Recurrent Outbreaks Research Articles

Understanding the Transmission Dynamics of the Chikungunya Virus in Africa.

The Chikungunya virus (CHIKV) poses a significant global public health concern, especially in Africa. Since its first isolation in Tanzania in 1953, CHIKV has caused recurrent outbreaks, challenging healthcare systems in low-resource settings. Recent outbreaks in Africa highlight the dynamic nature of CHIKV transmission and the challenges of underreporting and underdiagnosis. Here, we review the literature and analyse publicly available cases, outbreaks, and genomic data, providing insights into the epidemiology, genetic diversity, and transmission dynamics of CHIKV in Africa. Our analyses reveal the circulation of geographically distinct CHIKV genotypes, with certain regions experiencing a disproportionate burden of disease. Phylogenetic analysis of sporadic outbreaks in West Africa suggests repeated emergence of the virus through enzootic spillover, which is markedly different from inferred transmission dynamics in East Africa, where the virus is often introduced from Asian outbreaks, including the recent reintroduction of the Indian Ocean lineage from the Indian subcontinent to East Africa. Furthermore, there is limited evidence of viral movement between these two regions. Understanding the history and transmission dynamics of outbreaks is crucial for effective public health planning. Despite advances in surveillance and research, diagnostic and surveillance challenges persist. This review and secondary analysis highlight the importance of ongoing surveillance, research, and collaboration to mitigate the burden of CHIKV in Africa and improve public health outcomes.

Ethiopia National Cholera Elimination Plan 2022-2028: Experiences, Challenges, and the Way Forward.

Cholera remains a significant public health concern in Ethiopia. More than 15.9 million Ethiopians, constituting 15% of the total population, live in areas with a history of recurrent cholera outbreaks. The last 9 years of national cholera surveillance data show the country has been experiencing cholera outbreaks every year. The current cholera outbreak, starting in August 2022, has affected the entire country, with 841 reported cases and a 3.13% case fatality rate (CFR) in 2022, and >30 000 cases with nearly a 1.4% CFR in 2023. In line with "Ending Cholera-A Global Roadmap to 2030," the government of Ethiopia is committed to eliminate cholera in the country and has prepared its "National Cholera Elimination Plan (NCP): 2022-2028" with aims to achieve zero local transmission in cholera hotspot areas by 2028 and 90% fatality reduction from the recent (2020-2022) average of 1.8% CFR. The plan is multisectoral, has a clear coordination platform, contains all interventions with in-depth situational analysis, is concordant with existing plans and strategies, and is cascaded at the regional level and implemented with existing government and public structures. Nationwide, total 118 cholera hotspot woredas (districts) were identified, and a comprehensive situation analysis of the existing cholera outbreak response capacity was assessed. This multisectoral and multiyear NCP has forecasted around US$404 million budget estimates with >90% allocated to improving the country's water, sanitation, and hygiene (US$222 million; 55% of total NCP budget) and case management (US$149 million; 37%). The cholera vaccination strategy included in the NCP exhibited a 5-year oral cholera vaccine (OCV) introduction plan with 2 doses (30 604 889 doses) and single dose (3 031 266 doses) in selected cholera hotspot areas. However, its implementation is challenged due to a lack of financial support, inability to get the requested vaccine for targeted hotspot woredas (due to the current shortage of doses in the OCV global stockpile), recurrent cholera outbreaks, and high humanitarian needs in the country. It is recommended to have a sustainable financial mechanism to support implementation, follow the requested vaccine doses, and reorganize the planned coordination platform to foster the implementation.

The Emergence of Chemical Medicine in Early Modern Naples (1600–1660)

Despite the increasing interest in Italian medicine, comparatively little attention has been paid to the establishment of iatrochemistry. Though this process spread throughout the Peninsula, Naples witnessed an impressive growth of chemical research and the outbreak of a conflict between the medical establishment and the chemical physicians. The purpose of this article is to explore the emergence of chemical medicine in Naples in the period that precedes the founding (1663) of the Accademia degli Investiganti. In the first part of the seventeenth century, chemistry achieved recognition in settings like academies, pharmacies, hospitals, and monasteries. Chemical studies and the making of new remedies were spurred by the scientific exchange that Neapolitan savants established with scholars from different areas. The so-called medical pluralism and the recurrent outbreaks of epidemics stimulated the introduction of new chemical therapies, which coexisted with old ones. The establishment of chemical medicine was triggered by Marco Aurelio Severino (1580–1656), who, besides promoting chemical remedies, resorted to chemical theories, including Paracelsian ones, to account for physiological processes. Severino was the mentor of the chemical physicians who gave rise to the Accademia degli Investiganti. One of Severino’s disciples was Giuseppe Donzelli (1596–1670), who fostered chemical remedies in Naples.

The implementation of a new measles vaccine mandate in Germany: A qualitative study in local health departments.

Measles is a highly contagious disease with the potential for severe complications. Despite the availability of effective vaccines, there have been recurrent measles outbreaks in Germany over the past decades. In response, a new measles vaccine mandate was introduced on March 1, 2020, aimed at closing vaccination gaps in high-risk populations. This study evaluates the mandate's implementation, identifies operational challenges, assesses the impact of the Coronavirus disease 2019 pandemic, and investigates expert attitudes towards the new policy. Semi-structured expert interviews were conducted with staff members of 16 different local health departments in Germany. The interviews, carried out in April and May 2021, were electronically recorded, transcribed verbatim, and analyzed using the Framework method. The implementation of the measles vaccine mandate in local health departments varied substantially. Challenges in implementing the mandate primarily arose from uncertainties regarding procedural specifics, such as handling fraudulent medical certificates and imposing sanctions, leading to a call from many interviewees for uniform guidelines to ensure coherent implementation. At the time the measles vaccine mandate came into force, managing the Coronavirus disease 2019 pandemic was a priority in most local health departments, often delaying the implementation of the mandate. Despite the difficulties encountered, most experts considered the mandate to be an effective step towards measles elimination. The measles vaccine mandate has imposed a new responsibility on staff in German local health departments, which is associated with implementation challenges such as procedural uncertainties and vaccine hesitancy, but also the Coronavirus disease 2019 pandemic as a contextual impediment. Significant differences in the implementation approach underscore the need for harmonization to enhance implementation efficiency and public acceptance of the mandate. Despite the mandate's potential to increase vaccination rates, our findings advocate for a comprehensive approach, incorporating public education, accessible vaccination, and measures to address social disparities.

Descriptive epidemiology of spotty liver disease in Australian cage-free brown egg layer chicken flocks with a scratch area

Spotty Liver Disease (SLD), caused by Campylobacter hepaticus or C. bilis infection in adult female chickens continues to emerge as a major disease problem in cage-free production systems. Free range production has become the predominant system in Australian egg production and SLD is widespread in these farms. Previous studies have identified having a scratch area as a key determinant for SLD occurrence. An Australia-wide survey of egg production flocks with scratch areas was conducted regarding SLD including 48 individual flocks. Descriptive information on the facilities and flock management practices was reported. The incidence of SLD, age of first outbreak, initial mortality rate, duration of elevated mortality, and magnitude and duration of any associated egg production decline are described. Recurrence of SLD in the same flock was also reported and discussed. Therapies applied were recorded and assessed across SLD severity and duration. SLD occurred in 66.7% of layer flocks whose facility included a scratch area. Recurrent SLD outbreaks occurred in 31% of flocks experiencing SLD. Antibiotic medication reduced duration of mortality and egg production decline. Antibiotic therapy was associated with reduced duration of mortality and a less severe and shorter duration of egg production drops compared to untreated flocks. PCR detection of C. hepaticus in cloacal swabs and house dust samples and a serological ELISA test were compared and evaluated as diagnostic aids or as possible predictors of SLD outbreaks. The ELISA showed substantial agreement with detection of C. hepaticus in cloacal swabs by PCR. Examining composite house dust samples by PCR for C. hepaticus DNA appeared to be the most convenient and cost-effective aid to diagnosis and as a putative predictor for SLD outbreaks.

A highly effective ferritin-based divalent nanoparticle vaccine shields Syrian hamsters against lethal Nipah virus.

The Nipah virus (NiV), a highly deadly bat-borne paramyxovirus, poses a substantial threat due to recurrent outbreaks in specific regions, causing severe respiratory and neurological diseases with high morbidity. Two distinct strains, NiV-Malaysia (NiV-M) and NiV-Bangladesh (NiV-B), contribute to outbreaks in different geographical areas. Currently, there are no commercially licensed vaccines or drugs available for prevention or treatment. In response to this urgent need for protection against NiV and related henipaviruses infections, we developed a novel homotypic virus-like nanoparticle (VLP) vaccine co-displaying NiV attachment glycoproteins (G) from both strains, utilizing the self-assembling properties of ferritin protein. In comparison to the NiV G subunit vaccine, our nanoparticle vaccine elicited significantly higher levels of neutralizing antibodies and provided complete protection against a lethal challenge with NiV infection in Syrian hamsters. Remarkably, the nanoparticle vaccine stimulated the production of antibodies that exhibited superior cross-reactivity to homologous or heterologous henipavirus. These findings underscore the potential utility of ferritin-based nanoparticle vaccines in providing both broad-spectrum and long-term protection against NiV and emerging zoonotic henipaviruses challenges.

The 2023 Dengue Outbreak in Bangladesh: Exploring the Epidemiology in Hospitalized Patients.

For the past two decades, Bangladesh has faced recurrent dengue outbreaks, with the most recent occurring in 2023. We investigated the socioeconomic, clinical, and laboratory aspects of patients diagnosed with dengue during this outbreak. This observational study was conducted from July to September 2023 at Dhaka Medical College Hospital and Chittagong Medical College Hospital, and included 450 confirmed cases of dengue. Sociodemographic information was collected via face-to-face interviews, clinical examinations, and laboratory testing, which was done within 24 hours of admission. Dengue severity was classified according to the 2009 WHO dengue guidelines. Notably, 17% of patients experienced severe dengue, and 89% of those with nonsevere cases exhibited at least one warning sign. Most patients were young adults (mean age, 33 years), with a nearly equal male-to-female ratio. Common clinical presentations included fever (95%), myalgia (62%), and headache (58%), whereas warning signs such as vomiting (54%) and abdominal pain (39%) were prevalent. Plasma leakage indicators, including ascites, pleural effusion, and edema, were found predominantly in severe cases. Laboratory findings revealed leukopenia, thrombocytopenia, and elevated hepatic enzymes (alanine aminotransferase and aspartate aminotransferase) in nearly half the patients. An elevated hematocrit level was associated with severe dengue. We report that a substantial number of patients developed severe dengue during the epidemic in 2023, and provide detailed clinical-epidemiological profiles of the patients, offering valuable insight into management of dengue cases.

Development of recombinant proteins for vaccine candidates against serotypes O and A of Foot-and-Mouth Disease virus in Bangladesh.

Frequent vaccine failure leading to recurrent outbreaks of Foot-and-Mouth Disease (FMD) in livestock populations necessitates the development of a customizable vaccine platform comprising potential antigenic determinants of circulating lineages of FMD viruses. Artificially designed, chimaeric protein-based recombinant vaccines are novel approaches to combat the phylogenetically diverse FMD Virus (FMDV) strains. Among seven recognized serotypes, only serotypes O and A are dominantly circulating in Bangladesh and neighbouring countries of Asia, where transboundary transmission, recurrent outbreaks and emergence of novel lineages of FMDV are highly prevalent. The objective of this study was to develop multi-epitope recombinant proteins, procuring immunogenicity against circulating diverse genotypes of FMDV serotypes O and A. Two chimaeric proteins, named B1 (41.0 kDa) and B3 (39.3 kDa), have been designed to incorporate potential B-cell and T-cell epitopes selected from multiple FMDV strains, including previously reported and newly emerged sub-lineages. After expression, characterization and immunization of guinea pigs with a considerable antigen load of B1 and B3 followed by serological assays revealed the significant protective immunogenicity, developed from the higher (100 µg) doses of both antigens, against most of the currently prevalent serotype O and A strains of FMDV. The efficient expression, antigenic stability, and multivalent immunogenic potency of the chimaeric proteins strongly indicate their credibility as novel vaccine candidates for existing serotypes O and A of FMDV in Bangladesh and surrounding territories.

TSAF-Net: a rotated two-stage Cnaphalocrocis medinalis damage detection method based on anchor-free arbitrary-oriented proposal network.

Cnaphalocrocis medinalis (C.medinalis) is an agricultural pest with recurrent outbreaks. The investigation into automated pest and disease detection technology holds significant value for in-field surveys. Current generic detection methods are inadequate due to arbitrary orientations and a wide range of aspect ratios in damage symptoms. To tackle these issues, we put forward a rotated two-stage detection method for in-field C.medinalis surveys. This method relies on an anchor-free rotated region proposal network (AF-R2PN), bypassing the need for hyper-parameter optimization induced by predefined anchor boxes. An in-field C.medinalis dataset is constructed during on-site pest surveys to validate the effectiveness of our method. The experimental results show that our method can accomplish 80% average precision (AP), surpassing the corresponding horizontal detector by 2.3%. The visualization results of our work showcase its exceptional localization capability over generic detection methods, facilitating inspection by plant protectors. Meanwhile, our proposed method outperforms other state-of-the-art rotated detection algorithms. The AF-R2PN module can generate superior arbitrary-oriented proposals even with a decreased number of proposals, balancing inference speed and detection performance among other rotated two-stage methods. The proposed method exhibits superiority in detecting C. medinalis damage under complex field conditions. It provides greater practical applicability during in-field surveys, enhancing their efficiency and coverage. The findings hold significance for pest and disease monitoring, providing important technical support for agricultural production. © 2024 Society of Chemical Industry.

Beyond polio: Exploring non-polio enteroviruses, global health preparedness, and the "DiseaseX"paradigm.

Disease X represents the possibility that an unidentified infection may spread globally and start a pandemic. This study explored various aspects of emerging non-polio enteroviruses (NPEVs) as a possible source of "Disease X," an enigmatic agent declared by the World Health Organization,and discussed the potential impact of NPEVs on global public health. In this perspective article, we collected information from publicly available sources such as Google Scholar, PubMed, and Scopus. We used NPEVs, viral diseases, pandemics, and zoonotic diseases as keywords. We extracted information from the most relevant articles. Notable outbreaks caused by NPEVs include enterovirus D68 (EV-D68) and enterovirus A71 (EV-A71), among many others. With a focus on therapeutic and preventative components, alternate modes of therapy, and the development of broad-spectrum antivirals, this analysis looks at the origin, epidemiology, genetic alterations, transmission dynamics, and disease pathophysiology of NPEVs. The information presented in the review indicates the current risk assessment of NPEVs, taking into account the following factors: the need for research and therapeutic interventions, the diversity of clinical manifestations, the impact of genetic variability on virulence, the persistence of emergence despite vaccination efforts, recurrent outbreaks, and the global impact of these viruses. There is a possibility that NPEVs could trigger global pandemics based on their zoonotic origins and urges for complete readiness, continuous research, cooperation, and a comprehensive strategy to combat emerging infectious diseases in a constantly changing global environment. It is peak time to acknowledge how important it is to abide by safety and health laws to prevent these illnesses.

Tree Species-Dependent Inactivation of Coronaviruses and Enteroviruses on Solid Wood Surfaces.

The ongoing challenge of viral transmission, exemplified by the Covid pandemic and recurrent viral outbreaks, necessitates the exploration of sustainable antiviral solutions. This study investigates the underexplored antiviral potential of wooden surfaces. We evaluated the antiviral efficacy of various wood types, including coniferous and deciduous trees, against enveloped coronaviruses and nonenveloped enteroviruses like coxsackie virus A9. Our findings revealed excellent antiviral activity manifesting already within 10 to 15 min in Scots pine and Norway spruce, particularly against enveloped viruses. In contrast, other hardwoods displayed varied efficacy, with oak showing effectiveness against the enterovirus. This antiviral activity was consistently observed across a spectrum of humidity levels (20 to 90 RH%), while the antiviral efficacy manifested itself more rapidly at 37 °C vs 21 °C. Key to our findings is the chemical composition of these woods. Resin acids and terpenes were prevalent in pine and spruce, correlating with their antiviral performance, while oak's high phenolic content mirrored its efficacy against enterovirus. The pine surface absorbed a higher fraction of the coronavirus in contrast to oak, whereas enteroviruses were not absorbed on those surfaces. Thermal treatment of wood or mixing wood with plastic, such as in wood-plastic composites, strongly compromised the antiviral functionality of wood materials. This study highlights the role of bioactive chemicals in the antiviral action of wood and opens new avenues for employing wood surfaces as a natural and sustainable barrier against viral transmissions.

Past anthropogenic impacts revealed by trace elements in cave guano

Natural and human-induced toxic elements can accumulate in the environment, posing significant risks to human health and ecosystems. This study explores cave bat guano, an unconventional and relatively under-researched environmental repository, to reveal historical pollution trends and sources. Through trace elements analysis of a 1.5-m-thick guano deposit from Zidită Cave (Romania), we track changes in mining and metallurgy from 1000 CE–2012. We identified substantial pollution primarily from porphyry copper and Au–Ag–Te mines, but also impacts from usage of leaded gasoline and agricultural practices. Our record shows disruptions caused by the Bubonic plague around 1250 CE and a major surge ∼ 1500 CE. After the decline triggered by the European silver market collapse in 1525 CE, our study reveals a brief mining revival. This resurgence was followed by a continuous decline lasting until the early 1800s, driven by socio-economic upheavals and recurrent outbreaks of the bubonic plagues. The Industrial Revolution sparked prolonged growth that lasted until 1989 CE, only briefly interrupted by the Great Depression and World War II. Consequently, cave bat guano proves to be a critical resource for understanding spatial pollution patterns, both locally and regionally, and for identifying specific pollution sources.

The Epidemiological Features and Pathogen Spectrum of Respiratory Tract Infections, Istanbul, Türkiye, from 2021 to 2023.

Respiratory tract infections (RTIs) can lead to both recurrent seasonal epidemic outbreaks and devastating pandemics. The aim of this study was to evaluate the epidemiologic characteristics and pathogen spectrum of RTIs using a multiplex RT-PCR panel. A total of 9354 cases with suspected RTIs between February 2021 and July 2023 were included in this study. A total of 11,048 nasopharyngeal and oropharyngeal samples from these patients were analyzed for 23 respiratory tract pathogens using multiplex RT-PCR. H. influenzae and S. pneumoniae were considered as colonizing bacteria. At least one pathogen was detected in 70.66% of the samples; viral pathogens were detected in 48.41% of the samples, bacterial pathogens were detected in 16.06% of the samples, and viral + bacterial pathogens were detected in 35.53% of the samples. The most frequently detected viral pathogen was rhinovirus/enterovirus (RV/EV) (19.99%). Interestingly, in 2021, respiratory syncytial virus A/B showed atypical activity and replaced RV/EV as the most prevalent pathogen. Human bocavirus, H. influenzae, and S. pneumoniae were detected at higher rates in males (p: 0.038, p: 0.042, and p: 0.035, respectively), while SARS-CoV-2 and B. pertussis were detected at higher rates in females (p < 0.001 and p: 0.033). RTIs were found at higher rates in children (p < 0.001). SARS-CoV-2 and human coronaviruses 229E were detected at higher rates in adults (p < 0.001 and p: 0.001). This comprehensive study with a large sample size investigating RTI pathogens was the first in Türkiye. Understanding the current viral circulation using multiplex RT-PCR panels enables clinicians to predict the most likely pathogens affecting patients and contributes to patient management, in addition to anticipating potential threats.

Dengue Virus and Zika Virus Seroprevalence in the South Pacific Populations of the Cook Islands and Vanuatu

Arboviral diseases are serious threats to global health with increasing prevalence and potentially severe complications. Significant arthropod-borne viruses are the dengue viruses (DENV 1-4), the Zika virus (ZIKV), and the chikungunya virus (CHIKV). Among the areas most affected is the South Pacific Region (SPR). Here, arboviruses not only cause a high local burden of disease, but the region has also proven to contribute to their global spread. Outpatient serum samples collected between 08/2016 and 04/2017 on three islands of the island states of Vanuatu and the Cook Islands were tested for anti-DENV- and anti-ZIKV-specific antibodies (IgG) using enzyme-linked immunosorbent assays (ELISA). ELISA test results showed 89% of all test sera from the Cook Islands and 85% of the Vanuatu samples to be positive for anti-DENV-specific antibodies. Anti-ZIKV antibodies were identified in 66% and 52%, respectively, of the test populations. Statistically significant differences in standardized immunity levels were found only at the intranational level. Our results show that in both the Cook Islands and Vanuatu, residents were exposed to significant Flavivirus transmission. Compared to other seroprevalence studies, the marked difference between ZIKV immunity levels and previously published CHIKV seroprevalence rates in our study populations is surprising. We propose the timing of ZIKV and CHIKV emergence in relation to recurrent DENV outbreaks and the impact of seasonality as explanatory external factors for this observation. Our data add to the knowledge of arboviral epidemics in the SPR and contribute to a better understanding of virus spread, including external conditions with potential influence on outbreak dynamics. These data may support preventive and rapid response measures in the affected areas, travel-related risk assessment, and infection identification in locals and returning travelers.

Emergence of the novel infectious bursal disease virus variant in vaccinated poultry flocks in Egypt

ABSTRACT Since the detection of antigenically atypical very virulent Infectious bursal disease viruses (vvIBDV) in Egypt in 1999, the country has been experiencing recurrent outbreaks with high mortality rates and typical gross lesions associated with typical vvIBDV. However, a significant change occurred in 2023, marked by a notable increase in reported subclinical IBDV cases. To evaluate the field situation, samples from 21 farms in 2023 and 18 farms from 2021 and 2022, all of which had experienced IBD outbreaks based on clinical diagnosis, were collected, and subjected to VP2-HVR sequencing. Phylogenetic analysis revealed that all samples collected in 2021 and 2022 clustered with classical virulent strains and vvIBDV. In 2023, one sample clustered with the Egyptian vvIBDV, another with classical virulent IBDV, and the rest with the novel variant IBDV (nVarIBDV) circulating in China. The alignment of deduced amino acid sequences for VP2 showed that all Egyptian classic virulent strains were identical to the Winterfield or Lukert strains, while vvIBDV strains exhibited two out of the three typical residues found in Egyptian vvIBDV, namely Y220F and G254S, but not A321T. Meanwhile, all Egyptian variant strains exhibited typical residues found in nVarIBDV. However, all Egyptian variants showed a mutation at position 321 (321V), which represents the most exposed part of the capsid and is known to have a massive impact on IBDV antigenicity, except for one sample that had 318G instead. This report highlights the emergence of a new variant IBDV in Egypt, clustered with the Chinese new variants, spreading subclinically in broiler farms across a wide geographic area. RESEARCH HIGHLIGHTS New variant IBDV which emerged in Egypt clustered with Chinese nVarIBDV. nVarIBDV spread subclinically across a wide geographic area. Mutation at 321 represents capsid's most exposed part, a defining feature. Antigenically modified vvIBDV still circulating in Egypt with typical lesions.

Chikungunya-virus-specific CD4+ T cells are associated with chronic chikungunya viral arthritic disease in humans

Abstract Chikungunya virus (CHIKV) is a mosquito-borne Alphavirus that causes recurrent outbreaks in tropical and subtropical regions of the world. In the first 2-7 days of infection, most individuals experience high fever, skin rash and joint pain and swelling. However, about 30-60% of the infected individuals, primarily middle-age females, develop debilitating chronic arthritis-like symptoms such as joint pain, muscle aches and edema. Despite ongoing treatment and vaccine development efforts, the immune responses to CHIKV in humans remain largely understudied. In this study, we tested peripheral blood mononuclear cells (PBMCs) collected from a cohort of 39 individuals diagnosed with CHIKV disease during the 2014-2015 epidemic in Colombia against pools of overlapping sequentially spanning the entire CHIKV genome. Using high-resolution spectral flow cytometry, we detected robust CHIKV-specific CD4+ T cell responses, but not CD8+ T cell responses in the periphery. Patients experiencing chronic symptoms displayed a significantly higher abundance of CHIKV-specific memory CD4+ T cells, compared to their recovered counterparts. Furthermore, these CD4+ T cells displayed a significantly lower Th1 phenotype but were enriched in the Th17 phenotype, with the predominant production of TNFɑ. Overall, our work demonstrates that CD4+ T cells play a pivotal role in the pathogenesis of CHIKV and provides insight into possible therapeutic options.

Decoding the paradox: Understanding Elevated Hospitalization and Reduced Mortality in SARS-CoV-2 Variants

Introduction and aim: SARS-CoV-2 outbreaks occur cyclically, aligning with winter when vitamin D levels are lowest, except after new variant outbreaks. Adequate vitamin D is crucial for robust immune function. Hypovitaminosis diminishes immune responses, increasing susceptibility to viral infections. The manuscript explores the discrepancy between increased SARS-CoV-2 hospitalizations and lower mortality. Method​: SARS-CoV-2 mutants, including Delta, BQ, and XBB Omicron lineages, developed immune evasion capabilities, reducing the effectiveness of COVID-19 vaccines and bivalent boosters. The failure of COVID-19 vaccines to prevent infections and spread to others, coupled with the immune evasion exhibited by mutant viruses, contributed to continued SARS-CoV-2 outbreaks. Interestingly, dominant new mutants, despite their increased transmissibility, have caused fewer deaths. This article scrutinizes the mentioned incongruity through an analysis of published data. Results: Achieving herd immunity and eradicating SARS-CoV-2 has proven elusive due to ongoing mutagenesis and immune evasion, leading to recurrent viral outbreaks. The failure to approve repurposed early therapies for COVID-19 by regulators, as well as misinformation and weak strategies undertaken by leading health authorities, exacerbated the situation. Repurposed agents, including vitamin D and ivermectin, have demonstrated high efficacy against SARS-CoV-2 from the beginning, and remain unaffected by mutations. Despite their cost-effectiveness and widespread availability, regulatory approval for these generic agents in COVID-19 treatment is pending. Conclusion: Regulators hesitated to approve cost-effective, repurposed generic agents primarily to safeguard the temporary approval status of COVID-19 vaccines and anti-viral agents under Emergency Use Authorization, which persists. This reluctance overlooked the opportunity to implement an integrated approach with repurposed agents alongside COVID-19 vaccines, potentially reducing hospitalizations and fatalities and preventing outbreaks; this led to the failure to eradicate SARS-CoV-2 and becoming endemic. It is imperative that regulators now reconsider approving affordable generics for SARS-CoV-2 to effectively control future viral outbreaks. Non-technical Importance (Lay Abstract) Adequate vitamin D levels significantly bolster the human immune system—deficiency compromises immune responses and increases susceptibility, particularly to viruses. While new SARS-CoV-2 mutations like Omicron are less severe, they are more infectious and adept at evading immunity from vaccines; thus, they offer a limited spectrum of protection and duration. Primary COVID-19 vaccines have reduced disease severity but have failed to prevent viral spread, contributing to outbreaks. Booster doses had little effect on the virus but caused immune paresis, thus increasing susceptibility to infections. Regulators should consider approving generic, repurposed agents like vitamin D and ivermectin as adjunct therapies to address this challenge and better prepare for future pandemics. Proactively integrating vitamin D supplementation to fortify the immune system can mitigate vital outbreaks, alleviate hospital burdens, and reduce healthcare costs.

Newborn vaccination game model with potentially periodic behavior

We explore the complex dynamics of epidemics, considering the significant effects of disease transmission, newborn individuals, and mortality rate. Employing an evolutionary game theory approach, we model the vaccination aspect for newborns, incorporating potential periodic behavior. The goal is to create an engaging simulation that underscores the criticality of timely infant vaccinations. By introducing periodic elements, the game adds complexity, fostering player participation and awareness of vaccination schedules. In contrast to traditional intervention game models focused on adult vaccine behavior, our approach recognizes the unique challenges posed by newborn vaccination. We address the limitations of existing models by developing a generalized compartmental model, accommodating infection duration distribution, and accurately capturing both periodic and non-periodic disease trajectories. The results show that higher efficacy in a newborn vaccine program can potentially eradicate the disease, but higher effectiveness and cost may deter vaccination. Increased motivation cost boosts vaccination rates without impacting epidemic size, whereas lower costs stabilize vaccination rates. Lower vaccine costs call for increased government investment to counter hesitancy. However, reduced efficacy and lower motivation lead to higher Vaccine Fear Scores, discouraging participation. Our work also offers a unique perspective on the dilemma of newborn vaccination, providing solutions with closed-form expressions that may exhibit periodic or non-periodic behavior. This approach facilitates disease modelers in exploring the potential periodicity of newborn vaccination programs, aiding efforts to prevent recurrent outbreaks.

Detectable Viremia at Presentation Is a Predictor of Disease Severity in Chikungunya.

Background Chikungunya is a mosquito-borne re-emerging disease that has caused a significant number of outbreaks recently in diverse geographic settings across the globe. It leads to severe debilitating illness in a significant proportion of persons who are infected. Measures to limit the impact produced by recurrent outbreaks of the disease are limited and there is an urgent clinical need for early identification of those predisposed to develop severe disease. A comprehensive understandingregarding the proportion of individuals predisposed to developing severe disease is lacking as its correlation with detectable viremia is hinted at by some studies. In this context, we hypothesized that detectable viremia reflected in the diagnostic RT-PCR assay could be significantly associated with the development of severe disease in Chikungunya among those diagnosed on the basis of seroconversion. Our study aims to confirm the same in relation to disease severity among the suspected patients of Chikungunya in the setting of a tertiary care center. Methods In a prospective observational study at a tertiary care center, a total number of 1021 Chikungunya suspects presenting within seven days of illness were screened with Chikungunya Virus IgM ELISA from 2021 to 2023. Those having positive IgM results were further tested with RT-PCR in a blinded manner. According to the information entered into the predesigned form and the hospital follow-up/discharge data, the cases where symptoms like fever and joint pain persisted beyond two weeks were classified as severe versus those resolving within two weeks as mild. The patients in each group were compared for their clinical symptoms and association with the disease severity with detectable viremia (RT-PCR positivity). Results We identified a total of 178 (17.4%) lab-confirmed Chikungunya IgM-positive cases amongst the recruited patients. Here a total of 31 (18.9%) cases could be classified as severe and 133 (74.7%) as mild illness, the remaining 14 patients were excluded from analysis due to insufficientclinical data. Severe illness was significantly higher in elderly individuals belonging to more than 60 years (p = 0.01). Viremia was detected in 16 (9%), those with detectable viremia had higher odds (OR = 4.1) of manifesting as severe disease. Among the severe cases, the proportion of cases with RT-PCR positivity (8, 25.8%) at presentation was significantly higher (P = 0.01) versus those who presented with mild disease (7, 5.5%). Conclusion Our study reveals a correlation betweendetectable viremia in Chikungunya virus (CHIKV) patients and an increased risk of manifesting into a severe disease, where severe cases exhibited a significantly higher proportion of viremia, indicated by RT-PCR positivity. This study hints at the presence of viremia, joint symptoms, and elderly age as potentially useful clinical predictors of disease outcomes, these may serve as indicators for closer monitoring among individuals seeking medical attention due to Chikungunya infection.However, we need to validate these findings in future longitudinal studies incorporating multiple, time-bound follow-up data on clinical outcomes, viral titers, and itslong-term complications.

Comparing various bio-intensive pest management modules in rice

Rice is the key cereal crop in the tropics, supporting diverse pests and natural enemy populations. Recurrent pest outbreaks and yield losses led farmers to rely on extensive insecticide application, disturbing the stability of rice ecosystems and increasing residues in the harvestable products. A study has been conducted to assess the impact of various modules of Bio-Intensive Pest Management (BIPM) on its conservational potential and sustainability in comparison with Farmers’ Practices (FP) in Nalgonda district of Telangana state during kharif-2020. The BIPM practices included application of farm yard manure; rice husk ash; clipping of seedlings; alleyways and weekly release of Trichogramma japonicum in the main field; wet seed treatment and foliar application with Pseudomonas fluorescens (BIPM 1), Trichoderma asperellum strain TAIK1 (BIPM 2) and Bacillus cabrialesii strain BIK3 (BIPM 3). Whereas, FP 1 with need-based insecticide spraying and FP 2 with schedule-based insecticide spraying and Untreated control with (UC) with no intervention. The observations were taken by visual counts at 15-day intervals. The incidence of Cnaphalocrocis medinalis was highest in UC (9.50), followed by BIPM 1 (7.25) and least in FP 2 (2.50) whereas the highest mean population of Apanteles sp. was found in the untreated control (13.75), followed by BIPM 3 (9.50) and least in FP 2 (4.25). The Benefit Cost Ratios (BCR) of BIPM 3 (1.68) were highest followed by BIPM 1 (1.64) and least in FP 2 (1.40) elucidating that BIPM practices can be more economically feasible. The Shannon-Wiener Index for species diversity and species evenness was higher in BIPM treatments as compared to farmers’ practices indicating the potential of these BIPM treatments in natural pest control and maintaining crop ecosystem stability.