BackgroundNitazoxanide exerts antiviral activity in vitro and in vivo and anti-inflammatory effects, but its impact on patients hospitalized with COVID-19 pneumonia is uncertain.MethodsA multicentre, randomized, double-blind, placebo-controlled trial was conducted in 19 hospitals in Brazil. Hospitalized adult patients requiring supplemental oxygen, with COVID-19 symptoms and a chest computed tomography scan suggestive of viral pneumonia or positive RT-PCR test for COVID-19 were enrolled. Patients were randomized 1:1 to receive nitazoxanide (500 mg) or placebo, 3 times daily, for 5 days, and were followed for 14 days. The primary outcome was intensive care unit admission due to the need for invasive mechanical ventilation. Secondary outcomes included clinical improvement, hospital discharge, oxygen requirements, death, and adverse events within 14 days.ResultsOf the 498 patients, 405 (202 in the nitazoxanide group and 203 in the placebo group) were included in the analyses. Admission to the intensive care unit did not differ between the groups (hazard ratio [95% confidence interval], 0.68 [0.38–1.20], p = 0.179); death rates also did not differ. Nitazoxanide improved the clinical outcome (2.75 [2.21–3.43], p < 0.0001), time to hospital discharge (1.37 [1.11–1.71], p = 0.005), and reduced oxygen requirements (0.77 [0.64–0.94], p = 0.011). C-reactive protein, D-dimer, and ferritin levels were lower in the nitazoxanide group than the placebo group on day 7. No serious adverse events were observed.ConclusionsNitazoxanide, compared with placebo, did not prevent admission to the intensive care unit for patients hospitalized with COVID-19 pneumonia.Clinical Trial RegistrationBrazilian Registry of Clinical Trials (REBEC) RBR88bs9x; ClinicalTrials.gov, NCT04561219.

Toxoplasmosis, caused by Toxoplasma gondii, has traditionally been considered an important water and foodborne protozoonosis with important public health considerations. Although felids play a well-established role as definitive hosts, canine epidemiological involvement in the parasite’s life cycle remains questionable and controversial. The increasing closeness of the human-dog bond, particularly seen in urban settings, has been recognized as a historically unprecedented worldwide movement. Sharing daily lives in the same households, dogs may be exposed to similar associated risks of T. gondii infection as their owners. Thus, epidemiological assessment of the intra-domiciled environment, especially among socio-economically different human populations, may provide novel information regarding the actual role of dogs in animal and human toxoplasmosis. Despite spatial approaches being recently used for other water and foodborne diseases, no study has been conducted on the simultaneous spatial seroprevalence of both human and animal IgG anti-T. gondii antibodies in urban areas of major cities. Accordingly, the aim of the present study was to assess the seroprevalence and associated variables of Toxoplasma infection in owners and their domiciled dogs in Londrina, southern Brazil. Human and canine seroprevalence rates and variables associated with seroprevalence were investigated through representative random sampling among 564 households, which included 597 owners and 729 dogs. Overall, statistically significant differences between the seroprevalence of human and dog anti-T. gondii antibodies were found by Immunofluorescence Antibody Testing in 248/597 (41.54%) owners and 119/729 (16.32%) dogs. Through multiple analysis, significant concomitant variables for seropositivity of household individuals (people and dogs) were determined, including public sewer service, yard cleaning frequency, and having a dirty yard. Although no statistically significant multiple logistic model was observed among owners, univariate analysis detected associations with monthly income, soil contact, and occupation. Among dogs, the absence of other dogs and the absence of a dirty yard were concomitant significantly protective associated factors. Age differences between seropositive and seronegative individuals was significant only for human beings, with the median age of negative individuals significantly higher than positive individuals. Although no spatial clusters were identified for humans or residences, a significant cluster was identified for dogs. In conclusion, characteristics of urban toxoplasmosis may include significantly higher owner seroprevalence than their owned dogs, with canine seroprevalence directly associated with having more dogs and a dirty backyard, and spatial differences in both human and dog exposures. Although not a good indicator for human foodborne diseases, dogs may be a reliable sentinel for environmental infection. Moreover, such a holistic approach may provide crucial information for more focused prevention and...

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Leishmaniasis remains one of the world's most devastating neglected tropical diseases. It mainly affects developing countries, where it often co-exists with chronic malnutrition, one of the main risk factors for developing the disease. Few studies have been published, however, on the relationship between leishmaniasis progression and malnutrition. The present paper reports the influence of protein malnutrition on the immune response and visceral disease development in adult hamsters infected with Leishmania infantum fed either standard or low protein diets. The low protein diet induced severe malnutrition in these animals, and upon infection with L. infantum 33% had severe visceral leishmaniasis compared to only 8% of animals fed the standard diet. The infected, malnourished animals showed notable leukocyte depletion, mild specific antibody responses, impairment of lymphoproliferation, presence of parasites in blood (16.67% of the hamsters) and significant increase of the splenic parasite burden. Animals fed standard diet suffered agranulocytosis and monocytopenia, but showed stronger specific immune responses and had lower parasite loads than their malnourished counterparts. The present results show that protein malnutrition promotes visceral leishmaniasis and provide clues regarding the mechanisms underlying the impairment of the immune system.