Interim safety and immunogenicity results from an NDV-based COVID-19 vaccine phase I trial in Mexico.

There is still a need for safe, efficient, and low-cost coronavirus disease 2019 (COVID-19) vaccines that can stop transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we evaluated a vaccine candidate based on a live recombinant Newcastle disease virus (NDV) that expresses a stable version of the spike protein in infected cells as well as on the surface of the viral particle (AVX/COVID-12-HEXAPRO, also known as NDV-HXP-S). This vaccine candidate can be grown in embryonated eggs at a low cost, similar to influenza virus vaccines, and it can also be administered intranasally, potentially to induce mucosal immunity. We evaluated this vaccine candidate in prime-boost regimens via intramuscular, intranasal, or intranasal followed by intramuscular routes in an open-label non-randomized non-placebo-controlled phase I clinical trial in Mexico in 91 volunteers. The primary objective of the trial was to assess vaccine safety, and the secondary objective was to determine the immunogenicity of the different vaccine regimens. In the interim analysis reported here, the vaccine was found to be safe, and the higher doses tested were found to be immunogenic when given intramuscularly or intranasally followed by intramuscular administration, providing the basis for further clinical development of the vaccine candidate. The study is registered under ClinicalTrials.gov identifier NCT04871737.

Knowledge, attitudes, perceptions, and COVID-19 hesitancy in a large public university in Mexico city during the early vaccination rollout.

BACKGROUND: Vaccination against COVID-19 is a primary tool for controlling the pandemic. However, the spread of vaccine hesitancy constitutes a significant threat to reverse progress in preventing the disease. Studies conducted in Mexico have revealed that vaccination intention in Mexico among the general population ranges from 62 to 82%. OBJECTIVE: To know the prevalence of COVID-19 vaccine hesitancy and associated factors among academics, students, and administrative personnel of a public university in Mexico City. METHODS: We administered an online survey investigating sociodemographic aspects, knowledge, attitudes, practices, and acceptance/hesitancy regarding the COVID-19 vaccine. Using generalized linear Poisson models, we analyzed factors associated with vaccine hesitancy, defined as not intending to be vaccinated within the following six months or refusing vaccination. RESULTS: During May and June 2021, we studied 840 people, prevalence of vaccine hesitancy was 6%. Hesitancy was significantly associated with fear of adverse effects, distrust of physician's recommendations, lack of knowledge regarding handwashing, age younger than 40 years, refusal to use face masks, and not having received influenza vaccination during the two previous seasons. CONCLUSIONS: Vaccine hesitancy in this population is low. Furthermore, our results allowed us the identification of characteristics that can improve vaccine promotion.

Safety and immunogenicity of a live recombinant Newcastle disease virus-based COVID-19 vaccine (Patria) administered via the intramuscular or intranasal route: Interim results of a non-randomized open label phase I trial in Mexico.

There is still a need for safe, efficient and low-cost coronavirus disease 2019 (COVID-19) vaccines that can stop transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we evaluated a vaccine candidate based on a live recombinant Newcastle disease virus (NDV) that expresses a stable version of the spike protein in infected cells as well as on the surface of the viral particle (AVX/COVID-12-HEXAPRO, also known as NDV-HXP-S). This vaccine candidate can be grown in embryonated eggs at low cost similar to influenza virus vaccines and it can also be administered intranasally, potentially to induce mucosal immunity. We evaluated this vaccine candidate in prime-boost regimens via intramuscular, intranasal, or intranasal followed by intramuscular routes in an open label non-randomized non-placebo-controlled phase I clinical trial in Mexico in 91 volunteers. The primary objective of the trial was to assess vaccine safety and the secondary objective was to determine the immunogenicity of the different vaccine regimens. In the interim analysis reported here, the vaccine was found to be safe and the higher doses tested were found to be immunogenic when given intramuscularly or intranasally followed by intramuscular administration, providing the basis for further clinical development of the vaccine candidate. The study is registered under ClinicalTrials.gov identifier NCT04871737. Funding was provided by Avimex and CONACYT.

Sofosbuvir as a potential alternative to treat the SARS-CoV-2 epidemic.

As of today, there is no antiviral for the treatment of the SARS-CoV-2 infection, and the development of a vaccine might take several months or even years. The structural superposition of the hepatitis C virus polymerase bound to sofosbuvir, a nucleoside analog antiviral approved for hepatitis C virus infections, with the SARS-CoV polymerase shows that the residues that bind to the drug are present in the latter. Moreover, a multiple alignment of several SARS-CoV-2, SARS and MERS-related coronaviruses polymerases shows that these residues are conserved in all these viruses, opening the possibility to use sofosbuvir against these highly infectious pathogens.

A yellow flag on the horizon: The looming threat of yellow fever to North America.

OBJECTIVES: Yellow fever virus historically was a frequent threat to American and European coasts. Medical milestones such as the discovery of mosquitoes as vectors and subsequently an effective vaccine significantly reduced its incidence, in spite of which, thousands of cases of this deathly disease still occur regularly in Sub-Saharan Africa and the Amazonian basin in South America, which are usually not reported. An urban outbreak in Angola, consecutive years of increasing incidence near major Brazilian cities, and imported cases in China, South America and Europe, have brought this virus back to the global spotlight. The aim of this article is to underline that the preventive YFV measures, such as vaccination, need to be carefully revised in order to minimize the risks of new YFV outbreaks, especially in urban or immunologically vulnerable places. Furthermore, this article highlights the diverse factors that have favored the spread of other Aedes spp.-associated arboviral diseases like Dengue, Chikungunya and Zika, to northern latitudes causing epidemics in the United States and Europe, emphasizing the possibility that YFV might follow the path of these viruses unless enhanced surveillance and efficient control systems are urgently initiated.

Vaccination Status and Other Preventive Measures in Medical Schools. Big Needs and Opportunities.

BACKGROUND: Proper immunization and knowledge in infection prevention are key factors in protecting medical students. AIM OF THE STUDY: To describe the status on vaccination recommended for healthcare workers (HCW) and infection prevention knowledge. METHODS: We conducted a cross-sectional study on medical students at clinical years of medical school from a public University in Mexico. RESULTS: A total of 1,824 medical students responded the survey. One thousand ninety (59.8%) were women. Median age was 22 years. One thousand six hundred twenty-two (88.9%) knew their childhood immunization status. One thousand seventy-one (58.7%) were vaccinated against influenza for the 2016-2017 season; 1667 (91.4%) had been vaccinated at least once against hepatitis B, only 315 (18.9%) of vaccinated had received a full course with 3 doses. Most students were vaccinated against measles, mumps and rubella during childhood, 542 (29.7%) received an additional dosage during or after adolescence. Six hundred ninety-seven (38.2%) were concerned about vaccine's safety. A total of 1,431 (78.5%) properly identified situations were standard precautions are recommended, and 1540 (84.4%) had received some training on safe care delivery and personal protective equipment. Regarding needle-stick injuries, 1165 (63.9%) had been informed on the protocols to follow if an injury occurred. Three hundred forty-nine (19.1%) had suffered needle-stick injuries, only 125 (35.8%) received immediate medical attention at the point of care. CONCLUSIONS: Most medical students were not vaccinated as recommended, and they were not adequately instructed on safe practices for medical attention, nor advised or followed when a health-care related accident occurs. The results may be useful for implementation strategies on vaccination compliance and training on infection prevention.

Are RNA Viruses Candidate Agents for the Next Global Pandemic? A Review.

Pathogenic RNA viruses are potentially the most important group involved in zoonotic disease transmission, and they represent a challenge for global disease control. Their biological diversity and rapid adaptive rates have proved to be difficult to overcome and to anticipate by modern medical technology. Also, the anthropogenic change of natural ecosystems and the continuous population growth are driving increased rates of interspecies contacts and the interchange of pathogens that can develop into global pandemics. The combination of molecular, epidemiological, and ecological knowledge of RNA viruses is therefore essential towards the proper control of these emergent pathogens. This review outlines, throughout different levels of complexity, the problems posed by RNA viral diseases, covering some of the molecular mechanisms allowing them to adapt to new host species-and to novel pharmaceutical developments-up to the known ecological processes involved in zoonotic transmission.

Infection Control in Limited Resources Countries: Challenges and Priorities.

PURPOSE OF REVIEW: The purpose of this article is to review the current status of health care-related infections (HCRI) in low- and middle-income countries (LMIC). RECENT FINDINGS: HCRI in LMIC are being recognized as an important health problem globally. Despite important efforts, complex medical and non-medical problems prevail. The HCRI burden in LMIC is bigger than in developed countries, with prevalence between 5.7 and 19.1%. The impact on patients, their families, and the hospital systems is high, but has been largely underestimated. During the last 30 years, some progress has been made, with an increased awareness from the medical community and some very successful programs; however, there is a huge gap for improvement and success. In many health care facilities, there is a need of functional surveillance programs, continuous supply of antiseptics, safe water supply, personal protective equipment, essential antibiotics to treat infections, appropriate number of health care personnel trained in infection control, and appropriate health care infrastructure and political commitment.

Self-report of gingival problems and periodontitis in indigenous and non-indigenous populations in Chiapas, Mexico.

OBJECTIVE: To estimate the prevalence of self-reported gingival and periodontal conditions and their association with smoking, oral hygiene, indigenous origin, diabetes and location (urban or rural) in indigenous and non-indigenous adults in Chiapas, Mexico. METHODS: A cross-sectional study of 1,749 persons, ≥20 years of age, living in four rural and four urban marginal localities in Comitán (Chiapas, México). The variables investigated were: age; sex; indigenous origin; oral hygiene; halitosis; chewing ability; gingival conditions; periodontitis; smoking; alcoholism; diabetes; and location. Bivariate analysis and a logistic regression model were used to identify the association of periodontitis with the independent variables. RESULTS: In total, 762 (43.6%) indigenous and 987 (56.4%) non-indigenous persons were interviewed. Their mean age was 41 ± 14 years, 66.7% were women and 43.8% lived in rural locations. Gingival problems were reported by 68.5% and periodontitis by 8.7%. In total, 17.9% had used dental services during the previous year, 28.7% wore a removable partial or a complete dental prosthesis, 63.7% had lost at least one tooth, the prevalence of diabetes was 9.2% and the prevalence of smoking was 12.2%. The logistic regression model showed that age, diabetes and the interaction between rural location and indigenous origin were associated with the presence of periodontitis. CONCLUSIONS: Indigenous people living in rural areas are more likely to have periodontitis. It is necessary to promote oral health practices in indigenous and marginalised populations with a focus on community-oriented primary care.

Structural Analysis of Monomeric RNA-Dependent Polymerases: Evolutionary and Therapeutic Implications.

The crystal structures of monomeric RNA-dependent RNA polymerases and reverse transcriptases of more than 20 different viruses are available in the Protein Data Bank. They all share the characteristic right-hand shape of DNA- and RNA polymerases formed by the fingers, palm and thumb subdomains, and, in many cases, "fingertips" that extend from the fingers towards the thumb subdomain, giving the viral enzyme a closed right-hand appearance. Six conserved structural motifs that contain key residues for the proper functioning of the enzyme have been identified in all these RNA-dependent polymerases. These enzymes share a two divalent metal-ion mechanism of polymerization in which two conserved aspartate residues coordinate the interactions with the metal ions to catalyze the nucleotidyl transfer reaction. The recent availability of crystal structures of polymerases of the Orthomyxoviridae and Bunyaviridae families allowed us to make pairwise comparisons of the tertiary structures of polymerases belonging to the four main RNA viral groups, which has led to a phylogenetic tree in which single-stranded negative RNA viral polymerases have been included for the first time. This has also allowed us to use a homology-based structural prediction approach to develop a general three-dimensional model of the Ebola virus RNA-dependent RNA polymerase. Our model includes several of the conserved structural motifs and residues described in other viral RNA-dependent RNA polymerases that define the catalytic and highly conserved palm subdomain, as well as portions of the fingers and thumb subdomains. The results presented here help to understand the current use and apparent success of antivirals, i.e. Brincidofovir, Lamivudine and Favipiravir, originally aimed at other types of polymerases, to counteract the Ebola virus infection.

Specific Proteins in Nontuberculous Mycobacteria: New Potential Tools.

Nontuberculous mycobacteria (NTM) have been isolated from water, soil, air, food, protozoa, plants, animals, and humans. Although most NTM are saprophytes, approximately one-third of NTM have been associated with human diseases. In this study, we did a comparative proteomic analysis among five NTM strains isolated from several sources. There were different numbers of protein spots from M. gordonae (1,264), M. nonchromogenicum type I (894), M. nonchromogenicum type II (935), M. peregrinum (806), and M. scrofulaceum/Mycobacterium mantenii (1,486) strains, respectively. We identified 141 proteins common to all strains and specific proteins to each NTM strain. A total of 23 proteins were selected for its identification. Two of the common proteins identified (short-chain dehydrogenase/reductase SDR and diguanylate cyclase) did not align with M. tuberculosis complex protein sequences, which suggest that these proteins are found only in the NTM strains. Some of the proteins identified as common to all strains can be used as markers of NTM exposure and for the development of new diagnostic tools. Additionally, the specific proteins to NTM strains identified may represent potential candidates for the diagnosis of diseases caused by these mycobacteria.

Social Determinants and Their Impact on Visual Impairment in Southern Mexico.

PURPOSE: Visual impairment in disadvantaged populations in Mexico has been scarcely reported. We compared the prevalence of visual impairment and its associated risk factors in populations in rural compared to urban areas of the Mexican southern state of Chiapas. METHODS: In a population-based study, the prevalence of visual impairment in rural and urban areas of Comitan, Chiapas, was estimated. All eligible individuals aged ≥20 years living in rural areas were invited to participate; persons from urban areas were chosen randomly. Individuals were considered of indigenous (IND) origin either by self-report or if they spoke an IND language. Visual acuity (VA) and pinhole VA were measured using a tumbling E chart. VA was defined as normal (better than or equal to 20/60), moderate impairment (worse than 20/60 but better than or equal to 20/200), severe impairment (worse than 20/200 but better than or equal to 20/400), or blindness (worse than 20/400). RESULTS: Data on VA were obtained from 969 persons (610 rural, 359 urban) whose mean age was 43.3 years (standard deviation 15.6 years). Prevalence of moderate visual impairment was higher in rural (10.2%, 95% confidence interval, CI, 7.2-14.2%) than urban (3.9%, 95% CI 1.9-7.9%) areas (p < 0.001). Persons with moderate visual impairment were older and less educated (both p < 0.001). Rural individuals aged 50 years and older had 4.4 times (95% CI 1.8-11.3, p = 0.002) the likelihood of having moderate visual impairment compared with urban persons. CONCLUSION: Unfavorable socioeconomic conditions were associated with higher prevalence of moderate visual impairment in rural compared with urban populations in Mexico.

Low complexity regions (LCRs) contribute to the hypervariability of the HIV-1 gp120 protein.

Low complexity regions (LCRs) are sequences of nucleic acids or proteins defined by a compositional bias. Their occurrence has been confirmed in sequences of the three cellular lineages (Bacteria, Archaea and Eucarya), and has also been reported in viral genomes. We present here the results of a detailed computer analysis of the LCRs present in the HIV-1 glycoprotein 120 (gp120) encoded by the viral gene env. The analysis was performed using a sample of 3637 Env polyprotein sequences derived from 4117 completely sequenced and translated HIV-1 genomes available in public databases as of December 2012. We have identified 1229 LCRs located in four different regions of the gp120 protein that correspond to four of the five regions that have been identified as hypervariable (V1, V2, V4 and V5). The remaining 29 LCRs are found in the signal peptide and in the conserved regions C2, C3, C4 and C5. No LCR has been identified in the hypervariable region V3. The LCRs detected in the V1, V2, V4, and V5 hypervariable regions exhibit a high Asn content in their amino acid composition, which very likely correspond to glycosylation sites, which may contribute to the retroviral ability to avoid the immune system. In sharp contrast with what is observed in gp120 proteins lacking LCRs, the glycosylation sites present in LCRs tend to be clustered towards the center of the region forming well-defined islands. The results presented here suggest that LCRs represent a hitherto undescribed source of genomic variability in lentivirus, and that these repeats may represent an important source of antigenic variation in HIV-1 populations. The results reported here may exemplify the evolutionary processes that may have increased the size of primitive cellular RNA genomes and the role of LCRs as a source of raw material during the processes of evolutionary acquisition of new functions.

Weight gain and metabolic complications in preterm infants with nutritional support.

OBJECTIVE: To analyze the weight gain and to describe the metabolic complications in preterm newborns with nutritional support (NS) and to describe nutritional practices in the first month of hospitalization for 52 preterm newborns. MATERIAL AND METHODS: Descriptive and prospective study of preterm infants (30-36 gestational weeks), with birth weight > 1 kg, hospital stay > 12 days, without respiratory support or complications, conducted at a public hospital in Leon, Guanajuato, Mexico from January to November 2006. Weight, serum glucose, insulin, cholesterol, triglycerides, gamma-glutamyltransferase, creatinine, urea nitrogen, type of NS (parenteral PN, enteral EN, mixed MN), energy content, and macronutrient intake were measured weekly. To obtain representative data, nutritional practices were not altered by the study protocol. One way ANOVA and Wilcoxon tests were used in data analyses. RESULTS: Overall, 52 newborns were included, averaging 33 gestational weeks and 1,590 g of weight. The NS was started by the fourth day on average. Parenteral nutrition was the most frequent NS during the first 2 weeks (75%). Energy and macronutrient supply was 50% less than the recommended. Weight gain ranged from -100 to 130 g/week. Parenteral nutrition showed better weekly weight gain, followed by EN. The metabolic complication rate per person-day was greater for MN (0.56), than for EN (0.16) or PN (0.09). Routine surveillance of weight and metabolic complications was deficient. CONCLUSIONS: Late onset of NS, insufficient energy supply, and deficient surveillance were obstacles to weight gain and to prevent the metabolic complications in these newborns.

Domestic influenza vaccine production in Mexico: a state-owned and a multinational company working together for public health.

The Mexican Government developed a plan in 2004 for pandemic influenza preparedness that included local production of influenza vaccine. To achieve this, an agreement was concluded between Birmex - a state-owned vaccine manufacturer - and sanofi pasteur, a leading developer of vaccine technology. Under this agreement, sanofi pasteur will establish a facility in Mexico to produce antigen for up to 30 million doses of egg-based seasonal vaccine per year, and Birmex will build a facility to formulate, fill and package the inactivated split-virion influenza vaccine. As at November 2010, the sanofi pasteur facility has been completed and the Birmex plant is under construction. Most of the critical equipment has been purchased and is in the process of validation. In addition to intensive support from sanofi pasteur for the transfer of the technology, the project is supported by the Mexican Ministry of Health, complemented by Birmex's own budget and grants from the WHO developing country influenza technology transfer project.

Povidone-iodine against sodium hypochlorite as skin antiseptics in volunteers.

BACKGROUND: This study was conducted to compare the antiseptic efficacy of sodium hypochlorite of electrochemical production with that of povidone-iodine in human voluntaries. METHODS: Three areas of 25 cm(2) each were selected from the forearms; 1 was designated as control to determine the baseline bacterial count; and 2 more were selected to swab 10% povidone-iodine or 10% sodium hypochlorite. Every volunteer was studied on 3 separated occasions. Quantitative skin cultures were performed on agar plates containing a neutralizer. RESULTS: Forty-eight healthy subjects were enrolled for a total of 144 determinations for every antiseptic and control. The bacterial counts from the control areas showed a median of 1500 colony-forming units (CFU)/cm(2). For the areas treated with sodium hypochlorite, the median was 192 CFU/cm(2). For the areas treated with povidone-iodine, the median was 231 CFU/cm(2). When the colony counts for the areas treated with antiseptics were compared with those of the controls, the difference was significant (Kruskal-Wallis test (H) = 55.7, P < .001). The difference in counts between the areas treated with antiseptics was not significant (difference in z values <1960). CONCLUSION: The present study did not find differences in antiseptic action between 10% povidone iodine and 10% sodium hypochlorite.

Elevated prevalence of hepatitis B in Mexican hemodialysis patients. A multicentric survey.

BACKGROUND AND AIMS: The prevalence of hepatitis B virus (HBV) infection in patients on renal replacement has been reduced in developed countries, but information from developing nations is currently scarce and high prevalence rates are suspected. We undertook this study to analyze the prevalence of HBV infection and identify risk factors associated with it in a sample of Mexican hemodialysis patients. METHODS: A cross-sectional study was performed in patients on hemodialysis in Mexico. Adult patients from 10 hemodialysis centers were randomly selected. Patients answered a questionnaire for risk factors for HB infection and a blood sample was taken for HBsAg determination. RESULTS: We included 368 patients, 197 (53.5%) male, with a median age of 52 years (range: 18-93 years). In 26 patients HBsAg was positive with a prevalence of 7.1% (95% CI 4.4-9.7). Hepatitis C (HCV) was also tested, and 31 patients were positive with a prevalence of 8.4% (95% CI 5.5-11.2). Two patients (0.5%) were co-infected. Patients infected with HBV had been on hemodialysis longer (median time 50.5 months in HB positive vs. 34 months in HB negative; p = 0.005) and had history of more transfusions (median number of transfusions 5.5 vs 2; p < 0.009) compared with patients without HBV infection. CONCLUSIONS: The prevalence of HBV infection in patients on maintenance hemodialysis in Mexico is about 7%, 35 times higher compared with the general population (0.2%).