Asymptomatic rheumatic heart disease in South African schoolchildren: Implications for addressing chronic health conditions through a school health service

When new evidence comes to light, it compels us to contemplate the implications of such evidence for health policy and practice. This article examines recent research evidence on the prevalence of asymptomatic rheumatic heart disease (RHD) in  South Africa and considers the implications for the Integrated School Health  Programme (ISHP). RHD is still a major burden of disease in developing countries, and elimination of this preventable condition ranks high among World Heart  Federation goals. If left untreated, it becomes a chronic health condition that  individuals have to cope with into their adult lives. The ISHP regards the health  needs of children with chronic health conditions, which include conditions such as RHD, as a key service component. However, the chronic health component of the ISHP is still poorly developed and can benefit from good evidence to guide implementation. A recent study to ascertain the prevalence of RHD in asymptomatic schoolchildren through mass screening affords an opportunity to reflect on whether, and how, asymptomatic chronic health conditions in schoolchildren could be addressed, and what the implications would be if this were done through a school-based programme such as the ISHP

Feasibility of Pulse Oximetry Pre-discharge Screening Implementation for detecting Critical Congenital heart Lesions in newborns in a secondary-level maternity hospital in the Western Cape, South Africa: The ‘POPSICLe’ study

Background. Early detection of critical congenital heart disease (CCHD) through newborn pulse oximetry (POx) screening is an effective strategy for reducing paediatric morbidity and mortality rates and has been adopted by much of the  developed world.Objectives. To document the feasibility of implementing pre-discharge POx  screening in well babies born at Mowbray Maternity Hospital, a busy government hospital in Cape Town, South Africa. Parent and staff acceptance was assessed.Methods. We conducted a prospective study of predischarge POx screening in one postnatal ward, following informed parental consent.Results. During the 4-month study period, 1 017 of 2 256 babies discharged  (45.1%) were offered POx screening and 1 001 were screened; 94.0% of tests took <3 minutes to perform, 4.3% 3 - 5 minutes and 1.7% >5 minutes. Eighteen patients needed second screens and three required third screens. Only 3.1% protocol errors were made, all without consequence. The vast majority (91.6%) of nursing staff reported insufficient time to perform the study screening in addition to their daily tasks, but ~75% felt that with a full nursing staff complement and if done routinely (not part of a study), pre-discharge POx screening could be successfully instituted at our facility. Over 98% of the mothers had positive comments. Two babies failed screening and required echocardiograms; one was diagnosed with CCHD and the other with neonatal sepsis. The sensitivity and specificity were 50% (95%  confidence interval (CI) 1.3 - 98.7%) and 99.9% (95% CI 99.4 - 100%),  respectively, with a percentage correct of 99.8%.Conclusions. POx screening was supported and accepted by staff and parents. If there are no nursing staff shortages and if it is done routinely before discharge, not as part of a study, we conclude that POx screening could be implemented  successfully without excessive false positives or errors, or any additional burden to cardiology services

The burden of cardiovascular disease in sub-Saharan Africa

Correspondence: The burden of cardiovascular disease in sub-Saharan Africa by Anthony Mbewu

Syngamus trachea in free-ranging white stork (Ciconia ciconia) nestlings in Switzerland.

Syngamosis is a disease caused by the strongylid nematode Syngamus trachea, which infects the respiratory tract of various bird species around the world. The parasite appears to be harmful for a wide variety of avian orders, occasionally leading to a fatal outcome, particularly in young birds. The aim of this study was to examine the parasitic fauna in deceased or euthanized, free-ranging white storks nesting at the Zoo Basel in 2019 and 2020; and to assess the extent to which these parasites contributed to the wild birds' death. In five out of 24 necropsied white storks, an infection with S. trachea was diagnosed based on morphological analysis of adult nematode stages and eggs, in combination with PCR amplification and sequencing of DNA extracted from female worms. The main pathological changes affected the white storks' respiratory tract and a mixed cell tracheitis was diagnosed in the histopathological examination of three of the five infected birds. Some birds displayed additional lesions compatible with syngamosis, namely partially degenerated parasitic structures with concurrent granulomatous inflammation in the lung and multifocal acute hemorrhages in the bronchi and parabronchi. Coprological examinations (fecal flotation technique, fecal sedimentation technique, sodium acetate acetic acid formalin procedure and Ziehl-Neelsen staining) from the intestinal content as well as a PCR for Toxoplasma gondii on brain, lung, heart, liver, and spleen tissue yielded negative results in all examined individuals. In the absence of further major pathological findings, S. trachea was assumed to have significantly contributed to the death of the infected birds

Feasibility of Pulse Oximetry Pre-discharge Screening Implementation for detecting Critical Congenital heart Lesions in newborns in a secondary level maternity hospital in the Western Cape, South Africa: The ‘POPSICLe’ study

Background. Early detection of critical congenital heart disease (CCHD) through newborn pulse oximetry (POx) screening is an effective strategy for reducing paediatric morbidity and mortality rates and has been adopted by much of the developed world. Objectives. To document the feasibility of implementing pre-discharge POx screening in well babies born at Mowbray Maternity Hospital, a busy government hospital in Cape Town, South Africa. Parent and staff acceptance was assessed.Methods. We conducted a prospective study of predischarge POx screening in one postnatal ward, following informed parental consent.Results. During the 4-month study period, 1 017 of 2 256 babies discharged (45.1%) were offered POx screening and 1 001 were screened; 94.0% of tests took <3 minutes to perform, 4.3% 3 - 5 minutes and 1.7% >5 minutes. Eighteen patients needed second screens and three required third screens. Only 3.1% protocol errors were made, all without consequence. The vast majority (91.6%) of nursing staff reported insufficient time to perform the study screening in addition to their daily tasks, but ~75% felt that with a full nursing staff complement and if done routinely (not part of a study), pre-discharge POx screening could be successfully instituted at our facility. Over 98% of the mothers had positive comments. Two babies failed screening and required echocardiograms; one was diagnosed with CCHD and the other with neonatal sepsis. The sensitivity and specificity were 50% (95% confidence interval (CI) 1.3 - 98.7%) and 99.9% (95% CI 99.4 - 100%), respectively, with a percentage correct of 99.8%.Conclusions. POx screening was supported and accepted by staff and parents. If there are no nursing staff shortages and if it is done routinely before discharge, not as part of a study, we conclude that POx screening could be implemented successfully without excessive false positives or errors, or any additional burden to cardiology services

Exon deletions and intragenic insertions are not rare in ataxia with oculomotor apraxia 2

<p>Abstract</p> <p>Background</p> <p>The autosomal recessively inherited ataxia with oculomotor apraxia 2 (AOA2) is a neurodegenerative disorder characterized by juvenile or adolescent age of onset, gait ataxia, cerebellar atrophy, axonal sensorimotor neuropathy, oculomotor apraxia, and elevated serum AFP levels. AOA2 is caused by mutations within the senataxin gene (<it>SETX</it>). The majority of known mutations are nonsense, missense, and splice site mutations, as well as small deletions and insertions.</p> <p>Methods</p> <p>To detect mutations in patients showing a clinical phenotype consistent with AOA2, the coding region including splice sites of the <it>SETX </it>gene was sequenced and dosage analyses for all exons were performed on genomic DNA. The sequence of cDNA fragments of alternative transcripts isolated after RT-PCR was determined.</p> <p>Results</p> <p>Sequence analyses of the <it>SETX </it>gene in four patients revealed a heterozygous nonsense mutation or a 4 bp deletion in three cases. In another patient, PCR amplification of exon 11 to 15 dropped out. Dosage analyses and breakpoint localisation yielded a 1.3 kb LINE1 insertion in exon 12 (patient P1) and a 6.1 kb deletion between intron 11 and intron 14 (patient P2) in addition to the heterozygous nonsense mutation R1606X. Patient P3 was compound heterozygous for a 4 bp deletion in exon 10 and a 20.7 kb deletion between intron 10 and 15. This deletion was present in a homozygous state in patient P4.</p> <p>Conclusion</p> <p>Our findings indicate that gross mutations seem to be a frequent cause of AOA2 and reveal the importance of additional copy number analysis for routine diagnostics.</p

Safety of streptococcus pyogenes vaccines: anticipating and overcoming challenges for clinical trials and post marketing monitoring

Streptococcus. pyogenes (Strep A) infections result in a vastly underestimated burden of acute and chronic disease globally. The Strep A Vaccine Global Consortium (SAVAC) mission is to accelerate the development of safe, effective and affordable S. pyogenes vaccines. The safety of vaccine recipients is of paramount importance. A single S. pyogenes vaccine clinical trial conducted in the 1960s raised important safety concerns. A SAVAC Safety Working Group was established to review the safety assessment methodology and results of more recent early phase clinical trials and to consider future challenges for vaccine safety assessments across all phases of vaccine development. No clinical or biological safety signals were detected in any of these early phase trials in the modern era. Improvements in vaccine safety assessments need further consideration, particularly for pediatric clinical trials, large-scale efficacy trials, and preparation for post-marketing pharmacovigilance

Spectrum of cardiac disease in maternity in a low-resource cohort in South Africa

Background: Lack of evidence-based data on the spectrum of cardiovascular disease (CVD) in pregnancy or in the postpartum period, as well as on maternal and fetal outcome, provides challenges for treating physicians, particularly in areas of low resources. The objectives of this study were to investigate the spectrum of disease, mode of presentation and maternal and fetal outcome of patients referred to a dedicated Cardiac Disease and Maternity Clinic (CDM). Methods: The prospective cohort study was conducted at a single tertiary care centre in South Africa. Two hundred and twenty-five women presenting with CVD in pregnancy, or within 6 months postpartum, were studied over a period of 2 years. Clinical assessment, echocardiography and laboratory tests were performed at baseline and follow-up visits. Prepartum, peripartum and postpartum complications were grouped into cardiac, neonatal and obstetric events. Results: Ethnicity was black African (45%), mixed ethnicity (32%), white (15%), Indian/others (8%) and 12% were HIV positive. Of the 225 consecutive women (mean age 28.8±6.4), 196 (86.7%) presented prepartum and 73 in modified WHO class I. The 152 women presenting in a higher risk group (modified WHO class II-IV) were offered close follow-up at the CDM clinic and were diagnosed with congenital heart disease (32%, 15 operated previously), valvular heart disease (26%, 15 operated previously), cardiomyopathy (27%) and other (15%). Women presenting with symptoms of CVD or heart failure postpartum (n=30) presented in a higher New York Heart Association, had higher heart rates (p42 days postpartum. Perinatal death occurred in 1/152 (0.7%) - translating to a perinatal mortality rate of 7/1000 live births. Conclusions: Disease patterns were markedly different to that seen in the developed world. However, joint obstetric-cardiac care in the low-resource cohort was associated with excellent survival outcome rates of pregnant mothers (even with complex diseases) and their offspring and was similar to that seen in the western world. Mortality typically occurred in the postpartum period, beyond the standard date of recording maternal death

Sex differences in the etiology and burden of heart failure across country income level: analysis of 204 countries and territories 1990–2019

Background Heart failure (HF) is a global epidemic. Objective To assess global sex differences in HF epidemiology across country income levels. Methods and results Using Global Burden of Disease (GBD) data from 204 countries and territories 1990–2019, we assessed sex differences in HF prevalence, etiology, morbidity, and temporal trends across country sociodemographic index or gross national income. We derived age-standardized rates. Of 56.2 million (95% uncertainty interval [UI] 46.4–67.8 million) people with HF in 2019, 50.3% were females and 69.2% lived in low- and middle-income countries; age-standardized prevalence was greater in males and in high-income countries. Ischaemic and hypertensive heart disease were top causes of HF in males and females, respectively. There were 5.1 million (95% UI 3.3–7.3 million) years lived with disability, distributed equally between sexes. Between 1990 and 2019, there was an increase in HF cases, but a decrease in age-standardized rates per 100 000 in males (9.1%, from 864.2 to 785.7) and females (5.8%, from 686.0 to 646.1). High-income regions experienced a 16.0% decrease in age-standardized rates (from 877.5 to 736.8), while low-income regions experienced a 3.9% increase (from 612.1 to 636.0), largely consistent across sexes. There was a temporal increase in age-standardized HF from hypertensive, rheumatic, and calcific aortic valvular heart disease, and a decrease from ischaemic heart disease, with regional and sex differences. Conclusion Age-standardized HF rates have decreased over time, with larger decreases in males than females; and with large decreases in high-income and small increases in low-income regions. Sex and regional differences offer targets for intervention

Disruption of the IS6-AID Linker Affects Voltage-gated Calcium Channel Inactivation and Facilitation

Two processes dominate voltage-gated calcium channel (CaV) inactivation: voltage-dependent inactivation (VDI) and calcium-dependent inactivation (CDI). The CaVβ/CaVα1-I-II loop and Ca2+/calmodulin (CaM)/CaVα1–C-terminal tail complexes have been shown to modulate each, respectively. Nevertheless, how each complex couples to the pore and whether each affects inactivation independently have remained unresolved. Here, we demonstrate that the IS6–α-interaction domain (AID) linker provides a rigid connection between the pore and CaVβ/I-II loop complex by showing that IS6-AID linker polyglycine mutations accelerate CaV1.2 (L-type) and CaV2.1 (P/Q-type) VDI. Remarkably, mutations that either break the rigid IS6-AID linker connection or disrupt CaVβ/I-II association sharply decelerate CDI and reduce a second Ca2+/CaM/CaVα1–C-terminal–mediated process known as calcium-dependent facilitation. Collectively, the data strongly suggest that components traditionally associated solely with VDI, CaVβ and the IS6-AID linker, are essential for calcium-dependent modulation, and that both CaVβ-dependent and CaM-dependent components couple to the pore by a common mechanism requiring CaVβ and an intact IS6-AID linker