The Oxente Chagas Bahia Project: evaluating the efficacy of a rapid diagnostic test and treatments for Chagas disease.

Chagas disease (CD), caused by Trypanosoma cruzi, is a life-threatening neglected anthropozoonosis primarily transmitted by triatomine bugs. Affecting an estimated 5.7 million people globally, CD has significant morbidity and mortality, particularly in Latin America. The Oxente Chagas Bahia Project aims to screen approximately 30,000 individuals, validate a rapid diagnostic test in a real-world setting, and provide crucial data on its diagnostic performance and cost-effectiveness. Additionally, a biobank will be established to support further research on disease biomarkers and treatment cure rates. By enhancing access to timely diagnosis and treatment, the project will evaluate a strategy to reduce the CD burden.

Access to Medicines for Treating People With Cryptococcal Meningitis.

Cryptococcal meningitis accounts for 1 in 5 AIDS-related deaths globally. World Health Organization guidelines strongly recommend a single high dose of liposomal amphotericin B as part of preferred treatment, but this drug remains unaffordable in most low- and middle-income countries. A proactive approach is needed from manufacturers and other stakeholders to improve access.

Environmental risk assessment of PPP application in European soils and potential ecosystem service losses considering impacts on non-target organisms.

The use of Plant Protection Products (PPPs) is leading to high exposure scenarios with potential risk to soil organisms, including non-target species. Assessment of the effects of PPPs on non-target organisms is one of the most important components of environmental risk assessment (ERA) since they play crucial functions in ecosystems, being main driving forces in different soil processes. As part of the framework, EFSA is proposing the use of the ecosystem services approach for setting specific protection goals. In fact, the services provided by soil organisms can be impacted by the misuse of PPPs in agroecosystems. The aim of this work was to assess PPPs potential risk upon ecosystem services along European soils, considering impacts on earthworms and collembola. Four well-known (2 insecticides-esfenvalerate and cyclaniliprole- and 2 fungicides - picoxystrobin and fenamidone-) worst case application (highest recommended application) were studied; exploring approaches for linked observed effects with impacts on ecosystem services, accounting for their mode of action (MoA), predicted exposure, time-course effects in Eisenia fetida and Folsomia sp. and landscape variability. The selected fungicides exerted more effects than insecticides on E. fetida, whereas few effects were reported for both pesticides regarding Folsomia sp. The most impacted ecosystem services after PPP application to crops appeared to be habitat provision, soil formation and retention, nutrient cycling, biodiversity, erosion regulation, soil remediation/waste treatment and pest and disease regulation. The main factors to be taken into account for a correct PPP use management in crops are discussed.

Randomized clinical trial of nitazoxanide or sofosbuvir/daclatasvir for the prevention of SARS-CoV-2 infection.

BACKGROUND: The COVER trial evaluated whether nitazoxanide or sofosbuvir/daclatasvir could lower the risk of SARS-CoV-2 infection. Nitazoxanide was selected given its favourable pharmacokinetics and in vitro antiviral effects against SARS-CoV-2. Sofosbuvir/daclatasvir had shown favourable results in early clinical trials. METHODS: In this clinical trial in Johannesburg, South Africa, healthcare workers and others at high risk of infection were randomized to 24 weeks of either nitazoxanide or sofosbuvir/daclatasvir as prevention, or standard prevention advice only. Participants were evaluated every 4 weeks for COVID-19 symptoms and had antibody and PCR testing. The primary endpoint was positive SARS-CoV-2 PCR and/or serology ≥7 days after randomization, regardless of symptoms. A Poisson regression model was used to estimate the incidence rate ratios of confirmed SARS-CoV-2 between each experimental arm and control. RESULTS: Between December 2020 and January 2022, 828 participants were enrolled. COVID-19 infections were confirmed in 100 participants on nitazoxanide (2234 per 1000 person-years; 95% CI 1837-2718), 87 on sofosbuvir/daclatasvir (2125 per 1000 person-years; 95% CI 1722-2622) and 111 in the control arm (1849 per 1000 person-years; 95% CI 1535-2227). There were no significant differences in the primary endpoint between the treatment arms, and the results met the criteria for futility. In the safety analysis, the frequency of grade 3 or 4 adverse events was low and similar across arms. CONCLUSIONS: In this randomized trial, nitazoxanide and sofosbuvir/daclatasvir had no significant preventative effect on infection with SARS-CoV-2 among healthcare workers and others at high risk of infection.

Myeloid neoplasms with features intermediate between primary myelofibrosis and chronic myelomonocytic leukemia.

Monocytosis can develop during disease course in primary myelofibrosis simulating that seen in chronic myelomonocytic leukemia, and should not lead to disease reclassification. In contrast, at presentation, rare cases have clinical, morphologic, and molecular genetic features truly intermediate between primary myelofibrosis and chronic myelomonocytic leukemia. The taxonomy and natural history of these diseases are unclear. We identified cases which either: (1) fulfilled the 2008 World Health Organization criteria for primary myelofibrosis but had absolute monocytosis and, when available, chronic myelomonocytic leukemia-related mutations (ASXL1, SRSF2, TET2) or (2) fulfilled criteria of chronic myelomonocytic leukemia but had megakaryocytic proliferation and atypia, marrow fibrosis, and myeloproliferative-type driver mutations (JAK2, MPL, CALR). Patients with established primary myelofibrosis who developed monocytosis and those with chronic myelomonocytic leukemia with marrow fibrosis were excluded. By combining the pathology databases of two large institutions, six eligible cases were identified. Patients were predominantly male and elderly with monocytosis at diagnosis (average 17.5%/2.3 × 103/µl), organomegaly, primary myelofibrosis-like atypical megakaryocytes admixed with a variable number of chronic myelomonocytic leukemia-like hypolobated forms, variable myelodysplasia, marrow fibrosis and osteosclerosis. All had a normal karyotype and no myelodysplasia-associated cytogenetic abnormalities. Five of the patients in whom a more extensive molecular characterization was performed showed co-mutations involving JAK2 or MPL and ASXL1, SRSF2, TET2, NRAS, and/or KRAS. Disease progression has occurred in all and two have died. Rare patients present with features that overlap between primary myelofibrosis and chronic myelomonocytic leukemia and are thus difficult to classify based on current World Health Organization criteria. Biologically, these cases likely represent primary myelofibrosis with monocytosis, dysplasia, and secondary (non-driver) mutations at presentation. Alternatively, they may represent a true gray zone of neoplasms. Their clinical behavior appears aggressive and innovative therapeutic approaches may be beneficial in this particular subset.

HER2 FISH classification of equivocal HER2 IHC breast cancers with use of the 2013 ASCO/CAP practice guideline.

The status of human epidermal growth factor receptor 2 (HER2, ERBB2) determines the eligibility of breast cancer patients to receive HER2-targeted therapy. The majority of HER2 testing in the U.S. is performed using a combination of immunohistochemistry (IHC) screening followed by fluorescence in situ hybridization (FISH) for IHC equivocal cases. In 2013, the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) updated the guideline for HER2 testing. This study evaluates the impact of the 2013 ASCO/CAP updated guideline on final HER2 FISH classification of breast cancers with an equivocal IHC result. For each case, we reported a FISH result according to the 2013 updated guideline and recorded a separated result using the 2007 guideline for investigational purpose. McNemar's test and Bowker's symmetry test were used to compare the classifications by the two guidelines. Among 172 HER2 IHC 2+ equivocal cases, use of the 2103 guideline changed classifications in 36 cases (21 %) when compared with the results expected by use of the 2007 guideline, and yielded a higher proportion of positive (28.5 vs. 23.3 %) and equivocal (16.3 vs. 4.1 %), and a lower proportion of negative (55.2 vs. 72.7 %) cases (p < 0.001). The major classification change with use of the updated guideline is from the HER2 FISH negative to equivocal in 26 cases (15 %). Our study has shown that implementation of the 2013 ASCO/CAP updated guideline has significant impact on HER2 classification for breast cancers with an equivocal HER2 IHC result and therefore increased the use of HER2-targeted therapy. Our data have also shown that reflex FISH is effective for final classification of the IHC equivocal cases and that polysomy 17 (CEP17 copy number ≥3/cell) is present in a significantly higher proportion of cases with an equivocal HER2 FISH classification.

Low and high dietary folic acid levels perturb postnatal cerebellar morphology in growing rats.

The brain is particularly sensitive to folate metabolic disturbances, because methyl groups are critical for brain functions. This study aimed to investigate the effects of different dietary levels of folic acid (FA) on postnatal cerebellar morphology, including the architecture and organisation of the various layers. A total of forty male OFA rats (a Sprague-Dawley strain), 5 weeks old, were classified into the following four dietary groups: FA deficient (0 mg/kg FA); FA supplemented (8 mg/kg FA); FA supra-supplemented (40 mg/kg FA); and control (2 mg/kg FA) (all n 10 per group). Rats were fed ad libitum for 30 d. The cerebellum was quickly removed and processed for histological and immunohistochemical analysis. Slides were immunostained for glial fibrillary acidic protein (to label Bergmann glia), calbindin (to label Purkinje cells) and NeuN (to label post-mitotic neurons). Microscopic analysis revealed two types of defect: partial disappearance of fissures and/or neuronal ectopia, primarily in supra-supplemented animals (incidence of 80 %, P≤0·01), but also in deficient and supplemented groups (incidence of 40 %, P≤0·05), compared with control animals. The primary fissure was predominantly affected, sometimes accompanied by defects in the secondary fissure. Our findings show that growing rats fed an FA-modified diet, including both deficient and supplemented diets, have an increased risk of disturbances in cerebellar corticogenesis. Defects caused by these diets may have functional consequences in later life. The present study is the first to demonstrate that cerebellar morphological defects can arise from deficient, as well as high, FA levels in the diet.

Endoscopic ultrasound guided fine needle aspiration with fluorescence in situ hybridization analysis in 104 patients with pancreatic mass.

BACKGROUND AND AIM: Diagnosis of pancreatic malignancy is often based on cytological specimens collected by endoscopic ultrasound guided fine needle aspiration (EUS FNA). Several factors can decrease sensitivity of EUS FNA for pancreatic cancer: well-differentiated tumors, pancreatitis, blood, necrosis and slides with low cellularity. The objective of this study is to report on the use of fluorescence in situ hybridization (FISH) analysis combined with cytology in pancreatic masses. METHODS: EUS database and medical records of patients referred for EUS between January 2009 through august 2013 were reviewed. Data on cytology, FISH and surgical pathology were reviewed. Surgical pathology, death or extended clinical follow-up were used to verify correct diagnosis of malignancy. FISH performed using a four-set DNA probe for chromosomes 3, 7, 17, and band 9p21 in patients with inconclusive immediate cytology reading. Sensitivity of cytology and FISH were compared. RESULTS: Study cohort comprised of 104 patients with FISH analysis on EUS FNA specimens of pancreatic masses (74 adenocarcinoma, 7 neuroendocrine tumor and 23 benign. Sensitivity of cytology and FISH for carcinoma was respectively: 62% and 81%. Sensitivity of FISH + cytology was 89%. The specificity of FISH and cytology was 100%. The most common abnormality on FISH was a 9p21 deletion seen in 43 patients (58%) followed by polysomy of 7 (46%). FISH detected malignancy in 23 patients with negative cytology. CONCLUSIONS: In patients with inconclusive immediate cytology reading, FISH is superior to cytology and improves overall sensitivity. The 9p21 deletion is the most common abnormality seen in this cohort of patients with pancreatic cancer.

Sentinel lymph node detection using 99mTc combined with methylene blue cervical injection for endometrial cancer surgical management: a prospective study.

OBJECTIVE: The aim of this study is to evaluate the effectiveness of a combined technique for sentinel lymph node (SLN) localization and surgical staging of endometrial carcinoma. METHODS: This is a single-center prospective observational study carried out from September 2011 to December 2013 including women with a diagnosis of endometrial cancer and scheduled for surgery. A regional lymph node mapping was obtained using SPECT-CT (cervical injection of Tc) the day before surgery. On the day of surgery, methylene blue was injected in the cervical tissue. The SLNs were identified intraoperatively guided both by a γ-probe and visual inspection of the blue dye. A pelvic and/or para-aortic lymphadenectomy was completed. A histological analysis was performed on all the removed lymph nodes. We calculated the detection rate for SLN and its negative predictive value (NPV) for malignancy. RESULTS: Fifty patients underwent surgery. The SLN was isolated in 46 patients with detection rate of 92% (95% confidence interval, 80.77-97.78). The mean number of detected SLNs per patient was 1.54 (range, 1-5); the average number of non-SLNs removed was 17 (5-34) per patient. The most common SLN location was the external iliac lymph node chain, 33 (46.47%). Five SLNs (7.1%) were isolated in the para-aortic chain. Three SLN cases (5.9%) were positive for malignant cells; the totality of the remaining non-SLNs was negative. The NPV of the SLN was 100% (95% confidence interval, 89.79-99.79). Finally, pathologic findings were 42 endometrioid types (84%), 3 carcinosarcomas (6%), 4 clear cell (8%), and 1 serous papillary tumor (2%). CONCLUSIONS: The SLN analysis may be useful to assess the presence or absence of lymph node metastases. Its high NPV may be used as criteria to avoid unnecessary lymphadenectomies in endometrial cancer patients.

Acute urinary retention caused by OVHIRA syndrome.

Obstructed hemivagina and ipsilateral renal anomaly (OVHIRA) syndrome is a congenital urogenital malformation that associates a bifid uterus with a longitudinal vaginal septum, resulting in a blind hemivagina and an ipsilateral renal agenesis. The clinical presentation is highly variable, delaying diagnosis and leading to important complications. An 18-year-old woman was diagnosed with OVHIRA syndrome following acute urinary retention. An agenesis in the left-sided renal system and an enormous pelvic mass compressing the adjacent structures were revealed in the intravenous urography. Nuclear magnetic resonance was the imaging modality that provided most diagnostic information, defining the pelvic mass as a giant left hematometrocolpos contained with a longitudinal vaginal septum. Resection of the septum was performed draining all reduced hematic content and both hemiuteri communicated with a single vagina, resulting in an asymptomatic patient. OVHIRA syndrome is a little known entity that can occur atypically, which makes the diagnosis difficult and delays the treatment. It is important to maintain a high degree of clinical suspicion to avoid irreversible complications.

Novel approaches to enable equitable access to monoclonal antibodies in low- and middle-income countries.

Monoclonal antibodies (mAbs) are revolutionizing management of non-communicable diseases in high-income countries and are increasingly being advanced for a range of infectious diseases (IDs). However, access to existing mAbs is limited in low- and middle-income countries (LMICs), and investment in developing fit-for-purpose mAbs for IDs that disproportionately affect LMICs has been limited. Underlying these access barriers are systemic challenges, including a lack of commercial incentives to target LMIC markets and complexity in manufacturing and regulatory processes. Novel strategies are needed to overcome systemic access barriers for mAbs. We outline key areas where new approaches could address these barriers, based on a multistakeholder consultation in March 2023. Three disease-market archetypes are identified to guide thinking about business models tailored to different contexts. New business models are needed to incentivize development and manufacturing of ID mAbs and to ensure mAbs are optimized with a target product profile and cost of goods that enable use in diverse LMIC settings. Lessons can be applied from voluntary licensing strategies and product development partnerships that have shown success in catalysing development and affordable supply for a range of infectious diseases. Technology transfer will be key to expand LMIC research and manufacturing capacity and to enable sustainable and diversified supply. Improved market intelligence, demand aggregation mechanisms, and portfolio-based manufacturing models could be used to de-risk commercial investment and establish a sustainable manufacturing ecosystem for affordable mAbs. Novel regulatory approaches and robust technology transfer may reduce data requirements and timelines for biosimilar approvals. Trailblazer products, with coordinated "end-to-end" support from funders, can demonstrate proof of concept for pathways to accessible mAbs across a broader range of LMICs. Research funders; local, regional, global health agencies; and, private sector partners should commit to implementing innovative partnerships and end-to-end strategies that enable equitable access to mAbs for infectious diseases in LMICs.

Paving the way for affordable and equitable liposomal amphotericin B access worldwide.

Amphotericin B has long been crucial for treating many serious infectious diseases, such as invasive fungal infections and visceral leishmaniasis, particularly for patients who are immunocompromised, including those with advanced HIV infection. The conventional amphotericin B deoxycholate formulation has largely been replaced in high-income countries with liposomal amphotericin B (LAmB), which has many advantages, including lower rates of adverse events, such as nephrotoxicity and anaemia. Despite an evident need for LAmB in low-income and middle-income countries, where mortality from invasive fungal infections is still substantial, many low-income and middle-income countries still often use the amphotericin B deoxycholate formulation because of a small number of generic formulations and the high price of the originator LAmB. The pricing of LAmB is also highly variable between countries. Overcoming supply barriers through the availability of additional quality-assured, generic formulations of LAmB at accessible prices would substantially facilitate equitable access and have a substantial effect on mortality attributable to deadly fungal infections.

Maternal folic acid-deficient diet causes congenital malformations in the mouse eye.

BACKGROUND: The eye is a very complex structure derived from the neural tube, surface ectoderm, and migratory mesenchyme from a neural crest origin. Because structures that evolve from the neural tube may be affected by a folate/folic acid (FA) deficiency, the aim of this work was to investigate whether a maternal folic acid-deficient diet may cause developmental alterations in the mouse eye. METHODS: Female C57BL/6J mice (8 weeks old) were assigned into two different folic acid groups for periods ranging between 2 and 16 weeks. Animals were killed at gestation day 17. Hepatic folate was analyzed, and the eyes from 287 fetuses were macroscopically studied, sectioned and immunolabeled with anti-transforming growth factor (TGF)-ß2 and anti-TGF-ßRII. RESULTS: Mice exposed to a FA-deficient diet exhibited numerous eye macroscopic anomalies, such as anophthalmia and microphthalmia. Microscopically, the eye was the most affected organ (43.7% of the fetuses). The highest incidence of malformations occurred from the 8th week onward. A statistically significant linear association between the number of maternal weeks on the FA-deficient diet and embryonic microscopic eye malformations was observed. The optic cup derivatives and structures forming the eye anterior segment showed severe abnormalities. In addition, TGF-ß2 and TGF-ßRII expression in the eye was also altered. CONCLUSION: This study suggests that an adequate folic acid/folate status plays a key role in the formation of ocular tissues and structures, whereas a vitamin deficiency is negatively associated with a normal eye development even after a short-term exposure.

Strategic actions to advance multipurpose prevention technologies in low- and middle-income countries.

Background: HIV, other sexually transmitted infections (STIs) and unintended pregnancies are critical and interlinked health risks for millions of women of reproductive age worldwide. Multipurpose prevention technologies (MPTs) offer an innovative approach for expanding combined pregnancy and/or disease prevention. So far, MPT development efforts have focused mostly on HIV prevention, but about half of product candidates comprise compounds active against non-HIV STIs as well. This review aims to provide a framework that promotes the efficient advancement of the most promising preclinical products through the development pathway and into the hands of end-users, with a focus on women in low- and middle-income countries (L/MICs). Methods: This mini review provides a summary of the current landscape of the MPT field. It comprises a landscape assessment of MPTs in development, complemented by a series of 28 in-depth, semi-structured key informant interviews (KIIs) with experts representing different L/MIC perspectives. Main results: We identified six primary action strategies to advance MPTs for L/MICs, including identification of key research gaps and priorities. For each action strategy, progress to date and key recommendations are included. Conclusions: To realize the life-saving potential of MPTs and maximize the momentum made to date, a strategic, collaborative and well-funded response to the gaps and next steps outlined in this paper is critical. A coordinated response can add rigor and efficiency to the development process, to successfully advance the most promising MPT products to the hands of end-users.

Risks of metabolic syndrome in the ADVANCE and NAMSAL trials.

Introduction: The ADVANCE and NAMSAL trials evaluating antiretroviral drugs have both reported substantial levels of clinical obesity in participants. As one of the main risk factors for metabolic syndrome, growing rates of obesity may drive metabolic syndrome development. This study aims to evaluate the risk of metabolic syndrome in the ADVANCE and NAMSAL trials. Methods: The number of participants with metabolic syndrome was calculated at baseline and week 192 as central obesity and any of the following two factors: raised triglycerides, reduced HDL-cholesterol, raised blood pressure and raised fasting glucose. Differences between the treatment arms were calculated using the χ2 test. Results: Across all visits to week 192, treatment-emergent metabolic syndrome was 15% (TAF/FTC + DTG), 10% (TDF/FTC + DTG) and 7% (TDF/FTC/EFV) in ADVANCE. The results were significantly higher in the TAF/FTC + DTG arm compared to the TDF/FTC/EFV arm (p < 0.001), and the TDF/FTC + DTG vs. the TDF/FTC/EFV arms (p < 0.05) in all patients, and in females. In NAMSAL, the incidence of treatment-emergent metabolic syndrome at any time point was 14% (TDF/3TC + DTG) and 5% (TDF/3TC + EFV) (p < 0.001). This incidence was significantly greater in the TDF/3TC/DTG arm compared to the TDF/3TC/EFV arm in all patients (p < 0.001), and in males (p < 0.001). Conclusion: In this analysis, we highlight treatment-emergent metabolic syndrome associated with dolutegravir, likely driven by obesity. Clinicians initiating or monitoring patients on INSTI-based ART must counsel for lifestyle optimisation to prevent these effects.

Predicting environmental concentrations and the potential risk of Plant Protection Products (PPP) on non-target soil organisms accounting for regional and landscape ecological variability in european soils.

Plant Protection Products (PPP) raise concerns as their application may cause effects on some soil organisms considered non-target species which could be highly sensitive to some pesticides. The European Food and Safety Authority (EFSA), in collaboration with the Joint Research Centre (JRC) of the European Commission, has developed guidance and a software tool, Persistence in Soil Analytical Model (PERSAM), for conducting soil exposure assessments. EFSA PPR Panel has published recommendations for the risk assessment of non-target soil organisms. We have used PERSAM for calculating PPPs predicted environmental concentrations (PECs); and used the estimated PEC for assessing potential risks using Toxicity Exposure Ratios (TER) for selected soil organisms and good agricultural practices. Soil characteristics and environmental variables change along a latitudinal axis through the European continent, influencing the availability of PPP, their toxicity upon soil biota, and hence, impacting on the risk characterization. Although PERSAM includes as input geographical information, the information is aggregated and not further detailed in the model outputs. Therefore, there is a need to develop landscape based environmental risk assessment methods addressing regional variability. The objective was to integrate spatially explicit exposure (PECs) and effect data (biological endpoints i.e. LC50, NOEC, etc.) to estimate the risk quotient (TER) of four PPP active substances (esfenvalerate, cyclaniliprole, picoxystrobin, fenamidone) on non-target species accounting European landscape and agricultural variability. The study was focused on the effects produced by the above-mentioned pesticides on two soil organisms: E. fetida earthworms and Folsomia sp. collembolans. After running PERSAM assuming a worst case application of PPPs, PECs in total soil and pore water were obtained for different depths in northern, central and southern European soils. With this data, soil variability and climatic differences among soils divided in three large Euroregions along a latitudinal transect (Northern, Central, Southern Europe) were analysed. Summarising, a trend to accumulate higher PECs and TERs in total soil was observed in the north decreasing towards the south. Higher PECs and TERs could be expected in pore water in southern soils, decreasing towards the north. The risk disparity between pollutant concentrations at different soils compartments should be taken into account for regulatory purposes, as well as the potential landscape variabilities among different Euroregions.

Cervical cancer screening in low- and middle-income countries: A systematic review of economic evaluation studies.

Economic assessments are relevant to support the decision to incorporate more cost-effective strategies to reduce Cervical Cancer (CC) mortality. This systematic review analyzes the economic evaluation studies of CC prevention strategies (HPV DNA-based tests and conventional cytology) in low- and middle-income countries. Medline, EMBASE, CRD, and LILACS were searched for economic evaluation studies that reported cost and effectiveness measures of HPV DNA-based tests for CC screening and conventional cytology in women, without age, language, or publication date restrictions. Selection and data extraction were carried out independently. For comparability of results, cost-effectiveness measures were converted to international dollars (2019). Report quality was assessed using the CHEERS checklist. The Dominance Matrix Ranking (DRM) was used to analyze and interpret the results. The review included 15 studies from 12 countries, with cost-effectiveness analyzes from the health system's perspective and a 3% discount rate. The strategies varied in age and frequency of screening. Most studies used the Markov analytical model, and the cost-benefit threshold was based on the per capita GDP of each country. The sensitivity analysis performed in most studies was deterministic. The completeness of the report was considered sufficient in most of the items evaluated by CHEERS. The Dominance Interpretation (DRM) varied; in 6 studies, the HPV test was dominant, 5 studies showed a weak dominance evaluating greater effectiveness of the HPV test at a higher cost, yet in 2 studies conventional cytology was dominant. Although the context-dependent nature of economic evaluations, this review points out the challenge of methodological standardization in the analytical models.

Comparing Prospective Incident Severe Acute Respiratory Syndrome Coronavirus 2 Infection Rates During Successive Waves of Delta and Omicron in Johannesburg, South Africa.

In high-risk individuals in Johannesburg, during the Delta coronavirus disease 2019 wave, 22% (125/561) were positive, with 33% symptomatic (2 hospitalizations; 1 death). During Omicron, 56% (232/411) were infected, with 24% symptomatic (no hospitalizations or deaths). The remarkable speed of infection of Omicron over Delta poses challenges to conventional severe acute respiratory syndrome coronavirus 2 control measures.