Exploring the reasons for low pertussis vaccine effectiveness in Ontario,Canada, 2006–2008: a Canadian Immunization Research Network study

ObjectivesAlthough pertussis vaccines have been widely used for many decades, a burden of illness persists. Resurgences in Ontario, Canada, have not been substantial in the past decade, but an outbreak of pertussis occurred in Toronto between 1 October 2005 and 31 March 2006. Previous Ontario studies found high vaccine effectiveness (VE) in the initial years post-immunization. In order to explore the impact of outbreaks and external factors on VE, we investigated pertussis VE during the period 2006–2008.MethodsWe assessed pertussis VE using a frequency-matched case-control study for the period 1 March 2006 to 31 December 2008. We used logistic regression to estimate VE by age, time since last vaccination, and vaccination status according to the Ontario recommended schedule. We compared analyses including and excluding cases from Toronto, and to two recent Ontario pertussis VE studies.ResultsWe included 1797 confirmed cases and 7188 matched controls. Most cases were under 4 years of age during the study period. Pertussis VE was 3.8% (95% CI: − 21.0, 24.0) in the period 15–364 days following the last pertussis vaccine dose, and increased with increasing time since vaccination. Pertussis VE in the first 15–364 days excluding Toronto increased to 57.1% (95% CI: 26.0, 75.1), but the trend of increasing VE with time since vaccination persisted. Although VE was higher in older (6–11 years) than younger (0–5 years) children, it was lower at 12–13 years than after 14 years.ConclusionVE was lower in comparison with other studies conducted in Ontario, particularly in younger children. Various factors occurring during the study period may have influenced the results, including clinical testing of asymptomatic contacts, laboratory testing and methods and reporting practice, and a sensitive case definition. Further studies are needed to optimize methods for measuring VE to inform pertussis vaccine policy.     

Physical inactivity and its predictors among adolescents in Saudi Arabia: A cross-sectional comparison between cities with and without a Healthy Cities Program

Objectives:To estimate the prevalence of insufficient physical activity and excessive screen time among adolescents living in cities participating in the Healthy Cities Program (HCP) and cities not running the program in the Qassim region of Saudi Arabia.Methods:We surveyed 1133 adolescents from the Qassim region using systematic random sampling between April and September 2017. Multivariable logistic regression analyses were conducted to investigate the predictors of insufficient levels of PA and excessive screen time.Results:The prevalence of <60 minutes of moderate- to vigorous-intensity physical activity/day was 82.4% and <3 days of vigorous intensity physical activity/week among adolescents was 59%. There was no significant association between living in healthy cities (HCPs) and insufficient levels of physical activity. The odds of excessive screen time were higher in HCPs than in cities not running the program (NHCPs) (OR: 1.49). The odds of insufficient daily PA (OR: 2.19) are higher among girls than boys. Increasing age is positively associated with insufficient weekly PA (OR: 1.19). The prevalence of excessive recreational screen time is 84.6% with higher odds in HCPs than in NHCPs (OR: 1.51).Conclusion:Our findings report a lack of evidence of any impact of the HCP on adolescents’ physical activity behaviors. This outcome warrants a further in-depth evaluation of the process and outcomes of the HCP in Saudi Arabia.     

An Update on Vitamin D Deficiency Status in Malaysia

Vitamin D is essential for maintaining serum calcium levels, ensuring sufficient bone mineralization, immunomodulatory properties, and a protective effect on the cardiovascular system, renal disease, cancer, as well as in pregnancy. Vitamin D deficiency is prevalent worldwide, and it is not related to a country’s development index. However, the data on vitamin D deficiencies are primarily taken from out-of-date, small-scale studies on target age groups or specific diseases, rather than from large-scale, population-based surveys. In Malaysia, for the past 16 years, studies were conducted involving adult men and women, pregnant women, postmenopausal women, adolescent, and children especially with specific diseases such as spina bifida, epilepsy, chronic liver disease, and atopic dermatitis. Only a few large surveys were conducted involving children and adolescents. Across the specific target population studied, vitamin D deficiency and insufficiency were seen particularly among females, Indians, and those of Malay ethnicity. This is related to widely known causes of vitamin D deficiency such as skin type (melanin) and sun avoidant lifestyles that include covering clothes, largely practiced by Malay Muslims in Malaysia. Other related causes or the high-risk groups are breastfed infants, the elderly, the obese, those on medications, and those characterized by fat malabsorption and geophysical factors. Vitamin D deficiency can be managed with pharmacological or non-pharmacological approaches, depending on the severity. The objective is to raise serum vitamin D to a normal level, hence, relieving the symptoms and reducing the adverse health outcomes. Despite no clear guidelines in treating vitamin D deficiency in Malaysia, this condition can be prevented with taking adequate vitamin D in food resources, sun exposure, or supplementation. Special attention should be given to high-risk groups including infants, obese patients, and the elderly.     

Could Guillain–Barré syndrome be triggered by COVID‐19 vaccination?

Due to SARS‐COV‐2 (COVID‐19) pandemic and its catastrophic impact on society, the FDA granted emergency use authorization for some vaccines. Possible rare side effects could not have been observed in this relatively short period. We are reporting an elderly lady with multiple comorbidities who presented with progressive lower limb weakness that started seven days after receiving the first dose of the COVID‐19 vaccine. The electrodiagnostic study showed demyelinating polyneuropathy with secondary axonal degeneration consistent with Guillain–Barré syndrome. We ruled out other possible causes for GBS, suggesting a postvaccine nature for her presentation. The patient received intravenous immunoglobulin (IVIG) for five days and gradually improved, which supports our initial diagnosis.     

Effects of abrupt changes in cycle length on atrial refractory periods in man

While the electrophysiologic effects of sudden changes in cycle length on the His-Purkinje System and ventricular myocardial refractoriness are better known, the behavior of atrial myocardium in this regard is poorly understood. The effects of an abrupt long to short cycle length change (11 patients: group A) and/or short to long cycle length alteration (18 patients: group B) on the atrial effective and functional refractory period were assessed during electrophysiologic studies. The values thus obtained were compared to those observed during the scanning of both constant long and constant short cycle lengths of the same duration. In group A the effective and functional refractory periods of the right atrium measured 250 +/- 38 msec and 296 +/- 31 msec during a constant long cycle length of 709 +/- 80 msec, whereas the same parameters had values of 228 +/- 30 msec and 260 +/- 32 msec, respectively, at a constant short cycle length of 436 +/- 81 msec. With an abrupt change in cycle length from long to short (a change of 273 +/- 75 msec), the effective and functional atrial refractory periods were 225 +/- 29 and 267 +/- 29 msec in that order, and these values closely approximated those seen with a constant short cycle length. Similarly, the two atrial refractory period parameters in group B measured 218 +/- 16 msec and 262 +/- 19 msec during a constant short cycle length of 414 +/- 68 msec and were 236 +/- 17 msec and 284 +/- 21 msec, respectively, at a constant long cycle length of 689 +/- 92 msec.(ABSTRACT TRUNCATED AT 250 WORDS)     

High-dose rifampin improves bactericidal activity without increased intracerebral inflammation in animal models of tuberculous meningitis

Tuberculous meningitis (TB meningitis) is the most severe form of tuberculosis (TB), requiring 12 months of multidrug treatment for cure, and is associated with high morbidity and mortality. High-dose rifampin (35 mg/kg/d) is safe and improves the bactericidal activity of the standard-dose (10 mg/kg/d) rifampin-containing TB regimen in pulmonary TB. However, there are conflicting clinical data regarding its benefit for TB meningitis, where outcomes may also be associated with intracerebral inflammation. We conducted cross-species studies in mice and rabbits, demonstrating that an intensified high-dose rifampin-containing regimen has significantly improved bactericidal activity for TB meningitis over the first-line, standard-dose rifampin regimen, without an increase in intracerebral inflammation. Positron emission tomography in live animals demonstrated spatially compartmentalized, lesion-specific pathology, with postmortem analyses showing discordant brain tissue and cerebrospinal fluid rifampin levels and inflammatory markers. Longitudinal multimodal imaging in the same cohort of animals during TB treatment as well as imaging studies in two cohorts of TB patients demonstrated that spatiotemporal changes in localized blood-brain barrier disruption in TB meningitis are an important driver of rifampin brain exposure. These data provide unique insights into the mechanisms underlying high-dose rifampin in TB meningitis with important implications for developing new antibiotic treatments for infections.     

Key associations for hepatitis C virus genotypes in the Middle East and North Africa

This study aimed to investigate the epidemiology of hepatitis C virus (HCV) genotypes in the Middle East and North Africa (MENA) through an analytical and quantitative meta-regression methodology. For the most common genotypes 1, 3, and 4, country/subregion explained more than 77% of the variation in the distribution of each genotype. Genotype 1 was common across MENA, and was more present in high-risk clinical populations than in the general population. Genotype 3 was much more present in Afghanistan, Iran, and Pakistan than the rest of countries, and was associated with transmission through injecting drug use. Genotype 4 was broadly disseminated in Egypt in all populations, with overall limited presence elsewhere. While genotype 2 was more present in high-risk clinical populations and people who inject drugs, most of the variation in its distribution remained unexplained. Genotypes 5, 6, and 7 had low or no presence in MENA, limiting the epidemiological inferences that could be drawn. To sum up, geography is the principal determinant of HCV genotype distribution. Genotype 1 is associated with transmission through high-risk clinical procedures, while genotype 3 is associated with injecting drug use. These findings demonstrate the power of such analytical approach, which if extended to other regions and globally, can yield relevant epidemiological inferences.     

Haptoglobin phenotype and risk of cervical neoplasia: a case-control study

BACKGROUND: Haptoglobin is an acute-phase glycoprotein that influences host response to infections and tumours. The haptoglobin locus is polymorphic with 2 classes of alleles (Hp(1) and Hp(2)) yielding 3 phenotypes: Hp1-1, Hp2-2, and Hp2-1 with structurally and functionally distinct protein products, suggesting that haptoglobin polymorphism may influence susceptibility to infections and cancers. METHODS: We examined the relation between haptoglobin phenotype and high-grade cervical intraepithelial neoplasia (CIN) in a hospital-based case-control study. Cases (n = 307) were women with biopsy-confirmed CIN-2 or CIN-3. Controls (n = 358) were a random sample of women with normal cytology. The PGMY polymerase chain reaction and reverse line blot methods were used for HPV detection and genotyping. Haptoglobin phenotype was determined by polyacrylamide gel electrophoresis. RESULTS: Among controls, phenotype distribution corresponded to allele frequencies of 0.39 for Hp(1) and 0.61 for Hp(2) with no significant deviation from the Hardy-Weinberg equilibrium (p=0.66). With all women included in the analysis, the Hp1-1 phenotype was associated with increased risk of CIN (OR contrasting Hp1-1 vs. Hp2-2 = 1.0; 95% CI: 0.6-1.5). However, in analyses restricted to HPV-positive participants, the Hp1-1 phenotype was associated with 2.7-fold (95% CI: 1.0-7.2) higher risk of CIN. CONCLUSIONS: If confirmed, these findings indicate an increased risk of CIN among women with the Hp1-1 phenotype.     

Growth factors mobilize CXCR4 low/negative primitive hematopoietic stem/progenitor cells from the bone marrow of nonhuman primates.

Abstract The chemokine receptor CXCR4 is expressed by CD34 + hematopoietic stem/progenitor cells (HSC/HPC). Several investigators have suggested that expression of CXCR4 may be an important characteristic of HSC/HPC. We studied the dynamic expression of CXCR4 during growth factor-induced mobilization of HSC in a clinically relevant nonhuman primate model, Papio anubis (baboons). We evaluated whether CXCR4 expression in HSC/HPC varies during steady-state hematopoiesis as well as during growth factor-induced mobilization. Peripheral blood stem cells from 5 baboons were mobilized with growth factors. During mobilization, there was a consistent stepwise increase in the proportion of peripheral blood CD34 + cells that were CXCR4 -. The highest number of CD34 + CXCR4 - cells appeared in the peripheral blood at the same time as the maximum number of assayable colony-forming cells. The cloning efficiency of the CD34 + CXCR4 - population was 3-fold greater than that of CD34 + CXCR4 + cells, and the frequency of cobblestone area-forming cells was 6 times higher in the CD34 + CXCR4 - population in comparison to CD34 + CXCR4 + cells. Furthermore, the most quiescent CD34 + cells isolated on the basis of low Hoechst 33342 (Ho) and rhodamine 123 (Rho) staining (Ho Low /Rho Low ) were highly enriched in the CXCR4 Low/- cell population. Ex vivo incubation of mobilized peripheral blood CD34 + cells with growth factors for 40 hours resulted in increasing numbers of cells expressing CXCR4. Peripheral blood stem cell grafts containing CD34 + cells that consisted of predominantly CXCR4 - cells were able to rapidly engraft lethally irradiated baboons. Because the overwhelming number of CD34 + cells within the mobilized peripheral blood grafts were CXCR4 - and were capable of rescuing lethally irradiated baboons, it seems unlikely that the expression of CXCR4 in vitro is an absolute requirement for HSC homing and engraftment. In summary, our data suggest the dynamic nature of CXCR4 expression on CD34 + cells during growth factor-induced HSC/HPC mobilization. In addition, our data indicate that the lack of CXCR4 expression is possibly a characteristic of relatively more primitive HSC/HPC characterized by a higher proliferative capacity.