Microscopic agglutination test: Variables that affect the time of serological confirmation of human leptospirosis cases

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Microscopic magnification: 1000×." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Julián Verona, Noelia Cecilia Dirialdi, María Virginia Mutti, Marcelo Carlos Scioli, Fernando Andrés Thougnon Islas, Germán Emilio Curi Antún, Lisandro Juan Sgariglia, María Guillermina Homar, José Andrés Legato, Agustina Costa, María Laura Maldonado, José A. Di Conza, Mirta R. 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"apellidos" => "Litterio Bürki" ] ] ] ] "resumen" => array:1 [ 0 => array:3 [ "titulo" => "Highlights" "clase" => "author-highlights" "resumen" => "<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">•Bacteremia by Arcanobacterium haemolyticum in a twenty-year-old immunocompetent patient.</li><li class="elsevierStyleListItem" id="lsti0010">•Rough biotype of this strain correlates with intergenic sequence of aln upstream region.</li><li class="elsevierStyleListItem" id="lsti0015">•Treatment with vancomycin plus piperacillin/tazobactam was effective.</li><li class="elsevierStyleListItem" id="lsti0020">•Lemierre's syndrome was discarded.</li></ul>" ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0325754120300043?idApp=UINPBA00004N" "url" => "/03257541/0000005200000004/v1_202012180643/S0325754120300043/v1_202012180643/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S0325754120300237" "issn" => "03257541" "doi" => "10.1016/j.ram.2019.12.004" "estado" => "S300" "fechaPublicacion" => "2020-10-01" "aid" => "384" "copyright" => "Asociación Argentina de Microbiología" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Rev Argent Microbiol. 2020;52:272-7" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "Original article" "titulo" => "Incorporation of the rapid HIV test in a sexually-transmitted disease clinic in Buenos Aires: Dramatic increase in the frequency of HIV diagnosis" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:3 [ 0 => "en" 1 => "en" 2 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "272" "paginaFinal" => "277" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Incorporación del test rápido del HIV en una clínica de enfermedades de transmisión sexual en Buenos Aires: aumento dramático en la frecuencia de diagnóstico del HIV" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Nicolas Morando, María Lucía Gallo Vaulet, Asunta Melgar, Marcelo Rodríguez Fermepin, Ricardo Casco, María de los Ángeles Pando" "autores" => array:6 [ 0 => array:2 [ "nombre" => "Nicolas" "apellidos" => "Morando" ] 1 => array:2 [ "nombre" => "María Lucía Gallo" "apellidos" => "Vaulet" ] 2 => array:2 [ "nombre" => "Asunta" "apellidos" => "Melgar" ] 3 => array:2 [ "nombre" => "Marcelo Rodríguez" "apellidos" => "Fermepin" ] 4 => array:2 [ "nombre" => "Ricardo" "apellidos" => "Casco" ] 5 => array:2 [ "nombre" => "María de los Ángeles" "apellidos" => "Pando" ] ] ] ] "resumen" => array:1 [ 0 => array:3 [ "titulo" => "Highlights" "clase" => "author-highlights" "resumen" => "<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">•The use of the RHT significantly increased the frequency of HIV diagnosis.</li><li class="elsevierStyleListItem" id="lsti0010">•Approximately one of three individuals had never tested for HIV previously.</li><li class="elsevierStyleListItem" id="lsti0015">•No access to medical care and irregular condom use associated with no HIV testing.</li><li class="elsevierStyleListItem" id="lsti0020">•Tendency toward a higher HIV prevalence in patients with no prior HIV testing.</li><li class="elsevierStyleListItem" id="lsti0025">•Use of RHT slightly incremented the receipt of confirmatory results.</li></ul>" ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0325754120300237?idApp=UINPBA00004N" "url" => "/03257541/0000005200000004/v1_202012180643/S0325754120300237/v1_202012180643/en/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "Brief report" "titulo" => "Microscopic agglutination test: Variables that affect the time of serological confirmation of human leptospirosis cases" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "278" "paginaFinal" => "282" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Exequiel Scialfa, Mariana Rivero, Sergio Moreno, Marcela Ortiz, Fabricio Bongiorno" "autores" => array:5 [ 0 => array:4 [ "nombre" => "Exequiel" "apellidos" => "Scialfa" "email" => array:1 [ 0 => "escialfa@yahoo.com.ar" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Mariana" "apellidos" => "Rivero" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 2 => array:3 [ "nombre" => "Sergio" "apellidos" => "Moreno" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "Marcela" "apellidos" => "Ortiz" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 4 => array:3 [ "nombre" => "Fabricio" "apellidos" => "Bongiorno" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Departamento de Zoonosis Rurales (Ministerio de Salud de la provincia de Buenos Aires), Azul, Provincia de Buenos Aires, Argentina" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Centro de Investigación Veterinaria de Tandil (CIVETAN-CONICET-CIC), Facultad de Ciencias Veterinarias, Universidad Nacional del Centro de la Provincia de Buenos Aires, Tandil, Provincia de Buenos Aires, Argentina" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Facultad de Ciencias, Veterinarias Universidad Nacional del Centro de la Provincia de Buenos Aires, (UNCPBA), Tandil, Provincia de Buenos Aires, Argentina" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Facultad de Agronomía, Universidad Nacional del Centro de la Provincia de Buenos Aires (UNCPBA), Azul, Provincia de Buenos Aires, Argentina" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Test de microaglutinación: variables que afectan el tiempo de confirmación de los casos humanos de leptospirosis" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2868 "Ancho" => 1508 "Tamanyo" => 235620 ] ] "descripcion" => array:1 [ "en" => "(A) Days elapsed between the onset of clinical manifestations and the collection of the first sample for the serological diagnosis of the disease. (B) Days between the collection of the first clinical sample for serological diagnosis and admission at the specific diagnostic laboratory. (C) Cross-reaction between serogroups used as antigens in MAT, according to the days of the course of disease. (D) Antibody titers for serogroups used as antigens in MAT, according to the days of the course of disease." ] ] ] "textoCompleto" => "Leptospirosis is a widely recognized zoonosis (caused by Leptospira spp.) with a worldwide distribution. The incidence of the disease in the human and animal population is highly variable, depending on the type of ecosystems (urban and rural), the variations in environmental conditions, and the presence of the host<a class="elsevierStyleCrossRef" href="#bib0080">7</a>. Although rodents and canines are considered the main sources of infection for humans, other hosts such as cattle and swine have been associated with human cases of leptospirosis. The infected animal excretes the microorganism in the urine, intermittently and for a variable period of time, (depending on the animal species and serovar); the survival of leptospires in the environment will depend on the environmental conditions (temperature and humidity) and the pH of the soil, requiring a neutral to slightly alkaline pH. Infections in humans occur through direct contact with the urine of infected animals or indirectly by contact with contaminated water. In Argentina, leptospirosis is an important public health concern due to the occurrence of human cases and outbreaks of disease<a class="elsevierStyleCrossRef" href="#bib0090">9</a>. Buenos Aires and Santa Fe provinces have recorded the highest number of leptospirosis cases in Argentina, due in part to the fact that these districts have diagnostic laboratories that allow to identify the cases. Outbreaks in both humans and animals are usually related to floods, periods of heavy rainfall and high humidity<a class="elsevierStyleCrossRefs" href="#bib0080">7,8</a>.To perform the microscopic agglutination test (MAT), the International Leptospirosis Society of the World Health Organization (WHO-ILS) suggests the use of 19 strains in the antigen panel. However, based on previous studies, in order to expedite the diagnosis, reduce costs and facilitate the management and maintenance of the panel used in the routine MAT, most of the reference laboratories in Argentina use 10–12 of the 19 suggested strains<a class="elsevierStyleCrossRef" href="#bib0065">4</a>. In a study carried out by Jacob et al.<a class="elsevierStyleCrossRef" href="#bib0065">4</a> with samples from all over the country, it was observed that the serogroups presumably infecting humans were: Icterohaemorrhagiae (31%), Pomona (15%), Ballum (14%), Canicola (10%), Sejroe (4%) and Tarassovi (2%)<a class="elsevierStyleCrossRef" href="#bib0065">4</a>. However, in Buenos Aires province, according to previous serological studies, Canicola, Sejroe and Ballum serogroups were the most reactive serogroups in human cases<a class="elsevierStyleCrossRef" href="#bib0080">7</a>.Leptospirosis is considered an endemic disease in Buenos Aires province, with human cases recorded annually from different cities in both rural and urban areas. The highest notification rate of human cases (single cases and multiple cases in outbreaks) is recorded mainly in the period of March-July of each year. Confirmed cases of leptospirosis predominantly correspond to male adults. In relation to the probable source of infection in the region, human cases are associated with contact with water sources, rodents and domestic animals, especially dogs<a class="elsevierStyleCrossRefs" href="#bib0070">5,7,8</a>.Buenos Aires province is currently divided into 12 Health Regions (HR), and is composed of 135 cities (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The Department of Rural Zoonoses (which is located Azul city) receives human clinical samples from seven HR (I, II, III, IV, VIII, IX and X); although occasionally some samples are referred from the other regions (V, VI, VII, XI and XII), with headquarters in San Martin, Lomas de Zamora, Moreno, Ensenada and La Matanza respectively. MAT is used in the diagnosis of the disease and for epidemiological studies (serological prevalence); this technique is considered the “gold standard” in the serological diagnosis of leptospirosis in human and animals<a class="elsevierStyleCrossRefs" href="#bib0050">1,2</a>. Although it is a highly specific test, its sensitivity depends on the days of evolution of the disease, being lower in the acute stage (first week). The dilution of the serum is kept in contact with an equal volume of a leptospiral suspension. MAT titers may be affected by the quality of the antigen suspensions and the strains used, and the significance of a titer in a single sample depends on residual titers due to past infections<a class="elsevierStyleCrossRef" href="#bib0060">3</a>. The aim of this study was to describe the variables that influence the delay in the serological confirmation of leptospirosis in human cases (period 2006–2014) in Buenos Aires province.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>Samples and epidemiological information from suspected cases of leptospirosis from Buenos Aires province are referred to the Leptospirosis Laboratory of the Department of Rural Zoonoses. A retrospective analytical study was conducted using epidemiological and serological data from confirmed human cases of leptospirosis in Buenos Aires province during the period 2006–2014. All confirmed human cases of leptospirosis were included in the notification form, and all the variables analyzed were recorded; confirmed human cases that did not have epidemiological data (date of onset of the disease, time of clinical sample collection for the diagnosis of the disease, date of admission to the reference laboratory and date of confirmation of the case) were excluded.MAT was performed using a panel of live strains of leptospires (Canicola, Hardjo, Hebdomadis, Pomona, Copenhageni, Pyrogenes and Wolffi serovars of Leptospira interrogans, Castellonis and Tarassovi serovars of Leptospira borgpetersenii, and Grippotyphosa serovars of Leptospira kirschneri) maintained on Ellinghausen–McCullough–Johnson–Harris medium (EMJH medium: Difco Laboratories, Detroit, Michigan, USA). For MAT, an initial dilution of sera of 1:25 was started, and the positive ones were diluted until a negative result was obtained. Any sample with an absence of 50% of free leptospires or agglutination thereof with respect to the control was considered to be positive. In the confirmation of human cases of the disease, the cross-reaction to different serogroups, the titers reached, the onset date of the clinical manifestations and the kinetics of antibodies from paired samples were taken into account. A confirmed case was defined as a titer of ≥1:200 for three or more serogroup, or when the serological conversion was observed in paired samples.With the epidemiological and serological diagnostic data obtained from 90/150 confirmed human cases of leptospirosis (period 2006–2014) by the Department of Rural Zoonoses, the following was analyzed:<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0030">•Days between:<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0035">∘The onset of illness (clinical manifestation) and date of serum sample collection for diagnosis (time of clinical suspicion).</li><li class="elsevierStyleListItem" id="lsti0040">∘Collection of the clinical sample and arrival at the reference laboratory.</li><li class="elsevierStyleListItem" id="lsti0045">∘The onset of the disease and serological confirmation of the case.</li></ul></li><li class="elsevierStyleListItem" id="lsti0050">•Detection of antibodies by MAT, number of reactive serogroups and titers reached.</li></ul>Analysis of the main components and the Kruskal–Wallis test was performed with the cases that required a sample and two samples separately using the INFOSTAT statistical package.In the 2006–2014 periods, the provincial reference laboratory received a diagnostic request for 2162 human suspected cases of leptospirosis from eleven health regions (HR IV, HR VIII and HR IX demanded 66.2% of the clinical samples for leptospirosis diagnosis). In 6.9% of the human cases (150/2162) it was possible to obtain serological confirmation by MAT; however, only in 90 of 150 confirmed human cases it was possible to obtain the information required for the analysis. With regard to the geographical distribution, the confirmed human cases were distributed in 22 cities of the province of Buenos Aires, belonging to the following health regions: HR IV (31/90), HR VIII (26/90), HR II (9/90), HR III (9/90), HR IX (8/90), HR I (5/90), HR X (1/90) and HR XI (1/90).Sixty-four percent of human cases could be confirmed by MAT with the first clinical sample, while the remaining 36% required a second sample for detection of serological conversion. Seventeen percent of the human cases (15/90) also required the serological diagnosis of other diseases with clinical and compatible epidemiology such as Hantavirus and the Argentine hemorrhagic fever disease.An average of 7.75 days (median: 8 days) elapsed between the onset of clinical manifestations and the sample collection time for the corresponding diagnosis (suspicion of disease); however, in 6.9% of human cases it was delayed between 15 and 20 days (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>A). Most of the samples (68.6%) reached the reference laboratory in about 10 days, 22.9% in about 20 days, and 8.6% in 21–27 days; with an average of 13.5 days and a median of 13 days (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>B).<elsevierMultimedia ident="fig0010"></elsevierMultimedia>Human cases were confirmed by MAT on an average of 21 days (range=6–65) from the onset of the first clinical signs (usually fever). With MAT, antibodies were detected on the fourth day after the onset of clinical manifestations (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>D). The cross-reaction between serogroups was evidenced from day 4 to day 40 of the course of the disease; on average, positive sera reacted with four serogroups (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>C). Ballum–Canicola was the most observed pattern, with titers ranging from 1:50 to 1:6400. The reactive serogroups used in MAT in positive human serum samples were Tarassovi, Canicola and Ballum.By analyzing the main components, we could explain the behavior of the variables both for the first samples (99.7%) and for the second ones (94.6%).In the first clinical samples a high correlation was observed between the variable “days between the onset of clinical signs and clinical sample collection” and the variable “days of detection of antibodies”. The time of confirmation of the human cases of leptospirosis was affected depending on the distance of the sanitary regions (from 5km to 450km) with the specific diagnostic laboratory (p=0.0009).The geographical distribution of confirmed human cases of leptospirosis, in addition to the high number of suspected cases and probable cases (which could not be confirmed by MAT), demonstrate that leptospirosis is endemic and underreported in the province of Buenos Aires. Clinical manifestations of human leptospirosis may be fever, jaundice, renal, hemorrhagic, meningeal and respiratory symptoms, and may cause death. The inclusion of Hantavirus and the Argentine hemorrhagic fever disease is common in the differential diagnostic (due to the clinical and epidemiological characteristics) in the region.Based on the number of suspected human cases of leptospirosis reported in the region, the confirmation rate by serology is very low; partly because the laboratory does not have a second clinical sample, only first samples with less than a week of evolution. Although the presence of antibodies was observed in sera from patients with less than seven days of disease evolution, and taking into account that the titers can persist for a long time, it would be necessary to rule out whether these antibodies corresponded to a past exposure, thus interfering with the current diagnosis. Another important aspect to avoid false negative results in MAT is the inclusion in the panel of all antigen serogroups circulating in the region.Serological confirmation of human cases was done on an average of 21 days after the onset of the illness (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). The arrival time of the clinical sample to the reference laboratory depended on the geographical location of the HR, the city or the health care center where the patient is hospitalized. In the case of HR I (located in the city of Bahía Blanca) and HR IX (located in the city of Azul), this variable did not influence the confirmation time. In addition to the distance (kilometers), in the health system of the Buenos Aires province there is no mechanism for collection and distribution of clinical samples from the health centers to the reference laboratory, being observed that 34% of the cases are delayed more than 10 days.<elsevierMultimedia ident="fig0015"></elsevierMultimedia>Another important aspect of the serological diagnosis was the cross-reactivity phenomenon (between two to eight serogroups), which was observed from day 4 of the disease until day 40, with antibody titers ranging from 1:50 to 1:6400. It was striking to observe (in seven patients) the presence of cross-reactivity with titer ≥1:800 from the fourth and fifth day; however, a possible error in the anamnesis and data record should be ruled out. The number of serogroups that cross-reacted decreased as the disease progressed. In the first 30 days, in 66% of sera a cross-reaction was observed for five serogroup on average. Of the 9 serogroups used as antigens in MAT, Ballum–Canicola was the most frequently observed pattern. Because the cross-reaction among serogroups can persist for more than 40 days, if it is desired to associate the antigenic response to the possible infectious serogroup, it will be necessary to obtain a serum sample after a few months, when the immune response becomes even more specific. However, canines and rodents in the region are considered potential risk factors for humans; this sometimes makes it possible to suspect the serogroups Canicola and Icterohaemorrhagiae as possible infectious agents.MAT is an important tool in the serological diagnosis of human leptospirosis in Buenos Aires province, allowing to confirm human cases in practically three weeks, and sometimes (64% of cases) with a single sample obtained seven or more days after the onset of the clinical manifestations. However, the serological techniques should be complemented with the polymerase chain reaction (PCR) and bacteriological tests (blood sample obtained in the first week of disease evolution) in the region. However, molecular testing is not available in restricted resource areas. By means of PCR, suspicious cases of the disease could be confirmed in the samples of patients within few days from the onset of clinical manifestation and when it is sometimes not possible to have a second clinical sample, mainly in fatal cases. We have observed that PCR has lower sensitivity than MAT in the acute period of the disease (1–7 days) when serum samples are used; however, this could be improved by using whole blood<a class="elsevierStyleCrossRef" href="#bib0075">6</a>. In a recent study, PCR was positive in serum samples from patients with a late course of the disease (more than 14 days), not agreeing with the accepted pathogenesis for leptospirosis<a class="elsevierStyleCrossRef" href="#bib0075">6</a>. In this work, real-time PCR reactions were used to detect Leptospira DNA, using LipL32-270F and LipL32-692R primers that amplify a 423-bp fragment, and Lepto F and Lepto R primers that generate an 87-bp amplicon from the DNA of Leptospira spp.<a class="elsevierStyleCrossRef" href="#bib0075">6</a> In some serum samples (7/14) we have observed positivity using primers that amplify fragments with less than 100bp in absence of amplification with primers that generate longer DNA fragments (423bp), which could be attributed to the high levels of degradation that this type of samples usually present when stored and transported from health centers, in many cases with deficient refrigeration. For this reason, for the performance of a correct molecular diagnosis, it is important to use primers that amplify fragments lower than 300-bp long to avoid false negative results due to the high DNA degradation of the sample. PCR is an important diagnostic tool and complementary to MAT. It is necessary to study more samples, improving the procedures used in our region and taking into account the difficulties of shipping and storage of the clinical materials.Furthermore, having a whole blood sample during the first week of the clinical course of the disease (prior to antibiotic therapy) would allow to attempt isolation and also to improve the sensitivity of the molecular diagnosis. Bacteriology is rarely used as a diagnostic method of human leptospirosis in the region, due to the need of a prolonged culture; however, this technique plays an important role in the epidemiology of the disease, providing information about the serotypes that are circulating in the region and their possible association with clinical manifestations in humans.The distance from the health centers to the reference laboratory was the most important variable that affected the time of confirmation of human leptospirosis cases, and the clinical samples took several days to reach it. The health system of Buenos Aires province should develop a mechanism for the collection and adequate distribution of clinical samples.Conflict of interestThere are no conflicts of interest to declare." 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The aim of the study was to describe the variables that influence the delay in the serological confirmation of leptospirosis in human cases (period 2006–2014) from Buenos Aires province. Sixty-four percent (64%) of cases could be confirmed by microscopic agglutination test (MAT) with the first sample. The time of confirmation of the human leptospirosis cases was on average 21 days from the onset of the first clinical signs, and varied depending on the distance of the different sanitary regions. The geographical distribution of the confirmed leptospirosis human cases, in addition to the high number of suspected cases and probable cases (which could not be confirmed by MAT), demonstrate that leptospirosis is endemic and underreported in Buenos Aires province, and that distance and lack of resources could be determinant factors of this situation." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "La leptospirosis se considera una enfermedad endémica en la provincia de Buenos Aires, con casos humanos registrados anualmente en áreas rurales y urbanas. El objetivo de este estudio fue describir las variables que influyen en el retraso de la confirmación serológica de la leptospirosis en humanos, a partir del análisis de los casos ocurridos en el período 2006-2014 en la provincia de Buenos Aires. El 64% de los casos fue confirmado por microaglutinación (MAT) con la primera muestra clínica. El tiempo de confirmación promedio fue de 21 días desde el inicio de los primeros signos clínicos; este valor se vio afectado por la distancia entre los centros de salud y los laboratorios de referencia en las distintas regiones sanitarias. La distribución geográfica de los casos confirmados de leptospirosis en humanos, además del alto número de casos sospechosos y probables (que no pudieron ser confirmados por MAT), demuestra que esta afección es endémica y se encuentra subregistrada en la provincia de Buenos Aires, y que la distancia y la falta de recursos serían factores determinantes de estas características." ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1129 "Ancho" => 1007 "Tamanyo" => 156352 ] ] "descripcion" => array:1 [ "en" => "Geographical distribution of the health regions in Buenos Aires province: HR I (Bahia Blanca), HR II (Pehuajó), HR III (Junín), HR IV (Pergamino), HR V (San Martin), HR VI (Lomas de Zamora), HR VII (Moreno), HR VIII (General Pueyrredón), HR IX (Azul), HR X (Chivilcoy), HR XI (Ensenada) and HR XII (La Matanza). 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Shah" 2 => "F.M.H. Ahmad" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Postgrad Med" "fecha" => "2005" "volumen" => "51" "paginaInicial" => "195" "paginaFinal" => "200" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16333192" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0055" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Interpretation of microscopic agglutination test for leptospirosis diagnosis and seroprevalence" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "C. Chirathaworn" 1 => "R. Inwattana" 2 => "Y. Poovorawan" 3 => "D. Suwancharoen" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Asian Pac J Trop Biomed" "fecha" => "2014" "volumen" => "4" "paginaInicial" => "162" "paginaFinal" => "164" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0060" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Leptospirosis serodiagnosis by the microscopic agglutination test" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "M.G.A. Goris" 1 => "R.A. Hartskeerl" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:3 [ "tituloSerie" => "Curr Protoc Microbiol" "fecha" => "2014" "volumen" => "32" ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0065" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Evaluación de un panel reducido de cepas de leptospiras para diagnóstico en humanos por micro aglutinación (MAT)" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:7 [ 0 => "P. Jacob" 1 => "M.F. Schemeling" 2 => "Y. Chiani" 3 => "N. Landolt" 4 => "E. Scialfa" 5 => "S. Fusco" 6 => "B. Vanasco" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:3 [ "tituloSerie" => "Salud Publica Mex" "fecha" => "2015" "volumen" => "57" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0070" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Brote de leptospirosis en bovinos y humanos en un tambo de Lincoln, provincia de Buenos Aires" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "A. Koval" 1 => "S. López" 2 => "G. Lagioia" 3 => "R. Bertino" 4 => "M. Romera" 5 => "E. Scialfa" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Vet Arg" "fecha" => "2017" "volumen" => "34" "paginaInicial" => "1" "paginaFinal" => "7" ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0075" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diagnóstico molecular y serológico de la leptospirosis humana en la provincia de Buenos Aires, Argentina" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "M. Recavarren" 1 => "E. Scialfa" 2 => "M. Rivero" 3 => "S. Quintana" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Rev Argent Zoonosis Enferm Infecc Emerg" "fecha" => "2014" "volumen" => "9" "paginaInicial" => "6" "paginaFinal" => "12" ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0080" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Actividades de vigilancia epidemiológica de la leptospirosis en el interior de la provincia de Buenos Aires" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:9 [ 0 => "E. Scialfa" 1 => "O. Gallicchio" 2 => "S. Grune" 3 => "M. Recabarren" 4 => "M. Rivero" 5 => "S. Quintana" 6 => "P. Aguirre" 7 => "D. San Anton" 8 => "B. Brihuega" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Rev Argent Zoonosis Enferm Infecc Emerg" "fecha" => "2017" "volumen" => "12" "paginaInicial" => "1" "paginaFinal" => "6" ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0085" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Brote de leptospirosis humana en trabajadores rurales de la localidad de Magdalena: posible asociación de los bovinos como fuente de infección" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "E. Scialfa" 1 => "O. Gallicchio" 2 => "S. Cerruti" 3 => "R. 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Tarabla" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.actatropica.2008.06.007" "Revista" => array:6 [ "tituloSerie" => "Acta Trop" "fecha" => "2008" "volumen" => "107" "paginaInicial" => "255" "paginaFinal" => "258" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18671932" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/03257541/0000005200000004/v1_202012180643/S0325754119301257/v1_202012180643/en/main.assets" "Apartado" => array:4 [ "identificador" => "37861" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Microbiología clínica y enfermedades infecciosas" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/03257541/0000005200000004/v1_202012180643/S0325754119301257/v1_202012180643/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0325754119301257?idApp=UINPBA00004N"]

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Test de microaglutinación: variables que afectan el tiempo de confirmación de los casos humanos de leptospirosis

Exequiel Scialfaa,

Corresponding author

escialfa@yahoo.com.ar

Corresponding author.

, Mariana Riverob,c, Sergio Morenoa, Marcela Ortiza, Fabricio Bongiornod

a Departamento de Zoonosis Rurales (Ministerio de Salud de la provincia de Buenos Aires), Azul, Provincia de Buenos Aires, Argentina

b Centro de Investigación Veterinaria de Tandil (CIVETAN-CONICET-CIC), Facultad de Ciencias Veterinarias, Universidad Nacional del Centro de la Provincia de Buenos Aires, Tandil, Provincia de Buenos Aires, Argentina

c Facultad de Ciencias, Veterinarias Universidad Nacional del Centro de la Provincia de Buenos Aires, (UNCPBA), Tandil, Provincia de Buenos Aires, Argentina

d Facultad de Agronomía, Universidad Nacional del Centro de la Provincia de Buenos Aires (UNCPBA), Azul, Provincia de Buenos Aires, Argentina

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          "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall"><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">&#8226;</span><p id="par0005" class="elsevierStylePara elsevierViewall">The use of the RHT significantly increased the frequency of HIV diagnosis&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">&#8226;</span><p id="par0010" class="elsevierStylePara elsevierViewall">Approximately one of three individuals had never tested for HIV previously&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">&#8226;</span><p id="par0015" class="elsevierStylePara elsevierViewall">No access to medical care and irregular condom use associated with no HIV testing&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">&#8226;</span><p id="par0020" class="elsevierStylePara elsevierViewall">Tendency toward a higher HIV prevalence in patients with no prior HIV testing&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">&#8226;</span><p id="par0025" class="elsevierStylePara elsevierViewall">Use of RHT slightly incremented the receipt of confirmatory results&#46;</p></li></ul></p></span>"
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    "titulo" => "Microscopic agglutination test&#58; Variables that affect the time of serological confirmation of human leptospirosis cases"
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          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">&#40;A&#41; Days elapsed between the onset of clinical manifestations and the collection of the first sample for the serological diagnosis of the disease&#46; &#40;B&#41; Days between the collection of the first clinical sample for serological diagnosis and admission at the specific diagnostic laboratory&#46; &#40;C&#41; Cross-reaction between serogroups used as antigens in MAT&#44; according to the days of the course of disease&#46; &#40;D&#41; Antibody titers for serogroups used as antigens in MAT&#44; according to the days of the course of disease&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0030" class="elsevierStylePara elsevierViewall">Leptospirosis is a widely recognized zoonosis &#40;caused by <span class="elsevierStyleItalic">Leptospira</span> spp&#46;&#41; with a worldwide distribution&#46; The incidence of the disease in the human and animal population is highly variable&#44; depending on the type of ecosystems &#40;urban and rural&#41;&#44; the variations in environmental conditions&#44; and the presence of the host<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">7</span></a>&#46; Although rodents and canines are considered the main sources of infection for humans&#44; other hosts such as cattle and swine have been associated with human cases of leptospirosis&#46; The infected animal excretes the microorganism in the urine&#44; intermittently and for a variable period of time&#44; &#40;depending on the animal species and serovar&#41;&#59; the survival of leptospires in the environment will depend on the environmental conditions &#40;temperature and humidity&#41; and the pH of the soil&#44; requiring a neutral to slightly alkaline pH&#46; Infections in humans occur through direct contact with the urine of infected animals or indirectly by contact with contaminated water&#46; In Argentina&#44; leptospirosis is an important public health concern due to the occurrence of human cases and outbreaks of disease<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">9</span></a>&#46; Buenos Aires and Santa Fe provinces have recorded the highest number of leptospirosis cases in Argentina&#44; due in part to the fact that these districts have diagnostic laboratories that allow to identify the cases&#46; Outbreaks in both humans and animals are usually related to floods&#44; periods of heavy rainfall and high humidity<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">7&#44;8</span></a>&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">To perform the microscopic agglutination test &#40;MAT&#41;&#44; the International Leptospirosis Society of the World Health Organization &#40;WHO-ILS&#41; suggests the use of 19 strains in the antigen panel&#46; However&#44; based on previous studies&#44; in order to expedite the diagnosis&#44; reduce costs and facilitate the management and maintenance of the panel used in the routine MAT&#44; most of the reference laboratories in Argentina use 10&#8211;12 of the 19 suggested strains<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">4</span></a>&#46; In a study carried out by Jacob et al&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">4</span></a> with samples from all over the country&#44; it was observed that the serogroups presumably infecting humans were&#58; Icterohaemorrhagiae &#40;31&#37;&#41;&#44; Pomona &#40;15&#37;&#41;&#44; Ballum &#40;14&#37;&#41;&#44; Canicola &#40;10&#37;&#41;&#44; Sejroe &#40;4&#37;&#41; and Tarassovi &#40;2&#37;&#41;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">4</span></a>&#46; However&#44; in Buenos Aires province&#44; according to previous serological studies&#44; Canicola&#44; Sejroe and Ballum serogroups were the most reactive serogroups in human cases<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">7</span></a>&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Leptospirosis is considered an endemic disease in Buenos Aires province&#44; with human cases recorded annually from different cities in both rural and urban areas&#46; The highest notification rate of human cases &#40;single cases and multiple cases in outbreaks&#41; is recorded mainly in the period of March-July of each year&#46; Confirmed cases of leptospirosis predominantly correspond to male adults&#46; In relation to the probable source of infection in the region&#44; human cases are associated with contact with water sources&#44; rodents and domestic animals&#44; especially dogs<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">5&#44;7&#44;8</span></a>&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Buenos Aires province is currently divided into 12 Health Regions &#40;HR&#41;&#44; and is composed of 135 cities &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; The Department of Rural Zoonoses &#40;which is located Azul city&#41; receives human clinical samples from seven HR &#40;I&#44; II&#44; III&#44; IV&#44; VIII&#44; IX and X&#41;&#59; although occasionally some samples are referred from the other regions &#40;V&#44; VI&#44; VII&#44; XI and XII&#41;&#44; with headquarters in San Martin&#44; Lomas de Zamora&#44; Moreno&#44; Ensenada and La Matanza respectively&#46; MAT is used in the diagnosis of the disease and for epidemiological studies &#40;serological prevalence&#41;&#59; this technique is considered the &#8220;gold standard&#8221; in the serological diagnosis of leptospirosis in human and animals<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">1&#44;2</span></a>&#46; Although it is a highly specific test&#44; its sensitivity depends on the days of evolution of the disease&#44; being lower in the acute stage &#40;first week&#41;&#46; The dilution of the serum is kept in contact with an equal volume of a leptospiral suspension&#46; MAT titers may be affected by the quality of the antigen suspensions and the strains used&#44; and the significance of a titer in a single sample depends on residual titers due to past infections<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">3</span></a>&#46; The aim of this study was to describe the variables that influence the delay in the serological confirmation of leptospirosis in human cases &#40;period 2006&#8211;2014&#41; in Buenos Aires province&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">Samples and epidemiological information from suspected cases of leptospirosis from Buenos Aires province are referred to the Leptospirosis Laboratory of the Department of Rural Zoonoses&#46; A retrospective analytical study was conducted using epidemiological and serological data from confirmed human cases of leptospirosis in Buenos Aires province during the period 2006&#8211;2014&#46; All confirmed human cases of leptospirosis were included in the notification form&#44; and all the variables analyzed were recorded&#59; confirmed human cases that did not have epidemiological data &#40;date of onset of the disease&#44; time of clinical sample collection for the diagnosis of the disease&#44; date of admission to the reference laboratory and date of confirmation of the case&#41; were excluded&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">MAT was performed using a panel of live strains of leptospires &#40;Canicola&#44; Hardjo&#44; Hebdomadis&#44; Pomona&#44; Copenhageni&#44; Pyrogenes and Wolffi serovars of <span class="elsevierStyleItalic">Leptospira interrogans</span>&#44; Castellonis and Tarassovi serovars of <span class="elsevierStyleItalic">Leptospira borgpetersenii</span>&#44; and Grippotyphosa serovars of <span class="elsevierStyleItalic">Leptospira kirschneri</span>&#41; maintained on Ellinghausen&#8211;McCullough&#8211;Johnson&#8211;Harris medium &#40;EMJH medium&#58; Difco Laboratories&#44; Detroit&#44; Michigan&#44; USA&#41;&#46; For MAT&#44; an initial dilution of sera of 1&#58;25 was started&#44; and the positive ones were diluted until a negative result was obtained&#46; Any sample with an absence of 50&#37; of free leptospires or agglutination thereof with respect to the control was considered to be positive&#46; In the confirmation of human cases of the disease&#44; the cross-reaction to different serogroups&#44; the titers reached&#44; the onset date of the clinical manifestations and the kinetics of antibodies from paired samples were taken into account&#46; A confirmed case was defined as a titer of &#8805;1&#58;200 for three or more serogroup&#44; or when the serological conversion was observed in paired samples&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">With the epidemiological and serological diagnostic data obtained from 90&#47;150 confirmed human cases of leptospirosis &#40;period 2006&#8211;2014&#41; by the Department of Rural Zoonoses&#44; the following was analyzed&#58;<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">&#8226;</span><p id="par0065" class="elsevierStylePara elsevierViewall">Days between&#58;<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">&#8728;</span><p id="par0070" class="elsevierStylePara elsevierViewall">The onset of illness &#40;clinical manifestation&#41; and date of serum sample collection for diagnosis &#40;time of clinical suspicion&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">&#8728;</span><p id="par0075" class="elsevierStylePara elsevierViewall">Collection of the clinical sample and arrival at the reference laboratory&#46;</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">&#8728;</span><p id="par0080" class="elsevierStylePara elsevierViewall">The onset of the disease and serological confirmation of the case&#46;</p></li></ul></p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">&#8226;</span><p id="par0085" class="elsevierStylePara elsevierViewall">Detection of antibodies by MAT&#44; number of reactive serogroups and titers reached&#46;</p></li></ul></p><p id="par0090" class="elsevierStylePara elsevierViewall">Analysis of the main components and the Kruskal&#8211;Wallis test was performed with the cases that required a sample and two samples separately using the INFOSTAT statistical package&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">In the 2006&#8211;2014 period<span class="elsevierStyleCrossOut">s</span>&#44; the provincial reference laboratory received a diagnostic request for 2162 human suspected cases of leptospirosis from eleven health regions &#40;HR IV&#44; HR VIII and HR IX demanded 66&#46;2&#37; of the clinical samples for leptospirosis diagnosis&#41;&#46; In 6&#46;9&#37; of the human cases &#40;150&#47;2162&#41; it was possible to obtain serological confirmation by MAT&#59; however&#44; only in 90 of 150 confirmed human cases it was possible to obtain the information required for the analysis&#46; With regard to the geographical distribution&#44; the confirmed human cases were distributed in 22 cities of the province of Buenos Aires&#44; belonging to the following health regions&#58; HR IV &#40;31&#47;90&#41;&#44; HR VIII &#40;26&#47;90&#41;&#44; HR II &#40;9&#47;90&#41;&#44; HR III &#40;9&#47;90&#41;&#44; HR IX &#40;8&#47;90&#41;&#44; HR I &#40;5&#47;90&#41;&#44; HR X &#40;1&#47;90&#41; and HR XI &#40;1&#47;90&#41;&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Sixty-four percent of human cases could be confirmed by MAT with the first clinical sample&#44; while the remaining 36&#37; required a second sample for detection of serological conversion&#46; Seventeen percent of the human cases &#40;15&#47;90&#41; also required the serological diagnosis of other diseases with clinical and compatible epidemiology such as <span class="elsevierStyleItalic">Hantavirus</span> and the Argentine hemorrhagic fever disease&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">An average of 7&#46;75 days &#40;median&#58; 8 days&#41; elapsed between the onset of clinical manifestations and the sample collection time for the corresponding diagnosis &#40;suspicion of disease&#41;&#59; however&#44; in 6&#46;9&#37; of human cases it was delayed between 15 and 20 days &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>A&#41;&#46; Most of the samples &#40;68&#46;6&#37;&#41; reached the reference laboratory in about 10 days&#44; 22&#46;9&#37; in about 20 days&#44; and 8&#46;6&#37; in 21&#8211;27 days&#59; with an average of 13&#46;5 days and a median of 13 days &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>B&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0110" class="elsevierStylePara elsevierViewall">Human cases were confirmed by MAT on an average of 21 days &#40;range<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>6&#8211;65&#41; from the onset of the first clinical signs &#40;usually fever&#41;&#46; With MAT&#44; antibodies were detected on the fourth day after the onset of clinical manifestations &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>D&#41;&#46; The cross-reaction between serogroups was evidenced from day 4 to day 40 of the course of the disease&#59; on average&#44; positive sera reacted with four serogroups &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>C&#41;&#46; Ballum&#8211;Canicola was the most observed pattern&#44; with titers ranging from 1&#58;50 to 1&#58;6400&#46; The reactive serogroups used in MAT in positive human serum samples were Tarassovi&#44; Canicola and Ballum&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">By analyzing the main components&#44; we could explain the behavior of the variables both for the first samples &#40;99&#46;7&#37;&#41; and for the second ones &#40;94&#46;6&#37;&#41;&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">In the first clinical samples a high correlation was observed between the variable &#8220;days between the onset of clinical signs and clinical sample collection&#8221; and the variable &#8220;days of detection of antibodies&#8221;&#46; The time of confirmation of the human cases of leptospirosis was affected depending on the distance of the sanitary regions &#40;from 5<span class="elsevierStyleHsp" style=""></span>km to 450<span class="elsevierStyleHsp" style=""></span>km&#41; with the specific diagnostic laboratory &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0009&#41;&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">The geographical distribution of confirmed human cases of leptospirosis&#44; in addition to the high number of suspected cases and probable cases &#40;which could not be confirmed by MAT&#41;&#44; demonstrate that leptospirosis is endemic and underreported in the province of Buenos Aires&#46; Clinical manifestations of human leptospirosis may be fever&#44; jaundice&#44; renal&#44; hemorrhagic&#44; meningeal and respiratory symptoms&#44; and may cause death&#46; The inclusion of <span class="elsevierStyleItalic">Hantavirus</span> and the Argentine hemorrhagic fever disease is common in the differential diagnostic &#40;due to the clinical and epidemiological characteristics&#41; in the region&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Based on the number of suspected human cases of leptospirosis reported in the region&#44; the confirmation rate by serology is very low&#59; partly because the laboratory does not have a second clinical sample&#44; only first samples with less than a week of evolution&#46; Although the presence of antibodies was observed in sera from patients with less than seven days of disease evolution&#44; and taking into account that the titers can persist for a long time&#44; it would be necessary to rule out whether these antibodies corresponded to a past exposure&#44; thus interfering with the current diagnosis&#46; Another important aspect to avoid false negative results in MAT is the inclusion in the panel of all antigen serogroups circulating in the region&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Serological confirmation of human cases was done on an average of 21 days after the onset of the illness &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46; The arrival time of the clinical sample to the reference laboratory depended on the geographical location of the HR&#44; the city or the health care center where the patient is hospitalized&#46; In the case of HR I &#40;located in the city of Bah&#237;a Blanca&#41; and HR IX &#40;located in the city of Azul&#41;&#44; this variable did not influence the confirmation time&#46; In addition to the distance &#40;kilometers&#41;&#44; in the health system of the Buenos Aires province there is no mechanism for collection and distribution of clinical samples from the health centers to the reference laboratory&#44; being observed that 34&#37; of the cases are delayed more than 10 days&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0140" class="elsevierStylePara elsevierViewall">Another important aspect of the serological diagnosis was the cross-reactivity phenomenon &#40;between two to eight serogroups&#41;&#44; which was observed from day 4 of the disease until day 40&#44; with antibody titers ranging from 1&#58;50 to 1&#58;6400&#46; It was striking to observe &#40;in seven patients&#41; the presence of cross-reactivity with titer &#8805;1&#58;800 from the fourth and fifth day&#59; however&#44; a possible error in the anamnesis and data record should be ruled out&#46; The number of serogroups that cross-reacted decreased as the disease progressed&#46; In the first 30 days&#44; in 66&#37; of sera a cross-reaction was observed for five serogroup on average&#46; Of the 9 serogroups used as antigens in MAT&#44; Ballum&#8211;Canicola was the most frequently observed pattern&#46; Because the cross-reaction among serogroups can persist for more than 40 days&#44; if it is desired to associate the antigenic response to the possible infectious serogroup&#44; it will be necessary to obtain a serum sample after a few months&#44; when the immune response becomes even more specific&#46; However&#44; canines and rodents in the region are considered potential risk factors for humans&#59; this sometimes makes it possible to suspect the serogroups Canicola and Icterohaemorrhagiae as possible infectious agents&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">MAT is an important tool in the serological diagnosis of human leptospirosis in Buenos Aires province&#44; allowing to confirm human cases in practically three weeks&#44; and sometimes &#40;64&#37; of cases&#41; with a single sample obtained seven or more days after the onset of the clinical manifestations&#46; However&#44; the serological techniques should be complemented with the polymerase chain reaction &#40;PCR&#41; and bacteriological tests &#40;blood sample obtained in the first week of disease evolution&#41; in the region&#46; However&#44; molecular testing is not available in restricted resource areas&#46; By means of PCR&#44; suspicious cases of the disease could be confirmed in the samples of patients within few days from the onset of clinical manifestation and when it is sometimes not possible to have a second clinical sample&#44; mainly in fatal cases&#46; We have observed that PCR has lower sensitivity than MAT in the acute period of the disease &#40;1&#8211;7 days&#41; when serum samples are used&#59; however&#44; this could be improved by using whole blood<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">6</span></a>&#46; In a recent study&#44; PCR was positive in serum samples from patients with a late course of the disease &#40;more than 14 days&#41;&#44; not agreeing with the accepted pathogenesis for leptospirosis<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">6</span></a>&#46; In this work&#44; real-time PCR reactions were used to detect <span class="elsevierStyleItalic">Leptospira</span> DNA&#44; using LipL32-270F and LipL32-692R primers that amplify a 423-bp fragment&#44; and Lepto F and Lepto R primers that generate an 87-bp amplicon from the DNA of <span class="elsevierStyleItalic">Leptospira</span> spp&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">6</span></a> In some serum samples &#40;7&#47;14&#41; we have observed positivity using primers that amplify fragments with less than 100<span class="elsevierStyleHsp" style=""></span>bp in absence of amplification with primers that generate longer DNA fragments &#40;423<span class="elsevierStyleHsp" style=""></span>bp&#41;&#44; which could be attributed to the high levels of degradation that this type of samples usually present when stored and transported from health centers&#44; in many cases with deficient refrigeration&#46; For this reason&#44; for the performance of a correct molecular diagnosis&#44; it is important to use primers that amplify fragments lower than 300-bp long to avoid false negative results due to the high DNA degradation of the sample&#46; PCR is an important diagnostic tool and complementary to MAT&#46; It is necessary to study more samples&#44; improving the procedures used in our region and taking into account the difficulties of shipping and storage of the clinical materials&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Furthermore&#44; having a whole blood sample during the first week of the clinical course of the disease &#40;prior to antibiotic therapy&#41; would allow to attempt isolation and also to improve the sensitivity of the molecular diagnosis&#46; Bacteriology is rarely used as a diagnostic method of human leptospirosis in the region&#44; due to the need of a prolonged culture&#59; however&#44; this technique plays an important role in the epidemiology of the disease&#44; providing information about the serotypes that are circulating in the region and their possible association with clinical manifestations in humans&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">The distance from the health centers to the reference laboratory was the most important variable that affected the time of confirmation of human leptospirosis cases&#44; and the clinical samples took several days to reach it&#46; The health system of Buenos Aires province should develop a mechanism for the collection and adequate distribution of clinical samples&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conflict of interest</span><p id="par0160" class="elsevierStylePara elsevierViewall">There are no conflicts of interest to declare&#46;</p></span></span>"
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      "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall"><ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">&#8226;</span><p id="par0005" class="elsevierStylePara elsevierViewall">64&#37; of cases are confirmed by MAT with the first clinical sample&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">&#8226;</span><p id="par0010" class="elsevierStylePara elsevierViewall">Human cases of leptospirosis are confirmed 21 days after the onset of clinical signs&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">&#8226;</span><p id="par0015" class="elsevierStylePara elsevierViewall">Ballum and Canicola were the most reactive serogroups&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">&#8226;</span><p id="par0020" class="elsevierStylePara elsevierViewall">The confirmation time depends on the distance of the health region from the reference laboratory&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">&#8226;</span><p id="par0025" class="elsevierStylePara elsevierViewall">The number of serogroups that cross-reacted decreased as the disease progressed&#46;</p></li></ul></p></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Leptospirosis is considered an endemic disease in Buenos Aires province&#44; Argentina&#44; with human cases reported annually from rural and urban areas&#46; The aim of the study was to describe the variables that influence the delay in the serological confirmation of leptospirosis in human cases &#40;period 2006&#8211;2014&#41; from Buenos Aires province&#46; Sixty-four percent &#40;64&#37;&#41; of cases could be confirmed by microscopic agglutination test &#40;MAT&#41; with the first sample&#46; The time of confirmation of the human leptospirosis cases was on average 21 days from the onset of the first clinical signs&#44; and varied depending on the distance of the different sanitary regions&#46; The geographical distribution of the confirmed leptospirosis human cases&#44; in addition to the high number of suspected cases and probable cases &#40;which could not be confirmed by MAT&#41;&#44; demonstrate that leptospirosis is endemic and underreported in Buenos Aires province&#44; and that distance and lack of resources could be determinant factors of this situation&#46;</p></span>"
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        "resumen" => "<span id="abst0015" class="elsevierStyleSection elsevierViewall"><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">La leptospirosis se considera una enfermedad end&#233;mica en la provincia de Buenos Aires&#44; con casos humanos registrados anualmente en &#225;reas rurales y urbanas&#46; El objetivo de este estudio fue describir las variables que influyen en el retraso de la confirmaci&#243;n serol&#243;gica de la leptospirosis en humanos&#44; a partir del an&#225;lisis de los casos ocurridos en el per&#237;odo 2006-2014 en la provincia de Buenos Aires&#46; El 64&#37; de los casos fue confirmado por microaglutinaci&#243;n &#40;MAT&#41; con la primera muestra cl&#237;nica&#46; El tiempo de confirmaci&#243;n promedio fue de 21 d&#237;as desde el inicio de los primeros signos cl&#237;nicos&#59; este valor se vio afectado por la distancia entre los centros de salud y los laboratorios de referencia en las distintas regiones sanitarias&#46; La distribuci&#243;n geogr&#225;fica de los casos confirmados de leptospirosis en humanos&#44; adem&#225;s del alto n&#250;mero de casos sospechosos y probables &#40;que no pudieron ser confirmados por MAT&#41;&#44; demuestra que esta afecci&#243;n es end&#233;mica y se encuentra subregistrada en la provincia de Buenos Aires&#44; y que la distancia y la falta de recursos ser&#237;an factores determinantes de estas caracter&#237;sticas&#46;</p></span>"
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          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Geographical distribution of the health regions in Buenos Aires province&#58; HR I &#40;Bahia Blanca&#41;&#44; HR II &#40;Pehuaj&#243;&#41;&#44; HR III &#40;Jun&#237;n&#41;&#44; HR IV &#40;Pergamino&#41;&#44; HR V &#40;San Martin&#41;&#44; HR VI &#40;Lomas de Zamora&#41;&#44; HR VII &#40;Moreno&#41;&#44; HR VIII &#40;General Pueyrred&#243;n&#41;&#44; HR IX &#40;Azul&#41;&#44; HR X &#40;Chivilcoy&#41;&#44; HR XI &#40;Ensenada&#41; and HR XII &#40;La Matanza&#41;&#46; The location of the provincial reference laboratory is indicated with a black star&#46;</p>"
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          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">&#40;A&#41; Days elapsed between the onset of clinical manifestations and the collection of the first sample for the serological diagnosis of the disease&#46; &#40;B&#41; Days between the collection of the first clinical sample for serological diagnosis and admission at the specific diagnostic laboratory&#46; &#40;C&#41; Cross-reaction between serogroups used as antigens in MAT&#44; according to the days of the course of disease&#46; &#40;D&#41; Antibody titers for serogroups used as antigens in MAT&#44; according to the days of the course of disease&#46;</p>"
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            0 => array:3 [
              "identificador" => "bib0050"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Laboratory diagnosis of leptospirosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "S&#46;N&#46; Ahmad"
                            1 => "S&#46; Shah"
                            2 => "F&#46;M&#46;H&#46; Ahmad"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Postgrad Med"
                        "fecha" => "2005"
                        "volumen" => "51"
                        "paginaInicial" => "195"
                        "paginaFinal" => "200"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16333192"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0055"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Interpretation of microscopic agglutination test for leptospirosis diagnosis and seroprevalence"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "C&#46; Chirathaworn"
                            1 => "R&#46; Inwattana"
                            2 => "Y&#46; Poovorawan"
                            3 => "D&#46; Suwancharoen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Asian Pac J Trop Biomed"
                        "fecha" => "2014"
                        "volumen" => "4"
                        "paginaInicial" => "162"
                        "paginaFinal" => "164"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0060"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Leptospirosis serodiagnosis by the microscopic agglutination test"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "M&#46;G&#46;A&#46; Goris"
                            1 => "R&#46;A&#46; Hartskeerl"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:3 [
                        "tituloSerie" => "Curr Protoc Microbiol"
                        "fecha" => "2014"
                        "volumen" => "32"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0065"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Evaluaci&#243;n de un panel reducido de cepas de leptospiras para diagn&#243;stico en humanos por micro aglutinaci&#243;n &#40;MAT&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:7 [
                            0 => "P&#46; Jacob"
                            1 => "M&#46;F&#46; Schemeling"
                            2 => "Y&#46; Chiani"
                            3 => "N&#46; Landolt"
                            4 => "E&#46; Scialfa"
                            5 => "S&#46; Fusco"
                            6 => "B&#46; Vanasco"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:3 [
                        "tituloSerie" => "Salud Publica Mex"
                        "fecha" => "2015"
                        "volumen" => "57"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0070"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Brote de leptospirosis en bovinos y humanos en un tambo de Lincoln&#44; provincia de Buenos Aires"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "A&#46; Koval"
                            1 => "S&#46; L&#243;pez"
                            2 => "G&#46; Lagioia"
                            3 => "R&#46; Bertino"
                            4 => "M&#46; Romera"
                            5 => "E&#46; Scialfa"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Vet Arg"
                        "fecha" => "2017"
                        "volumen" => "34"
                        "paginaInicial" => "1"
                        "paginaFinal" => "7"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0075"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Diagn&#243;stico molecular y serol&#243;gico de la leptospirosis humana en la provincia de Buenos Aires&#44; Argentina"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "M&#46; Recavarren"
                            1 => "E&#46; Scialfa"
                            2 => "M&#46; Rivero"
                            3 => "S&#46; Quintana"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Rev Argent Zoonosis Enferm Infecc Emerg"
                        "fecha" => "2014"
                        "volumen" => "9"
                        "paginaInicial" => "6"
                        "paginaFinal" => "12"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0080"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Actividades de vigilancia epidemiol&#243;gica de la leptospirosis en el interior de la provincia de Buenos Aires"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:9 [
                            0 => "E&#46; Scialfa"
                            1 => "O&#46; Gallicchio"
                            2 => "S&#46; Grune"
                            3 => "M&#46; Recabarren"
                            4 => "M&#46; Rivero"
                            5 => "S&#46; Quintana"
                            6 => "P&#46; Aguirre"
                            7 => "D&#46; San Anton"
                            8 => "B&#46; Brihuega"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Rev Argent Zoonosis Enferm Infecc Emerg"
                        "fecha" => "2017"
                        "volumen" => "12"
                        "paginaInicial" => "1"
                        "paginaFinal" => "6"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0085"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Brote de leptospirosis humana en trabajadores rurales de la localidad de Magdalena&#58; posible asociaci&#243;n de los bovinos como fuente de infecci&#243;n"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "E&#46; Scialfa"
                            1 => "O&#46; Gallicchio"
                            2 => "S&#46; Cerruti"
                            3 => "R&#46; Zungri"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Rev Colegio Vet Prov Bs As"
                        "fecha" => "2004"
                        "volumen" => "28"
                        "paginaInicial" => "53"
                        "paginaFinal" => "54"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0090"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical characteristics and risk factors of human leptospirosis in Argentina &#40;1999&#8211;2005&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "N&#46;B&#46; Vanasco"
                            1 => "M&#46;F&#46; Schmeling"
                            2 => "J&#46; Lottersberger"
                            3 => "F&#46; Costa"
                            4 => "A&#46;I&#46; Ko"
                            5 => "H&#46;O&#46; Tarabla"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.actatropica.2008.06.007"
                      "Revista" => array:6 [
                        "tituloSerie" => "Acta Trop"
                        "fecha" => "2008"
                        "volumen" => "107"
                        "paginaInicial" => "255"
                        "paginaFinal" => "258"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18671932"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
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Article information

ISSN: 03257541
Original language: English

DOI:10.1016/j.ram.2019.11.005

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Year/Month	Html	Pdf	Total

2024 November	3	0	3
2024 October	73	20	93
2024 September	125	28	153
2024 August	101	24	125
2024 July	80	21	101
2024 June	61	22	83
2024 May	51	26	77
2024 April	59	18	77
2024 March	82	14	96
2024 February	82	11	93
2024 January	85	5	90
2023 December	75	11	86
2023 November	94	11	105
2023 October	111	24	135
2023 September	86	8	94
2023 August	77	4	81
2023 July	83	6	89
2023 June	105	14	119
2023 May	139	7	146
2023 April	124	9	133
2023 March	63	7	70
2023 February	50	7	57
2023 January	36	9	45
2022 December	39	13	52
2022 November	41	12	53
2022 October	47	8	55
2022 September	47	33	80
2022 August	35	12	47
2022 July	36	9	45
2022 June	21	9	30
2022 May	31	26	57
2022 April	28	15	43
2022 March	43	12	55
2022 February	72	8	80
2022 January	53	10	63
2021 December	73	14	87
2021 November	70	19	89
2021 October	62	18	80
2021 September	38	18	56
2021 August	46	18	64
2021 July	39	13	52
2021 June	14	18	32
2021 May	16	24	40
2021 April	107	17	124
2021 March	74	34	108
2021 February	73	32	105
2021 January	60	19	79
2020 December	41	32	73
2020 November	16	17	33
2020 October	15	10	25
2020 September	16	9	25
2020 August	12	14	26
2020 July	10	5	15
2020 June	11	13	24
2020 May	7	11	18
2020 April	7	5	12
2020 March	11	15	26
2020 February	9	11	20
2020 January	1	2	3

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