Structures of Leukotriene Biosynthetic Enzymes and Development of New Therapeutics.

Leukotrienes are potent immune-regulating lipid mediators with patho-genic roles in inflammatory and allergic diseases, particularly asthma. These autacoids also contribute to low-grade inflammation, a hallmark of cardiovascular, neurodegenerative, metabolic, and tumor diseases. Biosynthesis of leukotrienes involves release and oxidative metabolism of arachidonic acid and proceeds via a set of cytosolic and integral membrane enzymes that are typically expressed by cells of the innate immune system. In activated cells, these enzymes traffic and assemble at the endoplasmic and perinuclear membrane, together comprising a biosynthetic complex. Here we describe recent advances in our molecular understanding of the protein components of the leukotriene-synthesizing enzyme machinery and also briefly touch upon the leukotriene receptors. Moreover, we discuss emerging opportunities for pharmacological intervention and development of new therapeutics.

Fourth Controlled Human Infection Model (CHIM) meeting - CHIMs in endemic countries, May 22-23, 2023.

Earlier meetings laid the foundations for Controlled Human Infection Models (CHIMs), also known as human challenge studies and human infection studies, including Good Manufacturing Practice (GMP) production of the challenge agent, CHIM ethics, environmental safety in CHIM, recruitment, community engagement, advertising and incentives, pre-existing immunity, and clinical, immunological, and microbiological endpoints. The fourth CHIM meeting focused on CHIM studies being conducted in endemic countries. Over the last ten years we have seen a vast expansion of the number of countries in Africa performing CHIM studies, as well as a growing number of different challenge organisms being used. Community and public engagement with assiduous ethical and regulatory oversight has been central to successful introductions and should be continued, in more community-led or community-driven models. Valuable initiatives for regulation of CHIMs have been undertaken but further capacity building remains essential.

Coccidioidomycosis Seroincidence and Risk among Military Personnel, Naval Air Station Lemoore, San Joaquin Valley, California, USA1.

We conducted a retrospective cohort study that tested 2,000 US military personnel for Coccidioides antibodies in a disease-endemic region. The overall incidence of seroconversion was 0.5 cases/100 person-years; 12.5% of persons who seroconverted had illnesses requiring medical care. No significant association was found between demographic characteristics and seroconversion or disease.

Asia Pacific perspectives on the second year of the COVID-19 pandemic: A follow-up survey.

BACKGROUND: The Coronavirus disease 2019 (COVID-19) pandemic is currently in its third year. This follow-up survey was commissioned by the Asia Pacific Association of Allergy Asthma and Clinical Immunology (APAAACI) Task Force on COVID-19 to compare and contrast changes in the epidemiology, clinical profile, therapeutics and public health measures of the pandemic in the Asia Pacific region. METHODS: A questionnaire-based survey comprising 32 questions was electronically sent out to all 15 member countries of APAAACI using Survey Monkey® from 1 December 2021 to 28 February 2022. RESULTS: Seventeen responses were received from 14/15 (93.4%) member countries and 3 individual members. Mild-to-moderate COVID-19 predominated over severe infection, largely contributed by COVID-19 vaccination programmes in the region. The incidence of vaccine adverse reactions in particular anaphylaxis from messenger ribonucleic acid (mRNA) vaccines was no longer as high as initially anticipated, although perimyocarditis remains a concern in younger males. Novel therapeutics for mild-to-moderate disease including neutralizing antibodies casirivimab/imdevimab (REGEN-COV®) and sotrovimab (Xevudy®), anti-virals Paxlovid® (nirmatrelvir and ritonavir) and Molnupiravir pre-exposure prophylaxis for high-risk persons with Tixagevimab and Cilgavimab (Evusheld) are now also available to complement established therapeutics (e.g., remdesivir, dexamethasone and baricitinib) for severe disease. In the transition to endemicity, public health measures are also evolving away from containment/elimination strategies. CONCLUSIONS: With access to internationally recommended standards of care including public health preventive measures, therapeutics and vaccines among most APAAACI member countries, much progress has been made over the 2-year period in minimizing the morbidity and mortality from COVID-19 disease.

[Epidemiological behavior of leprosy in several Latin American countries, 2011-2020Comportamento epidemiológico da hanseníase em vários países da América Latina, 2011-2020]. / Comportamiento epidemiológico de la lepra en varios países de América Latina, 2011-2020.

Objective: To describe the epidemiological behavior of leprosy in several Latin American countries during 2011-2020, based on World Health Organization (WHO) indicators. Methods: Cross-sectional, descriptive and quantitative study with official data on incidence and prevalence in the general population, children, clinical form and cases with grade 2 disability from WHO records between 2011 and 2020. The eight countries in Latin America that reported most cases were selected and analyses were carried out using simple descriptive and comparative statistics between different variables. Results: During the study period, 301 312 cases of leprosy were reported in the selected countries: Argentina, Brazil, Colombia, Cuba, Dominican Republic, Mexico, Paraguay, and Venezuela. Brazil is the only country in the region with a prevalence greater than 1 per 10 000, representing 93.77% of all cases. Brazil and the Dominican Republic showed an increase in prevalence during 2011-2019, while in other countries the trend was decreasing. The disease is more frequent in men, and multibacillary cases significantly exceed paucibacillary ones. Brazil showed the highest incidences of cases of childhood leprosy and grade 2 disability during the evaluated period. Conclusion: In Latin America, leprosy is only considered a public health problem in Brazil; however, most countries in the region continue to report cases annually, revealing a lack of adequate medical care. This study confirmed the importance of active surveillance, early diagnosis and planning of actions against the disease in all the countries evaluated with the aim of reducing its transmission.

Objetivo: Descrever o comportamento epidemiológico da hanseníase em vários países de América Latina durante 2011-2020, tomando como base os indicadores da Organização Mundial da Saúde (OMS). Método: Estudo transversal, descritivo e quantitativo com dados oficiais de incidência e prevalência na população geral, em crianças, forma clínica e casos com incapacidade de grau 2 nos registros da OMS entre 2011 e 2020. Se selecionaram os oito países da América Latina que relataram a maioria dos casos e as análises foram avaliadas por meio de estatísticas descritivas e comparativas simples entre as variáveis. Resultados: No período, foram notificados 301 312 casos de hanseníase nos países selecionados: Argentina, Brasil, Colômbia, Cuba, México, Paraguai, República Dominicana e Venezuela. O Brasil é o único país da região com prevalência maior que 1 por 10 000 habitantes, representando 93,77% do total de casos. O Brasil e a República Dominicana mostraram um aumento na variação da prevalência durante 2011-2019, enquanto nos demais a tendência foi decrescente. A doença é mais frequente em homens e os casos multibacilares superam significativamente os paucibacilares. O Brasil apresentou as maiores incidências de hanseníase infantil e incapacidade de grau 2 durante o período avaliado. Conclusão: Na América Latina, a hanseníase só é considerada um problema de saúde pública no Brasil; no entanto, a maioria dos países da região continua notificando casos anualmente, revelando falta de assistência médica adequada. O presente estudo confirmou a importância da vigilância ativa, do diagnóstico precoce e do planejamento de ações contra a doença em todos os países avaliados, com o objetivo de reduzir e interromper a sua transmissão.

Potential Use for Serosurveillance of Feral Swine to Map Risk for Anthrax Exposure, Texas, USA.

Anthrax is a disease of concern in many mammals, including humans. Management primarily consists of prevention through vaccination and tracking clinical-level observations because environmental isolation is laborious and bacterial distribution across large geographic areas difficult to confirm. Feral swine (Sus scrofa) are an invasive species with an extensive range in the southern United States that rarely succumbs to anthrax. We present evidence that feral swine might serve as biosentinels based on comparative seroprevalence in swine from historically defined anthrax-endemic and non-anthrax-endemic regions of Texas. Overall seropositivity was 43.7% (n = 478), and logistic regression revealed county endemicity status, age-class, sex, latitude, and longitude were informative for predicting antibody status. However, of these covariates, only latitude was statistically significant (ß = -0.153, p = 0.047). These results suggests anthrax exposure in swine, when paired with continuous location data, could serve as a proxy for bacterial presence in specific areas.

Do different vaccination regimes affect the growth performance, immune status, carcase characteristics and meat quality of broilers?

1. A vaccination regime is a schedule for the administration of vaccines which may vary according to country or even by farm. This study aimed to measure the production and health performance of broilers treated with different vaccination regimes. 2. A total of 108 Cobb 500 broiler birds were randomly divided into three treatment groups, with six replicates consisting of six birds per replicate. Each treatment group was administered with different vaccination regimes against Newcastle Disease (ND), Infectious Bronchitis (IB) and Infectious Bursal Disease (IBD). Treatment 1 (T1) broilers were vaccinated against ND+IB and IBD on days 7 and 14 of age, respectively (control); Treatment 2 (T2) broilers were vaccinated against ND+IB on days 3 and 7 of age, and IBD on day 14; and Treatment 3 (T3) broilers were vaccinated against ND+IB on days 7 and 21 and IBD on day 14. Throughout the 42-day study period, data and samples were collected to determine the growth performance, immune status, carcase characteristics and meat quality. 3. There were significant differences (P < 0.05) on growth performance (body weight, body weight gain, feed intake and cumulative feed conversion ratio), white blood cell count (heterophils percentage, lymphocytes percentage and heterophils to lymphocytes ratio), carcase characteristics (kill-out weight, de-feathered weight, dressing percentage, drumsticks and gastrointestinal tract weight) and meat quality (cooking loss and drip loss) between treatments. T1 broilers showed better growth, white blood cell count, carcase characteristics and meat quality compared to T2 and T3 broilers. 4. Based on findings from the current work, vaccination against ND+IB and IBD on days 7 and 14 proved to be the best vaccination regime for broiler production, due to the better production performance and health status of broilers.

[The diseases of Russia: the medical geographical studies of I. Ya. Lerkhe].

The article analyses the process of establishment of medical knowledge concerning territories of the Russian Empire in XVIII century on the basis of written heritage of the Prussian physician Johann Jacob Lerche (1708-1780). The analysis is focused on forms of actual medical geographical studies practiced by European doctors and Lerche himself, first of all on his meteorological observations. The Lerche's interpretations of local natural and social phenomena in construction of medical characteristics of particular corners of the Empire in manuscript about endemics in Russia and Persia are analyzed. The assumption is proposed that studies of Russia implemented by Lerche are constructed on the analogy of summarizing academic descriptions of naturalists of XVIII century. Thereby, the works of Prussian physician seems to be participated in process of development of language of systematization and ranking of diseases and endowed category of "disease" with function of inherent to region characteristic such as climate, flora and fauna.

Crimean-Congo Hemorrhagic Fever Virus Endemicity in United Arab Emirates, 2019.

We conducted a cross-sectional survey of Crimean-Congo hemorrhagic fever virus (CCHFV) in dromedary camels and attached ticks at 3 locations in the United Arab Emirates. Results revealed a high prevalence of CCHFV-reactive antibodies in camels and viral RNA in ticks and camel serum, suggesting the virus is endemic in this country.

Blastomycosis in Minnesota, USA, 1999-2018.

Blastomycosis is a systemic disease caused by Blastomyces spp. fungi. To determine its epidemiology in blastomycosis-endemic Minnesota, USA, we evaluated all cases reported to public health officials during 1999-2018. We focused on time to diagnosis, exposure activities, and exposure location. A total of 671 cases and a median of 34 cases/year were reported. Median time to diagnosis was 31 days; 61% of patients were not tested for blastomycosis until they were hospitalized. The case-fatality rate was 10%, and patients who died were 5.3 times more likely to have a concurrent medical condition. Outdoor activities and soil exposure were reported by many patients, but no specific activity or exposure was common to most. Almost one third of patients were probably exposed in geographic areas other than their home county. Providers should consider alternative etiologies for patients with pneumonia not responding to antibacterial treatment, and public health officials should increase awareness in blastomycosis-endemic areas.

Human ophthalmomyiasis caused by Oestrus ovis-first report from Croatia and review on cases from Mediterranean countries.

Oestrus ovis is the most common cause of human ophthalmomyiasis. So far, majority of ophthalmomyiasis cases have been reported from Mediterranean countries, but not from Croatia. In current study, we present first two cases of human ophthalmomyiasis in Croatia, caused by O. ovis larvae. Reviewing a PubMed database, additional 259 cases of human ophthalmomyiasis in countries of Mediterranean basin have been reported. A total of 260 (99.62%) cases had external, while 1 (0.38%) had internal form of ocular myiasis. In all cases, O. ovis larvae were identified as the causative agent. O. ovis infestation is usually reported in shepherds and farmers although there is a high prevalence of infection in urban areas as well. Various climatic factors influence O. ovis larvipositional activity. Air temperature is the most important factor affecting O. ovis larviposition, while humidity, wind speed, and time of the day play only a moderate role. Most common symptoms of ophthalmomyiasis are irritation and redness, and in more than half of cases infestation is multiple. Ophthalmomyiasis interna is eye-compromising condition. Since there is reduced awareness among patients and medical professionals, the real number of ophthalmomyiasis cases is probably significantly higher than published. Global warming predisposes future increase of O. ovis prevalence in humans, which emphasizes the need for mandatory reporting and surveillance of disease.

Endemic diseases of geochemical origin and methodological approaches toward their prevention and elimination.

A new approach to the study of diseases of geochemical origin is presented, which is based on the hypothesis that all such geochemical endemias were not possible in conditions of virgin biosphere and are products of human civilization. Two genetically different types of endemic diseases of geochemical origin are distinguished, each having a specifically spatial structure: (1) diseases of natural origin due to natural element deficiency or excess in the particular zones or areas; (2) diseases of anthropogenic origin related to chemical transformation of the environment in the course of agricultural or industrial production. Anthropogenically provoked diseases of geochemical nature always occur in conditions of already formed natural geochemical heterogeneity. As each type of the endemic disease has a peculiar structure of spatial distribution, the present health risk can be mapped as a genetically two-layer structure, characterizing deviation of the existing geochemical conditions from those ideal for specific species. Parameters of geochemical conditions, which are ideal for humans and domesticated species, should be sought within the areas with undisturbed soil cover, where these species have been formed in their present form. The hypothesis is tested on example of thyroid diseases observed in iodine-deficient areas affected by a nuclear accident with 131I fallout. The developed approach is believed to serve as a practical tool for monitoring and prevention of endemic diseases of geochemical origin.

Building the capacity of users and producers of evidence in health policy and systems research for better control of endemic diseases in Nigeria: a situational analysis.

BACKGROUND: There is a current need to build the capacity of Health Policy and Systems Research + Analysis (HPSR+A) in low and middle-income countries (LMICs) as this enhances the processes of decision-making at all levels of the health system. This paper provides information on the HPSR+A knowledge and practice among producers and users of evidence in priority setting for HPSR+A regarding control of endemic diseases in two states in Nigeria. It also highlights the HPSR+A capacity building needs and interventions that will lead to increased HPSR+A and use for actual policy and decision making by the government and other policy actors. METHODS: Data was collected from 96 purposively selected respondents who are either researchers/ academia (producers of evidence) and policy/decision-makers, programme/project managers (users of evidence) in Enugu and Anambra states, southeast Nigeria. A pre-tested questionnaire was the data collection tool. Analysis was by univariate and bivariate analyses. RESULTS: The knowledge on HPSR+A was moderate and many respondents understood the importance of evidence-based decision making. Majority of researcher stated their preferred channel of dissemination of research finding to be journal publication. The mean percentage of using HPSR evidence for programme design & implementation of endemic disease among users of evidence was poor (18.8%) in both states. There is a high level of awareness of the use of evidence to inform policy across the two states and some of the respondents have used some evidence in their work. CONCLUSION: The high level of awareness of the use of HPSR+A evidence for decision making did not translate to the significant actual use of evidence for policy making. The major reasons bordered on lack of autonomy in decision making. Hence, the existing yawning gap in use of evidence has to be bridged for a strengthening of the health system with evidence.

Estimated dengue force of infection and burden of primary infections among Indian children.

BACKGROUND: Comprehensive, age-stratified dengue surveillance data are unavailable from India and many more dengue cases occur than are reported. Additional information on dengue transmission dynamics can inform understanding of disease endemicity and infection risk. METHODS: Using age-stratified dengue IgG seroprevalence data from 2556 Indian children aged 5-10 years, we estimated annual force of infection (FOI) at each of 6 sites using a binomial regression model. We estimated the ages by which 50 and 70% of children were first infected; and predicted seroprevalence in children aged 1-10 years assuming constant force-of-infection. Applying these infection rates to national census data, we then calculated the number of primary dengue infections occurring, annually, in Indian children. RESULTS: Annual force-of-infection at all sites combined was 11.9% (95% CI 8.8-16.2), varying across sites from 3.5% (95% CI 2.8-4.4) to 21.2% (95% CI 18.4-24.5). Overall, 50 and 70% of children were infected by 5.8 (95% CI 4.3-7.9) and 10.1 (95% CI 7.4-13.7) years respectively. In all sites except Kalyani, > 70% of children had been infected before their 11th birthday, and goodness-of-fit statistics indicated a relatively constant force-of-infection over time except at two sites (Wardha and Hyderabad). Nationwide, we estimated 17,013,527 children (95% CI: 14,518,438- 19,218,733), equivalent to 6.5% of children aged < 11 years, experience their first infection annually. CONCLUSIONS: Dengue force-of-infection in India is comparable to other highly endemic countries. Significant variation across sites exists, likely reflecting local epidemiological variation. The number of annual primary infections is indicative of a significant, under-reported burden of secondary infections and symptomatic episodes. TRIAL REGISTRATION: Registered retrospectively with clinicaltrials.gov ( NCT01477671 ; 18/11/2011) and clinical trials registry of India (ctri.nic.in; CTRI/2011/12/002243 ; 15/12/2011). Date of enrollment of 1st subject: 22/9/2011.

Enhanced Surveillance for Coccidioidomycosis, 14 US States, 2016.

Although coccidioidomycosis in Arizona and California has been well-characterized, much remains unknown about its epidemiology in states where it is not highly endemic. We conducted enhanced surveillance in 14 such states in 2016 by identifying cases according to the Council of State and Territorial Epidemiologists case definition and interviewing patients about their demographic characteristics, clinical features, and exposures. Among 186 patients, median time from seeking healthcare to diagnosis was 38 days (range 1-1,654 days); 70% had another condition diagnosed before coccidioidomycosis testing occurred (of whom 83% were prescribed antibacterial medications); 43% were hospitalized; and 29% had culture-positive coccidioidomycosis. Most (83%) patients from nonendemic states had traveled to a coccidioidomycosis-endemic area. Coccidioidomycosis can cause severe disease in residents of non-highly endemic states, a finding consistent with previous studies in Arizona, and less severe cases likely go undiagnosed or unreported. Improved coccidioidomycosis awareness in non-highly endemic areas is needed.

Selenium status of children in Kashin-Beck disease endemic areas in Shaanxi, China: assessment with mercury.

The causes of Kashin-Beck disease (KBD) in children are multifactorial, and particular consideration has been given to childhood selenium (Se) deficiency. In this study, dietary intake of Se and mercury (Hg) was determined at KBD areas to investigate the Se status and risks. Therefore, total Hg and Se levels were investigated in scalp hair samples and in daily intake food samples of 150 schoolchildren in Yongshou County of Shaanxi, China. The results showed that the average concentration of Se in children's hair has risen to 302 ng g-1 and significantly increased compared to the data reported decades ago. Children at KBD endemic areas likely have improved Se status due to the Se supplementation in food at recent decades. However, all the children in the study areas still showed lower Se status compared to those in other non-KBD areas of China. The probable daily intake of Se in the study areas was still lower after stopping Se supplementation in food at KBD areas, which is 17.96 µg day-1. Food produced locally cannot satisfy the lowest demand for Se nutrition for local residents. If the interactions of Se-Hg detoxification are considered, Hg intake from food exacerbates Se deficiency at the KBD areas.

Lessons from a decade of individual-based models for infectious disease transmission: a systematic review (2006-2015).

BACKGROUND: Individual-based models (IBMs) are useful to simulate events subject to stochasticity and/or heterogeneity, and have become well established to model the potential (re)emergence of pathogens (e.g., pandemic influenza, bioterrorism). Individual heterogeneity at the host and pathogen level is increasingly documented to influence transmission of endemic diseases and it is well understood that the final stages of elimination strategies for vaccine-preventable childhood diseases (e.g., polio, measles) are subject to stochasticity. Even so it appears IBMs for both these phenomena are not well established. We review a decade of IBM publications aiming to obtain insights in their advantages, pitfalls and rationale for use and to make recommendations facilitating knowledge transfer within and across disciplines. METHODS: We systematically identified publications in Web of Science and PubMed from 2006-2015 based on title/abstract/keywords screening (and full-text if necessary) to retrieve topics, modeling purposes and general specifications. We extracted detailed modeling features from papers on established vaccine-preventable childhood diseases based on full-text screening. RESULTS: We identified 698 papers, which applied an IBM for infectious disease transmission, and listed these in a reference database, describing their general characteristics. The diversity of disease-topics and overall publication frequency have increased over time (38 to 115 annual publications from 2006 to 2015). The inclusion of intervention strategies (8 to 52) and economic consequences (1 to 20) are increasing, to the detriment of purely theoretical explorations. Unfortunately, terminology used to describe IBMs is inconsistent and ambiguous. We retrieved 24 studies on a vaccine-preventable childhood disease (covering 7 different diseases), with publication frequency increasing from the first such study published in 2008. IBMs have been useful to explore heterogeneous between- and within-host interactions, but combined applications are still sparse. The amount of missing information on model characteristics and study design is remarkable. CONCLUSIONS: IBMs are suited to combine heterogeneous within- and between-host interactions, which offers many opportunities, especially to analyze targeted interventions for endemic infections. We advocate the exchange of (open-source) platforms and stress the need for consistent "branding". Using (existing) conventions and reporting protocols would stimulate cross-fertilization between research groups and fields, and ultimately policy making in decades to come.

A Rare Case of Schistosomiasis (Bilharzia) of the Bladder in a Non-Endemic Area.

BACKGROUND: Schistosomiasis or snail fever is an endemic parasitic infection caused by various trematodes of the genus Schistosoma. People acquire the disease through contact with water containing infected snails. It is one of the most widespread human parasitic infections in tropical and subtropical regions of the world such as Africa, South America, the Middle East, Asia and the Caribbean. In 1996, the World Health Organisation estimated that more than 200 million people living in rural areas are affected by this disease. However, the diagnosis is difficult in low prevalence areas because of a low index of suspicion. CASE REPORT: Herein, we present a case of a 14-year old boy who had intermittent passage of blood in urine for the past 3 years. Clinical examination and initial investigations did not reveal any abnormality. Bladder schistosomiasis was suspected after contrast-enhanced computed tomography and later confirmed by cystoscopic biopsy. CONCLUSIONS: Bladder schistosomiasis is a prevalent disease in the developing countries, but in non-endemic areas diagnosis may be often missed. The diagnosis should be considered in patients presenting with sporadic episodes of haematuria who have immigrated from or travelled to areas where this disease is endemic.

Effect of Geography on the Analysis of Coccidioidomycosis-Associated Deaths, United States.

Because coccidioidomycosis death rates vary by region, we reanalyzed coccidioidomycosis-associated mortality in the United States by race/ethnicity, then limited analysis to Arizona and California. Coccidioidomycosis-associated deaths were shown to increase among African-Americans but decrease among Native Americans and Hispanics. Separately, in a Native American cohort, diabetes co-varied with coccidioidomycosis-associated death.

Endemic melioidosis in residents of desert region after atypically intense rainfall in central Australia, 2011.

After heavy rains and flooding during early 2011 in the normally arid interior of Australia, melioidosis was diagnosed in 6 persons over a 4-month period. Although the precise global distribution of the causal bacterium Burkholderia pseudomallei remains to be determined, this organism can clearly survive in harsh and even desert environments outside the wet tropics.