A comparative analysis of two unrelated outbreaks in Latvia and Australia of acquired idiopathic megaesophagus in dogs fed two brands of commercial dry dog foods: 398 cases (2014-2018).

CASE DESCRIPTION: In Latvia in 2014, acquired idiopathic megaesophagus (AIME) was observed in increased numbers of dogs that consumed varieties of 1 brand of dog food. Within 2 years, 253 dogs were affected. In Australia in November 2017, 6 working dogs that consumed 1 diet of another brand of dog food developed AIME. In total, 145 Australian dogs were affected. CLINICAL FINDINGS: AIME was diagnosed predominantly in large-breed male dogs (> 25 kg [55 lb]). Regurgitation, weight loss, and occasionally signs consistent with aspiration pneumonia (coughing, dyspnea, or fever) were noted. Most Latvian dogs had mild to severe peripheral polyneuropathies as evidenced by laryngeal paralysis, dysphonia, weakness, and histopathologic findings consistent with distal axonopathy. In Australian dogs, peripheral polyneuropathies were not identified, and histopathologic findings suggested that the innervation of the esophagus and pharynx was disrupted locally, although limited samples were available. TREATMENT AND OUTCOME: Investigations in both countries included clinical, epidemiological, neuropathologic, and case-control studies. Strong associations between the dog foods and the presence of AIME were confirmed; however, toxicological analyses did not identify a root cause. In Latvia, the implicated dietary ingredients and formulations were unknown, whereas in Australia, extensive investigations were conducted into the food, its ingredients, the supply chain, and the manufacturing facilities, but a cause was not identified. CLINICAL RELEVANCE: A panel of international multidisciplinary experts concluded that the cause of AIME in both outbreaks was likely multifactorial, with the possibility of individualized sensitivities. Without a sentinel group, the outbreak in Australia may not have been recognized for months to years, as happened in Latvia. A better surveillance system for early identification of pet illnesses, including those associated with pet foods, is needed.

Analysis of the ex vivo and in vivo antiretroviral activity of gemcitabine.

Replication of retroviral and host genomes requires ribonucleotide reductase to convert rNTPs to dNTPs, which are then used as substrates for DNA synthesis. Inhibition of ribonucleotide reductase by hydroxyurea (HU) has been previously used to treat cancers as well as HIV. However, the use of HU as an antiretroviral is limited by its associated toxicities such as myelosuppression and hepatotoxicity. In this study, we examined the ribonucleotide reductase inhibitor, gemcitabine, both in cell culture and in C57Bl/6 mice infected with LP-BM5 murine leukemia virus (LP-BM5 MuLV, a murine AIDS model). Gemcitabine decreased infectivity of MuLV in cell culture with an EC50 in the low nanomolar range with no detectable cytotoxicity. Similarly, gemcitabine significantly decreased disease progression in mice infected with LP-BM5. Specifically, gemcitabine treatment decreased spleen size, plasma IgM, and provirus levels compared to LP-BM5 MuLV infected, untreated mice. Gemcitabine efficacy was observed at doses as low as 1 mg/kg/day in the absence of toxicity. Higher doses of gemcitabine (3 mg/kg/day and higher) were associated with toxicity as determined by a loss in body mass. In summary, our findings demonstrate that gemcitabine has antiretroviral activity ex vivo and in vivo in the LP-BM5 MuLV model. These observations together with a recent ex vivo study with HIV-1, suggest that gemcitabine has broad antiretroviral activity and could be particularly useful in vivo when used in combination drug therapy.