Building global vaccine manufacturing capacity: Spotlight on Africa.

Africa is set to experience a three-fold increase in vaccine demand by 2040, yet the continent possesses few domestic capabilities for vaccine production. This lack of production capacity, heavy reliance on foreign aid, disruptions of hard-won immunization progress due to the effects of the COVID-19 pandemic, and fluctuating vaccine market dynamics threaten to hinder ongoing efforts to increase vaccination rates on the continent. In order meet the vaccine demands of a rapidly growing population, and to be able to provide novel vaccines to its population in the future, the African continent must develop a sustainable vaccine manufacturing infrastructure. The African Union, in partnership with the Africa Centres for Disease Control and Prevention, recently set forth its Program for African Vaccine Manufacturing Framework for Action, which sets the goal of Africa producing 60 % of its vaccine needs by 2040. To meet these goals, African governments and their multinational, philanthropic, and private sector partners must work to secure low-cost financing and provide a favourable regulatory environment for nascent African vaccine manufacturers. Doing so will save lives, safeguard the health of the continent's current and future citizens, and contribute to economic growth through the development of local bioeconomies.

Relations of aortic stiffness with arterial damage beyond brachial pressure are both dependent and independent of central arterial pulsatile load.

AIM: We aimed to determine whether the impact of aortic stiffness on atherosclerotic or small vessel end organ damage beyond brachial blood pressure depends in-part on stiffness-induced increases in central arterial pressures produced by an enhanced resistance to flow (characteristic impedance, Zc). METHODS: We studied 1021 participants, 287 with stroke or critical limb ischaemia, and 734 from a community sample with atherosclerotic or small vessel end organ measures. Central arterial haemodynamics were determined from arterial pressure (SphygmoCor) and velocity and diameter assessments in the outflow tract (echocardiography). RESULTS: Although Zc and carotid-femoral pulse wave velocity (PWV) were correlated (P < 0.0001), these relations were not independent of confounders (P = 0.90). Both Zc and hence central arterial pressures generated by the product of Zc and aortic flow (Q) (PQxZc), as well as PWV were independently associated with carotid intima-media thickness, estimated glomerular filtration rate (eGFR), endothelial activation markers [vascular cell adhesion molecule-1 (V-CAM-1)] and events. With further adjustments for brachial pulse pressure (PP) or SBP, PWV and PQxZc were both associated with eGFR and V-CAM-1. Relationships between PWV and eGFR or V-CAM-1 were independent of PQxZc (P < 0.05) and relationships between PQxZc and eGFR and V-CAM-1 were independent of PWV (P < 0.005). Similarly, with adjustments for confounders and brachial PP or SBP, across the full adult lifespan, both aortic PWV and PQxZc were increased in those with arterial events (P < 0.005). Relationships between PWV and events were again independent of PQxZc (P < 0.005) and between PQxZc and events were independent of PWV (P < 0.0001). CONCLUSION: Beyond brachial blood pressure, the impact of aortic stiffness on arterial damage involves effects that are both dependent (proximal aortic Zc and hence PQxZc) and independent (full aortic length indexed by PWV) of central arterial pulsatile load. Hence, PWV and brachial PP may be insufficient to account for all of the damage mediated by increases in aortic stiffness.

Marked Arterial Functional Changes in Patients With Arterial Vascular Events Across the Early Adult Lifespan.

OBJECTIVE: The age at which arteriosclerosis begins to contribute to events is uncertain. We determined, across the adult lifespan, the extent to which arteriosclerosis-related changes in arterial function occur in those with precipitous arterial events (stroke and critical limb ischemia). Approaches and Results: In 1082 black South Africans (356 with either critical limb ischemia [n=238] or stroke [n=118; 35.4% premature], and 726 age, sex, and ethnicity-matched randomly selected controls), arterial function was evaluated from applanation tonometry and velocity and diameter measurements in the outflow tract. Compared with age- and sex-matched controls, over 10-year increments in age from 20 to 60years, multivariate-adjusted (including steady-state pressures) aortic pulse wave velocity, characteristic impedance (Zc), forward wave pressures (Pf), and early systolic pulse pressure amplification were consistently altered in those with arterial events. Increases in Zc were accounted for by aortic stiffness (no differences in aortic diameter) and Pf by changes in Zc and not aortic flow or wave re-reflection. Multivariate-adjusted pulse wave velocity (7.48±0.30 versus 5.82±0.15 m/s, P<0.0001), Zc (P<0.0005), and Pf (P<0.0001) were higher and early systolic pulse pressure amplification lower (P<0.0001) in those with precipitous events than in controls. In comparison to age- and sex-matched controls, independent of risk factors, pulse wave velocity, and Zc (P<0.005 and <0.05) were more closely associated with premature events than events in older persons and Pf and early systolic pulse pressure amplification were at least as closely associated with premature events as events in older persons. CONCLUSIONS: Arteriosclerosis-related changes in arterial function are consistently associated with arterial events beyond risk factors from as early as 20 years of age.

Complementary Impact of Carotid Intima-Media Thickness With Plaque in Associations With Noncardiac Arterial Vascular Events.

The ability of carotid intima-media thickness (IMT) to predict risk beyond plaque is controversial. In 952 participants (critical limb ischemia [CLI] or stroke, n = 473; community, n = 479), we assessed whether relationships with events for IMT complement the impact of plaque in young patients depending on the extent of thrombotic versus atherosclerotic disease. The extent of atherosclerotic versus thrombotic occlusion was determined in 54 patients with CLI requiring amputations. Thrombotic occlusion in CLI was associated with younger age (P < .0001) and less plaque (P = .02). Independent relations between plaque and CLI were noted in older (>50 years; P < .005 to <.0001) but not younger (P > .38) participants, while independent relations between plaque and stroke (P < .005 to <.0001) and between IMT and CLI (P < .0001) were noted in younger participants. Although in performance (area under the receiver operating curve) for event detection, IMT thresholds failed to add to plaque alone in older patients (0.680 ± 0.020 vs 0.664 ± 0.017, P = .27), IMT improved performance for combined stroke and CLI detection when added to plaque in younger patients (0.719 ± 0.023 vs 0.631 ± 0.026, P < .0001). Because in younger participants the high prevalence of thrombotic occlusion in CLI is associated with less plaque, IMT adds information in associations with arterial vascular events.

Carotid intima-media thickness, but not chronic kidney disease independently associates with noncardiac arterial vascular events in South Africa.

AIM: Although chronic kidney disease (CKD) as determined from estimated glomerular filtration rate (eGFR) is recommended for risk prediction by current hypertension guidelines, the equations to derive eGFR may not perform well in black Africans. We compared whether across the adult lifespan, eGFR or CKD are as closely associated with noncardiac arterial vascular events, as carotid intima-media thickness (IMT), in Africa. METHODS: In 1152 black South Africans [480 with noncardiac arterial events (294 with critical lower limb ischemia, 186 with stroke) of which 37% were premature] and 672 age, sex and ethnicity-matched controls from a randomly selected community sample, we assessed relations between eGFR, CKD or carotid IMT (B-mode ultrasound) and arterial events. RESULTS: From 20 years until old age, with or without adjustments, IMT was increased in those with as compared with without events (P < 0.01 at each decade of age). However, at any decade of age across the adult lifespan neither creatinine concentrations, nor eGFR were altered in those with arterial events (P > 0.28). Although IMT was strongly and independently associated with the odds of an event [odds ratio per 1 SD (0.171 mm) effect = 2.19, confidence interval = 1.75-2.78, P < 0.0001], neither creatinine concentrations (P = 0.89), modification of diet in renal disease-derived (P = 0.07), nor Chronic Kidney Disease Epidemiology Collaboration-derived [odds ratio per 1 SD (22.5 ml/min per 1.73 m) effect = 1.06, confidence interval = 0.89-1.27, P = 0.51] eGFR were independently associated with the odds of an event. Although many with premature events had an increased IMT (63%), few with either premature events (8%) or with events at an older age (21%) had CKD and CKD had a poor performance (0.539 ±â€Š0.011) and low sensitivity (16%) for event detection. CONCLUSION: In black South Africans, despite carotid IMT strongly associating with noncardiac arterial vascular events (stroke and critical lower limb ischaemia) consistently across the adult lifespan, few with events have CKD and CKD fails to associate with events.

Stent-Graft Relining in a Patient with Acute Aortic Aneurysm and a Completely Migrated Endograft.

Stent-graft migration and type I endoleaks are associated with a higher rate of reintervention and increased mortality and morbidity. This article describes a patient presented with an infrarenal aortic stent-graft which had migrated into the aortic sac with loss of all aortic neck attachment. The acutely expanding abdominal aortic aneurysm was treated by placing a second modular endograft within and above the migrated stentgraft. The patient returned 36 months later, with features of an acute myocardial infarction, severe bilateral lower limb ischemia, and renal failure. He was too ill for intervention and demised within 48 hours.

Stent-graft relining in a patient with acute aortic aneurysm and a completely migrated endograft

Abstract Stent-graft migration and type I endoleaks are associated with a higher rate of reintervention and increased mortality and morbidity. This article describes a patient presented with an infrarenal aortic stent-graft which had migrated into the aortic sac with loss of all aortic neck attachment. The acutely expanding abdominal aortic aneurysm was treated by placing a second modular endograft within and above the migrated stentgraft. The patient returned 36 months later, with features of an acute myocardial infarction, severe bilateral lower limb ischemia, and renal failure. He was too ill for intervention and demised within 48 hours.

Peripheral Arterial Disease in Sub-Saharan Africa: A Review.

IMPORTANCE: Peripheral arterial disease (PAD) causes significant morbidity and is an important risk factor for cardiovascular disease-related mortality. However, the burden of PAD in sub-Saharan Africa is poorly understood. OBJECTIVE: To assess epidemiological and clinical reports regarding PAD from sub-Saharan Africa such that the regional epidemiology and management of PAD could be described and recommendations offered. EVIDENCE REVIEW: A systematic search in PubMed, Medline, Embase, the Cumulative Index to Nursing and Allied Health Literature, and Google Scholar for reports pertaining to the epidemiology and/or management of PAD in sub-Saharan Africa was performed. Reports that met inclusion criteria were sorted into 3 categories: population epidemiology, clinical epidemiology, and surgical case series. Findings were extracted and described. FINDINGS: The search returned 724 records; of these, 16 reports met inclusion criteria. Peripheral arterial disease epidemiology and/or management was reported from 10 of the 48 sub-Saharan African countries. Peripheral arterial disease prevalence ranged from 3.1% to 24% of adults aged 50 years and older and 39% to 52% of individuals with known risk factors (eg, diabetes). Medical management was only described by 2 reports; both documented significant undertreatment of PAD as a cardiovascular disease risk factor. Five surgical case series reported that trauma and diabetes-related complications were the most common indications for vascular surgery. CONCLUSIONS AND RELEVANCE: The prevalence of PAD in sub-Saharan Africa may be equal to or higher than that in high-income countries, exceeding 50% in some high-risk populations. In addition to population-based studies that better define the PAD burden in sub-Saharan Africa, health systems should consider studies and action regarding risk factor mitigation, targeted screening, medical management of PAD, and defining essential vascular care.

Aorto-internal iliac artery endovascular reconstruction for critical limb ischaemia: a case report.

The internal iliac artery and cruciate anastomosis are important collateral vessels in severe aortoiliac occlusive disease. This report describes a patient with left leg rest pain due to occlusion of the left common and external iliac arteries. In addition, there was a high-grade stenosis of the right common iliac artery. Direct catheter canulation of the left internal iliac artery revealed that it was patent. Endovascular stent placement was successful in re-establishing blood flow into the left internal iliac artery. Ischaemic rest pain was relieved and the ankle brachial index was maintained at 0.85 at 6 months follow-up.

A case of Endovascular Treatment of Blunt Aortic Bifurcation Transection using peripheral stentgraft.

We present a case of endovascular management of aortic transection at the aortic bifurcation in a polytrauma patient.

Prevalence and patterns of infection in critically ill trauma patients admitted to the trauma ICU, South Africa.

INTRODUCTION: The aim of this study was to determine if any patterns of infection or bacterial resistance existed in critically ill polytrauma patients admitted to the intensive care unit (ICU) at the CM Johannesburg Academic Hospital (CMJAH). METHODS: This was a prospective, single-center study of patient laboratory records of 73 critically injured polytrauma patients admitted to an ICU. The data collected from each patient, beginning with admission and extending until discharge from the ICU, included age, gender, admission hemoglobin levels, injury severity score, length of ICU stay, microbiological cultures and sensitivity (MCS), and types and numbers of surgical procedures. RESULTS: Upon admission to the ICU, the injury severity score (ISS) was 40.86 (± 15.64). In total, 73.98% of the patients required the use of a ventilator during their ICU stay. The most prevalent organisms isolated from specimens were Pseudomonas aeruginosa (30.1%), Klebsiella species (25.7%), Acinetobacterbaumanni (16.4%), and Staphylococcus aureus (5.8%). Multi-drug resistance (MDR) was identified in 63% of patients, with Klebsiella (73.91%) and Pseudomonas (65.21%) occurring most frequently. Multivariate analysis showed MDR to be the only significant predictor associated with a higher risk for hospital mortality when age, gender, ventilation, duration of ICU stay, ISS score, and the number of surgeries undergone was taken into account. CONCLUSION: Critically ill polytrauma patients are at particularly high risk for Gram-negative sepsis.

Endovascular Treatment of an Acutely Thrombosed Abdominal Aortic Aneurysm.

BACKGROUND: Acute thrombosis of an infrarenal abdominal aortic aneurysm may be a life-threatening condition. REPORT: We describe a case of acute thrombosis of a 3.5-cm abdominal aortic aneurysm resulting in threatened lower limbs, in a high-risk surgical patient. Emergency stent-graft placement was undertaken using Fluency endoprostheses. The patient remains well at 1-year follow-up. CONCLUSION: High-risk surgical patients with acutely thrombosed abdominal aortic aneurysms may not be candidates for open surgery. Use of peripheral stent grafts in emergency situation has not been reported in such patients.

Large vessel adventitial vasculitis characterizes patients with critical lower limb ischemia with as compared to without human immunodeficiency virus infection.

OBJECTIVES: Whether a human immunodeficiency virus (HIV)-associated vasculitis in-part accounts for occlusive large artery disease remains uncertain. We aimed to identify the histopathological features that characterize large vessel changes in HIV sero-positive as compared to sero-negative patients with critical lower limb ischemia (CLI). MATERIALS AND METHODS: Femoral arteries obtained from 10 HIV positive and 10 HIV negative black African male patients admitted to a single vascular unit with CLI requiring above knee amputation were subjected to histopathological assessment. None of the HIV positive patients were receiving antiretroviral therapy. RESULTS: As compared to HIV negative patients with CLI, HIV positive patients were younger (p<0.01) and had a lower prevalence of hypertension (10 vs 90%, p<0.005) and diabetes mellitus (0 vs 50%, p<0.05), but a similar proportion of patients previously or currently smoked (80 vs 60%). 90% of HIV positive patients, but no HIV negative patient had evidence of adventitial leukocytoclastic vasculitis of the vasa vasorum (p<0.0001). In addition, 70% of HIV positive, but no HIV negative patient had evidence of adventitial slit-like vessels. Whilst T-lymphocytes were noted in the adventitia in 80% of HIV positive patients, T-lymphocytes were noted only in the intima in HIV negative patients. The presence of femoral artery calcified multilayered fibro-atheroma was noted in 40% of HIV positive and 90% of HIV negative patients with CLI. CONCLUSIONS: An adventitial vasculitis which characterizes large artery changes in CLI in HIV-infected as compared to non-infected patients, may contribute toward HIV-associated occlusive large artery disease.

Thoracic outlet syndrome in a patient with absent scalenus anterior muscle.

This case report describes the rare anomaly of an absent right anterior scalene muscle presenting with the symptoms and signs of the thoracic outlet syndrome. The thoracic outlet syndrome in our patient can be attributed to the absence of the right anterior scalene muscle, which resulted in the brachial plexus being in proximity to the subclavian vein and artery in a narrowed and abnormal interscalene space. In addition, the absence of the anterior scalene muscle resulted in the neurovascular structures being compressed onto the first rib in the costoclavicular space. The most likely cause of the presentation is, however, the possibility of the presence of aberrant muscle slips, which would cause compression of the structures in the anterior (venous) and posterior (neurological) sections of the thoracic outlet.

Chronic diseases are not being managed effectively in either high-risk or low-risk populations in South Africa.

BACKGROUND: Primary healthcare is the foundation of a country's healthcare system. Without an efficient and cost-effective programme, the level of healthcare offered across all levels of health management is adversely affected. OBJECTIVE: To analyse the effectiveness of the management of hypertension and diabetes mellitus (DM) among two distinct patient populations, one with significant cardiovascular risk factors and the other without. METHOD: We performed a case control study of a high-risk group of patients presenting with chronic critical limb ischaemia (CLI) to the Divisions of Vascular Surgery at Charlotte Maxeke Johannesburg Academic Hospital and Chris Hani Baragwanath Academic Hospital, and a randomly selected group of 'healthy' community participants from Johannesburg's South Western Townships (Soweto). RESULTS: We assessed 217 patients with CLI and 1 030 participants from the community. We assessed the number of patients who were not achieving their therapeuatic targets, among those known to be hypertensive (CLI: 44.7%; community: 59.9%) and diabetic (CLI: 83.5%; community: 66%). Undiagnosed diabetes affected 10.8% of patients with CLI and 11% of the community sample. CONCLUSION: Traditional vascular risk factors are managed poorly at both primary healthcare and at tertiary care levels. There is a need to identify factors that will address this issue.

Brachial blood pressure-independent relations between radial late systolic shoulder-derived aortic pressures and target organ changes.

Central aortic blood pressure (BP; BPc) predicts outcomes beyond brachial BP. In this regard, the application of a generalized transfer function (GTF) to radial pulse waves for the derivation of BPc is an easy and reproducible measurement technique. However, the use of the GTF may not be appropriate in all circumstances. Although the peak of the second shoulder of the radial waveform (P2) is closely associated with BPc, and, hence, BPc may be assessed without the need for a GTF, whether P2-derived BPc is associated with adverse cardiovascular changes independent of brachial BP is uncertain. Thus, P2- and GTF-derived aortic BPs were assessed using applanation tonometry and SphygmoCor software. Left ventricular mass was indexed for height(1.7) (n=678) and carotid intima-media thickness (IMT; n=462) was determined using echocardiography and vascular ultrasound. With adjustments for nurse-derived brachial pulse pressure (PP), P2-derived central PP was independently associated with left ventricular mass indexed for height(1.7) (partial r=0.18; P<0.0001) and IMT (partial r=0.40; P<0.0001). These relations were similar to nurse-derived brachial PP-independent relations between GTF-derived central PP and target organ changes (left ventricular mass indexed for height(1.7): partial r=0.17, P<0.0001; IMT: partial r=0.37, P<0.0001). In contrast, with adjustments for central PP, nurse-derived brachial PP-target organ relations were eliminated (partial r=-0.21 to 0.05). Twenty-four-hour, day, and night PP-target organ relations did not survive adjustments for nurse-derived brachial BP. In conclusion, central PP derived from P2, which does not require a GTF, is associated with cardiovascular target organ changes independent of brachial BP. Thus, when assessing adverse cardiovascular effects of aortic BP independent of brachial BP, P2-derived measures may complement GTF-derived measures of aortic BP.