ResearchPad - supplement-articles https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Scaling‐up interventions to improve infant and young child feeding in India: What will it take?]]> https://www.researchpad.co/article/elastic_article_10254 We assessed India's readiness to deliver infant and young child feeding (IYCF) interventions by examining elements related to policy, implementation, financing, and evidence. We based our analysis on review of (a) nutrition policy guidance and program platforms, (b) published literature on interventions to improve IYCF in India, and (c) IYCF program models implemented between 2007 and 2012. We find that Indian policies are well aligned with global technical guidance on counselling interventions. However, guidelines for complementary food supplements (CFS) need to be reexamined. Two national programs with the operational infrastructure to deliver IYCF interventions offer great potential for scale, but more operational guidance, capacity, and monitoring are needed to actively support delivery of IYCF counselling at scale by available frontline workers. Many IYCF implementation efforts to date have experimented with approaches to improve breastfeeding and initiation of complementary feeding but not with improving diet diversity or the quality of food supplements. Financing is currently inadequate to deliver CFS at scale, and governance issues affect the quality and reach of CFS. Available evidence from Indian studies supports the use of counselling strategies to improve breastfeeding practices and initiation of complementary feeding, but limited evidence exists on improving full spectrum of IYCF practices and the impact and operational aspects of CFS in India. We conclude that India is well positioned to support the full spectrum of IYCF using existing policies and delivery platforms, but capacity, financing, and evidence gaps on critical areas of programming can limit impact at scale.

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<![CDATA[First detection of <i>Theileria parva </i>in cattle from Cameroon in the absence of the main tick vector <i>Rhipicephalus appendiculatus</i> ]]> https://www.researchpad.co/article/elastic_article_6786 A major risk factor for the spread of livestock diseases and their vectors is the uncontrolled transboundary movement of live animals for trade and grazing. Such movements constrain effective control of tick‐transmitted pathogens, including Theileria parva. Only limited studies have been undertaken to identify ticks and tick‐borne diseases (TTBDs) affecting cattle in central African countries, including Cameroon. We hereby report the collection of baseline data on the prevalence of T. parva in Cameroon through a countrywide cross‐sectional survey, conducted in 2016, involving collection of blood samples from cattle from 63 sites across the five agro‐ecological zones (AEZs) of the country. ELISA‐based surveillance of infected cattle was performed on 479 randomly selected samples and revealed specific antibodies to T. parva in 22.7% and T. mutans in 41.1% of cattle. Screening of 1,340 representative DNA samples for the presence of T. parva identified 25 (1.86%) positives using a p104 antigen gene‐based nested PCR assay. The positives were distributed across agro‐ecological zones I, II, III and V. None of the p104 positive cattle exhibited clinical symptoms of East Coast fever (ECF). Using reverse line blot (RLB), 58 (4.3%) and 1,139 (85%) of the samples reacted with the T. parva and T. mutans oligonucleotide probes, respectively. This represents the first report of T. parva from Cameroon. Surprisingly, no Rhipicephalus appendiculatus ticks, the main vector of T. parva, were identified in a parallel study involving comprehensive morphological and molecular survey of tick species present in the country. Only two of the 25 p104 positive cattle were PCR‐positive for the CD8+ T‐cell target schizont‐expressed antigen gene Tp1. Cloning and sequencing of Tp1 amplicons revealed sequence identity with the reference T. parva Muguga. This new finding raises serious concerns of a potential spread of ECF into the central African region.

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<![CDATA[Perceptions of commercial snack food and beverages for infant and young child feeding: A mixed‐methods study among caregivers in Kathmandu Valley, Nepal]]> https://www.researchpad.co/article/Nb20cb267-ee0c-41da-b079-082df87cf0aa Ensuring nutritious complementary feeding is vital for child nutrition. Prior research in Kathmandu Valley found high consumption rates of commercially produced snack foods among young children, which are often energy‐dense/nutrient poor. This mixed‐methods study was conducted to elicit Nepali caregivers' perceptions of commercial snack foods and beverages and factors influencing their use for young child feeding. Seven facilitated focus group discussions (FGD) were conducted with Kathmandu Valley caregivers of children 12–23 months, and a survey of 745 primary caregivers of children 12–23 months of age was then conducted. During the FGD, caregivers reported commonly providing commercial food and beverage products to their children as snacks, and 98.6% of caregivers participating in the survey reported feeding their child such a food in the previous week. Because of processing and packaging, snack foods were not trusted by many FGD participants and considered as “junk foods” and not healthy for children. However, commercial snack foods were consistently ranked highly on convenience, both because of minimal preparation and ease of feeding; 48.5% of all surveyed caregivers reported providing a snack food because of convenience. Other family members' diets or provision of snack foods as treats also influenced children's consumption of these snack foods and beverages. This study indicates that caregivers of young children prefer snack options that are nutrient rich; however, this may conflict with preferences for foods that require minimal preparation and are appealing to young children. Such findings carry programmatic implications for interventions aiming to address children's diet quality in urban Nepal.

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<![CDATA[ <i>Rousettus aegyptiacus</i> Bats Do Not Support Productive Nipah Virus Replication]]> https://www.researchpad.co/article/Nc8ea3b91-0905-49ce-90d8-2dcb232023df Nipah virus (NiV) is a bat-borne zoonotic pathogen that can cause severe respiratory distress and encephalitis upon spillover into humans. NiV is capable of infecting a broad range of hosts including humans, pigs, ferrets, dogs, cats, hamsters, and at least 2 genera of bats. Little is known about the biology of NiV in the bat reservoir. In this study, we evaluate the potential for the Egyptian fruit bat (EFB), Rousettus aegyptiacus, to serve as a model organism for studying NiV in bats. Our data suggest that NiV does not efficiently replicate in EFBs in vivo. Furthermore, we show no seroconversion against NiV glycoprotein and a lack of viral replication in primary and immortalized EFB-derived cell lines. Our data show that despite using a conserved target for viral entry, NiV replication is limited in some bat species. We conclude that EFBs are not an appropriate organism to model NiV infection or transmission in bats.

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<![CDATA[A Cross-Reactive Humanized Monoclonal Antibody Targeting Fusion Glycoprotein Function Protects Ferrets Against Lethal Nipah Virus and Hendra Virus Infection]]> https://www.researchpad.co/article/N22228361-4048-4e08-bef5-61e56b524ea7

Abstract

Background

Nipah virus (NiV) and Hendra virus (HeV) are zoonotic paramyxoviruses that cause severe disease in both animals and humans. There are no approved vaccines or treatments for use in humans; however, therapeutic treatment of both NiV and HeV infection in ferrets and non-human primates with a cross-reactive, neutralizing human monoclonal antibody (mAb), m102.4, targeting the G glycoprotein has been demonstrated. In a previous study, we isolated, characterized, and humanized a cross-reactive, neutralizing anti-F mAb (h5B3.1). The mAb h5B3.1 blocks the required F conformational change needed to facilitate membrane fusion and virus infection, and the epitope recognized by h5B3.1 has been structurally defined; however, the efficacy of h5B3.1 in vivo is unknown.

Methods

The post-infection antiviral activity of h5B3.1 was evaluated in vivo by administration in ferrets after NiV and HeV virus challenge.

Results

All subjects that received h5B3.1 from 1 to several days after infection with a high-dose, oral-nasal virus challenge were protected from disease, whereas all controls died.

Conclusions

This is the first successful post-exposure antibody therapy for NiV and HeV using a humanized cross-reactive mAb targeting the F glycoprotein, and the findings suggest that a combination therapy targeting both F and G should be evaluated as a therapy for NiV/HeV infection.

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<![CDATA[Griffithsin Inhibits Nipah Virus Entry and Fusion and Can Protect Syrian Golden Hamsters From Lethal Nipah Virus Challenge]]> https://www.researchpad.co/article/Nf630db17-2b01-4bd6-a68c-8813be54f55f

Abstract

Nipah virus (NiV) is a highly pathogenic zoonotic paramyxovirus that causes fatal encephalitis and respiratory disease in humans. There is currently no approved therapeutic for human use against NiV infection. Griffithsin (GRFT) is high-mannose oligosaccharide binding lectin that has shown in vivo broad-spectrum activity against viruses, including severe acute respiratory syndrome coronavirus, human immunodeficiency virus 1, hepatitis C virus, and Japanese encephalitis virus. In this study, we evaluated the in vitro antiviral activities of GRFT and its synthetic trimeric tandemer (3mG) against NiV and other viruses from 4 virus families. The 3mG had comparatively greater potency than GRFT against NiV due to its enhanced ability to block NiV glycoprotein-induced syncytia formation. Our initial in vivo prophylactic evaluation of an oxidation-resistant GRFT (Q-GRFT) showed significant protection against lethal NiV challenge in Syrian golden hamsters. Our results warrant further development of Q-GRFT and 3mG as potential NiV therapeutics.

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<![CDATA[Molecular Diagnostics for Detection of Bacterial and Viral Pathogens in Community-Acquired Pneumonia]]> https://www.researchpad.co/article/N1e8b788c-6427-4749-93f6-321ead4d70d6

Abstract

Traditional microbiological methods for detection of respiratory tract pathogens can be slow, are often not sensitive, may not distinguish infection from colonization, and are influenced by previous antibiotic therapy. Molecular diagnostic tests for common and atypical causative pathogens of community-acquired pneumonia have the potential to dramatically increase the diagnostic yield and decrease the time required to render results. Unfortunately, these tests often lack standardization and are not widely available. Consideration should be given to the development and evaluation of companion molecular diagnostic tests for detection of respiratory pathogens in future clinical trials of antimicrobials intended to treat community-acquired pneumonia.

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<![CDATA[Acute Otitis Media and Acute Bacterial Sinusitis]]> https://www.researchpad.co/article/Nb108ccd0-83ae-4c29-87fb-69b10ccf7a9c

Abstract

Acute otitis media and acute bacterial sinusitis are 2 of the most common indications for antimicrobial agents in children. Together, they are responsible for billions of dollars of health care expenditures. The pathogenesis of the 2 conditions is identical. In the majority of children with each condition, a preceding viral upper respiratory tract infection predisposes to the development of the acute bacterial complication. It has been shown that viral upper respiratory tract infection predisposes to the development of acute otitis media in 37% of cases. Currently, precise microbiologic diagnosis of acute otitis media and acute bacterial sinusitis requires performance of tympanocentesis in the former and sinus aspiration in the latter. The identification of a virus from the nasopharynx in either case does not obviate the need for antimicrobial therapy. Furthermore, nasal and nasopharyngeal swabs are not useful in predicting the results of culture of the middle ear or paranasal sinus. However, it is possible that a combination of information regarding nasopharyngeal colonization with bacteria and infection with specific viruses may inform treatment decisions in the future.

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<![CDATA[Sequence-Based Human Leukocyte Antigen—B Typing of Patients Infected with Ebola Virus in Uganda in 2000: Identification of Alleles Associated with Fatal and Nonfatal Disease Outcomes]]> https://www.researchpad.co/article/Na7041707-ef9a-4c42-a5bf-7576f1325e0a

Abstract

The Sudan species of Ebola virus (SEBOV) causes severe, often fatal infection in ∼50% of infected humans. We sought to determine whether the human leukocyte antigen—B (HLA-B) locus has a role in the outcome of SEBOV disease by typing 77 cases from an outbreak in northern Uganda in 2000–2001. Sequence-based HLA-B typing was performed using leukocytes isolated from 77 patients. Statistical analysis and a predictive discriminant analysis (PDA) were applied to typing data. Epitope prediction software was also applied to SEBOV sequences. Statistically significant associations were found between certain sets of alleles and either fatal or nonfatal disease outcomes. Alleles B*67 and B*15 were associated with fatal outcomes, whereas B*07 and B*14 were associated with nonfatal outcomes. The PDA-derived functions that were produced were 81.8% accurate in classifying patients into their correct outcome group. Several epitopes predicted to bind strongly to HLA-B*07 molecules were identified in the viral polymerase, nucleoprotein, and VP35 protein. HLA-B alleles associated with either fatal or nonfatal outcomes of SEBOV disease were identified and can be used in a predictive model. Studies of HLA-B—restricted epitopes could contribute to characterization of protective host responses and to vaccine development.

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<![CDATA[Diagnostic Reverse-Transcription Polymerase Chain Reaction Kit for Filoviruses Based on the Strain Collections of all European Biosafety Level 4 Laboratories]]> https://www.researchpad.co/article/N34593a01-7534-474a-aec9-bd39d7bebd54

Abstract

A network of European biosafety level 4 laboratories has designed the first industry-standard molecular assay for all filoviruses species, based on the strain collections of all participants. It uses 5 optimized L gene primers and 3 probes, as well as an internal control with a separate detection probe. Detection limits (probit analysis, 95% detection chance) were as follows: Zaire ebolavirus, 487 copies/mL of plasma; Sudan ebolavirus Maleo, 586 copies/mL; Sudan ebolavirus Gulu, 1128 copies/mL; Cote d'Ivoire ebolavirus, 537 copies/mL; Reston ebolavirus, 4546 copies/mL; Lake Victoria marburgvirus Musoke, 860 copies/mL; and Lake Victoria marburgvirus Ravn, 1551 copies/mL. The assay facilitates reliable detection or exclusion screening of filovirus infections.

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<![CDATA[Antibody Repertoire of Human Polyclonal Antibodies Against Ebola Virus Glycoprotein Generated After Deoxyribonucleic Acid and Protein Vaccination of Transchromosomal Bovines]]> https://www.researchpad.co/article/Nc2a2656c-11b2-410e-a0b1-fafa62938f8d

Abstract

Several Ebola vaccines and therapeutics are under clinical development. However, limited knowledge exists on the quality of antibody response generated by different Ebola vaccines. In this study, antibody repertoire induced by vaccination of transchromosomal bovine (TcB) with Ebola virus (EBOV) glycoprotein ([GP]; recombinant GP [rGP]) encoded by either deoxyribonucleic acid (DNA) or nanoparticle-based vaccine platform was analyzed using EBOV genome fragment phage display library and surface plasmon resonance (SPR)-based real-time kinetics assay to measure antibody affinity maturation to both native and partially denatured Ebola GP as well as GP containing the receptor binding domain but lacking the mucin-like domain. Immunoglobulin (IgG) obtained from rGP nanoparticle-vaccinated TcB demonstrated ~4-fold higher binding affinity compared with DNA-vaccinated TcB-induced IgG against the native rGP’s. The rGP nanoparticle vaccine generated a more robust and diverse antibody immune response to the native EBOV-GP compared with the DNA vaccine, which may explain the protective efficacy observed for these antibody preparations.

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<![CDATA[New Vaccine Design and Delivery Technologies]]> https://www.researchpad.co/article/N0994c359-fe5f-4fd1-a17a-7b37dc415c7c

Abstract

Technological advances in immunology, protein design, and genetic delivery have unlocked new possibilities for vaccine concepts and delivery technologies that were previously inaccessible. These next-generation vaccine design efforts are particularly promising in their potential to provide solutions to challenging targets for which conventional approaches have proven ineffective—for example, a universal influenza vaccine. In this perspective, we discuss emerging approaches to vaccine design and engineering based on recent insights into immunology, structural biology, computational biology, and immunoengineering. We anticipate that these cutting-edge, interdisciplinary approaches will lead to breakthrough vaccine concepts for ever-evolving and (re)emerging influenza viruses, with important ramifications for global public health.

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<![CDATA[Marburg Virus Angola Infection of Rhesus Macaques: Pathogenesis and Treatment with Recombinant Nematode Anticoagulant Protein c2]]> https://www.researchpad.co/article/Nb6375af2-c459-41bd-9db8-2d7cffebaab3

Abstract

Background. The procoagulant tissue factor (TF) is thought to play a role in the coagulation disorders that characterize filoviral infections. In this study, we evaluated the pathogenesis of lethal infection with the Angola strain of Marburg virus (MARV-Ang) in rhesus macaques and tested the efficacy of recombinant nematode anticoagulant protein c2 (rNAPc2), an inhibitor of TF/factor VIIa, as a potential treatment.

Methods. Twelve rhesus macaques were challenged with a high dose (1000 pfu) of MARV-Ang. Six macaques were treated with rNAPc2, and 6 macaques served as control animals.

Results. All 6 control animals succumbed to MARV-Ang challenge by day 8 (mean, 7.3 days), whereas 5 of 6 rNAPc2-treated animals died on day 9 and 1 rNAPc2-treated animal survived. The disease course for MARVAng infection appeared to progress more rapidly in rhesus macaques than has been previously reported for other strains of MARV. In contrast to Ebola virus (EBOV) infection in macaques, up-regulation of TF was not as striking, and deposition of fibrin was a less prominent pathologic feature of disease in these animals.

Conclusions. These data show that the pathogenicity of MARV-Ang infection appears to be consistent with the apparent increased human virulence attributed to this strain. The apparent reduced efficacy of rNAPc2 against MARV-Ang infection, compared with its efficacy against EBOV infection, appears to be associated with differences in TF induction and fibrin deposition.

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<![CDATA[MagaZorb: A simple tool for rapid isolation of viral nucleic acids]]> https://www.researchpad.co/article/Na9534c76-6658-4829-8c55-75980c8b8e8a

Abstract

Effective isolation of nucleic acids from samples containing viral materials is an essential step for accurate diagnosis of viral infections. The necessity of this critical step before analytical identification and diagnosis of viral infections is paramount to screening programs and to identifying and monitoring epidemics and pandemics. With molecular assays rapidly evolving into routine practice, clinical laboratories face several challenges, including presence of small amounts of viral nucleic acids in abundant levels of genomic DNA and total RNA, processing of various sample types, and carry-over of polymerase chain reaction inhibitors, which could significantly affect polymerase chain reaction and microarray results. MagaZorb nucleic acid isolation technology overcomes these challenges and offers a simple and reliable method for isolation of highquality and high-yield nucleic acids. Although the MagaZorb technology is readily adaptable to automated platforms, it is also well suited to laboratories in remote areas of resource-poor countries, because a simple magnet is the only device required to perform the procedure manually. Performance characteristics and clinical application of the MagaZorb technology are briefly described here.

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<![CDATA[Clinical Vignettes: Donor-Derived Infections]]> https://www.researchpad.co/article/N41d457df-58c9-47f0-8b92-3e2970e015a6

Abstract

Patients undergoing solid organ transplantation (SOT) may acquire infections from the transplanted organ. Routine screening for common infections are an established part of the pretransplant evaluation of donors and recipients. Likewise, strategies exist for prophylaxis and surveillance for common donorassociated infections including hepatitis B, CMV and EBV. However, despite advances in diagnostic testing to evaluate the infectious risk of donors, unanticipated transmission of pathogens occurs, particularly when donors are asymptomatic or have subtle or unusual manifestations of a transmissible Infection. Infectious diseases (ID) providers play an integral role in donor and recipient risk assessment and can advise transplant centers on organ utilization and guide evaluation and management of the SOT recipient. Consideration of the donor cause of death and preceding clinical syndromes are important for characterizing the potential risk for recipient infection. This allows a more accurate analysis of the risk: benefit of accepting a life-saving organ and risk of infection. ID providers and transplant teams should work closely with organ procurement organizations (OPOs) to solicit additional donor information when a donor-derived infection is suspected so that reporting can be facilitated to ensure communication with the care-teams of other organ recipients from the same donors. National advisory committees work closely with federal agencies to provide oversight, guide policy development, and assess outcomes to assist with the prevention and management of donor-transmitted disease through organ transplantation. The clinical vignettes in this review highlight some of the complexities in the evaluation of potential donor transmission.

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<![CDATA[The effect of cow udder score on subsequent calf performance in the Nebraska Sandhills]]> https://www.researchpad.co/article/Nfb90831b-f7e8-4d12-a112-57f0bd064bd6 ]]> <![CDATA[Lower Respiratory Infections Among Hospitalized Children in New Caledonia: A Pilot Study for the Pneumonia Etiology Research for Child Health Project]]> https://www.researchpad.co/article/N33a884e8-2434-4a41-88b8-1054f289de37

Abstract

We conducted a prospective pilot study over a 1-year period in New Caledonia in preparation for the Pneumonia Research for Child Health (PERCH) project. The pathogens associated with hospitalized lower respiratory infections in children were identified through the use of culture of induced sputum and blood, urinary antigen detection, polymerase chain reaction (PCR) on respiratory specimens, and serology on paired sera. Respiratory viruses were detected on respiratory specimens by immunofluorescence and PCR, and by serology on paired sera. Pathogens were detected in 87.9% of the 108 hospitalized cases. Viruses represented 81.6% of the 152 pathogens detected. Respiratory syncytial virus and rhinovirus were the most frequent, accounting for 32.2% and 24.3% of the pathogens identified, respectively. Only 26.3% of 99 induced sputum specimens collected were determined to be of good quality, which may be a consequence of the collection method used.

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<![CDATA[Molecular Diagnosis of Respiratory Tract Infection in Acute Exacerbations of Chronic Obstructive Pulmonary Disease]]> https://www.researchpad.co/article/N167d723b-5359-4a4a-aa80-d227d1fe16f1

Abstract

Acute exacerbations are significant events in the course of chronic obstructive pulmonary disease. Modern diagnostic techniques have revealed an infectious cause for the majority of exacerbations. Common respiratory viruses contribute to 25%–50% of exacerbations. Detection of viral nucleic acids in nasopharyngeal swab or sputum samples has become the preferred method to study viral exacerbations instead of viral cultures and serologic examination. Clinical application of such molecular detection requires additional studies to clarify interpretation of a positive result. Bacteria account for 25%–50% of exacerbations. Studies comparing molecular detection of bacteria in sputum with conventional culture techniques have shown that a substantial proportion of bacteria are not detected by the latter method. However, as with molecular viral detection, clinical application of molecular bacterial diagnosis requires additional studies. Although still faced with several challenges and requiring additional development, it is quite likely that molecular methods will become the preferred methods for determining the etiology of exacerbations of chronic obstructive pulmonary disease.

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<![CDATA[Development and Implementation of Multiplex TaqMan Array Cards for Specimen Testing at Child Health and Mortality Prevention Surveillance Site Laboratories]]> https://www.researchpad.co/article/Na15845b6-0dfd-425b-88ac-cb934902aeda

Abstract

Child Health and Mortality Prevention Surveillance (CHAMPS) laboratories are employing a variety of laboratory methods to identify infectious agents contributing to deaths of children <5 years old and stillbirths in sub-Saharan Africa and South Asia. In support of this long-term objective, our team developed TaqMan Array Cards (TACs) for testing postmortem specimens (blood, cerebrospinal fluid, lung tissue, respiratory tract swabs, and rectal swabs) for >100 real-time polymerase chain reaction (PCR) targets in total (30–45 per card depending on configuration). Multipathogen panels were configured by syndrome and customized to include pathogens of significance in young children within the regions where CHAMPS is conducted, including bacteria (57 targets covering 30 genera), viruses (48 targets covering 40 viruses), parasites (8 targets covering 8 organisms), and fungi (3 targets covering 3 organisms). The development and application of multiplex real-time PCR reactions to the TAC microfluidic platform increased the number of targets in each panel while maintaining assay efficiency and replicates for heightened sensitivity. These advances represent a substantial improvement in the utility of this technology for infectious disease diagnostics and surveillance. We optimized all aspects of the CHAMPS molecular laboratory testing workflow including nucleic acid extraction, quality assurance, and data management to ensure comprehensive molecular testing of specimens and high-quality data. Here we describe the development and implementation of multiplex TACs and associated laboratory protocols for specimen processing, testing, and data management at CHAMPS site laboratories.

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<![CDATA[FDA Perspectives on Diagnostic Device Clinical Studies for Respiratory Infections]]> https://www.researchpad.co/article/N93971fc9-f440-4924-abb0-997c5b620969

Abstract

Two pathways are described for submission to FDA for clearance of a diagnostic device: a Premarket Application (PMA), which can lead to approval of a diagnostic device, and a Premarket Notification, which can lead to clearance. The latter is often called a 510(k), named for the statute providing for this path. Recent FDA clearance of molecular-based multiplex panels represents the beginning of a new era for the diagnosis of respiratory infections. The ability to test for multiple pathogens simultaneously, accompanied by the increasing availability of molecular-based assays for newly recognized respiratory pathogens will likely have a major impact on patient care, drug development, and public health epidemiology. We provide a general overview of how FDA evaluates new diagnostics for respiratory tract infections and the agency’s expectations for sponsors developing new tests in this area.

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