Type I cAMP-Dependent Protein Kinase Delays Apoptosis in Human Neutrophils at a Site Upstream of Caspase-3

Current data suggest that apoptosis controls neutrophil numbers in tissues. We analyzed roles for and the sites of action for the cAMP-dependent protein kinases (cAPKs) in apoptosis induced in human neutrophils by in vitro storage, cycloheximide (CHX) exposure, and anti-Fas exposure. Treatment with 8-chlorophenylthio-cAMP (8-CPT-cAMP) prolonged the time required for 50% of the cells to exhibit apoptotic morphology (t 50) from 16.3 to 41.8 h (in vitro culture), from 2.4 to 7.8 h (CHX), and from 4.8 to 6.5 h (anti-Fas). CHX ± 8-CPT-cAMP did not significantly alter resting intracellular calcium levels and H-89, a selective inhibitor of cAPK, had no effect on apoptosis in the absence of the analogue. In contrast, site-selective cAMP analogues that specifically activated the type I cAPK, but not type II cAPK, synergistically attenuated apoptosis. Exposure to 8-CPT-cAMP delayed, in parallel, the activity of caspase-3 (CPP-32β), whereas mitogen-activated protein kinase kinase (MAPKK) inhibitor, PD98059, had no effect on CHX-induced apoptosis ± 8-CPT-cAMP. Together these results indicate that type I cAPK activation is necessary and sufficient to mediate cAMP-induced delay in human neutrophil apoptosis induced by several mechanisms and suggest that one of the major sites of cAPK action is upstream of caspase-3 (CPP-32β) activation

Immunopathogenesis of Orthopoxviridae: insights into immunology from smallpox to monkeypox (mpox)

Since 2019, notable global viral outbreaks have occurred necessitating further research and healthcare system investigations. Following the coronavirus disease 2019 (COVID-19) pandemic, in 2022, whilst severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains evolved, monkeypox virus (MPXV) infections became more evident. MPXV is of the Orthopoxviridae genus, belonging to the family Poxviridae. Zoonotic transmission (animal-to-human transmission) may occur. The Orthopoxviridae genus includes other orthopoxviruses (OPXVs) present in animal host reservoirs that include cowpox viruses (CPXVs), vaccinia virus (VACV), and variola virus (VARV), with the latter being a causal agent of smallpox and excessive mortality. This review aims to present facts about MPXV-specific pathogenesis, epidemiology, and immunology alongside historical perspectives. MPXV was rarely reported outside Africa before April 2000. Early research since 1796 contributed towards the eradication of VARV leading to immunisation strategies. The World Health Organisation (WHO) announcement that VARV had been eradicated was confirmed in 1980. On the 23rd of July 2022, the WHO announced MPXV as a health emergency. Therefore, concern due to the propagation of MPXV causing monkeypox (mpox) disease requires clarity. Infected hosts display symptoms like extensive cellular-initiated rashes and lesions. Infection with MPXV makes it difficult to differentiate from other diseases or skin conditions. Antiviral therapeutic drugs were typically prescribed for smallpox and mpox disease; however, the molecular and immunological mechanisms with cellular changes remain of interest. Furthermore, no official authorized treatment exists for mpox disease. Some humans across the globe may be considered at risk. Historically, presenting symptoms of mpox resemble other viral diseases. Symptoms include rashes or lesions like Streptococcus, but also human herpes viruses (HHVs), including Varicella zoster virus (VZV)

Surveillance for Invasive Meningococcal Disease in Children, US–Mexico Border, 2005–20081

We reviewed confirmed cases of pediatric invasive meningococcal disease in Tijuana, Mexico, and San Diego County, California, USA, during 2005–2008. The overall incidence and fatality rate observed in Tijuana were similar to those found in the US, and serogroup distribution suggests that most cases in Tijuana are vaccine preventable

Surveillance for Invasive Meningococcal Disease in Children, US–Mexico Border, 2005–20081

We reviewed confirmed cases of pediatric invasive meningococcal disease in Tijuana, Mexico, and San Diego County, California, USA, during 2005–2008. The overall incidence and fatality rate observed in Tijuana were similar to those found in the US, and serogroup distribution suggests that most cases in Tijuana are vaccine preventable

Association between Meningococcal Meningitis and Santa Ana Winds in Children and Adolescents from Tijuana, Mexico: A Need for Vaccination

Background: Based on previous studies (regional and national), Tijuana, Baja California, Mexico (across the border from San Diego, California, USA), has been shown to have the highest rate of meningococcal meningitis (MeM) in the country. However, the reason for this high incidence has not yet been established. To explain this regional/endemic public health problem, we aimed to evaluate whether there is a climatic association with MeM in the region. In the “African Meningitis Belt,” the Harmattan seasons are associated with MeM outbreaks; similarly, the Santa Ana winds (SAWs) seasons are characterized by hot and dry winds (similar to Harmattan seasons) that occur seasonally in Southwest California, USA, and Northwest Baja California, Mexico. Objectives: We aimed to determine a potential association of SAWs with MeM in Tijuana, Baja California, Mexico, which in turn may partially explain the high rate of this disease in the region. Methods: Based on our previously published data obtained from thirteen years of active surveillance of MeM and a 65-year review showing the seasonal occurrence of SAWs, we estimated the risk ratio (RR) for the total case numbers of MeM (51 cases of children < 16 years old) vs. bacterial meningitis not caused by Neisseria meningitidis (NMeM, 30 cases, same age group) during seasons with and without SAWs. Results: We found an association between SAWs and MeM, but not with NMeM (RR = 2.06, p = 0.02 (95% CI 1.1 to 3.8), which may partially explain the high endemicity of this deadly disease in this part of the globe. Conclusion: This study shows a new potential climatic association with MeM and provides more information that justifies universal meningococcal vaccination in Tijuana, Mexico

Children with lymphadenitis associated with Bacillus Calmette-Guérin (BCG) vaccination do not experience more infections when compared with BCG-vaccinated children without lymphadenitis: a three years paired-cohort in Mexico

Objectives: Vaccination against tuberculosis with live-attenuated Bacillus Calmette-Guérin (BCG) is widely used even though its effectiveness is controversial. BCG-lymphadenitis (BCG-LA) is its most common complication. Some studies have proposed that BCG-LA can be associated with primary immunodeficiencies (PIs). This study’s aim is to see whether patients who developed BCG-LA (named as ‘LA’) developed more infections than BCG-vaccinated children without BCG-LA (named as ‘NON-LA’). Methods: From January 2009 to April 2014, 31 LA children were seen at the outpatient clinic of the General Hospital of Tijuana, Mexico. Among them, 22 (70.97%), 5 (16.13%) and 4 (12.9%) had axillary, supraclavicular, or both BCG-LA, respectively. No treatment was given and complications were not seen. Per LA subject, a NON-LA not \u3e1 month of age difference and same gender was paired and followed for 3 years to look for ambulatory infections (AINFs), acute otitis media (AOM) and hospitalizations. Surveillance per patient was performed by phone monthly, and they were seen at the clinic every 4 months. All patients were HIV-negative and had no family history of PI. Statistical analyses used were relative risk (RR) with confidence intervals (CI), t test for independent variables and z test. Results: In total 62 subjects were enrolled: 31 LA paired with 31 NON-LA. Between them, there were no differences in age, day care attendance and breastfeeding. There were no differences in the total number of AINF per patient (LA: 18.61 avg. ± 5.03 SD versus NON-LA: 18.19 avg. ± 4.17 SD, RR = 1.06, 95% CI = 0.33–0.66), AOM total episodes (LA: 30 versus NON-LA: 26, RR = 0.87, 95% CI = 0.31–0.68) and hospitalizations (LA: 5 versus NON-LA: 4, RR = 1, 95% CI = 0.25–0.74). Conclusions: This cohort strongly suggests that BCG-LA in healthy children is not associated with more episodes of AINF and hospitalizations, when paired and compared with children BCG-vaccinated without BCG-LA

Influenza Vaccination during Pregnancy: A Descriptive Study of the Knowledge, Beliefs, and Practices of Mexican Gynecologists and Family Physicians

Background: Influenza in pregnancy is associated with elevated morbidity and mortality. Influenza vaccines are safe and effective in pregnancy. There are no Mexican surveys of physicians on knowledge, beliefs, and practices towards influenza and influenza immunization during pregnancy. Methods: A 32-question descriptive survey was conducted, addressing the general knowledge of influenza as well as beliefs and practices regarding influenza vaccination during pregnancy among Mexican physicians responsible for prenatal care, traditionally Obstetricians (OBGYNs) and Family Physicians (FPs). Results: A total of 206 surveys were available, 98 (47.6%) from OBGYNs and 108 (52.4%) from FPs, representing an estimated 2472 daily pregnancy consultations. In total, 54 of the 206 respondents (26.2%) were not aware that influenza is more severe during pregnancy, 106 of the 206 respondents (51.5%) ignored the potential side effects of influenza infection on the fetus, and 56.8% did not know when to vaccinate pregnant women. Pregnancy as a risk factor for developing influenza complications was only known by 99 of the 206 respondents (48.1%), and 6.1% believed that vaccination does not confer protection to the fetus. Conclusions: The current beliefs of Mexican OBGYNs and FPs for both influenza morbidity and mortality, and the importance of influenza vaccination during pregnancy are suboptimal. The drivers of these beliefs should be assessed to improve influenza vaccination recommendations, as knowledge alone is not sufficient

Economic burden of meningococcal disease in children and adolescents in Tijuana, Mexico

Invasive meningococcal disease (IMD) is an uncommon but serious and potentially fatal condition mainly affecting children and adolescents. Active surveillance between 2005 and 2016 at Tijuana General Hospital, Mexico, indicated that the incidence of IMD in Tijuana was higher than previously thought, at 2.69 per 100,000 population aged <16 years. The objective of this study was to estimate the economic burden associated with 51 IMD cases in children aged <16 years identified over the 11 years of active surveillance at Tijuana General Hospital, Mexico. Healthcare resource usage for the IMD cases was obtained from the hospital database and combined with unit costs from the hospital purchasing department or national databases to estimate total healthcare costs over a follow-up period of 3 months. Societal costs were represented by the value of lost wages for parents or guardians. All costs were expressed in US$. Over the 11-year study period there were 51 IMD cases, of which 13 (25$1,054,499 (average per case US$20,676), of which direct healthcare costs comprised US$1,029,948 (average per case US$20,195) and societal costs US$24,551 (average per case US$481). Extrapolated to the population of Tijuana region aged <16 years, the estimated annual economic burden of IMD was US$268,794. The major cost driver was the cost of hospitalization. These data illustrate the significant economic burden associated with IMD in Tijuana, and will be useful in assessing optimal vaccination programs against meningococcal disease in Mexico

Pediatric meningitis due to and Group B Streptococcus in Tijuana, Mexico: active/prospective surveillance, 2005–2018

Introduction: In Mexico, Neisseria meningitidis is considered to be a rare cause of bacterial meningitis (BM), however, one national publication using active surveillance has suggested the opposite. Group B Streptococcus (GBS) is also considered to be infrequent in young infants as a cause of BM in central Mexico. Streptococcus pneumoniae vaccination using the 13-valent conjugate vaccine (PCV13) started in our region in May 2012. We focused our research on whether N. meningitidis and GBS are important causes of BM, and to examine the effectiveness of PCV13 on pneumococcal BM. Methods: From October 2005 to September 2018, active/prospective surveillance looking for all patients admitted with suspected BM <16 years of age was performed at the Tijuana, Mexico, General Hospital. Tijuana, Mexico to San Diego, Unites States of America (USA), is the most transited border in the world. Isolation of pathogens was by either conventional culture or Real Time-polymerase chain reaction (RT-PCR), all patients were followed during and 3 months after discharge, and a descriptive analysis was performed. The effectiveness of PCV13 was determined by comparing the proportion of cases per month on pneumococcal BM before and after its implementation. Results: There were 86 confirmed BM cases. N. meningitidis was the leading cause (60.5%, and 61.5% caused by serogroup C), followed by S. pneumoniae (18.6%). PCV13 effectiveness on pneumococcal BM was of 64.3% and was associated with the disappearance of serotype 19A. A total of 22 infants <3 months old had BM; GBS was the leading cause at this age group (27.3%), followed by N. meningitidis (22.7%). The overall mortality was 24%. Conclusions: BM by N. meningitidis is endemic in Tijuana, Mexico, and meningococcal vaccination should be seriously considered in the region. PCV13 is currently showing high effectiveness on pneumococcal BM, and we need to continue active surveillance to see whether maternal screening/prophylaxis for GBS should also be introduced in the region

12 years active surveillance for pediatric pleural empyema in a Mexican hospital: effectiveness of pneumococcal 13-valent conjugate vaccine, and early emergence of methicillin-resistant

Background: Previous publications have proved the effectiveness of the 13-valent pneumococcal conjugate vaccine (PCV13) on pneumococcal pleural empyema (PnPE) in children, with little emergence of other pathogens. We searched the literature to establish whether PCV13 reduces PnPE, and to identify other pathogens causing pleural empyemas (PEs). Material and methods: From October 2005 to January 2018 (12.3 years) we performed active surveillance for all cases of PE at the General Hospital of Tijuana, Mexico. Isolates from pleural fluid (PF) were identified by conventional culture, and since 2014, polymerase chain reaction (PCR) was added for all culture-negative PFs. Streptococcus pneumoniae serotypes were detected by either Quellung reaction (Statens Serum Institute®) or PCR. Clinical, imagenological, laboratorial and microbiological evaluation was performed on each patient. Statistical analysis was purely descriptive. Results: A total of 64 PEs were identified (5.28/year). Median age was 51 months (1–191), hospitalization days 18 (4–35). Decortication was performed in 42%, and two children died (3.2%). Bacterial identification was obtained from 51 (80%). S. pneumoniae was the leading cause (29 = 56.8%), followed by Staphylococcus aureus (14 = 27.4%), Streptococcus pyogenes (3–5 = 9%) and others (5 = 9.8%). PCV13 was initiated in May 2012, and its impact on serotype-specific PnPE was 81% (much fewer than serotype 3) and for all PnPE 56.1%; however, for all PE −2.1% due to an increase of PE caused by S. aureus for all but one methicillin-resistant S. aureus (MRSA). Conclusions: Following 12.3 years of active surveillance, PCV13 has shown impact on both serotype-specific and all PnPEs; however, an increase of PEs by MRSA has emerged. Continuous surveillance is crucial to establish whether this epidemiological finding is transitory or not