would be accomplished, so the interruption of vertical transmission can be an achievable goal.
Cross-sectional study of malnutrition and associated factors among school aged children in rural and urban settings of Fogera and Libo Kemkem districts, Ethiopia
(Public Library of Science (PLOS), 2014-09-29) Herrador, Zaida; Sordo, Luis; Gadisa, Endalamaw; Moreno, Javier; Nieto Martinez, Francisco Javier; Benito, Agustin; Aseffa, Abraham; Cañavate, Carmen; Custodio, Estefania; UBS Optimus Foundation; RETICS-Investigación colaborativa en Enfermedades Tropicales (RICET-ISCIII) (España); Instituto de Salud Carlos III
INTRODUCTION: Little information is available on malnutrition-related factors among school-aged children ≥5 years in Ethiopia. This study describes the prevalence of stunting and thinness and their related factors in Libo Kemkem and Fogera, Amhara Regional State and assesses differences between urban and rural areas. METHODS: In this cross-sectional study, anthropometrics and individual and household characteristics data were collected from 886 children. Height-for-age z-score for stunting and body-mass-index-for-age z-score for thinness were computed. Dietary data were collected through a 24-hour recall. Bivariate and backward stepwise multivariable statistical methods were employed to assess malnutrition-associated factors in rural and urban communities. RESULTS: The prevalence of stunting among school-aged children was 42.7% in rural areas and 29.2% in urban areas, while the corresponding figures for thinness were 21.6% and 20.8%. Age differences were significant in both strata. In the rural setting, fever in the previous 2 weeks (OR: 1.62; 95% CI: 1.23-2.32), consumption of food from animal sources (OR: 0.51; 95% CI: 0.29-0.91) and consumption of the family's own cattle products (OR: 0.50; 95% CI: 0.27-0.93), among others factors were significantly associated with stunting, while in the urban setting, only age (OR: 4.62; 95% CI: 2.09-10.21) and years of schooling of the person in charge of food preparation were significant (OR: 0.88; 95% CI: 0.79-0.97). Thinness was statistically associated with number of children living in the house (OR: 1.28; 95% CI: 1.03-1.60) and family rice cultivation (OR: 0.64; 95% CI: 0.41-0.99) in the rural setting, and with consumption of food from animal sources (OR: 0.26; 95% CI: 0.10-0.67) and literacy of head of household (OR: 0.24; 95% CI: 0.09-0.65) in the urban setting. CONCLUSION: The prevalence of stunting was significantly higher in rural areas, whereas no significant differences were observed for thinness. Various factors were associated with one or both types of malnutrition, and varied by type of setting. To effectively tackle malnutrition, nutritional programs should be oriented to local needs.
Molecular identification of Leishmania tropica and L. infantum isolated from cutaneous human leishmaniasis samples in central Morocco.
(Medknow Publications, 2020-01) Echchakery, Mohamed; Chicharro, Carmen; Boussaa, S; Nieto Martinez, Francisco Javier; Ortega, Sheila; Carrillo, Eugenia; Moreno, Javier; Boumezzough, Ali
Cutaneous leishmaniasis (CL) in Marrakesh-Safi region located in the central-south part of Morocco is a public health problem. This study assessed the efficiency of a microscopic examination method in establishing the diagnosis of CL and PCR for the characterization and identification of the circulating Leishmania strains in different CL foci of the study area. A total of 297 smears obtained from cutaneous lesions of suspected patients with CL were stained with May-Grünwald Giemsa (MGG) for microscopic examination. For each positive smear, genomic DNA was extracted and PCR-analysed, targeting the small subunit ribosomal ribonucleic acid (ssu rRNA) gene to detect Leishmania DNA. Then, the internal transcribed spacer 1 (ITS1) was amplified and sequenced in order to identify the Leishmania species. The sensitivity and specificity of the conventional microscopy with ssu rRNA gene were compared by Leishmania nested PCR (LnPCR) and ITS1 gene by ITS-PCR. A total of 257 smears were positive in the microscopic examination, i.e. the detection rate of amastigotes by optical microscopy was 86.53% (257/297). The LnPCR was found to have a specificity and a sensitivity of 100%, each. Interestingly, the sequencing results showed that 99.61% (256/257) of the isolates had Leishmania tropica and 0.39% (1/257) had L. infantum infection. Though, classical microscopic examination is useful and economical, it is not sensitive enough, especially in endemic regions where several Leishmania species coexist. In such situations, PCR constitutes a complementary method for the identification of the causal species. The results indicate that both the L. tropica (dominant) and L. infantum are the causative agents of CL in the Marrakesh-Safi region. The rate of CL infection is high in Imintanout, and Chichaoua provinces. Hence, early diagnosis and prompt treatment of CL patients is necessary to prevent its extension to neighboring localities.
Comparison of new diagnostic tools for management of pediatric Mediterranean visceral leishmaniasis
(American Society for Microbiology (ASM), 2006-07) Cruz, Israel; Chicharro, Carmen; Nieto Martinez, Francisco Javier; Bailo-Barroso, Begoña; Cañavate, Carmen; Figueras, María-Concepción; Alvar, Jorge; Gilead Sciences (Spain); World Health Organization (WHO/OMS); RETICS-Investigación colaborativa en Enfermedades Tropicales (RICET-ISCIII) (España); Instituto de Salud Carlos III
New techniques are available for diagnosing leishmaniasis, but their efficacy in the identification of pediatric visceral leishmaniasis (VL) has not been compared with that of traditional methods. Blood, bone marrow, and urine samples were taken from 25 children with VL during their first clinical episode, 22 days after the start of treatment with liposomal amphotericin B (3 mg/kg/day on 6 days over a 10-day period), and when a relapse was suspected during follow-up. The results obtained suggest that antibody detection techniques, the antigen detection in urine (KAtex kit), and Leishmania nested PCR (LnPCR) analysis of the blood could be used for diagnosis of the first clinical episode. After treatment, clinical improvement was associated with negativization of Novy-MacNeal-Nicolle culture and microscopy of bone marrow aspirate, KAtex test, and LnPCR blood analysis results. Interestingly, LnPCR analysis of the bone marrow aspirate showed that sterile cure was not achieved in eight patients, two of which suffered a relapse within 10 to 20 weeks. All of the new noninvasive techniques tested showed high diagnostic sensitivity. However, LnPCR analysis of the bone marrow was the most sensitive; this test was able to detect the persistence of parasites and predict potential relapses.
A randomised, double-blind, controlled efficacy trial of the LiESP/QA-21 vaccine in naïve dogs exposed to two leishmania infantum transmission seasons
(Public Library of Science (PLOS), 2014-10-09) Oliva, Gaetano; Nieto Martinez, Francisco Javier; Foglia Manzillo, Valentina; Cappiello, Silvia; Fiorentino, Eleonora; Di Muccio, Trentina; Scalone, Aldo; Moreno, Javier; Chicharro, Carmen; Carrillo, Eugenia; Butaud, Therese; Guegand, Laurie; Martin, Virginie; Cuisinier, Anne-Marie; McGahie, David; Gueguen, Sylvie; Cañavate, Carmen; Gradoni, Luigi; Virbac (France)
Canine leishmaniasis is an important zoonosis caused by uncontrolled infection with Leishmania infantum, where an inappropriate immune response is not only responsible for permitting this intracellular parasite to multiply, but is also responsible for several of the pathological processes seen in this disease. Effective canine vaccines are therefore a highly desirable prevention tool. In this randomised, double-blinded, controlled trial, the efficacy of the LiESP/QA-21 vaccine (CaniLeish, Virbac, France) was assessed by exposing 90 naïve dogs to natural L. infantum infection during 2 consecutive transmission seasons, in two highly endemic areas of the Mediterranean basin. Regular PCR, culture, serological and clinical examinations were performed, and the infection/disease status of the dogs was classified at each examination. The vaccine was well-tolerated, and provided a significant reduction in the risk of progressing to uncontrolled active infection (p = 0.025) or symptomatic disease (p = 0.046), with an efficacy of 68.4% and a protection rate of 92.7%. The probability of becoming PCR positive was similar between groups, but the probability of returning to a PCR negative condition was higher in the vaccinated group (p = 0.04). In conclusion, we confirmed the interest of using this vaccine as part of a comprehensive control program for canine leishmaniasis, and validated the use of a protocol based on regular in-depth assessments over time to assess the efficacy of a canine leishmaniasis vaccine.