Canine leproid granuloma caused by a member of the Mycobacterium tuberculosis complex.

Canine leproid granuloma (CLG) is a chronic form of dermatitis that has been associated with nontuberculous mycobacterial infections in Africa, Oceania, the Americas, and Europe. We report here a case of CLG associated with a member of the Mycobacterium tuberculosis complex (MTBC), which could be of public health concern. An 8-y-old pet dog developed 0.5-1-cm diameter, raised, firm, nonpruritic, alopecic, painless skin nodules on the external aspects of both pinnae. Histologic examination revealed severe pyogranulomatous dermatitis with intracellular Ziehl-Neelsen-positive bacilli that were immunoreactive by immunohistochemistry using a polyclonal primary antibody that recognizes tuberculous and nontuberculous Mycobacterium species. DNA extracted from formalin-fixed, paraffin-embedded skin sections was tested by a Mycobacterium genus-specific nested PCR assay targeting the 16S rRNA gene. BLAST sequence analysis of 214-bp and 178-bp amplicons showed 99.5% identity with members of the MTBC; however, the agent could not be identified at the species level. Although CLG has been associated traditionally with nontuberculous mycobacterial infections, the role of Mycobacterium spp. within the MTBC as a cause of this condition, and the role of dogs with CLG as possible sources of MTBC to other animals and humans, should not be disregarded given its zoonotic potential.

Diagnostic Investigation of 100 Cases of Abortion in Sheep in Uruguay: 2015-2021.

The aim of this work was to identify causes of abortion through laboratory investigations in sheep flocks in Uruguay. One hundred cases of abortion, comprising 58 fetuses, 36 fetuses with their placentas, and 6 placentas were investigated in 2015-2021. Cases were subjected to gross and microscopic pathologic examinations, and microbiological and serological testing for the identification of causes of abortion, including protozoal, bacterial, and viral pathogens. An etiologic diagnosis was determined in 46 (46%) cases, including 33 (33%) cases caused by infectious pathogens, as determined by the detection of a pathogen along with the identification of fetoplacental lesions attributable to the detected pathogen. Twenty-seven cases (27%) were caused by Toxoplasma gondii, 5 (5%) by Campylobacter fetus subspecies fetus, and 1 (1%) by an unidentified species of Campylobacter. Fourteen cases (14%) had inflammatory and/or necrotizing fetoplacental lesions compatible with an infectious etiology. Although the cause for these lesions was not clearly identified, T. gondii was detected in 4 of these cases, opportunistic bacteria (Bacillus licheniformis, Streptococcus sp.) were isolated in 2 cases, and bovine viral diarrhea virus 1 subtype i (BVDV-1i) was detected in another. Campylobacter jejuni was identified in 1 (1%) severely autolyzed, mummified fetus. BVDV-2b was identified incidentally in one fetus with an etiologic diagnosis of toxoplasmosis. Microscopic agglutination test revealed antibodies against ≥1 Leptospira serovars in 15/63 (23.8%) fetuses; however, Leptospira was not identified by a combination of qPCR, culture, fluorescent antibody testing nor immunohistochemistry. Neospora caninum, Chlamydia abortus, Chlamydia pecorum, Coxiella burnetii and border disease virus were not detected in any of the analyzed cases. Death was attributed to dystocia in 13 (13%) fetuses delivered by 8 sheep, mostly from one highly prolific flock. Congenital malformations including inferior prognathism, a focal hepatic cyst, and enterohepatic agenesis were identified in one fetus each, the latter being the only one considered incompatible with postnatal life. Toxoplasmosis, campylobacteriosis and dystocia were the main identified causes of fetal losses. Despite the relatively low overall success rate in establishing an etiologic diagnosis, a systematic laboratory workup in cases of abortion is of value to identify their causes and enables zoonotic pathogens surveillance.

Fiebre Q: revisión histórica de casos humanos en Uruguay. Abordaje desde la complementariedad entre las ciencias médicas y veterinarias / Q fever: historical review of human cases in Uruguay. A complementary approach from the medical and veterinarian sciences / Febre Q: revisão histórica de casos humanos no Uruguai. Abordagem a partir da complementaridade entre as ciências médicas e veterinárias

Resumen: La fiebre Q es una zoonosis distribuida mundialmente, causada por Coxiella burnetii. Los bovinos, ovinos y caprinos son la fuente más frecuente de infección en humanos, en los que la enfermedad es de notificación obligatoria ante el Ministerio de Salud Pública. Revisamos las publicaciones que describen casos de fiebre Q en humanos en Uruguay, con foco en sus características epidemiológicas, y discutimos las pruebas diagnósticas disponibles localmente. Se incluyeron nueve trabajos publicados e información del registro de enfermedades profesionales. Colectivamente fueron analizadas 2.715 personas con sospecha de fiebre Q entre 1956-2019, siendo 959 (35,3%) seropositivas. Los diagnósticos se basaron en serología, clínica y/o antecedentes de exposición laboral. Epidemiológicamente, el ganado o material proveniente del mismo fueron considerados las fuentes más probables de exposición en la mayoría de los casos. Según el ámbito de ocurrencia, no sistemáticamente reportado, los casos se registraron principalmente por exposición a ovinos y bovinos en frigoríficos o en la cadena cárnica (positivos/evaluados: 863/1540; seropositivos sintomáticos: 585); y en menor medida a bovinos lecheros (sector lácteo (positivos/evaluados:20/58; seropositivos sintomáticos: 17) y laboratorio diagnóstico (positivos/evaluados:2/4; seropositivos sintomáticos: 1)), o rumiantes silvestres (seropositivos/evaluados:25/117; seropositivos sintomáticos: 17). Hipertermia, cefaleas y sudoración fueron reportados. La inhalatoria fue asumida como la vía de infección en todos los casos. Actualmente no están disponibles localmente pruebas de PCR para detección de C. burnetii en humanos, siendo una limitante en el diagnóstico, particularmente en etapas tempranas. La colaboración interdisciplinaria de profesionales de salud humana y animal es esencial en el abordaje de esta zoonosis.

Summary: Q fever is a globally distributed zoonosis caused by the bacteria Coxiella burnetii. Bovines, sheep and goats are the most frequent source of infection in humans, and it is mandatory for the latter to report the disease to the Ministry of Public Health. We reviewed the literature describing cases of Q fever in humans in Uruguay, focusing on epidemiological characteristics, and we discussed the diagnostic tests locally available. Nine published studies were included in the review, as well as the information in the professional diseases registry. 2.715 people with a suspicion of Q fever were collectively analyzed between 1956-2019, 959 (55.3%) of them being seropositive. Diagnosis were based on serology, clinical examination and/or a history of exposure while working. Epidemiologically, the cattle or material originating in it were considered as the most probable sources of exposure in most cases. Depending on the context cases arose, which were not systematically reported, they were mainly caused by exposure to sheep and cows in meat processing plants or in the meat chain (positive/evaluated: 863/1540; seropositive or symptomatic: 585); and to a lesser extent dairy cattle (milk sector (positive/evaluated: 20/58; symptomatic seropositive: 17) and diagnostic laboratory (positive/evaluated: 2/4; symptomatic seropositive: 1)) or wild ruminants (positive/evaluated: 25/117; symptomatic seropositive: 17). Hyperthermia, headaches and sweating were reported. In all cases inhalation was adopted as the source of infection. Today, there are no PCR tests to detect C. burnetii in humans available locally, what constitutes a limitation to diagnosis, in particular in early stages. Interdisciplinary collaboration between animal and human health professionals is key to approach this zoonosis.

Resumo: A febre Q é uma zoonose mundial causada por Coxiella burnetii. Bovinos, ovinos e caprinos são a fonte mais frequente de infecção em humanos, nos quais a doença é de notificação compulsória ao Ministério da Saúde Pública. Revisamos as publicações que descrevem casos de febre Q em humanos no Uruguai, enfocando em suas características epidemiológicas, e discutimos os testes diagnósticos disponíveis localmente. Foram incluídos nove trabalhos publicados e informações do registro de doenças ocupacionais. Foram analisadas 2.715 pessoas com suspeita de febre Q entre 1956-2019, das quais 959 (35,3%) eram soropositivas. Os diagnósticos foram baseados na sorologia, sintomas e/ou história de exposição ocupacional. Do ponto de vista epidemiológico, o gado ou material preveniente de gado foram considerados as fontes mais prováveis de exposição na maioria dos casos. De acordo com o lugar de ocorrência, não notificado sistematicamente, os casos foram registrados principalmente por exposição a ovinos e bovinos em matadouros ou na cadeia da carne (positivos/avaliados: 863/1540; soropositivos sintomáticos: 585); e em menor proporção gado leiteiro (setor leiteiro (positivo/avaliado: 20/58; soropositivo sintomático: 17) e laboratório de diagnóstico (positivo/avaliado: 2/4; soropositivo sintomático: 1)), ou ruminantes silvestres (soropositivo/avaliado: 25/117; soropositivos sintomáticos: 17). Hipertermia, dores de cabeça e sudorese foram relatados. A inalação foi assumida como via de infecção em todos os casos. Atualmente, os testes de PCR para detecção de C. burnetii em humanos não estão disponíveis localmente, sendo uma limitação no diagnóstico, principalmente em estágios iniciais. A colaboração interdisciplinar de profissionais de saúde humana e animal é essencial no enfrentamento dessa zoonose.

Serological Evidence of Human Infection with Coxiella burnetii after Occupational Exposure to Aborting Cattle.

Cattle are broadly deemed a source of Coxiella burnetii; however, evidence reinforcing their role in human infection is scarce. Most published human Q fever outbreaks relate to exposure to small ruminants, notably goats. Anti-phase II C. burnetii IgG and IgM were measured by indirect fluorescent antibody tests in 27 farm and veterinary diagnostic laboratory workers to ascertain whether occupational exposure to cattle aborting due to C. burnetii was the probable source of exposure. Four serological profiles were identified on the basis of anti-phase II IgG and IgM titres. Profile 1, characterised by high IgM levels and concurrent, lower IgG titres (3/27; 11.1%); Profile 2, with both isotypes with IgG titres higher than IgM (2/27; 7.4%); Profile 3 with only IgG phase II (5/27; 18.5%); and Profile 4, in which neither IgM nor IgG were detected (17/27; 63.0%). Profiles 1 and 2 are suggestive of recent C. burnetii exposure, most likely 2.5-4.5 months before testing and, hence, during the window of exposure to the bovine abortions. Profile 3 suggested C. burnetii exposure that most likely predated the window of exposure to aborting cattle, while Profile 4 represented seronegative individuals and, hence, likely uninfected. This study formally linked human Q fever to exposure to C. burnetii infected cattle as a specific occupational hazard for farm and laboratory workers handling bovine aborted material.

Coxiella burnetii abortion in a dairy farm selling artisanal cheese directly to consumers and review of Q fever as a bovine abortifacient in South America and a human milk-borne disease.

Coxiella burnetii is a highly transmissible intracellular bacterium with a low infective dose that causes Q fever (coxiellosis), a notifiable zoonotic disease distributed worldwide. Livestock are the main source of C. burnetii transmission to humans, which occurs mostly through the aerogenous route. Although C. burnetii is a major abortifacient in small ruminants, it is less frequently diagnosed in aborting cattle. We report a case of C. burnetii abortion in a lactating Holstein cow from a dairy farm producing and selling artisanal cheese directly to consumers in Uruguay, and review the literature on coxiellosis as a bovine abortifacient in South America and as a milk-borne disease. The aborted cow had severe necrotizing placentitis with abundant intratrophoblastic and intralesional C. burnetii confirmed by immunohistochemistry and PCR. After primo-infection in cattle, C. burnetii remains latent in the lymph nodes and mammary glands, with milk being a significant and persistent excretion route. Viable C. burnetii has been found in unpasteurized milk and cheeses after several months of maturing. The risk of coxiellosis after the consumption of unpasteurized dairy products, including cheese, is not negligible. This report raises awareness on bovine coxiellosis as a potential food safety problem in on-farm raw cheese manufacturing and sales. The scant publications on abortive coxiellosis in cattle in South America suggest that the condition has probably gone underreported in all countries of this subcontinent except for Uruguay. Therefore, we also discuss the diagnostic criteria for laboratory-based confirmation of C. burnetii abortion in ruminants as a guideline for veterinary diagnosticians.

Molecular prevalence of Coxiella burnetii in bulk-tank milk from bovine dairy herds: Systematic review and meta-analysis.

Coxiella burnetii is an obligate intracellular zoonotic bacterium that causes Q fever. Ruminants, including cattle, are broadly known to be reservoirs for this bacterium. Since 2006, many research groups have evaluated the herd-level prevalence of C. burnetii in cattle by molecular techniques on composite milk samples. This study explored the global C. burnetii herd-level prevalence from studies done on bovine bulk-tank milk (BTM) samples using PCR-based analysis. Also, moderators were investigated to identify sources of heterogeneity. Databases (CAB Abstracts, Medline via Ovid, PubMed, Web of Science and Google Scholar) were searched for index articles on C. burnetii prevalence in BTM samples by PCR published between January-1973 and November-2018. Numerous studies (1054) were initially identified, from which seventeen original publications were included in the meta-analysis based on the pre-defined selection criteria. These studies comprised 4031 BTM samples from twelve countries. A random-effects model was used because of considerable heterogeneity (I 2 = 98%) to estimate the herd-level prevalence of C. burnetii as 37.0%(CI95%25.2-49.5%). The average herd size appeared to account for a high level of the heterogeneity. No other moderators (geographic location, gross national income or notification criteria for Q fever) seemed to be determinant. This systematic evaluation demonstrated a high molecular prevalence of C. burnetii in BTM samples both in European and non-European countries, evidencing a widespread herd-level circulation of this agent in bovine dairy farms around the world. Meta-regression showed herd size as the most relevant moderator with the odds of a BTM sample testing positive doubling with every unit increase.

Natural lymphatic ("atypical") actinobacillosis in cattle caused by Actinobacillus lignieresii.

Bovine actinobacillosis is typically characterized by pyogranulomatous glossitis (wooden tongue). The involvement of other tissues, generally the skin or lymph nodes, has been regarded as atypical or cutaneous. We describe herein 2 outbreaks of actinobacillosis affecting primarily the lymph nodes of the head and neck. The disease affected 40 of 540 lactating cows in a dairy herd, and 5 of 335 two-y-old steers in a beef herd. Multiple or single, occasionally ulcerated nodules were observed in the region of the mandible, neck, and shoulder, including the parotid, submandibular, retropharyngeal, and prescapular lymph nodes. The histologic lesions were multifocal pyogranulomatous lymphadenitis, dermatitis, and cellulitis with Splendore-Hoeppli material. One steer had an exophytic pyogranuloma in the gingiva and another died because of ruminal tympany secondary to oropharyngeal and esophageal obstruction by a pyogranulomatous mass. Actinobacillus lignieresii was isolated from the lesions and identified by amplification, sequencing, and analysis of the 16S ribosomal (r)DNA gene. Seven of 8 cows recovered after treatment with sodium iodide. Lymphatic actinobacillosis is a frequent disease in Uruguay, southern Brazil, and Argentina. Morbidity is 1-50%; mortality is <1%. A. lignieresii apparently penetrates the intact oral and pharyngeal mucosa, infecting primarily the regional lymph nodes. Later, lesions may extend to the subcutaneous tissue and the skin, causing ulceration. Affected cattle with draining pyogranulomas contaminate the environment, favoring disease transmission, and should be treated with sodium iodide or antibiotics and isolated from the herd in order to control the disease.