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An efficacious tuberculosis (TB) vaccine is critical to reducing the global burden of TB. TB vaccine trials require the identification of multiple sites globally that have both a high incidence of TB and the capacity to conduct a clinical trial. To expand the diversity of potential phase III TB vaccine trial sites to be considered for inclusion, we describe a novel epidemiologic method that incorporates approaches from a variety of public health practices. Our approach incorporates analytic methodology to enable quantification and validation of qualitative information from disparate data sources, and epidemiologic analysis to systematically assess site-specific TB epidemiology. The integration of robust data-driven practices, and more quantitatively focused analysis, allowed for the objective evaluation of sites, which resulted in the identification of sites and catchment areas with high TB burden that may not have been previously considered. This suggests that an integrated epidemiologic methodology, not traditionally utilized for clinical trial site evaluations, could be integrated into site feasibility assessments as it results in more rapid site identification and reduces unintended bias.
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India's dense human and animal populations, agricultural economy, changing environment, and social dynamics support conditions for emergence/re-emergence of zoonotic diseases that necessitate a One Health (OH) approach for control. In addition to OH national level frameworks, effective OH driven strategies that promote local intersectoral coordination and collaboration are needed to truly address zoonotic diseases in India. We conducted a literature review to assess the landscape of OH activities at local levels in India that featured intersectoral coordination and collaboration and supplemented it with our own experience conducting OH related activities with local partners. We identified key themes and examples in local OH activities. Our landscape assessment demonstrated that intersectoral collaboration primarily occurs through specific research activities and during outbreaks, however, there is limited formal coordination among veterinary, medical, and environmental professionals on the day-to-day prevention and detection of zoonotic diseases at district/sub-district levels in India. Examples of local OH driven intersectoral coordination include the essential role of veterinarians in COVID-19 diagnostics, testing of human samples in veterinary labs for Brucella and leptospirosis in Punjab and Tamil Nadu, respectively, and implementation of OH education targeted to school children and farmers in rural communities. There is an opportunity to strengthen local intersectoral coordination between animal, human and environmental health sectors by building on these activities and formalizing the existing collaborative networks. As India moves forward with broad OH initiatives, OH networks and experience at the local level from previous or ongoing activities can support implementation from the ground up.
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COVID-19 , Leptospirose , Saúde Única , Animais , Criança , Humanos , Índia/epidemiologia , Zoonoses/prevenção & controleRESUMO
Climate change impacts global ecosystems at the interface of infectious disease agents and hosts and vectors for animals, humans, and plants. The climate is changing, and the impacts are complex, with multifaceted effects. In addition to connecting climate change and infectious diseases, we aim to draw attention to the challenges of working across multiple disciplines. Doing this requires concentrated efforts in a variety of areas to advance the technological state of the art and at the same time implement ideas and explain to the everyday citizen what is happening. The world's experience with COVID-19 has revealed many gaps in our past approaches to anticipating emerging infectious diseases. Most approaches to predicting outbreaks and identifying emerging microbes of major consequence have been with those causing high morbidity and mortality in humans and animals. These lagging indicators offer limited ability to prevent disease spillover and amplifications in new hosts. Leading indicators and novel approaches are more valuable and now feasible, with multidisciplinary approaches also within our grasp to provide links to disease predictions through holistic monitoring of micro and macro ecological changes. In this commentary, we describe niches for climate change and infectious diseases as well as overarching themes for the important role of collaborative team science, predictive analytics, and biosecurity. With a multidisciplinary cooperative "all call," we can enhance our ability to engage and resolve current and emerging problems.
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COVID-19 , Doenças Transmissíveis Emergentes , Doenças Transmissíveis , Humanos , Animais , Ecossistema , Mudança Climática , COVID-19/epidemiologia , Doenças Transmissíveis/epidemiologia , Doenças Transmissíveis Emergentes/epidemiologiaRESUMO
Cooperative research programs aimed at reducing biological threats have increased scientific capabilities and capacities in Kazakhstan. The German Federal Foreign Office's German Biosecurity Programme, the United Kingdom's International Biological Security Programme and the United States Defense Threat Reduction Agency's Biological Threat Reduction Program provide funding for partner countries, like Kazakhstan. The mutual goals of the programs are to reduce biological threats and enhance global health security. Our investigation examined these cooperative research programs, summarizing major impacts they have made, as well as common successes and challenges. By mapping various projects across the three programs, research networks are highlighted which demonstrate best communication practices to share results and reinforce conclusions. Our team performed a survey to collect results from Kazakhstani partner scientists on their experiences that help gain insights into enhancing day-to-day approaches to conducting cooperative scientific research. This analysis will serve as a basis for a capability maturity model as used in industry, and in addition builds synergy for future collaborations that will be essential for quality and sustainment.
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Saúde Global , Cazaquistão , Estados UnidosRESUMO
The current COVID-19 pandemic demonstrates the need for urgent and on-demand solutions to provide diagnostics, treatment and preventative measures for infectious disease outbreaks. Once solutions are developed, meeting capacities depends on the ability to mitigate technical, logistical and production issues. While it is difficult to predict the next outbreak, augmenting investments in preparedness, such as infectious disease surveillance, is far more effective than mustering last-minute response funds. Bringing research outputs into practice sooner rather than later is part of an agile approach to pivot and deliver solutions. Cooperative multi- country research programs, especially those funded by global biosecurity programs, develop capacity that can be applied to infectious disease surveillance and research that enhances detection, identification, and response to emerging and re-emerging pathogens with epidemic or pandemic potential. Moreover, these programs enhance trust building among partners, which is essential because setting expectation and commitment are required for successful research and training. Measuring research outputs, evaluating outcomes and justifying continual investments are essential but not straightforward. Lessons learned include those related to reducing biological threats and maturing capabilities for national laboratory diagnostics strategy and related health systems. Challenges, such as growing networks, promoting scientific transparency, data and material sharing, sustaining funds and developing research strategies remain to be fully resolved. Here, experiences from several programs highlight successful partnerships that provide ways forward to address the next outbreak.
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COVID-19 , Doenças Transmissíveis , Doenças Transmissíveis/diagnóstico , Surtos de Doenças/prevenção & controle , Humanos , Pandemias , SARS-CoV-2RESUMO
High containment biological laboratories (HCBL) are required for work on Risk Group 3 and 4 agents across the spectrum of basic, applied, and translational research. These laboratories include biosafety level (BSL)-3, BSL-4, animal BSL (ABSL)-3, BSL-3-Ag (agriculture livestock), and ABSL-4 laboratories. While SARS-CoV-2 is classified as a Risk Group 3 biological agent, routine diagnostic can be handled at BSL-2. Scenarios involving virus culture, potential exposure to aerosols, divergent high transmissible variants, and zoonosis from laboratory animals require higher BSL-3 measures. Establishing HCBLs especially those at BSL-4 is costly and needs continual investments of resources and funding to sustain labor, equipment, infrastructure, certifications, and operational needs. There are now over 50 BSL-4 laboratories and numerous BSL-3 laboratories worldwide. Besides technical and funding challenges, there are biosecurity and dual-use risks, and local community issues to contend with in order to sustain operations. Here, we describe case histories for distinct HCBLs: representative national centers for diagnostic and reference, nonprofit organizations. Case histories describe capabilities and assess activities during COVID-19 and include capacities, gaps, successes, and summary of lessons learned for future practice.
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As the world looks forward to turning a corner in the face of the COVID-19 pandemic, it becomes increasingly evident that international research cooperation and dialogue is necessary to end this global catastrophe. Last year, we initiated a research topic: "Infectious Disease Surveillance: Cooperative Research in Response to Recent Outbreaks, Including COVID-19," which aimed at featuring manuscripts focused on the essential link between surveillance and cooperative research for emerging and endemic diseases, and highlighting scientific partnerships in countries under-represented in the scientific literature. Here we recognize the body of work published from our manuscript call that resulted in over 50 published papers. This current analysis describes articles and authors from a variety of funded and unfunded international sources. The work exemplifies successful research and publications which are frequently cooperative, and may serve as a basis to model further global scientific engagements.
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COVID-19 , Doenças Transmissíveis , Doenças Transmissíveis/epidemiologia , Humanos , Cooperação Internacional , Pandemias , SARS-CoV-2RESUMO
In 2019/2020, the emergence of coronavirus disease 2019 (COVID-19) resulted in rapid increases in infection rates as well as patient mortality. Treatment options addressing COVID-19 included drug repurposing, investigational therapies such as remdesivir, and vaccine development. Combination therapy based on drug repurposing is among the most widely pursued of these efforts. Multi-drug regimens are traditionally designed by selecting drugs based on their mechanism of action. This is followed by dose-finding to achieve drug synergy. This approach is widely-used for drug development and repurposing. Realizing synergistic combinations, however, is a substantially different outcome compared to globally optimizing combination therapy, which realizes the best possible treatment outcome by a set of candidate therapies and doses toward a disease indication. To address this challenge, the results of Project IDentif.AI (Identifying Infectious Disease Combination Therapy with Artificial Intelligence) are reported. An AI-based platform is used to interrogate a massive 12 drug/dose parameter space, rapidly identifying actionable combination therapies that optimally inhibit A549 lung cell infection by vesicular stomatitis virus within three days of project start. Importantly, a sevenfold difference in efficacy is observed between the top-ranked combination being optimally and sub-optimally dosed, demonstrating the critical importance of ideal drug and dose identification. This platform is disease indication and disease mechanism-agnostic, and potentially applicable to the systematic N-of-1 and population-wide design of highly efficacious and tolerable clinical regimens. This work also discusses key factors ranging from healthcare economics to global health policy that may serve to drive the broader deployment of this platform to address COVID-19 and future pandemics.
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In January 2019, the state of Minas Gerais experienced another environmental disaster with the collapse of a mining dam near the city of Brumadinho. This disaster has resulted in 256 deaths and 14 people still missing. Toxic mud has contaminated the Paraopeba River resulting in significant fish and wildlife deaths in the river and surrounding areas. The effect of environmental disasters such as this is felt across multiple sectors damaging ecosystems in agriculture, wildlife and human communities. Environmental disasters cause significant disruption of ecosystems, flooding, contamination of water supplies, and displacement of human populations, which can result in increases in transmission and outbreaks of mosquito-borne and zoonotic diseases that can become a serious and long-term public health problem for the region.
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Doenças Transmissíveis/epidemiologia , Desastres , Mineração , Rios , Brasil , Cidades , Controle de Doenças Transmissíveis , Ecossistema , Monitoramento Ambiental , Humanos , Poluentes Químicos da ÁguaRESUMO
Kazakhstan and the United States have partnered since 2003 to counter the proliferation of weapons of mass destruction. The US Department of Defense (US DoD) has funded threat reduction programs to eliminate biological weapons, secure material in repositories that could be targeted for theft, and enhance surveillance systems to monitor infectious disease outbreaks that would affect national security. The cooperative biological research (CBR) program of the US DoD's Biological Threat Reduction Program has provided financing, mentorship, infrastructure, and biologic research support to Kazakhstani scientists and research institutes since 2005. The objective of this paper is to provide a historical perspective for the CBR involvement in Kazakhstan, including project chronology, successes and challenges to allow lessons learned to be applied to future CBR endeavors. A project compendium from open source data and interviews with partner country Kazakhstani participants, project collaborators, and stakeholders was developed utilizing studies from 2004 to the present. An earlier project map was used as a basis to determine project linkages and continuations during the evolution of the CBR program. It was determined that consistent and effective networking increases the chances to collaborate especially for competitive funding opportunities. Overall, the CBR program has increased scientific capabilities in Kazakhstan while reducing their risk of biological threats. However, there is still need for increased scientific transparency and an overall strategy to develop a capability-based model to better enhance and sustain future research. Finally, we offer a living perspective that can be applied to further link related studies especially those related to One Health and zoonoses and the assessment of similar capability-building programs.
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BACKGROUND: A vaccine to prevent infection and disease caused by Plasmodium vivax is needed both to reduce the morbidity caused by this parasite and as a key component in efforts to eradicate malaria worldwide. Vivax malaria protein 1 (VMP001), a novel chimeric protein that incorporates the amino- and carboxy- terminal regions of the circumsporozoite protein (CSP) and a truncated repeat region that contains repeat sequences from both the VK210 (type 1) and the VK247 (type 2) parasites, was developed as a vaccine candidate for global use. METHODS: We conducted a first-in-human Phase 1 dose escalation vaccine study with controlled human malaria infection (CHMI) of VMP001 formulated in the GSK Adjuvant System AS01B. A total of 30 volunteers divided into 3 groups (10 per group) were given 3 intramuscular injections of 15 µg, 30 µg, or 60 µg respectively of VMP001, all formulated in 500 µL of AS01B at each immunization. All vaccinated volunteers participated in a P. vivax CHMI 14 days following the third immunization. Six non-vaccinated subjects served as infectivity controls. RESULTS: The vaccine was shown to be well tolerated and immunogenic. All volunteers generated robust humoral and cellular immune responses to the vaccine antigen. Vaccination did not induce sterile protection; however, a small but significant delay in time to parasitemia was seen in 59% of vaccinated subjects compared to the control group. An association was identified between levels of anti-type 1 repeat antibodies and prepatent period. SIGNIFICANCE: This trial was the first to assess the efficacy of a P. vivax CSP vaccine candidate by CHMI. The association of type 1 repeat-specific antibody responses with delay in the prepatency period suggests that augmenting the immune responses to this domain may improve strain-specific vaccine efficacy. The availability of a P. vivax CHMI model will accelerate the process of P. vivax vaccine development, allowing better selection of candidate vaccines for advancement to field trials.
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Vacinas Antimaláricas/imunologia , Malária Vivax/prevenção & controle , Plasmodium vivax/imunologia , Proteínas de Protozoários/imunologia , Adolescente , Adulto , Anticorpos Antiprotozoários/imunologia , Feminino , Humanos , Vacinas Antimaláricas/administração & dosagem , Vacinas Antimaláricas/efeitos adversos , Malária Vivax/imunologia , Malária Vivax/parasitologia , Masculino , Pessoa de Meia-Idade , Proteínas de Protozoários/administração & dosagem , Proteínas de Protozoários/efeitos adversos , Vacinação , Adulto JovemRESUMO
Microscopic examination of placental tissue can provide an accurate assessment of malaria infection during pregnancy. In this cross-sectional study of 193 women in Iquitos, Peru, 1.0% and 6.6% had parasites in the peripheral blood as detected by microscopy and polymerase chain reaction, respectively. However, 22% had placental malaria pigment indicating past, subclinical infections. Placental tissues with pigment from 24 cases were matched by gravidity and month of delivery to 24 controls and histopathologically examined. Cases had significantly higher number of monocytes in the intervillous space (44.7 versus 25.5; P = 0.012). Pigmented monocytes in fetal vessels were present in 33.3% of cases. This study demonstrated that subclinical malarial infection occurred frequently in pregnant women and is associated with increased presence of monocytes in the placenta. Pigmented monocytes in fetal vessels suggest parasites can breach the placental barrier and enter the fetal circulation.
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Malária Falciparum/patologia , Malária Vivax/patologia , Placenta/patologia , Complicações Parasitárias na Gravidez/patologia , Adolescente , Adulto , Estudos de Casos e Controles , Estudos Transversais , Feminino , Hemeproteínas/análise , Humanos , Malária Falciparum/sangue , Malária Falciparum/epidemiologia , Malária Vivax/sangue , Malária Vivax/epidemiologia , Monócitos/patologia , Parasitemia/sangue , Peru/epidemiologia , Pigmentos Biológicos/análise , Placenta/química , Placenta/parasitologia , Gravidez , Complicações Parasitárias na Gravidez/sangue , Complicações Parasitárias na Gravidez/epidemiologia , Adulto JovemRESUMO
The Amazon region of Iquitos, Peru is hypoendemic for Plasmodium vivax and P. falciparum. There is limited information regarding the epidemiology of malaria during pregnancy in this region. Passive surveillance for clinical malaria among pregnant women was conducted in eight health posts in 2004 and 2005. Community-based active surveillance was conducted to determine the incidence of malarial infection among pregnant women in the community of Zungarococha in 2004 and 2005. Passive surveillance demonstrated that pregnant women had a prevalence of clinical malaria of 7.5% in 2004 and 6.6% in 2005 compared with 20.6% and 22.4% of the total population. Active surveillance showed that pregnant women were 2.3 (95% confidence interval = 1.32-3.95, P = 0.004) times more likely to have a P. falciparum infection compared with non-pregnant women. This study demonstrated that because of detection bias, passive surveillance underestimates the burden of malarial infection during pregnancy, and that subclinical malarial infections may occur frequently among pregnant women in this region. Furthermore, pregnant women in this low-transmission and P. vivax-dominant setting, experience an increased risk for P. falciparum infection, but not P. vivax infection.
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Malária Falciparum/epidemiologia , Malária Vivax/epidemiologia , Complicações Parasitárias na Gravidez/epidemiologia , Adolescente , Adulto , Animais , Doenças Endêmicas , Feminino , Humanos , Pessoa de Meia-Idade , Peru/epidemiologia , Plasmodium falciparum/isolamento & purificação , Plasmodium vivax/isolamento & purificação , Gravidez , Prevalência , Fatores de RiscoAssuntos
Antígenos de Protozoários/imunologia , Vacinas Antimaláricas/imunologia , Malária Falciparum/imunologia , Plasmodium falciparum/imunologia , Animais , Formação de Anticorpos , Criança , Pré-Escolar , Humanos , Malária Falciparum/prevenção & controle , Análise em Microsséries , Proteínas Recombinantes/imunologiaRESUMO
In a prospective study of rhesus monkeys inoculated with Plasmodium coatneyi or saline on an infection/gestational timeline, we determined the serum levels of tumor necrosis factor-alpha (TNF-alpha), soluble tumor necrosis factor receptor type I (sTNFR-I), and soluble tumor necrosis factor receptor type II (sTNFR-II) in peripheral blood throughout primigravid pregnancy, malaria infection, and a combination of the two. Our goal was to determine the association between levels of TNF-alpha and of its 2 soluble receptors and the course of pregnancy and/or malaria and infant outcome. We found that any detectable level of TNF-alpha was always associated with fetal death and that the sTNFRs may be important for fetal protection, possibly through neutralizing the toxic effects of TNF-alpha. Our findings also showed that increased levels of sTNFR-II were associated specifically with malaria and not with normal pregnancy or even pregnancy with low birth weight due to other causes. In contrast, increases in sTNFR-I levels during the later half of normal pregnancies indicate that sTNFR-I may be important in regulating TNF-alpha levels in preparation for normal labor and delivery.
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Malária/fisiopatologia , Plasmodium/patogenicidade , Complicações Parasitárias na Gravidez/fisiopatologia , Receptores Tipo II do Fator de Necrose Tumoral/imunologia , Receptores Tipo I de Fatores de Necrose Tumoral/imunologia , Fator de Necrose Tumoral alfa/imunologia , Animais , Peso ao Nascer , Contagem de Células Sanguíneas , Modelos Animais de Doenças , Feminino , Morte Fetal/parasitologia , Macaca mulatta , Gravidez , Estudos Prospectivos , Receptores Tipo I de Fatores de Necrose Tumoral/sangue , Receptores Tipo II do Fator de Necrose Tumoral/sangue , Fatores de Tempo , Fator de Necrose Tumoral alfa/análiseRESUMO
We sought to define the risk of recurrence of invasive pneumococcal disease (IPD) and to define the characteristics of persons experiencing recurrent IPD through population-based surveillance. Cases of IPD were identified through the US Centers for Disease Control and Prevention's Active Bacterial Core Surveillance. Recurrent episodes were defined as isolation of Streptococcus pneumoniae from any normally sterile site > or =30 days after initial positive culture. Among 13,924 persons who survived their initial episode of IPD, 318 (2.3%) experienced > or =1 subsequent episode, for 376 total recurrences. The recurrence rate was 1294 episodes per 100,000 person-years, or 50 times the annual incidence of IPD. In multivariable analysis, a higher risk of recurrence was seen in persons infected with human immunodeficiency virus and in children <5 years old with chronic illness. Most (92%) persons with recurrence had a vaccine indication. The risk of recurrence among certain persons with IPD is extremely high.