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Corynebacterium pseudotuberculosis is a gram-positive bacterium and is the etiologic agent of caseous lymphadenitis (CL) in small ruminants. This disease is characterized by the development of encapsulated granulomas in visceral and superficial lymph nodes, and its clinical treatment is refractory to antibiotic therapy. An important virulence factor of the Corynebacterium genus is the ability to produce biofilm; however, little is known about the characteristics of the biofilm produced by C. pseudotuberculosis and its resistance to antimicrobials. Silver nanoparticles (AgNPs) are considered as promising antimicrobial agents, and are known to have several advantages, such as a broad-spectrum activity, low resistance induction potential, and antibiofilm activity. Therefore, we evaluate herein the activity of AgNPs in C. pseudotuberculosis, through the determination of minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), antibiofilm activity, and visualization of AgNP-treated and AgNP-untreated biofilm through scanning electron microscopy. The AgNPs were able to completely inhibit bacterial growth and inactivate C. pseudotuberculosis at concentrations ranging from 0.08 to 0.312 mg/mL. The AgNPs reduced the formation of biofilm in reference strains and clinical isolates of C. pseudotuberculosis, with interference values greater than 80% at a concentration of 4 mg/mL, controlling the change between the planktonic and biofilm-associated forms, and preventing fixation and colonization. Scanning electron microscopy images showed a significant disruptive activity of AgNP on the consolidated biofilms. The results of this study demonstrate the potential of AgNPs as an effective therapeutic agent against CL.

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Lymphadenitis is a commonly occurring and contagious disease in guinea pigs caused by different pathogens, including Streptococcus sp., Staphylococcus sp., and Corynebacterium sp. This study aimed to characterize the bacteria isolated from pus extracted from abscessed mandibular lymph nodes of diseased guinea pigs in Ecuador in 2019 and evaluate the in vitro antibacterial activity of the total extracts of three plant species. Isolates were recovered from three diseased guinea pigs with Lymphadenitis on a farm in Imbabura, Ecuador province. The bacteria were characterized through microbiological, biochemical, and molecular tests as Streptococcus equi subsp. zooepidemicus. Furthermore, the susceptibility of S. equi subsp. zooepidemicus to three plant extracts belonging to the Asteraceae family, Acmella ciliata, Bidens andicola, and Gazania splendens collected in Ecuador, were assessed in vitro by the microdilution method. Our data indicate that all the evaluated extracts showed activity, with a Minimum Inhibitory Concentration (MIC) of 22.50 mg/mL for Acmella ciliata, 11.25 mg/mL for Bidens andicola, and 5.60 mg/mL for Gazania splendens. Bidens andicola extract showed the highest efficacy with a % inhibition of 63.90 at the highest tested concentration (45 mg/mL). This is the first report on the bioactivity of these plant species against S. equi subsp. zooepidemicus.

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Sporotrichosis is a mycotic infection of the cutaneous and subcutaneous tissues caused by Sporothrix spp. that can also cause extracutaneous manifestations. This study aimed to characterize cutaneous and extracutaneous sporotrichosis lesions in cats. Over 1 year, 102 cats rescued by the Zoonoses Control Center of Belo Horizonte, Brazil, euthanized with clinical suspicion of feline sporotrichosis were evaluated. After euthanasia, the animals were evaluated by macroscopic, cytological, histopathological, and immunohistochemistry (IHC) examinations; fungal culture; and polymerase chain reaction (PCR). Sporothrix infection was identified by at least one diagnostic technique in all cats (n = 102) evaluated by postmortem examination, including 26/28 cases (93%) evaluated by IHC, 66/90 cases (73%) evaluated by cytology, 70/102 cases (68.6%) evaluated by histopathology, and 62/74 cases (84%) evaluated by fungal culture. Two cats had positive results only by fungal culture. Cytology and histopathology examinations were effective in diagnosing sporotrichosis, although IHC was needed to confirm the diagnosis in cats with low fungal loads. Sporothrix brasiliensis was confirmed by the sequencing of 3 samples. Skin lesions were characterized mainly by pyogranulomatous to granulomatous dermatitis (frequently with subcutaneous inflammation) with different intensities of Sporothrix spp. yeast. Extracutaneous findings associated with sporotrichosis included rhinitis or rhinosinusitis, lymphadenitis, pneumonia, meningitis, periorchitis, conjunctivitis, and glossitis. Extracutaneous infections were observed in 74/102 cases, and a possible association between the chronicity of the disease and the higher pathogenicity of this fungal species in cats requires further investigation.

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OBJECTIVE: To outline the characteristics of Kikuchi-Fujimoto disease (KFD) in children and analyze factors associated with severe and recurring courses. METHODS: Electronic medical records of children histopathologically diagnosed with KFD at Seoul National University Bundang Hospital from March 2015 to April 2021 were retrospectively reviewed. RESULTS: A total of 114 cases (62 males) were identified. The mean patient age was 12.0 ± 3.5 years. Most patients came to medical attention with cervical lymph node enlargement (97.4%) and fever (85%); 62% had a high-grade fever (≥39°C). Prolonged fever (≥14 days) was seen in 44.3% and was associated with a high-grade fever (P = .004). Splenomegaly, oral ulcer, or rash was present in 10.5%, 9.6%, and 15.8%, respectively. Laboratory findings showed leukopenia, anemia, and thrombocytopenia in 74.1%, 49%, and 24%, respectively. Sixty percent of cases had a self-limited course. Antibiotics were initially prescribed in 20%. A corticosteroid was prescribed in 40% of patients and was associated with oral ulcer (P = .045) and anemia (P = .025). Twelve patients (10.5%) had a recurrence with a median interval of 19 months. No risk factor for recurrence was identified in multivariable analysis. Clinical characteristics of KFD were similar between our current and previous studies. However, antibiotics use decreased (P < .001); nonsteroidal anti-inflammatory drugs use increased (P < .001), and, although statistically not significant, corticosteroid treatment also increased. CONCLUSIONS: Over a span of 18 years, the clinical characteristics of KFD did not change. Patients presenting with high-grade fever, oral ulcer, or anemia may benefit from corticosteroid intervention. All patients should be monitored for recurrence.

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Caseous lymphadenitis (CLA), an infectious disease caused by Corynebacterium pseudotuberculosis in small ruminants, is highly prevalent worldwide. Economic losses have already been associated with the disease, and little is known about the host-pathogen relationship associated with the disease. The present study aimed to perform a metabolomic study of the C. pseudotuberculosis infection in goats. Serum samples were collected from a herd of 173 goats. The animals were classified as controls (not infected), asymptomatic (seropositives but without detectable CLA clinical signs), and symptomatic (seropositive animals presenting CLA lesions), according to microbiological isolation and immunodiagnosis. The serum samples were analyzed using nuclear magnetic resonance (1H-NMR), nuclear Overhauser effect spectroscopy (NOESY), and Carr-Purcell-Meiboom-Gill (CPMG) sequences. The NMR data were analyzed using chemometrics, and principal component analysis (PCA) and partial least square discriminant analysis (PLS-DA) were performed to discover specific biomarkers responsible for discrimination between the groups. A high dissemination of the infection by C. pseudotuberculosis was observed, being 74.57% asymptomatic and 11.56% symptomatic. In the evaluation of 62 serum samples by NMR, the techniques were satisfactory in the discrimination of the groups, being also complementary and mutually confirming, demonstrating possible biomarkers for the infection by the bacterium. Twenty metabolites of interest were identified by NOESY and 29 by CPMG, such as tryptophan, polyunsaturated fatty acids, formic acid, NAD+, and 3-hydroxybutyrate, opening promising possibilities for the use of these results in new therapeutic, immunodiagnosis, and immunoprophylactic tools, as well as for studies of the immune response against C. pseudotuberculosis. KEY POINTS: • Sixty-two samples from healthy, CLA asymptomatic, and symptomatic goats were screened • Twenty metabolites of interest were identified by NOESY and 29 by CPMG • 1H-NMR NOESY and CPMG were complementary and mutually confirming.

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Streptococcus zooepidemicus is an emerging zoonotic pathogen involved in septicemic infections in humans and livestock. Raising guinea pigs in South America is an important economic activity compared to raising them as pets in other countries. An outbreak of severe lymphadenitis was reported in guinea pigs from farms in the Andean region. S. zooepidemicus was isolated from multiple cervical and mandibular abscesses. Isolate was characterized by multilocus sequence typing and phylogenetic analysis. This is the first molecular characterization of a highly pathogenic strain, showing major important virulence factors such as the M-like protein genes szP and mlpZ, the fimbrial subunit protein gene fszF, and the protective antigen-like protein gene spaZ. Additionally, this guinea pig strain was phylogenetically related to equines but distant from zoonotic and pig isolates reported in other countries.

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Caseous lymphadenitis is a chronic contagious disease that causes economic losses worldwide. Treatments are ineffective, thus demonstrating the importance of vaccination. In this study, rNanH and rPknG proteins from Corynebacterium pseudotuberculosis were associated with saponin or aluminum hydroxide adjuvants. Three experimental groups (10 animals each) were immunized with sterile 0.9% saline solution (G1), rNanH + rPknG + Saponin (G2), rNanH + rPknG + Al(OH)3 (G3). The mice received two vaccine doses 21 days apart. Animals were challenged 21 days after the last immunization and evaluated for 50 days, with endpoint criteria applied when needed. The total IgG production levels of the experimental groups increased significantly on day 42 when compared to the control (p < 0.05). When tested against rNanH, G2 had a better rate of anti-rNanH antibodies compared to G3. In the anti-rPknG ELISA, the levels of total IgG, IgG1, and IgG2a antibodies were higher in G2. The vaccines generated partial protection, with 40% of the animals surviving the challenge. The association of recombinant NanH and PknG proteins led to promising protection rates in mice, and although using different adjuvants did not interfere with the survival rate, it influenced the immune response generated by the vaccine formulations.

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Caseous lymphadenitis is a well-known disease caused by Corynebacterium pseudotuberculosis affecting small ruminants with small significance to human health because of its minor zoonotic potential. In both cases, few treatment options are available and conventional antimicrobial therapy is commonly refractory due to development of pyogranulomatous reactions, bringing great interest in discovering novel therapeutics for more suitable approaches. Dideoxynucleotides presented antibacterial action against various bacteria but were never described for C. pseudotuberculosis. Hypothesizing the antimicrobial action of 2',3'-dideoxiadenosine (ddATP) against C. pseudotuberculosis, we performed for the first time an investigation of its minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) in the ATCC® 19,410 strain and a well-characterized clinical isolate of C. pseudotuberculosis. We also assessed potential synergism with penicillin. ddATP showed a growth delay effect for C. pseudotuberculosis at 2 µmol/mL and a MIC and MBC of 4 µmol/mL against the ATCC® 19,410 strain, but not for the clinical strain. An antimicrobial effect was observed when using concentrations lower than the MIC of ddATP associated with penicillin for both strains tested. Our data suggest the potential of nucleotide analogs, especially adenosine, and its combination with penicillin, as a possible novel treatment for C. pseudotuberculosis-induced infections, and contributes with knowledge regarding alternative drugs to treat C. pseudotuberculosis infections.

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This study aimed to characterize the production and management systems of white Morada Novasheep herds and to present data on the occurrence of caseous lymphadenitis (CLA) and clinical mastitis (CM) in a population maintained in a semi-arid region. Blood samples were collected from adult females from herds of the Brazilian northeastern region. The first venous blood sample was used for a complete blood examination. The second blood sample was used to detect the presence of anti-C. pseudotuberculosis specific antibodies. The production and management systems of the herds were characterized using questionnaires, divided into three blocks of indicators: Facilities; Characterization of the production system; Health management. Body weight and hematological results were submitted to an analysis of variance, on which the fixed effect was clinical diagnosis, and the principal component analysis was performed to determine the main variables. For CLA, three herds stood out as having the highest rates of seropositivity (85.71, 79.41 and 60.45%). The same herds also had the highest occurrences of CM (9.30, 8.82 and 5.71%). The main variables that showed differences according the diagnosis of both diseases were blood granulocytes and lymphocytes. The study made it possible to observe the relationship between the best sanitary practices and the lowest occurrence rates of both CLA and CM. The diseases present considerable occurrence in sheep populations

Este estudo teve como objetivo caracterizar os sistemas de produção e manejo de rebanhos de ovelhas Morada Nova da variedade branca e apresentar dados sobre a ocorrência de linfadenite caseosa (CLA) e mastite clínica (MC) em uma população mantida em região semiárida. Amostras de sangue foram coletadas de fêmeas adultas de rebanhos da região nordeste do Brasil. A primeira amostra de sangue venoso foi utilizada para um exame de sangue completo. A segunda amostra de sangue foi utilizada para detectar a presença de anticorpos anti-C. anticorpos específicos de pseudotuberculosis. Os sistemas de produção e manejo dos rebanhos foram caracterizados por meio de questionários, divididos em três blocos de indicadores: Instalações; Caracterização do sistema de produção; Gestão de saúde do rebanho. O peso corporal e os resultados hematológicos foram submetidos a uma análise de variância, na qual o efeito fixo foi o diagnóstico clínico, e a análise de componentes principais foi realizada para determinar as variáveis principais. Para o CLA, três rebanhos se destacaram com os maiores índices de soropositividade (85,71, 79,41 e 60,45%). Os mesmos rebanhos também apresentaram as maiores ocorrências de MC (9,30, 8,82 e 5,71%). As principais variáveis que apresentaram diferenças de acordo com o diagnóstico de ambas as doenças foram granulócitos e linfócitos. O estudo possibilitou observar a relação entre as melhores práticas sanitárias e as menores taxas de ocorrência tanto de CLA quanto de MC. As doenças apresentam ocorrência considerável nas populações de ovinos

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Mapping B and T cell epitopes constitutes an important action for peptide vaccine design. PLD and CP40 virulence factors of Corynebacterium pseudotuberculosis biovar ovis, a causal agent of Caseous Lymphadenitis, have been evaluated in a murine model as good candidates for vaccine development. Therefore, the goal of this work was to in silico analyze B and T cell epitopes of the PLD and CP40 proteins of a Mexican isolate of Corynebacterium pseudotuberculosis ovis. The Immune Epitope Data Base and Resource website was employed to predict the linear and conformational B-cell, T CD4+, and T CD8+ epitopes of PLD and CP40 proteins of Corynebacterium pseudotuberculosis ovis Mexican strain 2J-L. Fifty B cell epitopes for PLD 2J-L and forty-seven for CP40 2J-L were estimated. In addition, T CD4+ and CD8+ cell epitopes were predicted for PLD 2J-L (MHC I:16 epitopes, MHC II:10 epitopes) and CP40 2J-L (MHC I: 15 epitopes, MHC II: 13 epitopes). This study provides epitopes, paying particular attention to sequences selected by different predictor programs and overlap sequences as B and T cell epitopes. PLD 2J-L and CP40 2J-L protein epitopes may aid in the design of a promising peptide-based vaccine against Caseous Lymphadenitis in Mexico.

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Caseous lymphadenitis (CLA), an infectious disease caused by Corynebacterium pseudotuberculosis in goats and sheep, is highly prevalent worldwide and is characterized by economic losses in small ruminant production. Currently available techniques for clinical and laboratory diagnosis of the disease lack market availability and/or sensitivity, and therefore, infected animals can remain in the herd, serving as a source of infection for other animals. The present study aimed to verify hematological and clinical biochemistry changes in goats naturally infected by C. pseudotuberculosis. One hundred seventy-three Canindé goats were included in this study, from which blood samples and caseous lesions were collected. The animals were classified as uninfected, asymptomatic, and symptomatic according to microbiological isolation and serological assays. A high dissemination of the infection was observed in the herd, with 86.13% of positive animals, being 74.57% asymptomatic and 11.56% symptomatic. In the hemogram and clinical biochemistry analyses, the only statistical difference found was a higher level of serum urea in asymptomatic individuals than in non-infected animals. In addition, this study points to the possibility of chronic CLA being potentially reflected in hepatic and renal biochemical markers.

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Kikuchi-Fujimoto disease is self-limited, has a good prognosis, is diagnosed histopathologically, is more common on the Asian continent, in women and in those under the age of 40, and is usually diagnosed by exclusion. We present the case of a 20-year-old male patient with no significant medical history who consulted due to persistent fever, enlarged lymph nodes, gastrointestinal symptoms and weight loss. He debuted with pancytopenia, elevated acute phase reactants and altered liver function, and underwent an excisional lymph node biopsy, whose findings were compatible with Kikuchi-Fujimoto disease. He was treated symptomatically with NSAIDs and was followed up one month after discharge, at which time there was no evidence of recurrent fever or other additional symptoms. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2553).

La enfermedad de Kikuchi Fujimoto es autolimitada, de buen pronóstico, de diagnóstico histo-patológico, cuya incidencia es mayor en el continente asiático en mujeres, en menores de 40 años y usualmente es un diagnóstico de exclusión. Presentamos el caso de un paciente masculino de 20 años sin antecedentes patológicos, quien consultó por fiebre persistente, adenopatías, síntomas gastrointestinales y pérdida de peso; debutó con pancitopenia, aumento de reactantes de fase aguda, alteración de función hepática y en quien se le practicó biopsia excisional de ganglio, la cual evidenció hallazgos compatibles con la enfermedad de Kikuchi Fujimoto. Se hace manejo sintomático con AINES y se realiza control al mes de egreso, donde no hay evidencia de recurrencia de picos febriles u otros síntomas adicionales. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2553).

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Caseous lymphadenitis (CLA) is a disease that affects small ruminants, and the best way to prevent its spread on a herd is through immunoprophylaxis. Thus, we aimed to evaluate the MBP:PLD:CP40 fusion protein as a new CLA immunogen. The fusion protein was constructed by combining Corynebacterium pseudotuberculosis PLD and CP40 proteins with maltose-binding protein (MBP) as an intrinsic adjuvant. The antigenicity, allergenic potential, prediction of B epitopes, binding to MHC receptors, and docking on the Toll-Like 2 receptor were evaluated in silico. MBP:PLD:CP40 was expressed and purified. 40 BALB/c were divided into four groups (G1 - control, G2 - Saponin, G3 - MBP:PLD:CP40, and G4 - rPLD + rCP40). Total IgG, IgG1, and IgG2a were quantified, and the expressions of cytokines after splenocyte in vitro stimulation were assessed. Mice were challenged 42 days after the first immunization. The in silico analysis showed that MBP:PLD:CP40 has immunogenic potential, does not have allergic properties, and can dock on the TRL2 receptor. MBP:PLD:CP40 stimulated the production of IgG1 antibodies in a fivefold proportion to IgG2a, and TNF and IL-17 were significantly expressed in response to the antigenic stimuli. When rPLD and rCP40 were used together for immunization, they could induce IFN-γ and IL-12, but with no detectable antibody production. The G3 and G4 groups presented a survival of 57.14% and 42.86%, respectively, while the G1 and G2 mice were all dead 15 days after the challenge. MBP:PLD:CP40 partially protected the mice against C. pseudotuberculosis infection and can be considered a potential new CLA immunogen. KEY POINTS: • The fusion protein induced more IgG1 than IgG2a antibodies; • The fusion protein also induced the expression of the TNF and IL-17 cytokines; • Mice inoculated with MBP:PLD:CP40 presented a 57.14% survival.

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Corynebacterium pseudotuberculosis is the causative bacterial agent of the zoonotic disease known as caseous lymphadenitis, and it presents several mechanisms of response to host defenses, including the presence of virulence factors (VFs). The genomes of these bacteria have several polymorphic markers known as microsatellites, or simple sequence repeats (SSRs), that can be used to characterize the genome, to study possible polymorphisms existing among strains, and to verify the effects of such polymorphic markers in coding regions and regions associated with VFs. In this study, several SSRs were identified within coding regions throughout the 54 genomes of this species, revealing possible polymorphisms associated with coding regions that could be used as strain-specific or serotype-specific identifiers of C. pseudotuberculosis. The similarities associated with SSRs amongst the different serum variants of C. pseudotuberculosis, biovars equi and ovis, were also evaluated, and it was possible to identify SSRs located in coding regions responsible for a VF enrolled in pathogenesis known to mediate bacterial adherence (SpaH-type pili virulence factor). Phylogenetic analyses revealed that strains sharing SSR patterns, including the possible polymorphisms identified in the same position of gene-coding regions, were displayed by strains with a common ancestor, corroborating with the Genome Tree Report of the NCBI. Statistical analysis showed that the microsatellite groups belonging to equi and ovis biovars have a significance of 0.006 (p-value) in similarity, thus indicating them as good biomarker candidates for C. pseudotuberculosis.

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In this study, we investigated the capacity of the recombinant proteins SpaC, NanH, SodC, and PLD of C. pseudotuberculosis to trigger protective humoral and cellular immune responses against experimentally induced C. pseudotuberculosis infection in sheep. The antigens were produced in a heterologous system and were purified by affinity chromatography. Nine sheep were randomly divided into three groups, which were immunized as follows: Group 1 (control)-a mix of adjuvants composed of the inactivated T1 strain of C. pseudotuberculosis and commercial Montanide™ISA 61 VG (T1M); Group 2-rSpaC, rSodC, rPLD, and T1M; Group 3-rNanH, rSodC, rPLD, and T1M. All groups were immunized twice (on days 0 and 30) and challenged on day 90 of the experiment. Humoral and cellular immune responses were evaluated by Enzyme-Linked Immunosorbent Assay (ELISA) to quantify the IgG antibodies and interferon-gamma (IFN-y). Both vaccine formulations with recombinant proteins (groups 2 and 3) could induce a significant humoral IgG immune response in sheep. The proteins rSodC, rPLD, and rNanH were more immunogenic, inducing significant levels of IgG antibodies after the first dose of the vaccine or after the challenge, maintaining constant levels until the end of the experiment. However, it was not possible to differentiate between the cellular responses induced by the vaccines. This lack of effectiveness points toward the need for further studies to improve the efficacy of this subunit-based vaccine approach.

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Corynebacterium pseudotuberculosis is the etiological agent of caseous lymphadenitis. The main clinical sign of this disease is the development of granulomas, especially in small ruminants; however, the pathways that are involved in the formation and maintenance of these granulomas are unknown. Cytokines and chemokines are responsible for the migration of immune cells to specific sites and tissues; therefore, it is possible that chemokines participate in abscess formation. This study aimed to evaluate the induction of chemokine production by two C. pseudotuberculosis strains in a murine model. A highly pathogenic (VD57) and an attenuated (T1) strain of C. pseudotuberculosis, as well as somatic and secreted antigens derived from these strains, was used to stimulate murine splenocytes. Then, the concentrations of the chemokines CCL-2, CCL-3, CCL-4, and CCL-5 and the cytokines IL-1 and TNF were measured in the culture supernatants. The VD57 strain had a higher ability to stimulate the production of chemokines when compared to T1 strain, especially in the early stages of stimulation, which can have an impact on granuloma formation. The T1 lysate antigen was able to stimulate most of the chemokines studied herein when compared to the other antigenic fractions of both strains. These results indicate that C. pseudotuberculosis is a chemokine production inducer, and the bacterial strains differ in their induction pattern, a situation that can be related to the specific behavior of each strain.

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Caseous Lymphadenitis (CLA) is an infectious disease that affects small ruminants, and the bacterium Corynebacterium pseudotuberculosis is its etiologic agent. This disease presents a high morbidity and a great economic impact on goat farming, leading to reduced milk and meat production and reproductive losses. The available data about the influence of C. pseudotuberculosis on the reproductive system were obtained after experimental inoculations. In this way, this study aimed to evaluate the influence of the natural infection by C. pseudotuberculosis on the luteal function and serum progesterone (P4) levels in goats. Sixteen female goats were diagnosed for the presence of C. pseudotuberculosis specific antibodies and divided into 2 groups: CLA positive and negative animals. They were submitted to estrous synchronization, followed by controlled mating. Corpus luteum and serum levels of P4 were evaluated on the 7th and 20th days after mating (D7 and D20). The ultrasonographic results were not statistically different between the 2 groups, as well as serum P4 levels on D7. However, a significant increase in serum P4 levels on the CLA positive group was identified on D20, along with a significant correlation between C. pseudotuberculosis specific antibody production, and P4 serum levels. The result of this study indicates that the infection by C. pseudotuberculosis may influence the reproductive status of female goats through an enhanced production of progesterone.

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The aims of the present study were (i) to genotype Corynebacterium pseudotuberculosis, C. silvaticum, and C. auriscanis strains using enterobacterial repetitive intergenic consensus (ERIC-PCR), and (ii) to analyze the epidemiological relationships among isolates according to biovar (Equi and Ovis), species, host, and geographical origin of the C. pseudotuberculosis strains. Sixty-eight C. pseudotuberculosis, nine C. silvaticum, and one C. auriscanis, C. pseudotuberculosis ATCC® 19410™ strain and the attenuated C. pseudotuberculosis 1002 vaccinal strain were fingerprinted by ERIC 1+2-PCR. Field strains were isolated from various hosts (cattle, buffaloes, sheep, goats, horses, dogs, and pigs) in six countries (Mexico, Portugal, Brazil, Equatorial Guinea, Egypt, and Israel). High genetic diversity was found among the studied Corynebacterium spp. isolates, clustering in 24 genotypes with a Hunter & Gaston diversity index (HGDI) of 0.937. The minimal spanning tree of Corynebacterium spp. revealed three clonal complexes, each associated with one bacterial species. Twenty-two genotypes were observed among C. pseudotuberculosis isolates, with an HGDI of 0.934. Three major clonal complexes were formed at the minimal spanning tree, grouped around the geographic origin of C. pseudotuberculosis isolates. These results reinforce the high typeability, epidemiological concordance, and discriminatory power of ERIC-PCR as a consistent genotyping method for C. pseudotuberculosis, which could be useful as an epidemiological tool to control caseous lymphadenitis. Moreover, our results also indicate the potential of ERIC 1+2-PCR for the genotyping of other species of Corynebacterium other than C. pseudotuberculosis.

Os objetivos do presente estudo foram (i) genotipar amostras de Corynebacterium pseudotuberculosis, C. silvaticum e C. auriscanis usando Enterobacterial Repetitive Intergenic Consensus (ERIC-PCR), bem como (ii) analisar as relações epidemiológicas entre os isolados de acordo com biovar (Equi e Ovis), espécie, hospedeiro e origem geográfica das amostras de C. pseudotuberculosis. Sessenta e oito isolados de C. pseudotuberculosis, nove C. silvaticum, um C. auriscanis, C. pseudotuberculosis ATCC® 19410 ™ e a amostra vacinal atenuada C. pseudotuberculosis 1002 foram tipificadas por ERIC 1 + 2-PCR. As amostras de campo foram isoladas de diferentes hospedeiros (bovinos, búfalos, ovinos, caprinos, equinos, cães e suínos) em seis países (México, Portugal, Brasil, Guiné Equatorial, Egito e Israel). Uma alta diversidade genética foi observada entre os isolados de Corynebacterium spp., agrupados em vinte e quatro genótipos com um índice de diversidade Hunter & Gaston (HGDI) de 0,937. A análise da minimal spanning tree (MST) de Corynebacterium spp. revelou três complexos clonais, cada um associado a uma espécie bacteriana. Vinte e dois genótipos foram observados entre isolados de C. pseudotuberculosis, com um HGDI de 0,934. Na análise da MST, três grandes complexos clonais foram formados, agrupando-se em torno da origem geográfica dos isolados de C. pseudotuberculosis. Esses resultados reforçam a alta tipabilidade, concordância epidemiológica e poder discriminatório do ERIC-PCR como método consistente de genotipagem para C. pseudotuberculosis, podendo ser útil como ferramenta epidemiológica no controle da linfadenite caseosa. Além disso, os resultados também indicam o grande potencial de ERIC 1 + 2-PCR para genotipagem de espécies do gênero Corynebacterium além de C. pseudotuberculosis.

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ABSTRACT Objective: To describe clinical, diagnostic and therapeutic characteristics of the periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome. Data source: Literature review in the PubMed database by using specific descriptors to identify all articles published in the English language in the last three years; 38 articles were found. After performing selection of titles and abstract analysis, 13 out of the 38 articles were fully read. Relevant studies found in the references of the reviewed articles were also included. Data synthesis: The PFAPA syndrome (Periodic Fever, Aphthous Stomatitis, Pharyngitis and cervical Adenitis) is a medical condition grouped among the periodic fever syndromes. The etiology is uncertain, but possibly multifactorial, and its symptoms are accompanied by recurrent febrile episodes although weight and height development are preserved. It is a self-limiting disease of benign course with remission of two to three years without significant interference in the patient's overall development. Treatment consists of three pillars: interruption of febrile episodes, increase in the interval between episodes, and remission. Conclusions: Despite several attempts to establish more sensitive and specific criteria, the diagnosis of PFAPA syndrome is still clinical and reached by exclusion, based on the modified Marshall's criteria. The most common pharmacological options for treatment include prednisolone and betamethasone; colchicine may be used as prophylaxis, and surgical treatment with tonsillectomy can be considered in selected cases.

RESUMO Objetivo: Descrever as características clínicas, diagnósticas e de tratamento da síndrome de febre periódica, estomatite aftosa, faringite e adenite (PFAPA). Fontes de dados: Revisão de literatura na base de dados PubMed, feita por meio de descritores específicos para identificar todos os artigos publicados em língua inglesa nos últimos três anos. Dos 38 artigos encontrados, foram encaminhados para leitura integral 13 publicações após seleção de títulos e análise de abstract. Estudos relevantes encontrados nas referências dos artigos revisados também foram incluídos. Síntese dos dados: A PFAPA é traduzida do inglês periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis. Caracterizada por etiologia ainda incerta e possivelmente multifatorial, seus sintomas são acompanhados por episódios recorrentes de febre associados a um desenvolvimento pôndero-estatural preservado. É uma doença autolimitada de curso benigno, com remissão em dois a três anos, sem interferências significativas no desenvolvimento do paciente pediátrico. O tratamento consiste em três pilares: interrupção da crise febril, aumento do intervalo entre crises e remissão. Conclusões: Apesar de várias tentativas de estabelecer critérios atuais mais sensíveis e específicos, o diagnóstico da síndrome PFAPA ainda é clínico e de exclusão com base nos critérios de Marshall modificados. As opções farmacológicas mais utilizadas para o tratamento são a prednisolona e betametasona; colchicina pode ser utilizada como profilaxia e o tratamento cirúrgico com tonsilectomia pode ser considerado em casos selecionados.