RTS,S/AS01E malaria vaccine induces IgA responses against CSP and vaccine-unrelated antigens in African children in the phase 3 trial

BackgroundThe evaluation of immune responses to RTS,S/AS01 has traditionally focused on immunoglobulin (Ig) G antibodies that are only moderately associated with protection. The role of other antibody isotypes that could also contribute to vaccine efficacy remains unclear. Here we investigated whether RTS,S/AS01_E elicits antigen-specific serum IgA antibodies to the vaccine and other malaria antigens, and we explored their association with protection.MethodsNinety-five children (age 5–17 months old at first vaccination) from the RTS,S/AS01_E phase 3 clinical trial who received 3 doses of RTS,S/AS01_E or a comparator vaccine were selected for IgA quantification 1 month post primary immunization. Two sites with different malaria transmission intensities (MTI) and clinical malaria cases and controls, were included. Measurements of IgA against different constructs of the circumsporozoite protein (CSP) vaccine antigen and 16 vaccine-unrelated Plasmodium falciparum antigens were performed using a quantitative suspension array assay.ResultsRTS,S vaccination induced a 1.2 to 2-fold increase in levels of serum/plasma IgA antibodies to all CSP constructs, which was not observed upon immunization with a comparator vaccine. The IgA response against 13 out of 16 vaccine-unrelated P. falciparum antigens also increased after vaccination, and levels were higher in recipients of RTS,S than in comparators. IgA levels to malaria antigens before vaccination were more elevated in the high MTI than the low MTI site. No statistically significant association of IgA with protection was found in exploratory analyses.ConclusionsRTS,S/AS01_E induces IgA responses in peripheral blood against CSP vaccine antigens and other P. falciparum vaccine-unrelated antigens, similar to what we previously showed for IgG responses. Collectively, data warrant further investigation of the potential contribution of vaccine-induced IgA responses to efficacy and any possible interplay, either synergistic or antagonistic, with protective IgG, as identifying mediators of protection by RTS,S/AS01_E immunization is necessary for the design of improved second-generation vaccines.Clinical trial registration: ClinicalTrials.gov: NCT008666191.     

Biochemical and Hematologic Parameters for Children in the Middle Belt of Ghana

Reference values derived from developed countries are used in many countries in Africa for interpretation of laboratory results obtained during routine healthcare and clinical trials. Use of locally derived reference values has been recommended. The purpose of the study was to establish age- and sex-specific reference values for children in the middle belt of Ghana. Reference values were determined for 21 biochemical and 18 hematologic parameters by using Clinical and Laboratory Standards Institute C28-A3 guidelines in a sample of 1,442 healthy children. Hemoglobin, hematocrit, mean cell volume, erythrocytes, urea, and creatinine were lower when compared with values from northern countries but alanine aminotransferase, aspartate aminotransferase, and total bilirubin were higher. A panel of locally relevant age- and sex-specific reference values was established for commonly used biochemical and hematologic tests in children in the middle part of Ghana. This will help in interpretation of laboratory results for clinical management of patients, screening, and safety monitoring during clinical trials.     

Women’s approval of domestic physical violence against wives: analysis of the Ghana demographic and health survey

Background

Intimate partner violence (IPV) has serious consequences for the physical, psychological, and reproductive and sexual health of women. However, the factors that make women to justify domestic violence against wives in many sub-Saharan African countries have not been explored. This study investigates factors that influence women approval of domestic physical violence among Ghanaian women aged 15–49.

Method

A nationally representative sampled data (N?=?10,607) collected in the 2003 and 2008 Ghana Demographic and Health Survey were used. Multivariate logistic regression was used to study the associations between women’s economic and socio-demographic characteristics and their approval of domestic physical violence against wives.

Results

Women aged 25–34 and 15–24 were 1.5 and 1.3 times, respectively, more likely to approve domestic physical violence against wives compared to those aged 35 years and above. Furthermore, women with no education (OR?=?3.1, CI?=?2.4–3.9), primary education (OR?=?2.6, CI?=?2.1–3.3) and junior secondary education (OR?=?1.8, CI?=?1.4–2.2) had higher probability of approving domestic physical violence compared to a woman who had secondary education or higher. Compared to women with Christian belief, Moslems (OR?=?1.5, CI?=?1.3–1.8) and Traditional believer (OR?=?1.7, CI?=?1.2–2.4) were more likely to approve domestic physical violence of wives. Women who were in the richest, rich and middle wealth index categories were less likely to approve domestic physical violence of wives compared to the poorest.

Conclusion

These findings fill a gap in understanding economic and socio-demographic factors associated with approval of domestic physical violence of wives. Interventions and policies should be geared at contextualizing intimate partner violence in terms of the justification of this behaviour, as this can play an important role in perpetration and victimization.

     

Transcranial Doppler ultrasonography in siblings with sickle cell disease

Summary. The risk of stroke in sickle cell disease (SCD) may be influenced by either genetic or environmental factors. Elevated blood flow velocity in the large cerebral arteries, detected by transcranial Doppler (TCD) ultrasonography, predicts an increased stroke risk in children with SCD. We undertook this study to investigate the possibility of a familial predisposition to elevated cerebral blood flow velocity, a surrogate marker for stroke risk. We analysed the results of TCD studies performed on 63 children from 29 families that had more than one child with SCD. We assessed the association of elevated cerebral blood flow velocity with sibling TCD results as well as age and haemoglobin level, which are factors known to affect cerebral blood flow velocity. Positive or negative TCD results were highly correlated between family members ( r =  0·61). The presence of a sibling with a positive TCD result was significantly associated with an elevated cerebral blood flow velocity in other siblings with SCD (odds ratio = 41·9, 95% confidence interval 8·2–214·7, P  < 0·001). Furthermore, children who had a sibling with a positive TCD result had a significantly higher TCD velocity than children with SCD but without a sibling who were matched for age, sex, genotype and haemoglobin level. Our results are consistent with a familial predisposition to cerebral vasculopathy in SCD.     

Adenosine A1 Receptor Mrna Expression and the Effects of Systemic Theophylline Administration On Respiratory Function 4 Months After C2 Hemisection

Abstract

Background: Previous studies from our laboratory have demonstrated that in an animal model of acute cervical spinal cord injury (SCI), respiratory function can be restored by theophylline. We also have shown that respiratory recovery occurs spontaneously after prolonged postinjury survival periods when a hemidiaphragm is paralyzed by an ipsilateral upper cervical (C2) spinal cord hemisection. Theophylline mediates functional recovery by central nervous system adenosine A1 receptor antagonism; however, it is unclear whether adenosine receptors are altered after prolonged postinjury periods and whether theophylline can further enhance restored respiratory function that occurs spontaneously.

Objective: To assess putative effects of systemic theophylline administration on further enhancing spontaneous respiratory muscle recovery 4 months after C2 hemisection in rats and to determine whether adenosine A1 receptor mRNA expression is altered in these animals.

Methods: Electrophysiologic assessment of respiratory activity in the phrenic nerves was conducted in C2 hemisected rats 4 months after hemisection under standardized conditions. Immediately thereafter, rats were killed and the cervical spinal cords were prepared for adenosine A1 receptor mRNA expression by in situ hybridization.

Results: Spontaneous recovery of respiratory activity in the ipsilateral phrenic nerve was detected in a majority (15/20) of C2 hemisected animals and amounted to 44.06% ± 2.3 8% when expressed as a percentage of activity in the homolateral phrenic nerve in noninjured animals. At the optimal dosage used in the acute studies, theophylline (15 mg/kg) did not enhance, but rather unexpectedly blocked, recovered respiratory activity in 4 out of 5 animals tested. At dosages of 5 mg/kg and 2.5 mg/kg, the drug blocked recovered respiratory activity in 3 out of 4 and 3 out of 5 animals tested, respectively. Quantitative analysis of adenosine A1 receptor mRNA expression did not reveal a significant difference between experimental animals and sham-operated animals.

Conclusion: The blockade or attenuation of spontaneously recovered respiratory activity following theophylline administration cannot be attributed to changes in adenosine A1 receptors because there were no significant differences in adenosine A1 mRNA expression with sham-operated animals. Lack of alteration in A1 mRNA expression 4 months after cervical SCI suggests that A1 receptor plasticity is not activated by chronic injury. Obliteration of spontaneous recovery with theophylline most likely involves a separate unknown mechanism. These findings suggest that there may be a limited therapeutic window for the clinical application of theophylline in SCI patients with respiratory deficits. Theophylline may be more effective clinically in the acute phase of injury rather than in the chronic phase.     

Association Between Whole-Body Vibration and Low-Back Disorders in Farmers: A Scoping Review

Introduction: Low-back disorders (LBDs) are the most common musculoskeletal problem among farmers, with higher prevalence rates than in other occupations. Farmers who operate tractors and other types of machinery can have substantial exposure to whole-body vibration (WBV). Although there appears to be an association between LBDs and WBV, the causal relationship is not clear. Objective: This scoping review investigates the association between WBV and LBDs specifically among farmers. Methods: Nine databases were searched using groups of terms for two concepts: ‘farming’ and ‘low back disorder’. Screening, data extraction, and quality assessment were performed by two reviewers independently. Included studies met the following criteria: focused on adult farmers/agricultural workers; assessed exposure to operating farm machinery such tractor, combine, or all-terrain vehicle; assessed LBDs as an outcome; and reported an inferential test to assess the relationship between WBV and LBD. Results: After 276 full texts screened, 11 articles were found to analyze WBV as a risk factor for LBDs. Three were case–control, five cross-sectional, and three retrospective cohorts. Four studies showed no association between WBV and LBDs, four a positive association, and three results were mixed depending on the exposure/outcome measure. Conclusion: A firm conclusion is difficult due to heterogeneity in, LBDs definition, type of farm commodity, study design, and statistical strategy. Direct comparisons and synthesis were not possible. Although retrospective cohort studies tended to show a relationship, future studies with a prospective cohort design could help clarify this association further.     

Epidemiology of human parvovirus B19 in children with sickle cell disease

Human parvovirus (HPV) B19 causes significant morbidity and mortality in children with sickle cell disease (SCD), but little data are published about the epidemiology of HPV B19 infection and its associated complications in this patient population. In this study, prevalence and incidence rates of HPV B19 were determined in 633 patients with SCD followed at The Children's Hospital of Philadelphia between November 1996 and December 2001. Thirty percent (30%) were HPV B19 immunoglobulin G (IgG) positive at first testing, and the 70% without evidence of past HPV B19 infection were tested annually. One hundred ten patients developed evidence of HPV B19 infection for an incidence rate of 11.3 per 100 patient years. Sixty-eight episodes of HPV B19-induced transient red cell aplasia occurred with the following clinical events: fever (89.7%), pain (61.8%), acute splenic sequestration (19.1%), and acute chest syndrome (11.8%). Pain, fever, and acute splenic sequestration were more frequent events with acute HPV B19 infections compared with acute events in uninfected patients. The results of this epidemiologic study, the largest and most comprehensive to date, justify the development of HPV B19 prevention strategies to diminish the frequent and often severe complications associated with HPV B19 infections in patients with SCD.     

Typical AVNRT--an update on mechanisms and therapy

Typical atrioventricular reentrant tachycardia (AVNRT) is the most common paroxysmal supraventricular tachycardia among adults, and accounts for considerable morbidity. The concept of dual pathway physiology remains useful, although this physiology likely results from the functional properties of anisotropic tissue within the triangle of Koch, rather than anatomically distinct tracts of conduction. Also, there remains debate regarding whether the critical reentrant circuit path requires participation of the atrium. In our opinion, current evidence favors functional anisotropic reentry limited to the subatrial tissues as the arrhythmia mechanism. Reasons for this are reviewed. Fortunately, typical AVNRT is readily amenable to definitive therapy by catheter-based radiofrequency energy delivery at the so-called slow pathway region located at the posterior Triangle of Koch. Anterior or left-sided approaches are very rarely indicated. Results from multiple series have shown this strategy to be both safe and effective, therefore ablation therapy should now be considered as the definitive therapy of choice for the majority of patients.     

Processing of a cowpea--groundnut blend into a miso-like product

A traditional salt-miso process was used to produce a miso-like product from a 50-50 mixture of cowpea and groundnuts in a 60-day fermentation process as part of a study to determine the suitability of local legumes as raw materials for the production of miso. The koji was freshly prepared from a locally obtained rice and Aspergillus oryzae spores obtained from Japan. An old miso sample also obtained from Japan was used as the source of lactic acid bacteria. The physico-chemical changes in the product associated with the fermentation and the functional and quality characteristics of the final product were determined. The study demonstrated the possibility of processing the legume blend into a miso-like product. The physico-chemical, functional and quality characteristics of the final product showed the suitability of the product for its intended use as a soup base. The product had a high protein and a moderately high lipid content (about 25% and 29%, respectively), which could contribute to the nutritional contents of diets.