Negative log-binomial model with optimal robust variance to estimate the prevalence ratio, in cross-sectional population studies.

BACKGROUND: Cross-sectional studies are useful for the estimation of prevalence of a particular event with concerns in specific populations, as in the case of diseases or other public health interests. Most of these studies have been carried out with binary binomial logistic regression model which estimates OR values that could be overestimated due to the adjustment of the model. Thus, the selection of the best multivariate model for cross-sectional studies is a priority to control the overestimation of the associations. METHODS: We compared the precision of the estimates of the prevalence ratio (PR) of the negative Log-binomial model (NLB) with Mantel-Haenszel (MH) and the regression models Cox, Log-Poisson, Log-binomial, and the OR of the binary logistic regression in population-based cross-sectional studies. The prevalence from a previous cross-sectional study carried out in Colombia about the association of mental health disorders with the consumption of psychoactive substances (e.g., cocaine, marijuana, cigarette, alcohol and risk of consumption of psychoactive substances) were used. The precision of the point estimates of the PR was evaluated for the NLB model with robust variance estimates, controlled with confounding variables, and confidence interval of 95%. RESULTS: The NLB model adjusted with robust variance showed accuracy in the measurements of crude PRs, standard errors of estimate and its corresponding confidence intervals (95%CI) as well as a high precision of the PR estimate and standard errors of estimate after the adjustment of the model by grouped age compared with the MH PR estimate. Obtained PRs and 95%CI entre NLB y MH were: cocaine consumption (2.931,IC95%: 0.723-11.889 vs. 2.913, IC95%: 0.786-12.845), marijuana consumption (3.444, IC95%: 1.856-6.391 vs. 3.407, IC95%: 1.848, 6.281), cigarette smoking (2.175,IC95%: 1.493, 3.167 vs. 2.209, IC95%: 1.518-3.214), alcohol consumption (1.243,IC95%: 1.158-1.334 vs. 1.241, IC95%: 1.157-1.332), and risk of consumption of psychoactive substances (1.086, IC95%: 1.047-1.127 vs. 1.086, IC95%: 1.047, 1.126). The NLB model adjusted with robust variance showed mayor precision when increasing the prevalence, then the other models with robust variance with respect to MH. CONCLUSIONS: The NLB model with robust variance was shown as a powerful strategy for the estimation of PRs for cross-sectional population-based studies, as high precision levels were identified for point estimators, standard errors of estimate and its corresponding confidence intervals, after the adjustment of confounding variables. In addition, it does not represent convergence issues for high prevalence cases (as it occur with the Log-binomial model) and could be considered in cases of overdispersion and with greater precision and goodness of fit than the other models with robust variance, as it was shown with the data set of the cross-sectional study used in here.

In vitro Susceptibility of Human Cell Lines Infection by Bovine Leukemia Virus.

Evidence of the presence of bovine leukemia virus (BLV) in human beings and its association with breast cancer has been published in the literature, proposing it as a zoonotic infection. However, not enough evidence exists about transmission pathways nor biological mechanisms in human beings. This study was aimed at gathering experimental evidence about susceptibility of human cell lines to BLV infection. Malignant and non-malignant human cell lines were co-cultured with BLV-infected FLK cells using a cell-to-cell model of infection. Infected human cell lines were harvested and cultured for 3 to 6 months to determine stability of infection. BLV detection was performed through liquid-phase PCR and visualized through in situ PCR. Seven out of nine cell lines were susceptible to BLV infection as determined by at least one positive liquid-phase PCR result in the 3-month culture period. iSLK and MCF7 cell lines were able to produce a stable infection throughout the 3-month period, with both cytoplasmic and/or nuclear BLV-DNA visualized by IS-PCR. Our results support experimental evidence of BLV infection in humans by demonstrating the susceptibility of human cells to BLV infection, supporting the hypothesis of a natural transmission from cattle to humans.

Evidence of bovine leukemia virus circulating in sheep and buffaloes in Colombia: insights into multispecies infection.

Bovine leukemia virus (BLV) is the causative agent of leukemia/lymphoma in cattle. However, previous evidence has shown its presence in other species of livestock as well as in humans, suggesting that other species can be accidental hosts of the virus. In viral infections, receptors that are common to different animal species are proposed to be involved in cross-species infections. For BLV, AP3D1 has been proposed to be its receptor, and this protein is conserved in most mammalian species. In Colombia, BLV has been reported in cattle with high prevalence rates, but there has been no evidence of BLV infections in other animal species. In this study, we tested for the virus in sheep (n = 44) and buffaloes (n = 61) from different regions of Colombia by nested PCR, using peripheral blood samples collected from the animals. BLV was found in 25.7% of the animals tested (12 buffaloes and 15 sheep), and the results were confirmed by Sanger sequencing. In addition, to gain more information about the capacity of the virus to infect these species, the predicted interactions of AP3D1 of sheep and buffaloes with the BLV-gp51 protein were analyzed in silico. Conserved amino acids in the binding domains of the proteins were identified. The detection of BLV in sheep and buffaloes suggests circulation of the virus in multiple species, which could be involved in dissemination of the virus in mixed livestock production settings. Due to the presence of the virus in multiple species and the high prevalence rates observed, integrated prevention and control strategies in the livestock industry should be considered to decrease the spread of BLV.

Risk factor for breast cancer development under exposure to bovine leukemia virus in Colombian women: A case-control study.

Viruses have been implicated in cancer development in both humans and animals. The role of viruses in cancer is typically to initiate cellular transformation through cellular DNA damage, although specific mechanisms remain unknown. Silent and long-term viral infections need to be present, in order to initiate cancer disease. In efforts to establish a causative role of viruses, first is needed to demonstrate the strength and consistency of associations in different populations. The aim of this study was to determine the association of bovine leukemia virus (BLV), a causative agent of leukemia in cattle, with breast cancer and its biomarkers used as prognosis of the severity of the disease (Ki67, HER2, hormonal receptors) in Colombian women. An unmatched, observational case-control study was conducted among women undergoing breast surgery between 2016-2018. Malignant samples (n = 75) were considered as cases and benign samples (n = 83) as controls. Nested-liquid PCR, in-situ PCR and immunohistochemistry were used for viral detection in blood and breast tissues. For the risk assessment, only BLV positive samples from breast tissues were included in the analysis. BLV was higher in cases group (61.3%) compared with controls (48.2%), with a statistically significant association between the virus and breast cancer in the unconditional logistic regression (adjusted-OR = 2.450,95%CI:1.088-5.517, p = 0.031). In this study, BLV was found in both blood and breast tissues of participants and an association between breast cancer and the virus was confirmed in Colombia, as an intermediate risk factor.

Co-Circulation of Bovine Leukemia Virus Haplotypes among Humans, Animals, and Food Products: New Insights of Its Zoonotic Potential.

Bovine leukemia virus (BLV) is the causative agent of leukemia/lymphoma in cattle. It has been found in humans and cattle-derived food products. In humans, it is described as a potential risk factor for breast cancer development. However, the transmission path remains unclear. Here, a molecular epidemiology analysis was performed to identify signatures of genetic flux of BLV among humans, animals, and food products. Sequences obtained from these sources in Colombia were used (n = 183) and compared with reference sequences available in GenBank. Phylogenetic reconstruction was performed in IQ-TREE software with the maximum likelihood algorithm. Haplotype (hap) distribution among the population was carried out with a median-joining model in Network5.0. Recombination events were inferred using SplitsTree4 software. In the phylogenetic analysis, no specific branches were identified for the Colombian sequences or for the different sources. A total of 31 haps were found, with Hap 1, 4, 5 and 7 being shared among the three sources of the study. Reticulation events among the different sources were also detected during the recombination analysis. These results show new insights about the zoonotic potential of BLV, showing evidence of genetic flux between cattle and humans. Prevention and control strategies should be considered to avoid viral dissemination as part of the One Health program policies.