Background/Objectives: Following previous successful Phase I clinical trials conducted in men and women in a non-endemic area for schistosomiasis in Brazil, the Sm14 vaccine was evaluated in an endemic region in Senegal. We report successful clinical trials in adults (Phase IIa) and school children (Phase IIb), respectively, of a Schistosoma mansoni 14 kDa fatty acid-binding protein (Sm14) vaccine + a glucopyranosyl lipid A (GLA-SE) adjuvant. Methods: Participants were evaluated based on clinical assessments, laboratory tests (including hematologic and biochemical analyses of renal and hepatic functions), and immunological parameters (humoral and cellular responses) up to 12 months after the first vaccination dose in the Phase IIa trial and after 120 days in the Phase IIb trial. Results: The results showed strong immunogenic responses and good tolerance in both adults and children, with no major adverse effects. Importantly, significant increases in Sm14-specific total IgG (IgG1 and IgG3) were observed as early as 30 days after the first vaccination, with high titres remaining at least 120 days afterwards. Sm14-specific total IgG serum levels were also significantly enhanced in adults and in both infected and non-infected, vaccinated children and elicited robust cytokine responses with increased TNFα, IFN-γ, and IL-2 profiles. Conclusions: Overall, the Sm14+GLA-SE vaccine is safe and highly immunogenic, with a clearly protective potential against schistosomiasis, supporting progression to the next Phase III clinical trials.
BACKGROUND:Chagas disease is a globally important chronic systemic parasitic infection caused by Trypanosoma cruzi.AIM:To determine the prevalence of antibodies against T cruzi in pregnant women from the state of Morelos, México.METHODS:1,620 sera from pregnant women were analyzed using two serological tests: ELISAc (native crude antigen) and ELISAr (recombinant, non-native antigen). Reactive samples were subsequently analyzed by indirect hemagglutination (IHA). Two detection approaches were used, in parallel (reactive samples by any method are positive) and serial (samples confirmed by IHA are positive). Sociodemographic and health factors associated with the presence of antibodies against T cruzi were evaluated using 95% odds ratios.RESULTS:A seroprevalence of 4.87% was obtained with parallel diagnosis and 0.43% in series. From the parallel results, the women who were attended at the general hospitals of Tetecala and Jojutla had respectively 2.2 and 2.0 times greater chance of presenting antibodies against T cruzi compared to the women who were attended at the General Hospital of Cuautla.CONCLUSION:The prevalence of antibodies against T cruzi in pregnant women from the state of Morelos fluctuated between 0.43 and 4.87%, depending on the antigen and the approach used. It is necessary to continue with the surveillance of the seroprevalence of antibodies against T cruzi in pregnant women from the state of Morelos, Mexico, using the techniques with the highest sensitivity and specificity available.
Chagas disease is a globally important chronic systemic parasitic infection caused by Trypanosoma cruzi.To determine the prevalence of antibodies against T cruzi in pregnant women from the state of Morelos, México.1,620 sera from pregnant women were analyzed using two serological tests: ELISAc (native crude antigen) and ELISAr (recombinant, non-native antigen). Reactive samples were subsequently analyzed by indirect hemagglutination (IHA). Two detection approaches were used, in parallel (reactive samples by any method are positive) and serial (samples confirmed by IHA are positive). Sociodemographic and health factors associated with the presence of antibodies against T cruzi were evaluated using 95% odds ratios.A seroprevalence of 4.87% was obtained with parallel diagnosis and 0.43% in series. From the parallel results, the women who were attended at the general hospitals of Tetecala and Jojutla had respectively 2.2 and 2.0 times greater chance of presenting antibodies against T cruzi compared to the women who were attended at the General Hospital of Cuautla.The prevalence of antibodies against T cruzi in pregnant women from the state of Morelos fluctuated between 0.43 and 4.87%, depending on the antigen and the approach used. It is necessary to continue with the surveillance of the seroprevalence of antibodies against T cruzi in pregnant women from the state of Morelos, Mexico, using the techniques with the highest sensitivity and specificity available.
We report the successful closure of Phase I clinical trials, comprising Phases Ia and Ib, of the vaccine candidate against human schistosomiasis: the Schistosoma mansoni 14 kDa fatty acid-binding protein (Sm14) + glucopyranosyl lipid A in squalene emulsion (GLA-SE). Shown here are the results of Phase Ib, an open, non-placebo-controlled, standardized-dose immunization trial involving 10 healthy 18–49-year-old women. Fifty micrograms of the Sm14 protein plus 10 µg GLA-SE per dose was given intramuscularly thrice at 30-day intervals. Participants were assessed clinically, biochemically, and immunologically for up to 120 days. In preambular experiments involving vaccinated pregnant female rabbits, we did not find any toxicological features in either the offspring or mothers, and the vaccine induced adaptive immunity in the animals. In women, no adverse events were observed, and vaccination induced high titers of anti-Sm14 serum IgG antibody production. Vaccination also elicited robust cytokine responses, with increased TNFα, IFNγ, and IL-2 profiles in all vaccinees on days 90 and 120. The completion of Phase I clinical trials, which were performed to the highest standards set by Good Clinical Research Practice (GCP) standards, and preclinical data in pregnant rabbits enabled the vaccine candidate to proceed to Phase II clinical trials in endemic areas.
The causes of the broad spectrum of severity in COVID-19 are unknown. A protective effect through humoral immunity from previous infections by viruses of the SARS-CoV-2 family could explain a mild form of this disease. This study aimed to address whether the presence of antibodies against human seasonal coronaviruses (HCoVs) could prevent severe manifestations of COVID-19. A cross-sectional study was carried out in 165 participants. The presence of pre-existent antibodies against the seasonal HCoV-OC43, HCoV-HKU1, HCoV-229E, and HCoV-NL63 were detected. From all of the seasonal HCoVs studied, it was only found that being seropositive to HCoV-229E presented an association (p = 0.012) with developing mild clinical symptoms of COVID-19 or being asymptomatic. Multinomial regression analysis showed that being seropositive to HCoV-229E is associated with mild or moderate clinical symptoms for COVID-19. Statistical analysis also showed that being female is associated with being asymptomatic for SARS-CoV-2 infection or developing mild COVID-19. A subgroup analysis taking only seropositive to HCoV-229E revealed that females are more likely to develop asymptomatic SARS-CoV-2 infection (OR = 27.242, 95% CI 2.092–354.706, p = 0.012). Our results suggest that previous infections by HCoV-229E could prevent more serious clinical manifestations of COVID-19, but these are not the only variables that influence this event.
Antibody-mediated immune response plays an important role in protection against reinfection. In the case of SARS-CoV-2 infection, the maximum duration of antibody response is still unknown. In this work, the generation of neutralizing antibodies (NAbs) and IgG antibodies against the S1 subunit (S1 IgG ) of SARS-CoV-2 and their possible duration were determined through decay models. 132 participants with SARS-CoV-2 infection were classified according to the severity of the disease. Seroconversion and persistence of S1 IgG antibodies and NAbs were determined by ELISA, samples were taken at two different times post-infection and duration of those antibodies was estimated using Linear Mixed Models (LMMs). The highest amount of S1 IgGs antibodies was associated with age (41 years or older), greater severity of COVID-19 and male gender. NAbs production was associated with the same variables, except for age. The percentage of NAbs decay is higher in the asymptomatic group (P = 0.033), while in S1 IgG antibodies decay, no statistical difference was found between the 4 severity groups. An exponential decay model was built by using a LMM and similarly, two dispersion regions where constructed. The duration of S1 IgG antibodies was 744 days (668–781) for first region and 744 days (453–1231) for the second. Regarding NAbs, an adaptative LMM was used to model a logistic function, determining a duration of 267 days (215–347). Humoral immunity to SARS-CoV-2 infection depends on the severity of the disease, gender and age. This immune response could be long-lasting as for other coronaviruses.
En esta comunicación especial de la revista Salud Pública de México se hace una breve descripción de la situación de la nueva patología causada por el nuevo coronavirus a la que la OMS ha denominado Covid-19. Se hace mención de los casos ocurridos en China continental y en el resto del mundo. Del mismo modo, se enfatiza el arduo trabajo que el gobierno de China y otros países están realizando para contener la epidemia. También se hace mención del papel que están desempeñando la OMS y otras organizaciones internacionales en las acciones de prevención y control de la enfermedad.
In this special communication of Salud Pública de México, a brief description of the main events of the new pathology (WHO has named as Covid-19) caused by coronavirus is discussed. The cases of Covid-19 occurred in China and the rest of the world are mentioned. At the same time is emphasized the effort that China and other countries around the world are making to contain the epidemic. Also, highlights the role that WHO and other international organizations are playing to prevent and control the epidemic.
In this special communication, a brief description is made of the main events of the new pathology (that WHO has named Covid-19) caused by coronavirus. The cases of Covid-19 occurred in mainland China and the rest of the world are mentioned. It is also emphasized the effort that China and other countries around the world are making to contain the epidemic. Also, it highlights the role that WHO and other international organizations are playing to prevent and control the epidemic.
This study aimed to assess and compare myocardical electrical and extracellular matrix remodeling in patients with heart failure (HF) with preserved ejection fraction (HFpEF) and with heart failure with reduced ejection fraction (HFrEF) using a contemporary multimodality approach. We recruited 47 individuals presenting HF (22 females, 25 males), NYHA classes II-III, stratified according to LVEF in HFpEF (n=23) and HFrEF (n=24). They underwent cardiac MRI (CMRI) including T1-mapping, echocardiography for global longitudinal strain (GLS), cardiopulmonary exercise test (CPET), cardiac sympathetic imaging with mIBG and biomarkers. Results show native-T1 and extracellular volume fraction (ECV) were not different between groups. The mIBG derived heart-to-mediastinum ratio (HMR) were reduced in both groups. Considering the entire cohort, as well as the HFrEF subgroup separately, ECV was inversely associated to HMR and to adjusted VO2 max, and positively associated to NT-proBNP, US-Troponin and to GLS. Considering the HFpEF subgroup separately, only ECV and GLS association remained significant. The study highlights that similar extracellular matrix remodeling, assessed by ECV, between both subgroups confirms diffuse fibrosis as part of the HFpEF cardiac phenotype, which may partially explain its unfavorable prognosis and limited response to anti-remodeling therapies.
There is an increasing incidence of allergic contact dermatitis to corticosteroids. However, this diagnosis is being undetected or misdiagnosed, since topical corticosteroids are the first line treatment for inflammatory skin disorders.
Background Aedes aegypti and Aedes albopictus are the main mosquito species responsible for dengue virus (DENV) transmission to humans in the tropical and subtropical regions of the world. The role of vertical transmission in the epidemiology of dengue and the maintenance of this arbovirus in nature during interepidemic periods remain poorly understood, and DENV vertical transmission could sustain the existence of virus reservoirs within Aedes populations. Methods Between April 2011 and October 2012, we monitored vertical transmission of DENV in Ae. aegypti and Ae. albopictus in 9 cities of 4 Mexican states. Aedes eggs were collected in ovitraps, then adults were reared under laboratory conditions and their heads were used to infect C6/36 cells. The presence of flavivirus was detected by immunofluorescence assays (IFA), and DENV infection was confirmed by RT-PCR. Results About 96% of reared adults were Ae. aegypti and 4.0% were Ae. albopictus. No infection was detected in Ae. albopictus, whereas 54 of 713 (7.8%) of Ae. aegypti pools tested positive. A minimum infection rate (MIR) of 2.52 per 1000 mosquitoes was estimated for Ae. aegypti. DENV-1, DENV-2 & DENV-3 serotypes were detected even during interepidemic periods. Conclusions This study reports the evidence of vertical transmission of dengue virus with viral isolation and molecular confirmation in Ae. aegypti eggs collected in four endemic regions of Central and Southern Mexico. Vertical transmission may play a role as a reservoir mechanism during mosquito dormancy in interepidemic periods but with minor participation in transmission during epidemic periods.
Expression vectors for industrial production should be stable and allow tight control of protein synthesis. This is necessary to ensure plasmid transmission to daughter cells in order to achieve a stable population capable of synthesizing high amounts of the target protein. A high-copy-number plasmid, pAE, was previously used for laboratory-scale production of recombinant human granulocyte colony-stimulating factor (rhG-CSF) and the Schistosoma mansoni fatty acid binding protein (rSm14), but it was unstable for large-scale production. Therefore, here we evaluated a new expression vector derived from pAE, pAR-KanI, which combines two plasmid replication strategies: a high-copy plasmid pUC origin of replication as pAE, and a par locus sequence derived from pSC101, which is typical of low copy plasmids, for rhG-CSF and rSm14 production in Escherichia coli. Clones bearing these constructs were cultivated in two complex media (2YT and auto-induction) and both yielded higher-than-95% resistant colonies, before and after induction, either with or without antibiotics. In 2YT medium, we obtained 244 μg/mL of rSm14, 181 μg/mL and 392 μg/mL for rhG-CSF, with and without glucose, respectively. In auto-induction medium without antibiotics, 147 μg/mL of rSm14 and 162 μg/mL of rhG-CSF were obtained. The new vector presented high stability for the production of both recombinant proteins in complex media in Escherichia coli, even in the absence of antibiotics, making the pAR-KanI a promising vector for industrial production of recombinant proteins.
The objective of this work was to evaluate the initial development of yellow passion fruit, as a function of the method of extracting the mucilage of the seeds (washing in water, fermentation in water and fermentation in water + sugar) and substrates (carbonized rice husk, coconut fiber and vermiculite). The completely randomized design with nine treatments and five replicates, with 50 seeds was used, in a 3 x 3 factorial arrangement (three mucilage extraction methods and three types of substrates). After 56 days of sowing, the following variables were evaluated seedling emergence percentage, number of leaves, leaf area, stem length and root largest length, dry mass of shoot and roots; and substrates characteristics such as pH, electric conductivity, density and water retention capacity. The emergence speed index was evaluated daily from sowing. It is verified that, except for the number of leaves and the shoot dry matter mass, the other variables were influenced by the study factors. In general, in the seeds without fermentation and fermentation in water mixed with sugar, the highest averages were obtained, regardless of the substrate used. Thus, both mucilage extraction methods and all tested substrates are indicated in the initial development of yellow passion fruit.
To achieve the goal of performing quality control on vaccines for foot-and-mouth disease several steps were performed in this study. First, the gene that encodes the 3ABC region of the A24 Cruzeiro strain (which is used in vaccine production) was amplified. Second, to improve protein stability, the 3ABC protein was mutated at the 3Cpro catalytic site and cloned the amplification products in the pET-SUMO expression vector. In the third step, the resulting recombinant protein was tested, which the polyclonal antibody recognized, with the semi-purified viral 3ABC protein using an immunoassay test. Fourth, the muted recombinant protein was used to produce a monoclonal antibody. Of the 217 clones obtained, two of them that were particularly stable (mAb2D3 and mAb3D12) were selected to work with. One showed better results, as characterized by immunoassay (ELISA), Western blotting, spot synthesis, and sequencing methodologies; it also showed high reactivity against the 3ABC protein. This kind of monoclonal antibodies, which was considered as immunochemical inputs, have been used in industrial processes as part of quality-control procedures, to evaluate the elimination of the 3ABC protein so as to ensure regulatory approval of the vaccine. They have also been used in immunological tests to distinguish infected from vaccinated animals.
To increase our understanding of the consequences of dengue virus infection during pregnancy, a retrospective analysis was performed on the medical records of all completed pregnancies (live births and pregnancy losses) at nine public hospitals in the Gulf of Mexico from January to October 2013. Eighty-two patients developed clinical, laboratory-confirmed dengue virus infections while pregnant. Of these, 54 (65.9%) patients were diagnosed with dengue without warning signs, 15 (18.3%) patients were diagnosed with dengue with warning signs, and 13 (15.9%) patients had severe dengue. Five (38.5%) patients with severe dengue experienced fetal distress and underwent emergency cesarean sections. Four patients delivered apparently healthy infants of normal birthweight while the remaining patient delivered a premature infant of low birthweight. Patients died of multiple organ failure during or within 10 days of the procedure. Severe dengue was also associated with obstetric hemorrhage (30.8%, four cases), preeclampsia (15.4%, two cases), and eclampsia (7.7%, one case). These complications were less common or absent in patients in the other two disease categories. Additionally, nonsevere dengue was not associated with maternal mortality, fetal distress, or adverse neonatal outcomes. In summary, the study provides evidence that severe dengue during pregnancy is associated with a high rate of fetal distress, cesarean delivery, and maternal mortality.
Our purpose was to validate a semiautomatic quantification of the skeletal tumor burden on 18F-fluoride PET/CT using manual quantification as a reference. Methods: We quantified 51 18F-fluoride PET/CT examinations performed on female breast cancer patients. Clinical information (age; time of disease presentation; presence of visceral metastases; and time to death, progression, or a bone event) was recorded. The total volume of 18F-fluoride–avid skeletal metastases and the total activity of 18F-fluoride–avid metastases were calculated manually and semiautomatically. Results: Manual and semiautomatic metrics correlated strongly (P < 0.0001; 95% confidence interval, 0.9300–0.9769). On multivariable analysis, the semiautomatic measures of total activity for 18F-fluoride–avid metastasis correlated significantly with overall survival (P = 0.0001) and progression-free survival (P = 0.0006). Approximate times for calculating skeletal tumor burden (semiautomatic vs. manual) were, respectively, 30 s versus 321 s in patients with fewer than 5 metastases, 120 s versus 640 s in patients with 5–10 metastases, and 240 s versus 1207s in patients with more than 10 metastases. Conclusion: Semiautomatic quantification of whole-body 18F-fluoride PET/CT skeletal tumor burden can replace manual quantification in breast cancer patients and is a strong independent biomarker of prognosis.
Intussusception is a known manifestation of Hereditary Angioedema however, only a handful of cases have been treated conservatively and most, if not all, have been adult patients. To our knowledge, this is the first case of a pediatric patient treated conservatively without undergoing a surgical procedure.