Characteristics of infections with ancestral, Beta and Delta variants of SARS-CoV-2 in the PHIRST-C community cohort study, South Africa, 2020-2021.

BACKGROUND: Data on the characteristics of individuals with mild and asymptomatic infections with different SARS-CoV-2 variants are limited. We therefore compared the characteristics of individuals infected with ancestral, Beta and Delta SARS-CoV-2 variants in South Africa. METHODS: We conducted a prospective cohort study in a rural and an urban site during July 2020-August 2021. Mid-turbinate nasal swabs were collected twice-weekly from household members irrespective of symptoms and tested for SARS-CoV-2 using real-time reverse transcription polymerase chain reaction (rRT-PCR). Differences in demographic and clinical characteristics, shedding and cycle threshold (Ct) value of infection episodes by variant were evaluated using multinomial regression. Overall and age-specific incidence rates of infection were compared by variant. RESULTS: We included 1200 individuals from 222 households and 648 rRT-PCR-confirmed infection episodes (66, 10% ancestral, 260, 40% Beta, 322, 50% Delta). Symptomatic proportion was similar for ancestral (7, 11%), Beta (44, 17%), and Delta (46, 14%) infections (p=0.4). After accounting for previous infection, peak incidence shifted to younger age groups in successive waves (40-59 years ancestral, 19-39 years Beta, 13-18 years Delta). On multivariable analysis, compared to ancestral, Beta infection was more common in individuals aged 5-12 years (vs 19-39)(adjusted odds ratio (aOR) 2.6, 95% confidence interval (CI)1.1-6.6) and PCR cycle threshold (Ct) value <30 (vs >35)(aOR 3.2, 95%CI 1.3-7.9), while Delta was more common in individuals aged <5 (aOR 6.7, 95%CI1.4-31.2) and 5-12 years (aOR 6.6 95%CI2.6-16.7)(vs 19-39) and Ct value <30 (aOR 4.5, 95%CI 1.3-15.5) and 30-35 (aOR 6.0, 95%CI 2.3-15.7)(vs >35). CONCLUSIONS: Consecutive SARS-CoV-2 waves with Beta and Delta variants were associated with a shift to younger individuals. Beta and Delta infections were associated with higher peak viral loads, potentially increasing infectiousness.

Web-based objective and structured assessment of point-of-care lung ultrasound skills in resource-limited settings.

BACKGROUND: Objective assessment of skills after training is essential for safe implementation of lung point-of-care ultrasound (POCUS). In low-and middle-income countries (LMIC) there is a need for assessment tools without onsite experts to scale up POCUS access. Our objective is to develop a web-based assessment tool and evaluate trainees across different countries and at different time points after initial lung POCUS training. METHODS: We adapted the objective and validated lung ultrasound score (LUS-OSAUS) to a web-based tool with quiz and practical skills test. Trainees were evaluated after a short (4-day) standardized lung POCUS training and were classified in distinct groups according to (i) their geographical location (Benin vs. South-Africa) and (ii) time elapsed since training (Benin 0 months vs. Benin 6 months). The Benin 6 months group had minimal continuous education. Skills test images were read by two blinded experts. We report the overall success rates and then compare these rates based on location and timing since training, using the Fischer's exact test. RESULTS: A total of 35 out of 43 participants completed the online LUS-OSAUS quiz and skills test. The overall success rate was 0.84 (95%CI 0.80-0.88), with lower success rates for "correct depth" 0.54 (0.37-0.71), "correct assessment of pleura" 0.63 (0.45-0.79) and "conclusion" 0.71 (0.54-0.85). There were no differences based on location, with respective rates of 0.86 (0.80-0.92) and 0.83 (0.75-0.91) (p-value = 0.125) for Benin and South Africa at 0 months, respectively. Similarly, there were no differences according to timing with success rates of 0.86 (0.80-0.92) and 0.82 (0.72-0.93) (p-value = 0.563) for Benin at 0 months and 6 months, respectively. CONCLUSION: Web-based objective and structured assessment of lung POCUS skills in LMIC following a short-standardized training is feasible and has a good overall success rate with consistent results across regions and up to 6 months after training given minimal continuous education. Overall, technical and POCUS-based clinical conclusion skills are the most difficult to acquire.

Vascular Endothelial Growth Factor C (VEGF-C) Sensitizes Lymphatic Endothelial Cells to Oxidative-Stress-Induced Apoptosis through DNA Damage and Mitochondrial Dysfunction: Implications for Lymphedema.

Secondary lymphedema is caused by damage to the lymphatic system from surgery, cancer treatment, infection, trauma, or obesity. This damage induces stresses such as oxidative stress and hypoxia in lymphatic tissue, impairing the lymphatic system. In response to damage, vascular endothelial growth factor C (VEGF-C) levels increase to induce lymphangiogenesis. Unfortunately, VEGF-C often fails to repair the lymphatic damage in lymphedema. The underlying mechanism contributing to lymphedema is not well understood. In this study, we found that surgery-induced tail lymphedema in a mouse model increased oxidative damage and cell death over 16 days. This corresponded with increased VEGF-C levels in mouse tail lymphedema tissue associated with macrophage infiltration. Similarly, in the plasma of patients with secondary lymphedema, we found a positive correlation between VEGF-C levels and redox imbalance. To determine the effect of oxidative stress in the presence or absence of VEGF-C, we found that hydrogen peroxide (H2O2) induced cell death in human dermal lymphatic endothelial cells (HDLECs), which was potentiated by VEGF-C. The cell death induced by VEGF-C and H2O2 in HDLECs was accompanied by increased reactive oxygen species (ROS) levels and a loss of mitochondrial membrane potential. Antioxidant pre-treatment rescued HDLECs from VEGF-C-induced cell death and decreased ROS under oxidative stress. As expected, VEGF-C increased the number of viable and proliferating HDLECs. However, upon H2O2 treatment, VEGF-C failed to increase either viable or proliferating cells. Since oxidative stress leads to DNA damage, we also determined whether VEGF-C treatment induces DNA damage in HDLECs undergoing oxidative stress. Indeed, DNA damage, detected in the form of gamma H2AX (γH2AX), was increased by VEGF-C under oxidative stress. The potentiation of oxidative stress damage induced by VEFG-C in HDLECs was associated with p53 activation. Finally, the inhibition of vascular endothelial growth factor receptor-3 (VEGFR-3) activation blocked VEGF-C-induced cell death following H2O2 treatment. These results indicate that VEGF-C further sensitizes lymphatic endothelial cells to oxidative stress by increasing ROS and DNA damage, potentially compromising lymphangiogenesis.

SARS-CoV-2 Seroprevalence after Third Wave of Infections, South Africa.

By November 2021, after the third wave of severe acute respiratory syndrome coronavirus 2 infections in South Africa, seroprevalence was 60% in a rural community and 70% in an urban community. High seroprevalence before the Omicron variant emerged may have contributed to reduced illness severity observed in the fourth wave.

Evaluation of host biomarkers for monitoring treatment response in spinal tuberculosis: A 12-month cohort study.

BACKGROUND: Monitoring treatment response is an important precaution in spinal tuberculosis (TB), particularly when the condition was clinically diagnosed rather than bacteriologically confirmed and when drug susceptibility testing was not performed. Conventional monitoring measures have limitations and there is a need for favourable alternatives. Therefore, this study aimed to investigate changes in immune biomarkers over the course of treatment for spinal TB and to compare these responses to the conventional monitoring measure, erythrocyte sedimentation rate (ESR). METHODS: Patients with spinal TB were recruited from a tertiary hospital in the Western Cape, South Africa, and provided blood samples at 0, 3, 6, 9 and 12 months of TB treatment. Blood samples were analysed for ESR, using standard techniques, and for 19 cytokines, using a multiplex platform. Changes in ESR and cytokine levels were investigated using a mixed model ANOVA and Least Significant Difference post-hoc testing. RESULTS: Twenty-six patients with spinal TB were included in the study although only fifteen remained in follow-up at 12 months. Seven biomarkers changed significantly over the course of treatment (CRP, Fibrinogen, IFN-γ, Ferritin, VEGF-A, ApoA1 and NCAM, p < 0.01) with a further three showing a strong trend towards change (CCL1, CXCL9 and GDF-15, 0.05 ≥ p ≤ 0.06). Responsive biomarkers could be approximately grouped according to patterns of progressive, initial or delayed change. ESR performed similarly to CRP, Fibrinogen and IFN-γ with all showing significant decreases between 0, 6 and 12- months of treatment. Individual ESR responses were variable. DISCUSSION: Individual ESR responses may be unreliable and support the investigation of multi-marker approaches to evaluating treatment response in spinal TB. Biomarkers of treatment response identified in the current study require validation in a larger study, which may also incorporate aspects such as evaluating biomarkers within the first week of treatment and the inclusion of a healthy control group.

Spinal Curvatures, Deformities, and the Level of Disability in People with Bilateral Spastic Cerebral Palsy Living in South Africa; A 6-Year Follow-Up Study During Adulthood.

OBJECTIVE: Determine if spinal curvatures, deformities, as well as level of disability (due to back pain) changes with aging in adults with bilateral spastic cerebral palsy after receiving orthopedic interval surgery approach treatment in childhood. DESIGN: Consecutive case-series SETTING: Urban South Africa PARTICIPANTS: Twenty-seven ambulatory adults with cerebral palsy MAIN OUTCOME MEASURES: Spinal curvatures (scoliosis, thoracic kyphosis and lumbar lordosis) and deformities (spondylolysis and spondylolisthesis) were determined with X-rays, while the level of disability was assessed with the Oswestry Disability Index. RESULTS: The prevalence of spinal abnormalities were: 30% scoliosis (mild: <30°), 0% thoracic hyperkyphosis, 15% lumbar hyperlordosis, 0%; spondylolysis, and 0% spondylolisthesis. No changes in scoliosis and lumbar lordosis angles were observed, while the change in thoracic kyphosis angle was smaller than the minimal clinically important difference and moved closer toward the norm-values for typically developing adults. Level of disability remained similar with 63% reporting minimal disability, 26% moderate disability and 11% severe disability. No associations with spinal curvatures were found. CONCLUSIONS: No clinically meaningful changes in spinal curvatures, deformities and level of disability due to pain were seen during the 6 years follow-up period in adults with cerebral palsy who have been treated with interval surgery approach in childhood.

SARS-CoV-2 Seroprevalence in a Rural and Urban Household Cohort during First and Second Waves of Infections, South Africa, July 2020-March 2021.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections may be underestimated because of limited access to testing. We measured SARS-CoV-2 seroprevalence in South Africa every 2 months during July 2020-March 2021 in randomly selected household cohorts in 2 communities. We compared seroprevalence to reported laboratory-confirmed infections, hospitalizations, and deaths to calculate infection-case, infection-hospitalization, and infection-fatality ratios in 2 waves of infection. Post-second wave seroprevalence ranged from 18% in the rural community children <5 years of age, to 59% in urban community adults 35-59 years of age. The second wave saw a shift in age distribution of case-patients in the urban community (from persons 35-59 years of age to persons at the extremes of age), higher attack rates in the rural community, and a higher infection-fatality ratio in the urban community. Approximately 95% of SARS-CoV-2 infections were not reported to national surveillance.

Incidence of spinal deformities and the relationship with physical status and back pain in ambulant adults with cerebral palsy and spastic diplegia.

PURPOSE: The purpose of this study was to determine the incidence of spinal deformities in ambulant adults with cerebral palsy (CP) and spastic diplegia, more than 15 years after orthopaedic interval surgery approach (ISA) treatment, and its relationship to contextual factors, level of pain and physical status. METHODS: Spinal X-rays, pain (Oswestry Disability Index (ODI) and location/frequency) questionnaires and physical examination assessing lower extremity muscle strength (Medical Research Council scale), motor control (selectivity scale) and muscle tone (Ashworth score) were conducted in 30 adults with spastic diplegic CP. RESULTS: Mild scoliosis (curve 12-22°) was determined in eight (28%) participants. Hyperkyphosis (> 50°) was reported in two (7%) and lumbar hyperlordosis (> 60°) in five (17%) participants. Pain was most commonly reported at cervical (n = 19, 63%) and lumbosacral (n = 18, 60%) area, resulting in 'moderate disability' for six (20%) and 'severe disability' for one (3%) participant. Most apparent physical abnormalities determined were hip abduction weakness and increased rectus femoris muscle tone. Regarding correlations, no relations were found for scoliosis curvature, but kyphosis curvature was related to females, ODI scores (lifting and sitting) and increased muscle tone of ankle plantar flexor muscles, lordosis curvature to passive hip extension mobility, and hip flexors and ankle plantar flexors muscle tone. CONCLUSION: Adults with spastic diplegic CP who received their first orthopaedic intervention more than 15 years ago (based on ISA) showed similar incidence of spinal deformities as reported in the younger CP population, suggesting stability of spinal curvature into adulthood. These slides can be retrieved under Electronic Supplementary Material.

The level of accomplishment and satisfaction in activity and participation of adults with cerebral palsy and spastic diplegia.

BACKGROUND: Orthopaedic surgery is commonly performed in children with cerebral palsy (CP) and spastic diplegia to improve functional mobility. However, no research has quantified levels of accomplishment and satisfaction in daily activities and participation long-term after surgery. Therefore, this study aimed to investigate 1) the level of accomplishment and satisfaction of life habits in adults with CP, 2) whether there were differences between Gross Motor Function Classification System (GMFCS) levels, and 3) associations with contextual factors, functional level and frequency of pain. METHODS: Levels of accomplishment and satisfaction in activity and participation were assessed using the Life-Habits 3.1 questionnaire in 30 adults with CP and spastic diplegia who received the first orthopaedic intervention more than 15 years ago (age: median [interquartile range (IQR)] = 27:8 [21:7-33:8] y:mo; GMFCS level I/II/III: n = 15/11/4). GMFCS and Functional Mobility Scale (FMS) assessed mobility over 5 m, 50 m and 500 m. Participants reported frequency of back pain and pain in the lower and upper limb. RESULTS: On average 63% of the participants were independent and faced no difficulties in the accomplishment of all life habits. Difficulties were mostly experienced for 'mobility', 'housing' and 'recreation' (all 61%). Participants were overall satisfied, with lowest scores for 'employment' (13% dissatisfied). Between the GMFCS levels, accomplishment scores of participants with level I were significantly higher than level II. In addition, negative associations were found between accomplishment of life habits and GMFCS level, FMS, and pain on spinal level. CONCLUSION: Levels of accomplishment and satisfaction were relatively high among adults with CP who underwent orthopaedic interventions during childhood. However, negative associations between accomplishment levels and level of functioning and back pain argue for rehabilitation programs specialized on these factors. This information is imperative for physicians and allied health care professionals to guide adults with CP during ageing.

Spastic diplegia in children with HIV encephalopathy: first description of gait and physical status.

AIM: The aim of this study was to explore the physical status and gait patterns of children with spastic diplegia secondary to human immunodeficiency virus encephalopathy (HIVE). METHOD: A cross-sectional study was conducted on children diagnosed with HIVE and spastic diplegia. Sociodemographic and clinical background information was obtained, followed by three-dimensional gait analysis (3DGA) and a physical examination including assessments of muscle tone, strength, motor control, contractures, and bony deformities of the lower extremities. RESULTS: Fourteen children (eight males, six females; mean age 5 y 8 mo [SD 9 mo], range 4 y 4 mo-6 y 10 mo) were studied. The cohort was divided into two groups based on distinctive gait patterns. Nine participants in group I showed only limited abnormalities. Group II displayed a more pathological gait pattern including stiff knee and equinus ankle abnormalities. Results of 3DGA, as with the physical examination outcomes, showed increased impairments from proximal to distal (except for hip extension). INTERPRETATION: This study provides a first description of distinctive gait patterns and related physical characteristics of children with HIVE and spastic diplegia. Further research is necessary.

SARS-CoV-2 correlates of protection from infection against variants of concern.

Serum neutralizing antibodies (nAbs) induced by vaccination have been linked to protection against symptomatic and severe coronavirus disease 2019. However, much less is known about the efficacy of nAbs in preventing the acquisition of infection, especially in the context of natural immunity and against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune-escape variants. Here we conducted mediation analysis to assess serum nAbs induced by prior SARS-CoV-2 infections as potential correlates of protection against Delta and Omicron infections, in rural and urban household cohorts in South Africa. We find that, in the Delta wave, D614G nAbs mediate 37% (95% confidence interval: 34-40%) of the total protection against infection conferred by prior exposure to SARS-CoV-2, and that protection decreases with waning immunity. In contrast, Omicron BA.1 nAbs mediate 11% (95% confidence interval: 9-12%) of the total protection against Omicron BA.1 or BA.2 infections, due to Omicron's neutralization escape. These findings underscore that correlates of protection mediated through nAbs are variant specific, and that boosting of nAbs against circulating variants might restore or confer immune protection lost due to nAb waning and/or immune escape. However, the majority of immune protection against SARS-CoV-2 conferred by natural infection cannot be fully explained by serum nAbs alone. Measuring these and other immune markers including T cell responses, both in the serum and in other compartments such as the nasal mucosa, may be required to comprehensively understand and predict immune protection against SARS-CoV-2.

Impact of diabetes on longevity and disability-free life expectancy among older South African adults: A prospective longitudinal analysis.

AIMS: We seek to understand the coexisting effects of population aging and a rising burden of diabetes on healthy longevity in South Africa. METHODS: We used longitudinal data from the 2015 and 2018 waves of the "Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa" (HAALSI) study to explore life expectancy (LE) and disability-free life expectancy (DFLE) of adults aged 45 and older with and without diabetes in rural South Africa. We estimated LE and DFLE by diabetes status using Markov-based microsimulation. RESULTS: We find a clear gradient in remaining LE and DFLE based on diabetes status. At age 45, a man without diabetes could expect to live 7.4 [95% CI 3.4 - 11.7] more years than a man with diabetes, and a woman without diabetes could expect to live 3.9 [95% CI: 0.8 - 6.9] more years than a woman with diabetes. Individuals with diabetes lived proportionately more years subject to disability than individuals without diabetes. CONCLUSIONS: We find large and important decrements in disability-free aging for people with diabetes in South Africa. This finding should motivate efforts to strengthen prevention and treatment efforts for diabetes and its complications for older adults in this setting.

Associations between cohort derived dementia and COVID-19 serological diagnosis among older Black adults in rural South Africa.

Objectives: This study investigates the association between cohort derived dementia and serologically confirmed SARS-CoV-2 infection, an underexplored phenomena in low-and middle-income countries. Examining this relationship in a rural South African community setting offers insights applicable to broader healthcare contexts. Methods: Data were collected from Black South Africans in the Mpumalanga province who participated in the Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa. Cohort derived dementia was developed using a predictive model for consensus-based dementia diagnosis. Multinomial logistic regression models estimated the association between predicted dementia probability in 2018 and SARS-CoV-2 infection risk in 2021, controlling for demographics, socioeconomic status, and comorbidities. Results: Fifty-two percent of the tested participants had serologically confirmed SARS-CoV-2 infections. In the fully adjusted model, cohort derived dementia was significantly associated with over twice the risk of serological diagnosis of COVID-19 (RRR = 2.12, p = 0.045). Conclusion: Complying with COVID-19 prevention recommendations may be difficult for individuals with impaired cognitive functioning due to their symptoms. Results can inform community-based public health initiatives to reduce COVID-19 transmission among South Africa's rapidly aging population.

Indirect effects of COVID-19 on maternal and child health in South Africa.

BACKGROUND: The unfinished burden of poor maternal and child health contributes to the quadruple burden of disease in South Africa with the direct and indirect effects of the COVID-19 pandemic yet to be fully documented. OBJECTIVE: To investigate the indirect effects of COVID-19 on maternal and child health in different geographical regions and relative wealth quintiles. METHODS: We estimated the effects of COVID-19 on maternal and child health from April 2020 to June 2021. We estimated this by calculating mean changes across facilities, relative wealth index (RWI) quintiles, geographical areas and provinces. To account for confounding by underlying seasonal or linear trends, we subsequently fitted a segmented fixed effect panel model. RESULTS: A total of 4956 public sector facilities were included in the analysis. Between April and September 2020, full immunisation and first dose of measles declined by 6.99% and 2.44%, respectively. In the follow-up months, measles first dose increased by 4.88% while full immunisation remained negative (-0.65%) especially in poorer quintiles. At facility level, the mean change in incidence and mortality due to pneumonia, diarrhoea and severe acute malnutrition was negative. Change in first antenatal visits, delivery by 15-19-year olds, delivery by C-section and maternal mortality was positive but not significant. CONCLUSION: COVID-19 disrupted utilisation of child health services. While reduction in child health services at the start of the pandemic was followed by an increase in subsequent months, the recovery was not uniform across different quintiles and geographical areas. This study highlights the disproportionate impact of the pandemic and the need for targeted interventions to improve utilisation of health services.

Estimating population level 24-h sodium excretion using spot urine samples in older adults in rural South Africa.

BACKGROUND: South Africa has introduced regulations to reduce sodium in processed foods. Assessing salt consumption with 24-h urine collection is logistically challenging and expensive. We assess the accuracy of using spot urine samples to estimate 24-h urine sodium (24hrUNa) excretion at the population level in a cohort of older adults in rural South Africa. METHODS: 24hrUNa excretion was measured and compared to that estimated from matched spot urine samples in 399 individuals, aged 40-75 years, from rural Mpumalanga, South Africa. We used the Tanaka, Kawasaki, International Study of Sodium, Potassium, and Blood Pressure (INTERSALT), and Population Mean Volume (PMV) method to predict 24hrUNa at the individual and population level. RESULTS: The population median 24hrUNa excretion from our samples collected in 2017 was 2.6 g (interquartile range: 1.53-4.21) equal to an average daily salt intake of 6.6 g, whereas 65.4% of participants had a salt excretion above the WHO recommended 5 g/day. Estimated population median 24hrUNa derived from the INTERSALT, both with and without potassium, showed a nonsignificant difference of 0.25 g (P = 0.59) and 0.21 g (P = 0.67), respectively. In contrast, the Tanaka, Kawasaki, and PMV formulas were markedly higher than the measured 24hrUNa, with a median difference of 0.51 g (P = 0.004), 0.99 g (P = 0.00), and 1.05 g (P = 0.00) respectively. All formulas however performed poorly when predicting an individual's 24hrUNa. CONCLUSION: In this population, the INTERSALT formulas are a well suited and cost-effective alternative to 24-h urine collection for the evaluation of population median 24hrUNa excretion. This could play an important role for governments and public health agencies in evaluating local salt regulations and identifying at-risk populations.

Improvements in Hypertension Control in the Rural Longitudinal HAALSI Cohort of South African Adults Aged 40 and Older, From 2014 to 2019.

BACKGROUND: Over half of the South African adults aged 45 years and older have hypertension but its effective management along the treatment cascade (awareness, treatment, and control) remains poorly understood. METHODS: We compared the prevalence of all stages of the hypertension treatment cascade in the rural HAALSI cohort of older adults at baseline and after four years of follow-up using household surveys and blood pressure data. Hypertension was a mean systolic blood pressure >140 mm Hg or diastolic pressure >90 mm Hg, or current use of anti-hypertension medication. Control was a mean blood pressure <140/90 mm Hg. The effects of sex and age on the treatment cascade at follow-up were assessed. Multivariate Poisson regression models were used to estimate prevalence ratios along the treatment cascade at follow-up. RESULTS: Prevalence along the treatment cascade increased from baseline (B) to follow-up (F): awareness (64.4% vs. 83.6%), treatment (49.7% vs. 73.9%), and control (22.8% vs. 41.3%). At both time points, women had higher levels of awareness (B: 70.5% vs. 56.3%; F: 88.1% vs. 76.7%), treatment (B: 55.9% vs. 41.55; F: 79.9% vs. 64.7%), and control (B: 26.5% vs. 17.9%; F: 44.8% vs. 35.7%). Prevalence along the cascade increased linearly with age for everyone. Predictors of awareness included being female, elderly, or visiting a primary health clinic three times in the previous 3 months, and the latter two also predicted hypertension control. CONCLUSIONS: There were significant improvements in awareness, treatment, and control of hypertension from baseline to follow-up and women fared better at all stages, at both time points.

Rapidly shifting immunologic landscape and severity of SARS-CoV-2 in the Omicron era in South Africa.

South Africa was among the first countries to detect the SARS-CoV-2 Omicron variant. However, the size of its Omicron BA.1 and BA.2 subvariants (BA.1/2) wave remains poorly understood. We analyzed sequential serum samples collected through a prospective cohort study before, during, and after the Omicron BA.1/2 wave to infer infection rates and monitor changes in the immune histories of participants over time. We found that the Omicron BA.1/2 wave infected more than half of the cohort population, with reinfections and vaccine breakthroughs accounting for > 60% of all infections in both rural and urban sites. After the Omicron BA.1/2 wave, we found few (< 6%) remained naïve to SARS-CoV-2 and the population immunologic landscape is fragmented with diverse infection/immunization histories. Prior infection with the ancestral strain, Beta, and Delta variants provided 13%, 34%, and 51% protection against Omicron BA.1/2 infection, respectively. Hybrid immunity and repeated prior infections reduced the risks of Omicron BA.1/2 infection by 60% and 85% respectively. Our study sheds light on a rapidly shifting landscape of population immunity in the Omicron era and provides context for anticipating the long-term circulation of SARS-CoV-2 in populations no longer naïve to the virus.

Correction of the Valgus Ankle with a Joint Sparing Supra-Malleolar Osteotomy: The Modified Wiltse Technique.

The valgus ankle is a common cause of pain, deformity, and disability in patients. Addressing these deformities with extraarticular osteotomies is a valuable, joint-sparing treatment option. The modified Wiltse osteotomy provides correction of the mechanical alignment as well as allowing inherent stability. Accurate templating of the Wiltse triangle enables reproducible, accurate intraoperative results.

Rapidly shifting immunologic landscape and severity of SARS-CoV-2 in the Omicron era in South Africa.

South Africa was among the first countries to detect the SARS-CoV-2 Omicron variant. Propelled by increased transmissibility and immune escape properties, Omicron displaced other globally circulating variants within 3 months of its emergence. Due to limited testing, Omicron's attenuated clinical severity, and an increased risk of reinfection, the size of the Omicron BA.1 and BA.2 subvariants (BA.1/2) wave remains poorly understood in South Africa and in many other countries. Using South African data from urban and rural cohorts closely monitored since the beginning of the pandemic, we analyzed sequential serum samples collected before, during, and after the Omicron BA.1/2 wave to infer infection rates and monitor changes in the immune histories of participants over time. Omicron BA.1/2 infection attack rates reached 65% (95% CI, 60% - 69%) in the rural cohort and 58% (95% CI, 61% - 74%) in the urban cohort, with repeat infections and vaccine breakthroughs accounting for >60% of all infections at both sites. Combined with previously collected data on pre-Omicron variant infections within the same cohorts, we identified 14 distinct categories of SARS-CoV-2 antigen exposure histories in the aftermath of the Omicron BA.1/2 wave, indicating a particularly fragmented immunologic landscape. Few individuals (<6%) remained naïve to SARS-CoV-2 and no exposure history category represented over 25% of the population at either cohort site. Further, cohort participants were more than twice as likely to get infected during the Omicron BA.1/2 wave, compared to the Delta wave. Prior infection with the ancestral strain (with D614G mutation), Beta, and Delta variants provided 13% (95% CI, -21% - 37%), 34% (95% CI, 17% - 48%), and 51% (95% CI, 39% - 60%) protection against Omicron BA.1/2 infection, respectively. Hybrid immunity (prior infection and vaccination) and repeated prior infections (without vaccination) reduced the risks of Omicron BA.1/2 infection by 60% (95% CI, 42% - 72%) and 85% (95% CI, 76% - 92%) respectively. Reinfections and vaccine breakthroughs had 41% (95% CI, 26% - 53%) lower risk of onward transmission than primary infections. Our study sheds light on a rapidly shifting landscape of population immunity, along with the changing characteristics of SARS-CoV-2, and how these factors interact to shape the success of emerging variants. Our findings are especially relevant to populations similar to South Africa with low SARS-CoV-2 vaccine coverage and a dominant contribution of immunity from prior infection. Looking forward, the study provides context for anticipating the long-term circulation of SARS-CoV-2 in populations no longer naïve to the virus.