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1.
Artigo em Inglês | MEDLINE | ID: mdl-32049261

RESUMO

Aedes aegypti is associated with epidemic diseases in Brazil, such as urban yellow fever, dengue, and more recently, chikungunya and Zika viruses infections. More information about Ae. aegypti infestation is fundamental to virological surveillance in order to ensure the effectiveness of control measures in use. Thus, the present study aims to identify and compare infestation and infectivity of Ae. aegypti females in Macapa city, Amapa State (Amazon region), Brazil, between the epidemiological weeks 2017/02 and 2018/20. A total number of 303 Ae. aegypti females were collected at 21 fixed collection points, 171 at the 10 collection points in the Marabaixo neighborhood and 132 at the 11 collection points in the Central neighborhood. Among the collected samples, only two were positive for dengue virus, with a 2.08% (2/96 pools) infectivity rate for Marabaixo. The difference between the medians of Ae. aegypti females captured in Central and Marabaixo sites was not statistically significant. The findings indicate similar mosquito infestation levels between the neighborhoods, and a low-level of mosquito infectivity, although dengue virus was found only in Marabaixo. Virological surveillance of Ae. aegypti was important to identify sites of infection and determine possible routes of transmission to enable health surveillance teams to adopt preventive strategies where infected mosquitoes are present and act faster.

2.
Vaccine ; 38(9): 2172-2182, 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32008879

RESUMO

Ever since its development in the 1930's, the live-attenuated Yellow Fever virus vaccine YF-17D has been highly effective. Despite the increasing knowledge on the immune biology of the YF-17D vaccine, most studies have focused only on a few types of immune cells and pathways or mainly on the primary adaptive immune response to YF-17D vaccination. Here, we examined humoral, innate and adaptive cellular responses in a longitudinal YF-17D vaccination study in Switzerland, comparing both primary and booster vaccination. In contrast to the strong innate and adaptive immune response to the primary vaccination, we find that the response to boosting is much reduced. Our data show an inverse association of neutralizing antibodies at baseline with vaccine virus replication and with the immune response upon boosting. These results suggest that booster vaccination may not have major immunological effects when neutralizing antibodies are present. Importantly, our study population was healthy adults in a non-endemic country and ultimately booster vaccine requirement must be assessed based on additional epidemiological and public health considerations in endemic areas.

3.
Lancet Infect Dis ; 20(2): 172, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32006508
4.
PLoS Negl Trop Dis ; 14(2): e0008034, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32017766

RESUMO

BACKGROUND: Zika virus has recently spread to South- and Central America, causing congenital birth defects and neurological complications. Many people at risk are flavivirus pre-immune due to prior infections with other flaviviruses (e.g. dengue virus) or flavivirus vaccinations. Since pre-existing cross-reactive immunity can potentially modulate antibody responses to Zika virus infection and may affect the outcome of disease, we analyzed fine-specificity as well as virus-neutralizing and infection-enhancing activities of antibodies induced by a primary Zika virus infection in flavivirus-naïve as well as yellow fever- and/or tick-borne encephalitis-vaccinated individuals. METHODOLOGY: Antibodies in sera from convalescent Zika patients with and without vaccine-induced immunity were assessed by ELISA with respect to Zika virus-specificity and flavivirus cross-reactivity. Functional analyses included virus neutralization and infection-enhancement. The contribution of IgM and cross-reactive antibodies to these properties was determined by depletion experiments. PRINCIPAL FINDINGS: Pre-existing flavivirus immunity had a strong influence on the antibody response in primary Zika virus infections, resulting in higher titers of broadly flavivirus cross-reactive antibodies and slightly lower levels of Zika virus-specific IgM. Antibody-dependent enhancement (ADE) of Zika virus was mediated by sub-neutralizing concentrations of specific IgG but not by cross-reactive antibodies. This effect was potently counteracted by the presence of neutralizing IgM. Broadly cross-reactive antibodies were able to both neutralize and enhance infection of dengue virus but not Zika virus, indicating a different exposure of conserved sequence elements in the two viruses. CONCLUSIONS: Our data point to an important role of flavivirus-specific IgM during the transient early stages of infection, by contributing substantially to neutralization and by counteracting ADE. In addition, our results highlight structural differences between strains of Zika and dengue viruses that are used for analyzing infection-enhancement by cross-reactive antibodies. These findings underscore the possible impact of specific antibody patterns on flavivirus disease and vaccination efficacy.

5.
BMC Infect Dis ; 20(1): 116, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32041533

RESUMO

BACKGROUND: Yellow fever vaccine exists for over 80 years and is considered to be relatively safe. However, in rare cases it can produce serious neurotropic and viscerotropic complications. We report a case of a patient who presented both viscerotropic and neurological manifestations after yellow fever vaccination. CASE PRESENTATION: We describe the case of a 37 years old man who developed after the yellow fever vaccination a yellow fever vaccine-associated viscerotropic disease followed by acute uveitis. Prolonged detection of yellow fever RNA in blood and urine was consistent with yellow fever vaccine-associated adverse event. The final outcome was good, although with persistent fatigue over a few months. CONCLUSIONS: Even if the yellow fever vaccine is relatively safe, physicians should be aware of its possible serious adverse effects.

6.
Int J Infect Dis ; 92: 189-196, 2020 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-31935537

RESUMO

Yellow fever (YF) is an acute viral hemorrhagic disease caused by the YF virus (arbovirus) which continues to cause severe morbidity and mortality in Africa. A case of YF was confirmed in Nigeria on the 12th of September 2017, 21 years after the last confirmed case. The patient belongs to a nomadic population with a history of low YF vaccination uptake, in the Ifelodun Local Government Area (LGA) of Kwara State, Nigeria. An active case search in Ifelodun and its five contiguous LGAs led to the listing of 55 additional suspect cases of YF within the period of the outbreak investigation between September 18 to October 6, 2017. The median age of cases was 15 years, and 54.4% were males. Of these, blood samples were collected from 30 cases; nine tested positive in laboratories in Nigeria and six were confirmed positive for YF by the WHO reference laboratory in the region; Institut Pasteur, Dakar. A rapid YF vaccination coverage assessment was carried out, resulting in a coverage of 46% in the LGAs, with 25% of cases able to produce their vaccination cards. All stages of the yellow fever vector, Aedes mosquito were identified in the area, with high larval indices (House and Breteau) observed. In response to the outbreak, YF surveillance was intensified across all States in Nigeria, as well as reactive vaccination and social mobilisation campaigns carried out in the affected LGAs in Kwara State. A state-wide YF preventive campaign was also initiated.

7.
Arch Virol ; 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31942645

RESUMO

Dengue virus (DENV) is the most common mosquito-borne viral disease. The World Health Organization estimates that 400 million new cases of dengue fever occur every year. Approximately 500,000 individuals develop severe and life-threatening complications from dengue fever, such as dengue shock syndrome (DSS) and dengue hemorrhagic fever (DHF), which cause 22,000 deaths yearly. Currently, there are no specific licensed therapeutics to treat DENV illness. We have previously shown that the MEK/ERK inhibitor U0126 inhibits the replication of the flavivirus yellow fever virus. In this study, we demonstrate that the MEK/ERK inhibitor AZD6244 has potent antiviral efficacy in vitro against DENV-2, DENV-3, and Saint Louis encephalitis virus (SLEV). We also show that it is able to protect AG129 mice from a lethal challenge with DENV-2 (D2S20). The molecule is currently undergoing phase III clinical trials for the treatment of non-small-cell lung cancer. The effect of AZD6244 on the DENV life cycle was attributed to a blockade of morphogenesis. Treatment of AG129 mice twice daily with oral doses of AZD6244 (100 mg/kg/day) prevented the animals from contracting dengue hemorrhagic fever (DHF)-like lethal disease upon intravenous infection with 1 × 105 PFU of D2S20. The effectiveness of AZD6244 was observed even when the treatment of infected animals was initiated 1-2 days postinfection. This was also followed by a reduction in viral copy number in both the serum and the spleen. There was also an increase in IL-1ß and TNF-α levels in mice that were infected with D2S20 and treated with AZD6244 in comparison to infected mice that were treated with the vehicle only. These data demonstrate the potential of AZD6244 as a new therapeutic agent to treat DENV infection and possibly other flavivirus diseases.

9.
Vaccine ; 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31911033

RESUMO

BACKGROUND: The live-attenuated yellow fever vaccine (YFV) is generally contraindicated in immunosuppressed patients. Our aim was to investigate if immunosuppressive therapy impairs the long-term protection against yellow fever virus in patients who had received YFV prior to the start of their immunosuppressive therapy. METHODS: Our study examined 35 healthy individuals and 40 immunosuppressed patients with autoimmune diseases or organ transplants. All individuals had received YFV prior to the onset of their immunosuppression. We analysed the long-term influence of the immunosuppressive therapy on the YFV protective immunity by measuring neutralising antibodies (NA) with the Plaque Reduction Neutralisation Test (PRNT). We assessed risk factors for a negative PRNT result (titre below 1: 10) and their influence on the magnitude of the NA. RESULTS: A median time interval of 21.1 years (interquartile range 14.4-31.3 years) after the YFV in all patients, a total of 35 immunosuppressed patients (88%) were seropositive (PRNT ≥ 1:10) compared to 31 patients (89%) in the control group. The geometric mean titres of NA did not differ between the groups. The duration of an underlying rheumatic disease was the only risk factor found for a lower magnitude of NA. An insufficient level of NA was found in nine subjects (12%) who had received a single dose of YFV (in one subject, the number of YFV doses was unknown). CONCLUSION: The use of an immunosuppressive drug started after the administration of the YFV did not affect long-term persistence of NA. A second dose of YFV may be necessary to secure long-term immunity.

10.
Rev Soc Bras Med Trop ; 53: e20190160, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31994659

RESUMO

Acute disseminated encephalomyelitis (ADEM) is a demyelinating autoimmune neuropathic condition characterized by extensive bilateral and confluent lesions in the cerebral white matter and cerebellum. The basal ganglia and gray matter may also be involved. In most cases, the symptoms are preceded by viral infection or vaccination. In this report, we present a case of ADEM associated with optic neuritis presenting alongside two potential triggering factors: chikungunya virus infection and yellow fever immunization.

11.
Artigo em Alemão | MEDLINE | ID: mdl-31802155

RESUMO

Vaccinations are an integral part of pre-travel care. Gaps in routine vaccination should be closed. In particular, measles and influenza are important in the context of travel medicine. Vaccinations against yellow fever and meningococcal disease may be required for international travel. This article provides information on these and other travel vaccinations against hepatitis A, typhoid fever, rabies, Japanese encephalitis and cholera.Yellow fever endemic areas are located in Africa and in South America; there is no yellow fever in Asia. The meningococcal vaccine (A, C, W, Y) is required for pilgrims to Saudi Arabia. Additionally, it is recommended for travellers visiting the African "meningitis belt" during the dry season. A polio booster is required for countries with endemic wild-type polio virus (WPV) or circulating vaccine derived poliovirus (cVDPV).Hepatitis A is a common vaccine-preventable infection in travellers. The hepatitis A vaccination should therefore be recommended to all travellers going to endemic areas. South Asia is the most important region where travel-associated typhoid fever is acquired and where at the same time antimicrobial resistance is emerging. Two different vaccines against typhoid fever are available in Germany. The vaccine efficacy is 50-70% for both vaccines. Contacts with potentially rabid animals are a common travel-related problem. At the same time, vaccines for state of the art postexposure care are not provided in many countries. According to recent WHO recommendations, two vaccinations are sufficient for pre-travel priming against rabies. Japanese encephalitis is rare in travellers. Vaccination should be offered in case of travel to rural and peri-urban areas. Cholera is extremely rare in travellers going to endemic areas. Cholera vaccination is therefore usually not indicated in the context of travel medicine.


Assuntos
Doença Relacionada a Viagens , Viagem , Vacinação , Animais , Alemanha , Febre Amarela
12.
EMBO Mol Med ; 12(1): e10375, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31746149

RESUMO

Live 17D is widely used as a prophylactic vaccine strain for yellow fever virus that induces potent neutralizing humoral and cellular immunity against the wild-type pathogen. 17D replicates and kills mouse and human tumor cell lines but not non-transformed human cells. Intratumoral injections with viable 17D markedly delay transplanted tumor progression in a CD8 T-cell-dependent manner. In mice bearing bilateral tumors in which only one is intratumorally injected, contralateral therapeutic effects are observed consistent with more prominent CD8 T-cell infiltrates and a treatment-related reduction of Tregs. Additive efficacy effects were observed upon co-treatment with intratumoral 17D and systemic anti-CD137 and anti-PD-1 immunostimulatory monoclonal antibodies. Importantly, when mice were preimmunized with 17D, intratumoral 17D treatment achieved better local and distant antitumor immunity. Such beneficial effects of prevaccination are in part explained by the potentiation of CD4 and CD8 T-cell infiltration in the treated tumor. The repurposed use of a GMP-grade vaccine to be given via the intratumoral route in prevaccinated patients constitutes a clinically feasible and safe immunotherapy approach.

13.
Bioorg Med Chem ; 28(2): 115252, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31864777

RESUMO

The mosquito Aedes aegypti is the vector of arboviruses such as Zika, Chikungunya, dengue and yellow fever. These infectious diseases have a major impact on public health. The unavailability of effective vaccines or drugs to prevent or treat most of these diseases makes vector control the main form of prevention. One strategy to promote mosquito population control is the use of synthetic insecticides to inhibit key enzymes in the metabolic pathway of these insects, particularly during larval stages. One of the main targets of the kynurenine detoxification pathway in mosquitoes is the enzyme 3-hydroxykynurenine transaminase (HKT), which catalyzes the conversion of 3-hydroxykynurenine (3-HK) into xanthurenic acid (XA). In this work, we report eleven newly synthesized oxadiazole derivatives and demonstrate that these compounds are potent noncompetitive inhibitors of HKT from Ae. aegypti. The present data provide direct evidence that HKT can be explored as a molecular target for the discovery of novel larvicides against Ae. aegypti. More importantly, it ensures that structural information derived from the HKT 3D-structure can be used to guide the development of more potent inhibitors.

14.
J Theor Biol ; 484: 110014, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31557473

RESUMO

Superinfection exclusion is a phenomenon whereby the co-infection of a host with a secondary pathogen is prevented due to a current infection by another closely-related pathogenic strain. We construct a novel vector-host mathematical model for two pathogens that exhibit superinfection exclusion and simultaneously account for vaccination strategies against them. We then derive the conditions under which an endemic disease will prevent the establishment of another through the action of superinfection exclusion and show that vaccination against the endemic strain can enable the previously suppressed strain to invade the population. Through appropriate parameterisation of the model for dengue and yellow fever we find that superinfection exclusion alone is unlikely to explain the absence of yellow fever in many regions where dengue is endemic, and that the rollout of the recently licensed dengue vaccine, Dengvaxia, is unlikely to enable the establishment of Yellow Fever in regions where it has previously been absent.

15.
São Paulo; SES/SP; 2020. 13 p. tab.
Não convencional em Português | LILACS, Sec. Est. Saúde SP, SESSP-CTDPROD, Sec. Est. Saúde SP | ID: biblio-1049840
16.
Vaccine ; 38(6): 1291-1301, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31859201

RESUMO

BACKGROUND: Recent upsurges in yellow fever outbreaks are increasing the demand for yellow fever vaccine, while enormously straining global vaccine supply. Fractional dose yellow fever vaccination is being considered as a dose-sparing strategy to address current vaccine shortages. This systematic review and meta-analysis aimed to assess the effects of fractional dose yellow fever vaccination, in comparison with those of standard dose vaccination. METHODS: We registered this review on the International Prospective Register of Systematic Reviews (PROSPERO, registration number: CRD42018084214), developed the protocol in line with the Preferred Reporting Items for Systematic Review and Meta-Analyses Protocols (PRISMA-P) and synthesised the evidence in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA). We stratified meta-analyses by vaccine dose. RESULTS: We retrieved 2524 records from the literature search, eleven of them potentially eligible. From these studies, we included eight eligible trials, with a total of 2371 participants. Seroconversion rates at four to five weeks following vaccination were similar between participants who received standard doses and participants who received fractional doses containing one-third (547 participants: risk ratio [RR] 1.02, 95% confidence interval [CI] 1.00-1.04), one-fifth (155 participants: RR 1.00, 95% CI 0.98-1.03), one-tenth (890 participants: RR 0.99, 95% CI 0.96-1.01), and one-fiftieth (661 participants: RR 0.97, 95% CI 0.92-1.02) of the standard dose. However, the rates of seroconversion were substantially lower among participants who received fractional doses containing one-hundredth and lower fractions of the standard dose. Immunogenicity similarly persisted 8-10 years following both fractional and standard dose vaccination. Minor adverse events following vaccination did not differ across doses, and no serious adverse events were reported in any study arm. CONCLUSIONS: These findings support the use of fractional dosing as a strategy for mitigating vaccine shortages. The strategy should be specifically considered for individuals who are young, immuno-competent and well nourished.

17.
J Biomol Struct Dyn ; : 1-17, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31854239

RESUMO

Yellow fever disease is considered a re-emerging major health issue which has caused recent outbreaks with a high number of deaths. Tropical countries, mainly African and South American, are the most affected by Yellow fever outbreaks. Despite the availability of an attenuated vaccine, its use is limited for some groups such as pregnant and nursing women, immunocompromised and immunosuppressed patients, elderly people >65 years, infants <6 months and patients with biological disorders like thymus disorders. In order to achieve new preventive measures, we applied immunoinformatics approaches to develop a multi-epitope-based subunit vaccine for Yellow fever virus. Different epitopes, related to humoral and cell-mediated immunity, were predicted for complete polyproteins of two Yellow fever strains (Asibi and 17 D vaccine). Those epitopes common for both strains were mapped into a set of 137 sequences of Yellow fever virus, including 77 sequences from a recent outbreak at the state of Minas Gerais, southeast Brazil. Therefore, the present work uses robust bioinformatics approaches for the identification of a multi-epitope vaccine against the Yellow fever virus. Our results indicate that the identified multi-epitope vaccine might stimulate humoral and cellular immune responses and could be a potential vaccine candidate against Yellow fever virus infection. Hence, it should be subjected to further experimental validations. Communicated by Ramaswamy H. Sarma.

18.
Popul Health Metr ; 17(1): 18, 2019 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-31823786

RESUMO

BACKGROUND: Control of the Aedes aegypti mosquito is central to reducing the risk of dengue, zika, chikungunya, and yellow fever. Randomised controlled trials, including the Camino Verde trial in Mexico and Nicaragua, demonstrate the convincing impact of community mobilisation interventions on vector indices. These interventions might work through building social capital but little is known about the relationship between social capital and vector indices. METHODS: A secondary analysis used data collected from 45 intervention clusters and 45 control clusters in the impact survey of the Mexican arm of the Camino Verde cluster randomised controlled trial. Factor analysis combined responses to questions about aspects of social capital to create a social capital index with four constructs, their weighted averages then combined into a single scale. We categorised households as having high or low social capital based on their score on this scale. We examined associations between social capital and larval and pupal vector indices, taking account of the effects of other variables in a multivariate analysis. We report associations as odds ratios and 95% confidence intervals. RESULTS: The four social capital constructs were involvement, participation, investment, and communication. Among the 10,112 households, those in rural communities were much more likely to have a high social capital score (OR 4.51, 95% CIca 3.26-6.26). Households in intervention sites had higher social capital, although the association was not significant at the 5% level. Households with high social capital were more likely to be negative for larvae or pupae (OR 1.38, 95% CIca 1.12-1.69) and for pupae specifically (OR 1.37, 95% CIca 1.08-1.74). There was interaction between intervention status and social capital; in multivariate analysis, a combined variable of intervention/high social capital remained associated with larvae or pupae (ORa l.56, 95% CIca 1.19-2.04) and with pupae specifically (ORa 1.65, 95% CIca 1.20-2.28). CONCLUSION: This is the first report of an association of high social capital with low vector indices. Our findings support the idea that the Camino Verde community mobilisation intervention worked partly through an interaction with social capital. Understanding such interactions may help to maximise the impact of future community mobilisation interventions.

19.
Mem Inst Oswaldo Cruz ; 114: e190187, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31826129

RESUMO

BACKGROUND: The Yellow Fever (YF) vaccine is produced by the inoculation of embryonated chicken eggs with YF17DD virus on the ninth day of development. Full embryos are collected on the twelfth day of development for vaccine formulation. Skeletal muscle tissue is the main site where biosynthesis of viral particles occurs. OBJECTIVES: This study aimed to analyse the experimental infection of skeletal muscle cells of chicken embryos by the 17DD Yellow Fever virus (YFV) in vivo and in vitro. METHODS: Chicken embryos infected with YF17DD virus were analysed by immunofluorescence using confocal and super-resolution microscopes. Primary cultures of skeletal muscle cells of non-infected chicken embryos were evaluated for susceptibility and permissiveness to YF17DD virus using different protocols. This evaluation was performed based on morphological, viral titration, molecular biology, and colorimetric techniques. FINDINGS: The present work phenotypically characterises embryonic chicken skeletal muscle cells as myogenic precursors expressing the Pax7 transcription factor in some cases. We demonstrated that these cells are susceptible to in vitro infection at different multiplicities of infection (MOIs), reproducing the same infection pattern observed in vivo. Furthermore, myogenic precursors and myoblasts are preferred infection targets, but establishment of infection does not depend on the presence of these cells. The peak of viral production occurred at 48 hpi, with decay occurring 72 hpi, when the cytopathic effect can be observed. MAIN CONCLUSIONS: In conclusion, the primary culture of chicken skeletal muscle cells is a good model for studying muscle cells infected with YF17DD virus. This culture system displays satisfactory emulation of the in vitro phenomenon observed, contributing to our understanding of virus infection dynamics and leading to the development of alternative methods of vaccine production.


Assuntos
Músculo Esquelético/virologia , Vacina contra Febre Amarela/imunologia , Vírus da Febre Amarela/imunologia , Animais , Células Cultivadas , Embrião de Galinha , Imunofluorescência , Cultura de Vírus , Replicação Viral/fisiologia , Vacina contra Febre Amarela/biossíntese , Vírus da Febre Amarela/crescimento & desenvolvimento
20.
Sci Transl Med ; 11(522)2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31826984

RESUMO

Flaviviruses such as dengue, yellow fever, Zika, West Nile, and Japanese encephalitis virus present substantial global health burdens. New vaccines are being sought to address safety and manufacturing issues associated with current live attenuated vaccines. Here, we describe a new insect-specific flavivirus, Binjari virus, which was found to be remarkably tolerant for exchange of its structural protein genes (prME) with those of the aforementioned pathogenic vertebrate-infecting flaviviruses (VIFs). Chimeric BinJ/VIF-prME viruses remained replication defective in vertebrate cells but replicated with high efficiency in mosquito cells. Cryo-electron microscopy and monoclonal antibody binding studies illustrated that the chimeric BinJ/VIF-prME virus particles were structurally and immunologically similar to their parental VIFs. Pilot manufacturing in C6/36 cells suggests that high yields can be reached up to 109.5 cell culture infectious dose/ml or ≈7 mg/liter. BinJ/VIF-prME viruses showed utility in diagnostic (microsphere immunoassays and ELISAs using panels of human and equine sera) and vaccine applications (illustrating protection against Zika virus challenge in murine IFNAR-/- mouse models). BinJ/VIF-prME viruses thus represent a versatile, noninfectious (for vertebrate cells), high-yield technology for generating chimeric flavivirus particles with low biocontainment requirements.

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