ACT structural concepts [3].
\r\n\tA quark exhibits confinement, which means that the quarks are not observed independently but always in combination with other quarks. This makes determining the properties (mass, spin, and parity) impossible to measure directly; these traits must be inferred from the particles composed of them. There are six flavors of quarks: up, down, strange, charm, bottom, and top. The flavor of the quark determines its properties.
\r\n\tThere are three generations of quarks, based on pairs of weak positive/negative, weak isospin. The first generation quarks are up and down quarks, the second-generation quarks are strange and charm quarks, the third generation quarks are top and bottom quarks. The up and down quarks make up protons and neutrons, seen in the nucleus of ordinary matter. They are the lightest and most stable. The heavier quarks are produced in high-energy collisions and rapidly decay into up and down quarks.
\r\n\tThe baryons and mesons known at the time fell into symmetric families of multiplets (octuplets, decuplets) sharing two identical quantum numbers (spin and parity), but differing in an ordered way in others (mass, charge, baryon number and strangeness). The mathematical group to fit this complex situation-SU3, the symmetric, unitary group of dimension 3-was proposed independently by Gell-Mann and Ne'eman. The validity of SU3 was demonstrated by the experiment. A major prediction was that a particle (the omega-minus), an isotopic singlet with spin = 3/2, positive parity, mass of roughly 1,680 MeV, negative charge, baryon number +1, strangeness = -3, and stable to strong decay, should exist to complete the 3/2+ baryon decuplet. It was therefore a major triumph for the scheme when the omega-minus, a baryon with the precise mass, charge, and strangeness predicted, was discovered in 1964. All these facts introduced a quark idea fully into modern physics.
\r\n\r\n\tThis book will be a self-contained collection of scholarly papers targeting an audience of practicing researchers, academics, PhD students and other scientists. The contents of the book will be written by multiple authors and edited by experts in the field.
",isbn:"978-1-83968-313-8",printIsbn:"978-1-83968-312-1",pdfIsbn:"978-1-83968-314-5",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,hash:"0d9403b5c874f6e63b0686cd7c432e00",bookSignature:"Prof. Zbigniew Piotr Szadkowski",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/10205.jpg",keywords:"Chiral Symmetries, Weak Interactions, Neutrinoless Double Beta Decay, Deep Inelastic Scattering, Quantum Chromodynamics (QCD), Color Confinement, Quarks Mixing, Cabibbo Angle, Kobayashi-Maskawa Matrix, Quarks Multiplets, CP-Nonconservation, Neutrino Oscillation",numberOfDownloads:66,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"July 6th 2020",dateEndSecondStepPublish:"October 8th 2020",dateEndThirdStepPublish:"December 7th 2020",dateEndFourthStepPublish:"February 25th 2021",dateEndFifthStepPublish:"April 26th 2021",remainingDaysToSecondStep:"5 months",secondStepPassed:!0,currentStepOfPublishingProcess:5,editedByType:null,kuFlag:!1,biosketch:"The designer of the 2nd level trigger for the fluorescence detector and the designer of the 1st level trigger and the Front-End Boards for the surface detector of the Pierre Auger Observatory.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"67836",title:"Prof.",name:"Zbigniew Piotr",middleName:null,surname:"Szadkowski",slug:"zbigniew-piotr-szadkowski",fullName:"Zbigniew Piotr Szadkowski",profilePictureURL:"https://mts.intechopen.com/storage/users/67836/images/system/67836.jpeg",biography:"Dr. Szadkowski completed his Ph.D. with a thesis 'Quarks mixing in chiral symmetries SU4 x SU4 and SU6 x SU6”. Habilitation: „Triggers in the Pierre Auger Observatory: Designs, Implementation and the Impact on the Experimental Results”.\r\nDevelopment of the FPGA-based 2nd level trigger for 24 fluorescence detectors and 1st level trigger for 1660 surface detectors of the Pierre Auger Observatory, FPGA based filters suppressing radio-frequency interferences (RFI) in radio detector of Auger Engineering Radio Array, FPGA based triggers for the Auger surface detectors dedicated for a recognition of very inclined EAS induced by 'old” proton showers or 'young” neutrino showers.\r\nDr. Szadkowski has worked as a research scientist in Michigan Technological University, Associate Professor in College de France, Senior Wissenschaftler, Bergische Universität Wuppertal, and currently is working as the head of the Department of High-Energy Astrophysics and as an Associate Professor at the University of Łódź.",institutionString:"University of Łódź",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"4",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"University of Łódź",institutionURL:null,country:{name:"Poland"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"20",title:"Physics",slug:"physics"}],chapters:[{id:"73971",title:"The Inter-Nucleon Up-to-Down Quark Bond and its Implications for Nuclear Binding",slug:"the-inter-nucleon-up-to-down-quark-bond-and-its-implications-for-nuclear-binding",totalDownloads:67,totalCrossrefCites:0,authors:[null]}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"247041",firstName:"Dolores",lastName:"Kuzelj",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/247041/images/7108_n.jpg",email:"dolores@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. 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Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"878",title:"Phytochemicals",subtitle:"A Global Perspective of Their Role in Nutrition and Health",isOpenForSubmission:!1,hash:"ec77671f63975ef2d16192897deb6835",slug:"phytochemicals-a-global-perspective-of-their-role-in-nutrition-and-health",bookSignature:"Venketeshwer Rao",coverURL:"https://cdn.intechopen.com/books/images_new/878.jpg",editedByType:"Edited by",editors:[{id:"82663",title:"Dr.",name:"Venketeshwer",surname:"Rao",slug:"venketeshwer-rao",fullName:"Venketeshwer Rao"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"64957",title:"The Evolution of the Composite Fuselage: A Manufacturing Perspective",doi:"10.5772/intechopen.82353",slug:"the-evolution-of-the-composite-fuselage-a-manufacturing-perspective",body:'\nA historical perspective provides an understanding of how the current state-of-practice for composite fuselage manufacturing has evolved. It also provides insight into what the future state of composite fuselage manufacturing might look like. Figure 1 shows a familiar graph that shows the increase in composites usage in military and commercial aircraft over time. Initial applications of carbon fiber reinforced composites (CFRP) in both commercial and military aircraft were limited mostly to non-structural applications such as fairings and flight control surfaces. Structural applications for military aircraft began to appear in the 1980s as composite usage grew to more than 20% of the weight of the structure. As the industry continued to mature, material and processes became better understood and cost effectiveness improved to the level that commercial aircraft manufacturers incorporated the technology into the latest generation of wide body and other new aircraft.
\nComposites usage.
Research and development of high performance composite materials and processes for aerospace applications in the Unites States was first conducted in the 1940s at Wright-Patterson Air Force Base in Dayton, Ohio [1]. The focus of this early research was primarily for military applications. This research has continued since that time and today, the Air Force Research Laboratory (AFRL), with support from industry, universities and other government agencies such as the Department of Advanced Research Projects Agency (DARPA) and the Department of Energy (DOE), continues to play a leading role in developing advanced materials for military applications. NASA initiated research devoted to the development of high performance composites for commercial aircraft and space vehicles in the late 1960s. Over the years, NASA has worked collectively with industry and academia to develop affordable technologies to improve safety and performance of aircraft and launch vehicles. The paper NASA Composite Materials Development: Lessons Learned and Future Challenges provides an excellent historical review of NASA’s role in the development of composite materials and processes [2].
\nA common characteristic shared between AFRL and NASA sponsored programs was the “building-block” approach for research and development programs that progressed through a series of steps, each one having an increase in complexity and cost that built upon the previous step. In general, programs started at a coupon level and looked at a wide range of samples to down select design approaches, materials of construction, tooling and manufacturing processes to build and test coupons, subcomponents and ultimately full scale components. Not unlike the Technology Readiness Levels applied to describe new technologies today, this approach was used successfully in programs such as the Air Force’s Large Aircraft Composite Fuselage (LACF) Program in the late 1980s and NASA’s Advanced Composites Technology (ACT) program in the mid 1990s.
\nThe B-2 Stealth Bomber program was also taking place during the 1980s and provided many lessons learned related to the manufacture of large composite primary structure. For the B-2, survivability performance was one of the primary reasons for the extensive use of carbon fiber composites—cost and producibility were not the most critical factors. Boeing was a prime subcontractor on the program and built the wing skins using Automated Tape Laying (ATL). This program presented the opportunity to demonstrate the productivity that was possible using automated lamination processes such as ATL and AFP.
\nAnother program which derived direct benefit from the ACT program is the V-22. Composites have been used extensively and aggressively in helicopters more than any other type of aircraft because weight is such a critical factor. The V-22 uses composites for the wings, fuselage skins, empennage, side body fairings, doors, and nacelles. AFP technology is used to fabricate the aft fuselage skin in one piece. Both Bell and Boeing also incorporate cocured, hat stiffened fuselage structures, using solid silicone mandrels, on their portions of the program.
\nThe LACF program was conducted in part by Northrop and was sponsored by the Air Force Wright Aeronautical Laboratory (AFWAL) during the 1980s. The program was part of an effort focused on manufacturing technology for the Linear Manufacturing of Large Aircraft Composite Primary Structure Fuselage. The multi-phase program was directed toward the definition and demonstration of manufacturing methods for cocuring stringer stiffened fuselage panels using (1) existing, qualified material systems; (2) automated skin fabrication; (3) inner mold line (IML) controlled tooling; (4) non-autoclave curing technology. Like many similar terms, in the 1980s “linear” manufacturing was a code word for “lean” and non-autoclave is referred to today as out-of-autoclave or OOA processes.
\nThe program followed a building-block approach through four phases (Figure 2):
Phase I—methods definition
Phase II—manufacturing methods establishment
Phase III—manufacturing verification
Phase IV—production demonstration
As the program moved through various phases, lessons learned where documented and applied to the next phase. Phase I lessons learned included:
Raw material required (tow bad, tape good) changes to improve panel quality using automated lamination equipment
Non-autoclave cured panel mechanical properties were equivalent to autoclave cured panels
IML tooling is very good at controlling stringer location and dimensions
IML provides very easy tool loading and bagging
Continuous roll forming can be used to preform preplied material into “C” channels ready for tool loading (Figure 3).
LACF program.
“I” beam formed from “C” channels.
Phase II lessons learned included:
Non-autoclave cure has risks associated with consumable bagging materials.
Integrally heated tooling strongly supports linear manufacturing.
Confirmed IML tooling is excellent for controlling stringer/skin dimensions and location.
Confirmed IML tooling and “I” beam stringer for part and tool removal.
Flat preplied laminates can be drape formed on gentle contours using IML cure tools.
Automation can be applied but presents reliability risks and potential equipment downtime.
Automation can produce a laminate that does not require additional debulking.
Roll forming of stringer “C” channels is important for linear manufacturing (Figure 4).
“C” channel roll forming machine.
Among the lessons learned as a result of Phases III and IV were the economics related to process scale up for both size and rate. This included ply cutting and kitting time for panel fabrication and backing paper removal and management issues affecting tow placement and stringer laminate preplying (Figure 5). Another lesson included gaining a better understanding of cocuring longitudinal “I” beams to the skin of a large fuselage panel. One nice feature of the “I” beam construction is that the tooling is not trapped after cure and the channel details that form the “C” of the “I” beam can be removed over any length. Disadvantages were also apparent including the number of laminate preform and tooling details needed to construct an “I” beam vs. the simplicity of the hat stiffener (Figure 6).
\nLaminate cross ply equipment.
“I” beam vs. hat stiffener.
Northrop developed hat stiffened fuselage skin manufacturing technology in support of the YF-23 (Figure 7). One critical problem to solve was the removal of hat stiffener mandrel tooling from the cured part. The fuselage tooling was OML controlled and constructed from CRFP prepreg to match the coefficient of thermal expansion (CTE) of the parts. The resin system used for the tooling was bismaleimide (BMI) and the tools were autoclave cured on male, machined monolithic graphite source tools. The hat stiffeners that run longitudinally along the skin were cocured using a silicone mandrel system developed by Northrop using Rubbercraft as a supplier.
\nYF-23 fuselage structure.
The silicone based solid mandrel system included a solid rubber mandrel, a butterfly caul and a resin end dam. The silicone mandrel was designed to be removed from the cured part after pulling and elongating the mandrel to reduce the cross section enough to release from the part. The butterfly caul was designed to help consistently control the OML of the hat stiffener. It also helped to greatly simplify the bagging process which allows for the use of a broader range of operators instead of relying solely on a highly skilled mechanic. The end dam was designed to be cheap and disposable and replace much of the inner bagging process complexity of sealing off the hat stiffener to prevent resin bleed during the cure cycle (Figure 8). This is not a hard process, but is critical and tedious.
\nSolid mandrel system.
Northrop subsequently applied this hat stiffener fabrication process technology to the fuselage of the F/A-18E/F as a prime subcontractor to Boeing on the program (Figure 9).
\nF/A-18E/F fuselage structure.
During this time period, it was recognized by many of the R&D programs that liquid molding processes presented the opportunity to use resins and fibers in their lowest-cost state by eliminating prepreg from the fabrication process. Other advantages included minimizing material scrap, simplifying raw material storage, and supporting non-autoclave fabrication processes. The development of net shape damage-tolerant textile preforms and the development of innovative liquid molding tooling concepts supported this opportunity. The Advanced Composites Technology (ACT) program included processes such as resin transfer molding (RTM) and pultrusion in the development efforts. The technologies have progressed to state-of-practice processes with both the 787 and the A350 programs using liquid molding and textile preform technology for fabricating fuselage frame elements.
\nThe objective of the ACT fuselage program was to develop composite primary structure for commercial airplanes with 20–25% less cost and 30–50% less weight than equivalent metallic structure [3]. The Advanced Technology Composite Aircraft Structure (ATCAS) program was performed by Boeing as the prime contractor under the umbrella of NASA’s ACT program and focused on fuselage structures. A large team of industry and university partners also supported the program. The primary objective of the ATCAS program was to develop and demonstrate an integrated technology that enables the cost and weight effective use of composite materials in fuselage structures for future aircraft.
\nThe area selected for study was identified as Section 46 on Boeing wide body aircraft (Figure 10). This section contains many of the structural details and manufacturing challenges found throughout the fuselage. This includes variations in design details to address high loads at the forward end and lower portions of the fuselage. The loads decrease toward the aft end and the upper portion of the fuselage, allowing for transitions in the thickness of the structure that are tailored to match the structural loading.
\nACT fuselage section [3].
A quadrant panel approach was selected for study as shown in Figure 11. The cross section is split into four segments, a crown, keel, and left and right side panels. The circumferential, four quadrant panel approach was selected with the idea of reducing assembly costs by reducing the number of longitudinal splices. This built-up assembly approach is baseline to metallic aircraft manufacturing and is similar to the approach Airbus selected for most of the fuselage of the A350.
\nACT quadrant panels [3].
Manufacturing process development and design trade studies contributed to the development of Cost Optimization Software for Transport Aircraft Design Evaluation (COSTADE) which allowed for defining and evaluating the cost-effectiveness and producibility of various designs. Included in the program were assessments of tooling, materials and process controls needed for future full-barrel fabrication like Boeing selected for the 787.
\nThe structural concepts studied included stiffened skin structures achieved by stand alone or combinations of cocuring, cobonding, bonding, and mechanical attachment of stringers and frames to monolithic or sandwich panel skins (Table 1). The crown section study selected fiber placed skins laminated on an IML controlled layup mandrel with the skin subsequently cut into individual panels and transferred to OML cure tools. Hat stiffeners used solid silicone mandrels located longitudinally along the IML of the skin panels for cocuring.
\nDetails | \nProcess | \n
---|---|
Skins | \nAFP (tow, hybrid AS4/S2) CTLM (contoured tape lamination machine, 12″ tape) | \n
Frames | \nBraiding/resin transfer molding (triaxial 2-D braid) Compression molding Stretch forming (thermoplastic, discontinuous fibers) Pultrusion/pull forming | \n
Stringers | \nHat—ATLM/drape forming (cocured, thickness variation) “J”—pultrusion | \n
Panel assembly | \nCocured/cobonded stringers, cobonded frames Cocured/cobonded stringers, fastened frames Sandwich panels, cobonded frames | \n
ACT structural concepts [3].
The recommended optimized panel design included cobonding of cured frame elements while cocuring the hat stiffeners and the skin. The cured frames were demonstrated using braided textile preforms and resin transfer molding (RTM). One of the main challenges of the crown panel concept was the bond integrity between the precured frames cobonded to a skin panel that is stiffened with cocured hat stringers. Alternative concepts the team considered during the review process included mechanically attached Z-section frames instead of cobonded J’s. The mechanically fastened frame approach greatly reduces the complexity of IML tooling needed to cocure the hat stiffeners and cobond the frames. This is especially true at the intersections of the frame and hat. Flexible caul plates and custom fit reusable bags became part of the tooling system needed to accomplish the fully integrated skin/stringer/frame structure. Producibility issues are complicated by the blind nature of the IML of the skin being completely covered by flexible cauls and the reusable bagging system. The structural arrangement shown in Figure 12 is very similar to the configurations that ended up on both the 787 and A350 programs.
\nACT crown panel structural arrangement [3].
The program studied the pultrusion process for producing skin stringers. Continuous resin transfer molding (CRTM) developed by Ciba-Geigy was one of the more promising technologies studied. Improved process control and reduced waste are among the perceived advantages; process maturity, constant cross-section stringers and costs associated with secondary bonding or cobonding are among the disadvantages.
\nAirbus has studied automating stringer fabrication using both pultrusion and RTM but felt limited by aspects of both processes. As an answer, Airbus developed their version of pultrusion RTM. Figure 13 shows equipment completed in 2011 that is being used to develop and qualify the process [4]. This hybrid fabrication approach allows the use of preform laminates instead of being limited to unidirectional reinforcements like traditional pultrusion and supports continuous production instead of batch processing associated with the traditional RTM. Instead of dipping the preform stack through a resin bath, it is pulled into an RTM tool that is open on both ends. To overcome resin being pushed out at both ends of the open tool, Airbus worked with resin suppliers to develop an epoxy resin with a parabolic temperature/viscosity curve. At 120°C resin viscosity is very low with high flow characteristics, but at both room temperature and at 180°C and higher, it is very viscous. The tool entry is cooled so the resin is too viscous to flow out; the middle is heated to obtain resin flow and cure; more heat is added at the end to increase resin viscosity to make sure it does not flow out and reduce cure pressure.
\nAirbus continuous pultrusion equipment [4]. Source: CTC Stade.
Even in the early days of development, industry leaders believed in the possibility of higher layup rates using AFP than was possible with hand layup, but the capabilities and the scale that the industry has achieved today is astounding. Almost as astounding as how the industry reinvented itself from a raw material cost saving technology to an enabling technology for large aircraft structural components.
\nIn the late 1980s and early 1990s Northrop and ATK/Hercules worked on several joint projects sponsored by the Air Force which included fiber placement development and application. The technology was in its infancy as ATK was developing tow placement (as it was more commonly referred to originally) from its roots in filament winding technology. The main prize in the early days was $5 per lb. high modulus carbon fiber and $15 per pound high temperature/high performance resin instead of the $60+ per pound price of prepreg. A wet process of running fiber through a resin bath prior to placement onto the layup mandrel was never able to realize the quality and consistency required by the design. This same process has been used in the large wind blade manufacturing process and it reminds us of how challenging (and messy!) that approach can be. In addition, the wind blade manufacturing industry has learned some valuable lessons from those early days of “build it as cheap as you can” using the lowest cost material you can deal with. While those early blades were built with lower manufacturing costs, the argument can be made that many of those blades failed very early in their lifecycle and required costly repairs or replacement to generate electricity. If the blade cannot turn because it has delaminated, it is not generating any electricity in addition to the cost of repair or replacement.
\nNot only did the technology not realize the cost savings of dry fiber and wet resin, it was forced to adopt prepreg technology into the process—namely dealing with backing paper and ADDING to the cost of unidirectional prepreg tape by requiring it to be slit into prepreg tows. At the time of the ATCAS program, the AFP process was still evolving from what was originally envisioned as a much lower raw material cost build up starting with a dry fiber/wet resin process instead of a costly unidirectional fiber prepreg. The baseline process the ATCAS program selected for fabricating fuselage skins was AFP using prepreg tow. The dry fiber/wet resin tow had evolved to prepreg tow in an attempt to improve process consistency. The process was selected based on several factors including the potential for reduced material cost (compared to prepreg tape), the potential to achieve high lay-up rates over contoured surfaces, and the potential to efficiently support a significant amount of ply tailoring. In addition, the fact that tow material does not require backing paper eliminated a perceived risk of greater machine downtime.
\nWhen compared with the quality and consistency of parts made with prepreg tape, tow preg and subsequent prepreg tow, was not acceptable. The variability seen in the quality of the resultant panels would require compensation in the design of the part, resulting in weight penalties. But this did not prove fatal to the technology, instead tow placement reinvented itself (Figure 14).
\nAFP process and tooling.
There have been many studies of the AFP process that have helped to shape and refine the characteristics and capabilities that exist in today’s equipment offerings. But the ACT program allowed Boeing to better understand, study, define and refine the process to guide the technology development based on the needs of the user community. Everything from tack of the initial plies to the tool surface, to overlaps and gaps in the laminate; the most efficient ways to handle window/door cutouts, laminate thickness transitions, lay-up rates for flat, curved, cylindrical and duct shaped parts, etc., etc. What has ended up on production on the 787 is not the direct result of that ACT program, but the ACT program created the path for subsequent AFP development to follow and improve upon.
\nOne clear thread throughout the development of composite fuselage fabrication processes that was recognized and considered very early on, was tooling. The fabrication of large composite fuselage structures was also enabled by the tooling required to support it. The ability of industry to produce tools using specified materials and built to the size, scale and accuracy required by aerospace and defense applications were critical factors. Large scale machining, laser measuring systems, and innovative thinking supported the transition to today’s composite fuselage manufacturing capability.
\nThe ACT program demonstrated how the producibility of large, integrated, composite fuselage structures depend heavily on the tooling to ensure compatibility of the skin cure tool, the cocured or cobonded stringer tooling and the frame tooling. Controlling these elements is necessary to minimize gaps and interference fit between cured detail components. Understanding the effect of tolerance accumulations, warpage, liquid and hard shim allowances and fastener pull-up forces creates the ability to calculate the impact on fuselage structural arrangement and weight, part manufacturing cost and risk and fuselage assembly and integration time. These elements become even more critical as the size of the fuselage grows to 787 and A350 proportions.
\nOne important note was the need for the stringer tooling to be extractable after cure and flexible enough to be able to accommodate skin thickness variations—especially the “joggles” or transitions up-across-down at each of the frame stations. These requirements drove the team toward silicone or flexible laminate mandrels—reusability was also a key consideration. The mandrels needed to be rigid enough for handling or to be used as drape or vacuum forming mandrels; durable and capable of withstanding a 350°F autoclave cure cycle and still be able to conform to skin ply sculpting and tailoring; and be able to be extracted after cure.
\nWhile the use of silicone mandrels and the flexible IML tooling proved adequate for controlling hat stiffener shape, quality and location for the demonstration panels, it was also recognized that silicone mandrels presented many challenges in both scale-up and production scenarios. Boeing started to develop hat shaped silicone bladders that fed autoclave pressure into the bladder throughout the cure to provide uniform pressure throughout the stringer. After cure, pressure in the bladder is released making it possible to remove the bladder.
\nAt this same time Rubbercraft was working with engineers on the C-17 program to develop and manufacture inflatable silicone bladders for use on the replacement composite tail (Figure 15). In 1991 on aircraft 51, a composite tail was integrated into the program. Rubbercraft produced silicone bladders with FEP film molded to the OML of the bladders that were used in IML tools to cocure hat stiffeners to the skin of the horizontal stabilizers. The tooling, bladders and hat stiffener design allowed for the bladders to be manufactured with substantial excess length that supported multiple cure cycles despite the dimensional shrinkage of the bladder in the longitudinal direction. The reusability over multiple cure cycles is key to the cost effectiveness of the inflatable bladder system. Rubbercraft product improvement was focused on bladder attributes that supported increasing the number of cure cycles the bladder could be used for (Figure 16).
\nC-17 horizontal stabilizer.
Inflatable bladder.
While Boeing was developing flexible IML tooling for cocuring hat stringers and cobonding frames on the ACT program, they evolved away from one-piece overall cauls to separate, individual flexible cauls constructed from graphite/epoxy fabric with a layer of Viton® fluoroelastomer and an outer layer of FEP film. The fluoroelastomer was shown to be more resistant to the epoxy resin and thus more durable than silicones or other rubbers. An added benefit—but perhaps not as well understood at the time—is the added resistance to permeability offered by both the FEP film and the Viton rubber. This helps to minimize the amount of autoclave gas on the inside the bladder from being introduced into the laminate through the permeability of the bladder system. Fluoroelastomer bladder development continues today in support of new programs and applications.
\nA comparison of OML and IML cure tool approaches demonstrates some of the tradeoffs that must be considered. OML tooling is less complex, less expensive, can be initiated as soon as the OML of the aircraft is established and is more forgiving of change than an IML tool. The IML tool requires less labor and risk for locating and maintaining locations of stiffeners and other elements and is much more simple to bag (Figures 17–20).
\nOML sector panel tool. Source: Premium Aerotec.
IML tool. Source: Boeing.
IML and OML cure tools [3].
IML and OML tooling.
The ACT program also looked at separate male winding mandrels for AFP and then transferring the uncured skin to an OML cure tool. The male layup mandrel improved layup rates and proved to be a less expensive approach to meet production rate than two cure tools. This also plays to the argument for a combined IML controlled layup mandrel and cure tool—as Boeing selected for the 787 program.
\nOne concern using IML controlled cure tooling is the ability to adequately control the aerodynamic shell of the fuselage. For the ACT program this meant meeting surface waviness criteria of ±0.025″ over a 2″ length using caul plates. The concern over aerodynamic surface control seems to be greatly diminished when you look at what has evolved on the 787 program. The recognition that every airplane has a slightly different OML based on a number of factors such as exact resin content percentage in the prepreg (within the nominal tolerance range of ±5%), the amount of resin bleed experienced during cure and the amount of cured material removed during the sanding, smoothing and preparation for painting process. The skin of a composite fuselage allows for greater tailoring of the skin thickness than is usually incorporated into a metal fuselage. At the base, the fuselage is skin is thicker because it carries more load related to passengers, cargo and landing gear. The structural loads at the top of the fuselage are limited primarily to overhead bins, air ducting, and electrical wiring and this allows for lower weight, thinner skins that predominantly function as aerodynamic surfaces. Regardless of where in space it exists, and even though it varies from aircraft-to-aircraft, the surface is sanded smooth enough to satisfy the surface waviness allowance and negligible difference between aircraft.
\nThe ATCAS team envisioned scenarios that included full one piece barrel fabrication. Significant cost savings were estimated from the elimination of longitudinal splices and the need to compensate for tolerance accumulation in assembly. Material out-time, segmented full barrel cure tooling and barrel warpage were the primary risks identified with full scale single piece barrel fabrication.
\nThe sector panel construction used on the A350 allows for the use of invar for all the fuselage tooling. This includes the IML controlled sector panels fabricated by Spirit for Section 15. The approach Spirit applied is very similar to the one used on the 787 with the exception of the use of sector panels instead of a one piece barrel breakdown mandrel (Figure 21).
\nTooling. Source: Boeing, Coast composites.
One enabling capability that supports the evolution of the current state-of-practice for composite fuselage manufacturing is large autoclaves. There are many, many, many, many research and historical, ongoing and planned for the future, development efforts focused on OOA (or non-autoclave as it was called in the 1980s) materials and processes with the goal of eliminating that monument, the autoclave. The goal is noble (and not new) and the development efforts are making great progress and will, someday in the future, represent a significant (if not all) portion of the composite structure on commercial passenger aircraft—just not today. We already see components made from liquid molding processes being used in specific applications and families of parts and components on aircraft like the 787 and A350, just not the primary fuselage panels and stringers—yet. The maturity, forgiving nature, and low risk of baseline autoclave cured systems made it an easy decision for programs like the 787 and A350 to progress knowing that it was just time and money required to build autoclaves large enough to meet the needs of the program. No new technology needed, just scale and incorporation of improvements being realized by the autoclave industry, such as control systems and operational efficiencies. Spirit even built their own liquid nitrogen generating plant onsite to service their large autoclaves (Figure 22).
\nAutoclaves. Source: Spirit, DLR.
The use of composites for high performance applications requires the ability to identify and ultimately eliminate structural defects that occur during manufacture, assembly, service, or maintenance. The entire field of nondestructive evaluation (NDE) has continued to develop and evolve in parallel to the growth of composite structure applications. It is both an enabling technology and one that has been driven by the market and the need. NDE of composites is a mature technology and has been used successfully for many years, however, the composite structures of today and tomorrow have grown in both scale and complexity. New and improved nondestructive testing (NDT) methods and technologies are necessary to improve detection capabilities, meet growing inspection needs, and address future nondestructive inspection (NDI) requirements. NDT methods currently used in aerospace applications span a broad range of technologies, from the simple coin tap test to fully automated, computerized systems that can inspect very large parts (Figures 23 and 24).
\nNDI methods [5].
Ultrasonic inspection.
Many of the newer NDI methods are “wide-area” inspection techniques, which enable more uniform and rapid coverage of a test surface which can improve productivity and minimize human error. Technical advances in both computing power and commercially available, multi-axis robots and/or gantry systems, now facilitate a new generation of scanning machines. Many of these systems use multiple end effector tools yielding improvements in inspection quality and productivity.
\nUltrasound is the current NDE method of choice to inspect large fiber reinforced airframe structures. Over the last 2 decades, ultrasound scanning machines using conventional techniques have been employed by all airframe OEMs and their top tier suppliers to perform these inspections. A limitation of ultrasonic inspection can be the requirement to use a couplant between probe and test part. VACRS (variable automatic couplant and recovery system) has helped changed the way very large area ultrasonic inspections are done [6]. The VACRS system uses a lightweight couplant and delivery/recovery system that makes it possible to conduct a C-scan with large ultrasonic arrays without the large water requirements. It works with Boeing’s mobile automated scanner (MAUS®) and other scanning systems on the market.
\nShearography and thermography are relatively fast, non-contact methods that require no coupling or complex scanning equipment. Laser shearography was initially applied to aircraft structure in 1987 by Northrop Grumman on the B-2 bomber. Since that time, laser shearography has emerged as an advanced, high-speed, high-performance inspection method.
\nAn enabler for more widespread use of bonded structure in commercial aircraft applications will be improvements in cost and capability related to quantification of real-time structural bond integrity. Adhesive bonds degrade slowly over time and are highly dependent on surface preparation. On older aircraft, the only gauge for bond integrity is age, environmental exposures and statistics — not the actual condition of bonds. The ability to detect weak adhesive bonds, before they disbond will lead to more integration of parts and reduced fastener count and a reduction in everything that is involved with creating holes in cured composite parts. Military air vehicle platforms are more aggressive in this pursuit and the “pay-for-performance” mindset, the lower production rates and the size, visibility, and objectives of the programs allow for more flexibility in bonded structure implementation. The commercial world is different and just like the widespread implementation of composite material on new aircraft, it will not happen unless there are compelling economic advantages and very low risk.
\nBoeing knew that the transport time required by land or marine shipping methods would not support a supply chain that included major partners located in Japan, Korea and Italy and that air transport would be the primary shipping method [7]. The Dreamlifter started as the Large Cargo Freighter (LCF) program and is a modified 747-400 freighter. The Dreamlifter and follows a historic trail of oversized or outsize aircraft, which includes the Airbus Beluga, that were borne out of the adage “necessity breeds invention”. The Dreamlifter is a dedicated transport used to deliver full 787 fuselage sections, wings, and horizontal tail from suppliers located across the US and the world. There are four Dreamlifters in operation supporting the 787 program.
\nThe innovation that was the Dreamlifter (Figure 25), also required equipment to support the loading and unloading of such large cargo. Hence was born the largest cargo loaders in the world. The first one designated DBL-100 (DBL has been reported as an acronym for “Damn Big Loader”), were designed for use exclusively with the Dreamlifter.
\nBeluga and Dreamlifter [7]. Source: Boeing, Airbus.
Airbus was originally a consortium formed by British, French, German, and Spanish aerospace companies. Historically, each of the Airbus partners makes an entire aircraft section, which would then be transported to a central location for final assembly—even after integration into a single company, the arrangement remained largely the same. When Airbus started in 1970, road vehicles were initially used for the movement of components and sections. As production volume grew quickly, a switch to air transport was required. Beginning in 1972, a fleet of four highly modified “Super Guppies” took over. These were former Boeing Stratocruisers from the 1940s that had been converted with custom fuselages and turbine engines. Airbus’ use of the Super Guppies led to the jest that that every Airbus took its first flight on a Boeing [8].
\nToday this need is handled by the Airbus A300-600ST (Super Transporter) or Beluga (Figure 25). The Beluga is a modified version of the A300-600 airliner adapted to carry aircraft parts and oversized cargo. The official name was originally Super Transporter, but the name Beluga, a whale, gained popularity based on the appearance of the airplane and has been officially adopted. Interestingly, the Beluga cannot carry most fuselage parts of the A380, which are instead transported by ship and road.
\nAirbus has an updated design, The Beluga XL, based on the larger Airbus A330-200. Five aircraft are planned to be built as replacements for the existing aircraft and used primarily for A350 work. The Beluga XL is designed with the capacity to ship two A350 wings simultaneously [9].
\nThe Boeing 787 and the Airbus A350 aircraft share many similarities in size, configuration, manufacturing methods and mission (Figure 26). The primary difference between the composite fuselage structures of the two programs is the exclusive usage of IML controlled cure tooling and full barrel fabrication applied by Boeing and the sector panel approach selected by Airbus with a high percent incorporation of cobonded fuselage skin stiffeners. The true results of these decisions will not be known until more information can be collected about actual fabrication and assembly costs being realized by Boeing and Airbus.
\n787 and A350 fuselage sections.
The ACT/ATCAS program had a tremendous influence on the direction Boeing selected for the 787 program. Lessons learned from all aspect of the program influenced everything from the material systems that were selected to the tooling materials, structural arrangement, and the selection of IML tooled, full barrel fuselage structures. Major considerations that influenced that decision were the concerns about the cost of the assembly of very large stiffened structure and the stresses induced on the structure due to assembly.
\nThe program helped Boeing better understand the assembly loads related to composite panel warpage from cured part spring back and cocured and/or cobonded stiffener or frame mislocation. At minimum, these loads need to be understood and accounted for in the part design. Boeing saw an opportunity to minimize these assembly related penalties to the design by the tooling and structural arrangement approach applied on the 787.
\nBoeing’s selection of the AFP process over a male mandrel that serves as both a layup and cure tool is forgiving enough to accommodate different caul plate approaches on different sections of the fuselage. All the fuselage sections use multiple caul plates that nest together to cover the entire outer mold line of the fuselage. The cauls are floating on the surface of the skin and move with the skin during cure to establish the cured part OML whenever and wherever it is at the time the resin gels and things stop moving. Shared characteristics of the cauls include the ability to be individually and positively located before cure and removed individually after cure. Also the ability to ensure the cauls do not interfere with each other during cure. However, differences do exist in the choice of material (either graphite reinforced composite cauls or aluminum cauls) and in the thickness of the caul. In some cases, the composite caul is very thick and stiff and will behave more rigidly during the cure cycle. In other barrel sections, a thin aluminum caul is employed, which will more closely conform to the surface of the as AFP laminated skin. Both extremes are successfully being used by different fabrication partners.
\nInvar was the material of choice for Sections 43, 44 and 46 and the tail. Invar tooling was not the right choice for Spirit as it designed the layup mandrel/cure tooling for Section 41. An invar tool of that size and weight would have imposed very expensive requirements on the foundation of the AFP machine that winds the skin. The size of the motors and energy required to turn and manipulate the mandrel during the fiber placement process was also determined to be prohibitive. Instead Spirit elected to fabricate graphite reinforced BMI mandrels fabricated on invar cure tools and then machined to final IML dimensions (Figure 27).
\nSpirit 787 Section 41. Photo: Bill Carey.
Composite tooling is also used for Sections 47 and 48. In addition to lower mandrel weight, faster heat up and cool down rates contributed to this decision.
\nAll the partners on the 787 program follow similar manufacturing processes for fabricating cocured, hat stiffened, full fuselage barrel sections. All use AFP over IML controlled male layup mandrels that also serve as cure tools. Each section (except the tail) uses multi-piece breakdown mandrels which are disassembled and removed from inside the fuselage after cure (Figures 28 and 29).
\n787 Section 43. Source: Boeing.
Sections 44 and 46. Source: Boeing.
Alenia manufactures Sections 44 and 46 of the 787. Section 44 is a composite half barrel section that covers the main wing box. The lower portion of this fuselage section is mostly metallic and the structure is designed to handle the primary loads from the wings and landing gear.
\nFabrication of fuselage barrel Sections 47 and 48 were originally contracted to Vought as part of their statement of work (SOW) on the 787 program. Financial pressures driven by initial program delays led to Boeing acquiring the Vought SOW including partnership in subassembly work with Alenia (Figures 30–32).
\n787 Sections 47 and 48. Source: Boeing.
787 Tail. Source: Boeing.
Airbus A350.
The tail is the only barrel section that does not require a breakdown cure mandrel. The natural draft angles allow for cured part removal by simply sliding the cured part off the mandrel.
\nBoeing achieved stretch version of the 787 by extending the fuselage sections on either side of the wing center of gravity. The 20′ stretch for the −9 was achieved by adding 10′ to Sections 43 and 47. The additional 18′ added for the −10 configurations was achieved by adding 10′ to the forward fuselage and 8′ aft end. When new AFP mandrels were added to meet production ramp-up rate needs and to meet the −9 configurations, the tools were designed to support −10 also.
\nWhile the focus of this paper has concentrated on developments in the United States, the composites community in Europe was just as active. There were many R&D programs that were directed at high performance composites design and manufacturing activities [10].
\nThe results of this work along with many lessons learned on historical programs fed into the approach taken on the A350XWB program (XWB stands for eXtra Wide Body). The A350 composite fuselage manufacturing approach is not as uniform as the method selected by Boeing on the 787.
\nThe A350 incorporates one complete barrel section, the tail, produced in Spain that uses an approach similar to the one used by Boeing and its partners on the 787 (Figure 33). The rest of the A350 fuselage follows a more conventional panel assembly approach, but with some unique manufacturing process used along the way. The use of AFP, invar tooling and longitudinally incorporated omega (like the Greek letter Ω) stiffeners, more traditionally called hat stiffeners, are also common between the programs. The panel approach used on the A350 supports long part lengths and this is reflected in Section 15 which is approximately 65′ in length. How the omega stiffeners are incorporated on the fuselage panels is quite different between sections and suppliers.
\nA350 fuselage panel and tail. Source: Airbus.
Spirit is a common key supplier on both programs and the fabrication approaches share some key characteristics. Spirit produces Section 15 of the A350 and applies the sector panel approach that is common throughout the fuselage. Spirit cocures the omegas using an IML controlled layup/cure tool with a stiff composite caul plate to control the aerodynamic OML surface smoothness. Uncured omega stiffeners are laminated, formed and located into troughs machined into the invar tool. Inflatable rubber bladders are located on top of the omega laminates and fill the void between the omega and the AFP skin that is laminated on top of over the assembly. The part is autoclave cured and the rubber bladders removed after cure leaving the cocured, and now hollow, omega on the panel (Figure 34).
\nA350 fuselage side panel. Source: Spirit.
The rest of the A350 fuselage structure uses cobonding to incorporate the omega stiffeners with the fuselage skin (Figure 35). Precured omega stiffeners are located onto green AFP skins with a layer of film adhesive between the elements and then autoclave cured (Figure 36). During the cobonding cycle shaped tube bags are located inside the cured stiffener and are open to autoclave pressure during the cure/cobonding cycle to ensure the already cured stringer does not collapse or become damaged when subjected to autoclave pressure (Figures 36 and 37).
\nA350 fuselage panel. Source: CTC Stade.
A350 precured omega stringers. Source: Deseret News, Jeffrey D. Allred; CW/Photos: Jeff Sloan.
A350 omega stringer cobonding [11].
Like the 787 program, liquid molding processes are used to fabricate fuselage frames which are mechanically attached to the skins. The structural arrangements and assembly methods used by both programs are remarkably similar.
\nOne significant difference (if not THE most significant difference) is the frame integration to the fuselage. The 787 incorporates a “mouse hole” in the frame that nests around the hat stiffener and is attached directly to the IML of the fuselage skin. Boeing can do this because the IML surface of the 787 is a tooled surface with features that have controlled heights and locations. This includes hat stiffeners and skin joggles. Both programs use fuselage frames produced using a closed molding process that tools the surface that mates with the skin. On the 787, this creates a tooled surface-to-tooled surface interface creating a very predictable assembly. Components fit together as well as it can be produced because early in the program, it paid the price of being designed for assembly (Figure 38).
\n787 fuselage.
The A350 fuselage frames are attached only at the crowns of the omega stiffeners using secondary clips. Airbus did not try to attach the frames directly to the skins because the IML of the fuselage skin is not a controlled surface. It is a bagged surface that might use caul plates to create uniform pressure and a smooth surface, but the IML surface “floats” depending on factors such as bagging, resin bleed and initial prepreg resin content. Just as the OML of each 787 fuselage “floats” and is different aircraft-to-aircraft depending on these same factors. Airbus uses a standard carbon fiber reinforced clip, molded from thermoplastic material, to absorb the skin fabrication tolerance in the assembly process (Figure 39).
\nA350 fuselage. Source: Borga Paquito.
There are several recently developed commercial aircraft, such as the Bombardier C Series, Mitsubishi’s MRJ, and Comac’s C919, that all have similar overall airframe architecture as the 787 and the A350. However, none of these aircraft incorporate an all composite fuselage. The advantages for composites on large, wide body aircraft have been validated by the short service history of the 787 and even shorter history of the A350. The debate regarding smaller aircraft achieving the same gains continues for Next Generation Single Aisles.
\nWide body aircraft spend much of their life cruising at 40,000 ft. and the structure is sized for pressure loads and structural needs—this provides adequate thickness for good damage tolerant designs. The fuselage designs for single aisle aircraft could be more efficient based on cabin pressure and structural loading alone. But, to provide for designs that will be tolerant of many more takeoff and landings and in service hazards such as luggage and catering carts, dropped tools and equipment, hail and bird strikes, the fuselage panels must be thicker and heavier, thus sacrificing weight.
\nWings are one area of implementation for composites on the single aisle upgrades and new aircraft of the future. The Boeing 777X has incorporated a composite wing into the design. A composite wing allows for a very high degree of laminate tailoring and can be designed and built for maximum efficiency. This creates an elegant wing that is incredible to watch in-flight, but appears alarmingly thin compared to conventional metal aircraft wings. But composite wings for high rates present challenges. Production rates of 12–14 per month for wide bodies have proven to be achievable. Building composite wings to support production rates as high as 60 aircraft per month for narrow bodies has not. Costs related to rate tooling alone can be daunting.
\nRemarkable advances in OOA technology might help provide a solution. Bombardier chose an OOA process for wings of the C-series and the MRJ is using an OOA system for the vertical tail wing box, a similar process to what United Aircraft (Russia) has announced for their MS-21 wing. Still, there are complex issues to resolve that will affect the timeline for OOA system usage on next generation, commercial, single aisle aircraft wings and fuselages. The industry is risk adverse and OOA systems are in their infancy compared to autoclave systems. The autoclave process has proven to be very forgiving and tolerant of variabilities that exist in raw materials, support materials, supply chain manufacturing processes and through final part fabrication. The effect of manufacturing variability is well understood and incorporated into efficient designs that contain minimal penalties for the unknown or less well understood. The same will not be true of OOA systems until more lessons learned have been earned. Many of these lessons will continue to come from military applications that are more aggressive in implementing new technologies. The benefit for the military is usually not cost; the benefit for the commercial world is always cost.
\nOn a little longer timeline affecting future composite fuselage construction is sensor and technologies related to structural health monitoring (SHM). This is a very large field with growing interest by many OEM’s in many applications by many industries, including aerospace, automotive, and power generation. Advances in this technical arena could be one of the next revolutionary changes or “step changes” (vs. evolutionary) to advance the industry. Advanced sensor technology could supplant many NDT applications by supporting in-situ “structural health monitoring.” Installed on or within composite structures, such systems would continuously monitor a component and detects degradation and damage as it occurs. This could eliminate the possibility of damage being overlooked and reduce costly downtime for manual inspections.
\nThe future of SHM and other smart composite structures includes morphing technology that changes part shape in-flight to create optimal flight conditions. Built-in sensing, computing, and actuation are emerging new frontiers for structures that self-tailor their properties for changing flight conditions. Similar developments include multi-functional composites—laminates that not only provide lightweight, load-bearing structures, but also perform additional functions such as energy harvesting and storage. The 20th International Conference on Composite Materials (July 19–24, 2015, Copenhagen, Denmark), featured more than 100 presentations on multifunctional composites [12].
\n3-D printing is another emerging technology that will impact the future of composite fuselage construction. Already making an impact in prototyping, early design and development, and tooling applications. Small, highly complex parts will follow the path being created by 3-D printed metallic parts. Larger applications are sure to follow. Nano technology may also develop as a viable standalone technology or perhaps integrated with 3-D printing. Remarkable innovations are surely on the horizon.
\nThe state-of-practice for dual aisle, wide body commercial aircraft fuselages has evolved over the past generation from minor aerodynamic composite fairings and flaps to entire composite fuselage structures. It has been a methodical, tenacious process that has included determined efforts by resources from the military and defense department, academia and many industry participants. It has been a global race between teams in the US and Europe with both competitors realizing a win-win outcome. Enormous technical advances were required on many fronts, from tooling to transportation. Equally enormous advances were requisite on the cost competitiveness of manufacturing and assembling composite materials in order to earn their way onto commercial aircraft platforms. New mid-market aircraft platforms from both sides of the Atlantic will be the launching pad for the next wave of technologies that have earned their way onto dual aisle commercial aircraft. After that, the industry anticipates direction on long awaited replacement designs for workhorse single aisle aircraft—composite fuselage or not?
\nA special “nod of the head” to my colleagues at Northrop and Rubbercraft and the many capable and knowledgeable engineers I worked with at Boeing, Spirit, Alenia, KHI and KAL (and others too numerous to callout).
\nNo conflict of interest exists with this research.
Special thank you to my family for your patience and support over the years—you know I love you.
\nThe goal of this work was to assess the current epidemiological and epizootological situations in the world largest focus of opisthorchiasis; to clarify the specific features in its clinical course, pathogenesis, and complications; to determine the natural, climatic, and social factors that enhance preservation of this focus; and to propose an algorithm for preventive activities.
\nThe tasks of this research are to study the epizootological situation and features of the circulation of Opisthorchis felineus in the Ob-Irtysh basin, assess the epidemiological situation of opisthorchiasis in Russia, and give recommendations on measures to prevent the disease.
\nThe concept of sustainable development [1] sets the control of unattended diseases as one of the global goals in the area of public health care; these diseases include the helminthic invasions in hyperendemic foci. The ongoing changes in all spheres of production and sale of raw materials and goods have led to serious violations of sanitary rules and norms, which deteriorate the epizootic situation for parasitic invasions in the world.
\nOpisthorchiasis, the trematodiasis caused by O. felineus Rivolta, 1884, is one of the relevant problems in both Russia (with its world largest Ob-Irtysh natural focus) and worldwide despite the implemented prevention measures. The relevance of this problem is determined by both its high incidence among adults and children, severity of the resulting pathology, and its chronic course.
\nThe socioeconomic factors, such as active migration of population, unawareness of opisthorchiasis among the newcomers to the region, poor knowledge about the rules for disinfection of local population, all-year-round consumption of fish, and homemade fish products, increase in the number of amateur fishermen and poachers, and vending of fish and fish products on unauthorized markets creates the conditions for the stable preservation of opisthorchiasis.
\nOne of the major factors that influence the level of O. felineus liver fluke invasion is a high rate of fish invasion by its metacercariae. The natural and climatic conditions that have established in the Ob-Irtysh basin support the active opisthorchiasis focus there.
\nA vast floodplain of the Ob-Irtysh basin, rich in lakes and meadows, and a developed network of first- and second-order tributaries enhance the maintenance of the Bithyniidae mollusks at a high level.
\nClose coexistence and cohabitation of the first intermediate host and cyprinid fish (second intermediate host) in the same habitats provide the implementation of liver fluke life cycle. In their abundance and species diversity, the cyprinid fish are the leader group in the Ob-Irtysh basin. A high infection rate of the prevalent fish species, which are of important commercial value, with O. felineus metacercariae is a major risk factor, influencing the incidence of this disease among local population.
\nThe liver fluke was for the first time described in 1884 by Sebastiano Rivolta, an Italian scientist. He isolated the parasite from the liver of a cat and a dog and named it the liver fluke, O. felineus, and the corresponding disease, opisthorchiasis. K.N. Vinogradov, a professor at the Tomsk University, discovered the liver fluke in the human liver in 1891. After the discovery by Vinogradov, human cases of opisthorchiasis were repeatedly recorded in 1892–1929 in Tomsk, Biysk, Novosibirsk, Tyumen oblast, Kuznetsk raion, and other localities. During WWII, a Russian soldier from Siberia died in one of the fascist concentration camps; his autopsy demonstrated 42,000 liver flukes in his liver and pancreas.
\nAs has been observed, the liver fluke is not met far and wide but rather near freshwater bodies. Brown in 1893 assumed that fish consumption is the source of liver fluke infection, which was later (1904) experimentally confirmed by M. Askanazy (Germany). In 1891, Vinogradov postulated the first intermediate host of liver fluke, which was experimentally confirmed by H. Vogel (Germany): he demonstrated that the first intermediate host was the mollusk Bithynia leachii (Sheppard, 1823).
\nThe study of opisthorchiasis commences in 1929 after publication of the information that 100 opisthorchiasis patients were admitted to the Tobolsk hospital over 6 months. This initiated organization of specialized helminthological expeditions to the Ob-Irtysh basin, headed by K.I. Skryabin. Numerous experiments have demonstrated that this region houses the largest opisthorchiasis focus. Russian helminthologists under the guidance of Skryabin paid significant attention to the study of O. felineus (1927–1929). The liver fluke larvae were for the first time discovered in the muscle of fish individuals inhabiting Siberian water bodies by N.N. Plotnikov and L.K. Zerchaninov in 1932.
\nAll these efforts allowed for discovery of a considerable incidence of opisthorchiasis among people, cats, and dogs along the Irtysh and Ob rivers up to the polar circle. In 1973, a cat was autopsied by an expedition organized by Skryabin in the north of the Tomsk oblast; eight cysts containing liver flukes were found in its liver; one of the cysts, medium in its size (similar to a walnut), contained 654 parasites.
\nThe following scientists contributed to the studies of the epidemic situation of opisthorchiasis: S.D. Titova (publications of 1946–1980), V.S. Myasoedov (publications of 1953, 1959, and 1960), M.P. Miroshnichenko (1954, 1955, and 1956), T.A. Bocharova (1971–2005), G.I. Golovko (1981–1986), and so on. The population migration to the oil and gas areas in the north of the Tomsk oblast increased the attention to this disease [3, 18, 19, 20, 21, 22, 24, 43].
\nThe liver fluke O. felineus has an intricate life cycle, which involves three hosts: the definitive host and two intermediate hosts; the life cycle comprises two free-living stages, the egg and cercaria (\nFigure 1\n).
\nLife cycle of O. felineus.
Infected domestic and wild animals that fed on fish and infected people, which are the definitive host of the liver fluke, are the sources of invasion. One trematode lays approximately 2000 eggs per day. The eggs are not viable when dry and are rapidly killed by sunlight but retain their viability for 15 months in a water body at a temperature of 4–7°C; all eggs die after 29 months [2].
\nWhen entering water with human and animal feces, the liver fluke eggs can be ingested with detritus by the first intermediate host, a Bithyniidae (genera Codiella and Opisthorchophorus) mollusk [2].
\nIn the Ob-Irtysh basin, the mollusks susceptible to the invasion inhabit only standing perennial silt water bodies. The mollusks are unable to migrate for a long distance and form local clusters. Presumably, the infection rate of mollusks depends on the population density and the distance from human dwellings [3].
\nThe infection rate of Bithyniidae mollusks in the upper reaches of Ob and Irtysh rivers within the Altai Krai is 2%, amounts to 6.1% within the Novosibirsk oblast, and varies in the range of 0.3–20.2% in the Irtysh basin in the Omsk oblast [4, 5]. The density of the mollusk population in the floodplain water bodies in the Tomsk oblast is 8100 individuals/m3; however, the prevalence of invasion is extremely low (3.7%), and the intensity is very high (on the average, 8130 ± 470 cercariae/mollusk). Coinvasions are extremely rare [6]. The infection rate of mollusks in the Tura and Pyshma river floodplains varies from 4 to 9%; the infection characteristics in the Khanty-Mansiysk Autonomous Okrug are also low, to 6.7% [7].
\nIn the mollusk gut, miracidia, free-swimming larvae, hatch from the eggs (\nFigure 1\n). A miracidium hatched from the egg enters the mollusk body cavity by passing through the gut wall to undergo a regressive metamorphosis there. It loses its larval organs (glands, epidermal plates, cilia, etc.) preserving only the germline cells and protonephridia to change into a mother sporocyst with a length up to 2 mm [2].
\nYoung sporocysts are transversely constricted to give smaller sporocysts, which propagate and form rediae. Rediae are sack-like structures with a large mouth and gut. When leaving the mother sporocyst, rediae migrate to the liver of mollusk to parthenogenetically reproduce.
\nIn the redia, tailed motile larvae—cercariae—are formed of the germ balls. The developmental stage in the mollusk takes 2–2.5 months (\nFigure 1\n) [2].
\nWith the maturation, cercariae leave the redia through the pore to migrate in the mollusk body leaving it for water, where they swim for 30–50 h. Up to 3500 cercariae can leave the mollusk during 24 h. The release of cercariae has two peaks, namely a pronounced midsummer peak and a flat spring one [2].
\nWhen encountering a cyprinid fish (ide, dace, roach, bream, Siberian roach, Caspian roach, tench, common rudd, common carp, asp, common bleak, etc.), the cercaria attaches to it; detaches its tail; loses its eyes and sensory organs; and penetrates into the muscles to form the inner and outer (a capsule of connective tissue) membranes and to transform into the next phase, metacercaria (\nFigure 1\n).
\nThe metacercariae have a size of 0.23–0.38 × 0.18–0.28 mm and are very survivable. The metacercariae become invasive 3–6 weeks after entering the fish and now are able to infect the definitive hosts—domestic and wild carnivores and omnivorous animals and humans. Metacercariae retain their viability in the fish body for 1–3 years and even to 9 years according to some data [8].
\nAs is known, only cyprinid species are suitable intermediate hosts for the metacercariae. Approximately 20 species of both aboriginal and alien cyprinid species of commercial or noncommercial value inhabit the rivers and lakes of the Ob-Irtysh basin, the most important fish species of commercial significance are the ide, bream, crucian carp, roach, and, to a lesser degree, dace [2].
\nThe rate of the fish infection by liver fluke metacercariae has been studied with different intensities in different periods. A large volume of data on the prevalence of fish infection in the Ob-Irtysh basin was accumulated in the 1990s to 2000s. Our data and the earlier results suggest high rates of infection of the ide, dace, and roach. The prevalence of ide and dace infection amounted to 20–100% and of roach, 2–80% with the intensity of infection of 1–1780 metacercariae per individual. These fish species are among the major carriers of O. felineus metacercariae and significantly contribute to the preservation of the opisthorchiasis focus. In addition, the bream and common bleak, alien species for this region, also appeared to be susceptible to the infection by liver fluke metacercariae and, correspondingly, have been involved in the maintenance and spreading of opisthorchiasis in Western Siberia [8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25].
\nThe definitive hosts are infected orally by consuming the cyprinid fish muscles infected by liver fluke. The metacercarial membrane is finally destroyed in the host stomach, and the young helminth migrates along bile ducts to the liver and gall bladder to reach the sexual maturity in 20–25 days (\nFigure 1\n) [2].
\nThe intensity of invasion of definitive hosts and their role in maintaining the strength of opisthorchiasis focus are different. As is assumed, in addition to humans who account for 56.6% of the invasion, cats (15.8%), dogs (3.6%), and pigs (to 0.9%) are also significant contributors to opisthorchiasis [26]. The total prevalence of cat invasion in the opisthorchiasis focus of the Khanty-Mansiysk Autonomous Okrug in the 2000s amounted to 48.2% (males were more frequently affected than females). The prevalence of dog invasion was lower, amounting to 17.14% [27]. An analogous study in Novosibirsk demonstrated the total prevalence of cat invasion of 7.9% with the intensity of 69.9 flukes and of dog invasion of 3.4% with the intensity of 23.8 flukes. Males appeared more affected among cats and females among dogs. The invasion parameters increase with animal age [28].
\nIn addition to domestic carnivores, wild carnivores (common fox, wolf, brown bear, lynx, polecat, sable, mink, muskrat, bank vole, and others) also contribute to the liver fluke circulation in natural foci. These animals play different roles in the epizootic process in opisthorchiasis: the animals living in the floodplain and constantly “supplying” the infectious material to the biotopes of the first intermediate host are actual players of the opisthorchiasis circulation in the Ob-Irtysh basin, whereas the remaining animals are potential sources of invasion. In general, foxes and muskrats account for the largest number of invaded wild animals. The rate of invasion in the floodplain of Ob river and its tributaries reaches 77% on the background of a growth in the prevalence characteristics from the upper to lower reaches. The intensity of invasion amounts to 10–500 liver flukes per individual. The invasion of the muskrat in Western Siberia reaches 33% [29]; however, this issue requires further studies.
\nThus, a complex multihost life cycle of this parasite enhances its long-term retention in wildlife and preservation of the natural opisthorchiasis focus in the Ob-Irtysh basin.
\nOpisthorchiasis is an important social problem in Russia. Two-thirds of the world distribution range of this pathogen concentrates in this country [30]. Opisthorchiasis accounts for approximately 80% of all helminthic diseases. According to the official statistical data, up to 26,000 cases are annually recorded. The actual number of opisthorchiasis patients taking into account the correction factor is 15-fold higher [31].
\nIn total, 106,362 cases of invasion were detected in 2014–2018. The maximum number of cases was recorded in 2014 (25,545 cases) and minimum, in 2017 (18,755 cases). The incidence rate of opisthorchiasis among population in 2018 decreased by 25.3% as compared with 2014, varying from 12.79 to 17.51 per 100,000 population (\nTable 1\n).
\nRegion of Russian Federation | \n2018 | \n2017 | \n2016 | \n2015 | \n2014 | \n|||||
---|---|---|---|---|---|---|---|---|---|---|
Total\n*\n\n | \nIR\n**\n\n | \nTotal\n*\n\n | \nIR\n**\n\n | \nTotal\n*\n\n | \nIR\n**\n\n | \nTotal\n*\n\n | \nIR\n**\n\n | \nTotal\n*\n\n | \nIR\n**\n\n | \n|
Russian Federation | \n19,077 | \n12.99 | \n18,755 | \n12.79 | \n20,846 | \n14.24 | \n22,139 | \n15.15 | \n25,545 | \n17.51 | \n
Yamalo-Nenets Autonomous Okrug | \n838 | \n155.6 | \n666 | \n124.2 | \n766 | \n143.4 | \n875 | \n162.0 | \n1228 | \n226.7 | \n
Khanty-Mansiysk Autonomous Okrug | \n5046 | \n299.6 | \n4309 | \n259.2 | \n4454 | \n272.5 | \n6024 | \n374.0 | \n7370 | \n461.5 | \n
Tyumen oblast | \n1483 | \n98.9 | \n1341 | \n90.7 | \n1384 | \n95.1 | \n1518 | \n106.2 | \n1831 | \n132.2 | \n
Tomsk oblast | \n1129 | \n104.7 | \n1251 | \n116.0 | \n1336 | \n124.1 | \n1557 | \n145.5 | \n1686 | \n158.4 | \n
Novosibirsk oblast | \n3252 | \n116.6 | \n3118 | \n112.2 | \n4109 | \n148.8 | \n3930 | \n143.1 | \n3505 | \n128.3 | \n
Kemerovo oblast | \n1386 | \n51.43 | \n1704 | \n62.91 | \n1800 | \n66.23 | \n1357 | \n49.8 | \n1547 | \n56.58 | \n
Omsk oblast | \n1427 | \n72.8 | \n1450 | \n73.27 | \n1469 | \n74.24 | \n1622 | \n81.99 | \n2035 | \n103.1 | \n
Altai Krai | \n869 | \n36.7 | \n818 | \n34.3 | \n959 | \n40.2 | \n791 | \n33.09 | \n1091 | \n45.48 | \n
Absolute values and incidence rate of opisthorchiasis in the Russian Federation and Western Siberian region in 2014–2018.
Morbidity data according to Form 2 “Data on infectious and parasitic diseases” approved by Order 52 of the Russian Federal State Statistics Service of January 28, 2014.
IR is the incidence rate of disease per 100,000 population.
The natural foci of opisthorchiasis are adjacent to the Ob, Irtysh, Ural, Volga, Kama, Don, Dnepr, Severnaya Dvina, and Biryusa rivers [32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42].
\nApproximately 80% of the opisthorchiasis cases are recorded in the territories adjacent to the Ob, Irtysh, and Tom river basins and their tributaries [43], housing the administrative centers of the Omsk, Novosibirsk, Tyumen, Tomsk, and Kemerovo oblasts and Khanty-Mansiysk and Yamalo-Nenets Autonomous Okrugs. Most part of the local population is affected (80–95%) [44, 45, 46]. The total incidence rate over 2014–2018 was 84,331 opisthorchiasis cases, accounting for 79.3% of the total cases in the Russian Federation.
\nThe Khanty-Mansiysk Autonomous Okrug heads the list of percentage of opisthorchiasis incidence (2.6–4.6) followed by Yamalo-Nenets Autonomous Okrug (1.2–2.3%), Novosibirsk oblast (1.1–1.5%), Tomsk oblast (1.0–1.6%), Tyumen oblast (0.9–1.3%), Omsk oblast (0.7–1.0%), Kemerovo oblast (0.5–0.7%), and Altai Krai (0.3–0.5%) [47, 48, 49, 50, 51].
\nThe incidence rate of opisthorchiasis in the analyzed regions varies, with the maximum exceeding 1.3–1.8-fold the minimal value. The highest incidence rates are recorded in the hyperendemic regions of Yamalo-Nenets (124.2–226.7) and Khanty-Mansiysk (259.2–461.5) Autonomous Okrugs, Tyumen oblast (90.7–132.2), Tomsk oblast (104.7–158.4), Novosibirsk oblast (112.2–148.8), and Omsk oblast (72.8–103.3). The Kemerovo oblast (49.8–66.23) and Altai Krai (33.09–45.48) are the regions with a high level of invasion. The incidence of opisthorchiasis in these regions severalfold exceeds the mean level for the Russian Federation with the Khanty-Mansiysk Autonomous Okrug heading the list (19–26-fold) followed by Yamalo-Nenets Autonomous Okrug (9–13-fold), Tomsk and Novosibirsk oblasts (7–10-fold), Omsk and Tyumen oblasts (5–8-fold), Kemerovo oblast (3–5-fold), and Altai Krai (2–3-fold).
\nAccording to the statistical data for 2014–2018, a decrease in the absolute characteristics and incidence rate was in general observed in all hyperendemic regions, which is explainable by inadequate diagnosing, registration, and recording of the cases as a result of decreased attention to the problem of opisthorchiasis.
\nOpisthorchiasis is mainly diagnosed among the adult population (over 90% cases in people aged 39–59); however, the level of child morbidity is rather high. Opisthorchiasis has been recorded in all age cohorts of children up to 17 years, with the age cohort of 7–14 years accounting for 60–80% of all cases recorded in children. In the Tomsk oblast, the children to 17 years old are the most affected as compared with other regions (29.7% in 2014–40.8% in 2018). In the mid-Ob river region, opisthorchiasis is detectable in children starting from 3 years (25–30%) with an increase at the age of 12–14 years (50–60%) to 100% in the adults [52]. In the child population of the city of Urai (Khanty-Mansiysk Autonomous Okrug), the most affected cohort is 7–14 (38%) and 14–17 (34%) years old versus 23 and 5% for the cohorts of 3–6 and 2–2 years [53]. An increase in the prevalence of infection among the children of 1–2 years (from 3.8 to 6.1%) is observed in the Tomsk oblast. Cases of opisthorchiasis in the children under 1 year have been recorded in Khanty-Mansiysk Autonomous Okrug (six cases in 2017).
\nIn 2008–2017, 43 cases of acute opisthorchiasis were recorded in the middle Ob basin. Among those infected, the proportion of women and men was 48.8 and 51.2%, respectively. In terms of age, the maximum number of cases of acute opisthorchiasis was recorded among people aged 20–39 years (74.4%), followed by those aged 40–49 and 50–59 years (9.3% each group), and people aged 15–19 years (7.0%).
\nThe largest number of cases of opisthorchiasis was recorded in May (20.9%) and June (32.6%), and less often opisthorchiasis was recorded in September and November (11.6% each). In other months, the infection was observed sporadically (1–2 cases). In 2008–2017, from 52.8% (2011) to 80.9% (2017) of people with recorded opisthorchiasis underwent dehelmintization (original data).
\nSince most rural population, including children, are involved in fishing, regular consumption of frozen and slightly salted freshwater fish is widespread; correspondingly, the incidence rate increases with age, and the cases of superinvasion are observable [54, 55].
\nThe morbidity patterns in the municipal entities of autonomous okrugs and oblasts are considerably different. However, the corresponding levels observed in the municipal entities of the north are higher by an order of magnitude. The significant differences in morbidity in different municipal entities of oblasts and autonomous okrugs are associated with different quality of clinical diagnostics, recording, and registration of opisthorchiasis cases rather than with the difference in diet pattern [56]. The facts that the child morbidity rate is higher than that in adults are explainable by that adult population rarer seeks medical help. Since the diet of children and adults does not significantly differ, it is likely that the adult population is highly affected with the prevalence of chronic disease courses [56].
\nThe urban population on the average accounts for 75–78% of the opisthorchiasis cases [31, 57]. However, the incidence among the rural population is higher than the urbane population. Characteristic of the urban life style is rarer consumption of freshwater fish and better adherence to good cooking practice [54].
\nOpisthorchiasis is a food-borne disease, with the pathogen transmission via eating the fish infected with the liver fluke metacercariae. The susceptibility to invasion is ubiquitous. The duodenal content induces larvae to excyst there wherefrom they migrate through the ampulla of Vater to the bile excretory ducts owing to a positive chemotaxis to bile. In 3–5 h, liver flukes (100%) are detectable in the liver, pancreas, and gall bladder (20–40%) [58, 59].
\nAfter 3–4 weeks, liver flukes turn into sexually mature maritae, producing eggs [58].
\nClinical manifestations of opisthorchiasis are manifold and depend on individual specific features of the host organism as well as infection intensity and duration [34, 60, 61]. Humans are unable to develop immunity to this pathogen; correspondingly, repeated consumption of the fish carrying metacercariae merely increases invasion [62, 63]. The counts of maritae in an individual can vary from solitary parasites to several tens and even hundreds [63].
\nThe incubation period of opisthorchiasis is on the average 2–3 weeks [58, 61]. The early (acute) and late (chronic) phases of this disease are distinguished [64]. The early phase lasts from several days to 4–8 weeks and longer [60], while the chronic phase may last for 10–20 and more years [64]. The disease may have unapparent or overt manifestations [58, 61, 65, 66].
\nCharacteristic of the subclinical case of opisthorchiasis early phase is a subfebrile temperature and insignificant eosinophilia on the background of normal leukocyte counts [58]. A subclinical course is observed in the children who have received the antigen during their embryonic development or the antibodies with mother’s milk [67, 68, 69]. This is the explanation why the manifestation of opisthorchiasis in the indigenous population of the north (Khanty and Mansi) is primary chronic with poor symptomatics and aggravation under adverse conditions, such as stress, infections, or surgery [58, 60, 61, 70, 71].
\nAn overt course of opisthorchiasis is usually observable in the patients who moved to the opisthorchiasis focus from the regions not endemic for the disease [58]. The acute phase starts abruptly and continues for 1–3 months or rarer, for 6–9 months [58, 62, 63]. A systemic allergic response determines development of inflammation in the lungs, gastrointestinal tract, musculoskeletal system, skin, and cardiovascular system [64]. The patients experience fever (from subfebrile to febrile for 1–3 weeks), eosinophilia (20–40%; sometimes, to 90%), intoxication, dyspeptic disorders (nausea, vomiting, and epigastric burning), moderate arthralgia and myalgia, and exanthems of various types [58, 60, 61, 64]; hepatocholangitic syndrome (right subcostal pain, increased liver, elevated transaminase activities, and elevated alkaline phosphatase activity) [58, 64], bronchopulmonary syndrome (hyperemic pharynx, retropharyngeal granulation, rhinitis, asthmatic bronchitis, eosinophilic infiltration in the lungs, and exudative pleurisy), and cardiovascular changes (palpitation, cardiac pain, hypotonia, and diffuse dystrophic changes in the myocardium detectable by electrocardiography) are observable [72].
\nA severe form of the acute opisthorchiasis can be represented by typhoid, hepatocholangitic, and gastroenteritic clinical variants [73]. Severe toxic and allergic responses appear as toxic epidemic necrolysis (Lyell’s syndrome), Stevens-Johnson syndrome, acute myocarditis, Quincke’s edema, or hives [60].
\nIn the absence of treatment, the acute phase transforms into a chronic one [63], which can continue for 20 years [61] and proceed either latently or with clinical manifestations [62]. A latent course is more frequent characteristic of the aboriginal population in the opisthorchiasis foci and in young people [60]. Patients have no complaints, and laboratory tests are normal. Opisthorchiasis is diagnosed in these cases only by chance during a periodic health examination or examination for other diseases [62]. In practice, this is the situation for 8% of several thousands of patients [63].
\nCharacteristics of a latent opisthorchiasis are periods of remission and exacerbation [62]. In an endemic focus, opisthorchiasis initially follows a chronic course without any acute manifestations. Clinical symptoms may appear 10–20 years after infection. Patients frequently develop the symptoms of cholangitis and cholecystitis (80–87% of the cases) [74, 75], including right subcostal pain, heaviness in the stomach, nausea, fat intolerance, dryness and bitter taste in the mouth [58], abdominal distention, frequent liquid stool [63], vomiting, eructation, hepatomegaly, and jaundice during exacerbation [73]. Part of the opisthorchiasis patients develops pancreatitis with a wave-like course (frequent alternation of remission and exacerbation periods); 45–50% of the patients experience gastritis, duodenitis, and gastric and duodenal ulcers [73, 76]. In case of gastric involvement, patients frequently develop intestinal dyspepsia and dysbacteriosis, with the absence of bifidobacteria or their decrease and an increased content of facultative opportunistic pathogenic microflora, such as Staphylococcus epidermidis and Staphylococcus aureus [74]. Patients complain of undue fatigability, petulance, sleep loss, headache, hyperhidrosis (frequently local, for example, sweaty hands), excessive salivation, pronounced dermographism, tremor (eyelids, tongue, and/or fingers), vasomotor vascular response, and subfebrile temperature [76, 77].
\nThe immunological response to antigens clinically manifests itself as an allergic syndrome, with skin itching, hives, recurrent Quincke’s edema, arthralgia, alimentary allergy, moderate eosinophilia, and specific IgE in the blood [61]. A constant presence of the liver fluke antigen wears off the immune system and decreases its ability to suppress infection [69, 78, 79].
\nChronic opisthorchiasis is a factor that is able to induce liver cancer development [63]. The early manifestations of liver cancer are an increase in the right subcostal pain and epigastria; their constant unceasing character, especially during nighttime; sensation of discomfort and heaviness; and pronounced dyspeptic disorders (anorexia, idiopathic weight loss, early satiety, abdominal distension, alternation of constipation and diarrhea, and so on). Weakness, general uneasiness, and sleep disorders rapidly worsen. The prescribed treatment of chronic opisthorchiasis fails to bring relief [80]. Hepatomegaly is characteristic of the liver cancer (the liver is dense, nodular, and painful); typical manifestations are hypochromic anemia, eosinophilia, accelerated ESR, and, in the case, of cancer, lymphopenia [80].
\nIn pancreatic cancer, patients more frequently experience weakness, vomiting, and progressive weight loss. In part of patients, vomiting is caused by impaired gastric emptying because of the tumor compression or its invasion to the duodenum. Patients lose 5–32 kg over 2–3 months [80].
\nThe main sign of pancreatic cancer is jaundice; it is persistent, increasing in its intensity, and accompanied by a high body temperature and chill. The fever and itching exhaust patients so that they lose sleep and experience growing adynamia and apathy. The liver may be increased; it has smooth surface and is less dense [80]. Characteristic of jaundice is a high concentration of bilirubin in the blood as well as increased alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase activities. Amylase activity is also increased in the liver and pancreatic cancers; thymol and sublimate tests are changed, which suggest an advanced cancer process [80].
\nPathogenesis is determined by the combined impact of parasites on the host body (mechanical, toxic, and neuroreflectory) and host body responses (immunopathological) [60, 61, 64].
\nIn the early phase, the immunopathological mechanisms with development of the immediate type allergic response are more pronounced [61, 64]. The liver fluke antigens enter the blood through mucosa and sensitize the organism (gastrointestinal tract, lungs, kidneys, liver, etc.) [60, 61]. The liver fluke metabolites induce toxic and allergic syndrome [58, 64], which are accompanied by edema, proliferation, desquamation of bile duct epithelium, and metaplasia of bile ducts with formation of goblet cells and small gland-like structures [58].
\nIn the late phase, the liver fluke metabolites induce an immune inflammation in many organs and systems [81, 82]. The immunopathological effect appears as a secondary immunodeficiency with prevalence of a delayed type allergic response; characteristics of this response are vascular involvement and regeneration of cell elements in the connective tissue with development of extensive fibroplasia [73, 83].
\nMechanical and toxic factors in the late stage become the most important [61, 64]. Young liver fluke individuals damage the bile duct walls by their spinules and the sexually mature individuals and by their oral and ventral suckers. Liver flukes consume the mucosal secretions and bile duct epithelium [45]. A mechanical stimulation of the walls of bile and pancreatic ducts interferes with the motor and secretory functions of the gastrointestinal tract [60].
\nInflammatory and proliferative processes are induced and developed in the mucosal lesions, as well as peroxidation is activated and antioxidant defense is damaged [60, 84].
\nClusters of liver flukes, their eggs, and crusts of desquamated epithelium in the ducts create a mechanical barrier for the outflow of bile and secretion, thereby enhancing the development of proliferative cholangitis and canaliculitis accompanied by different degrees of fibrosis in these organs [60].
\nFrequently, the pancreas responds to the presence of liver flukes and their metabolites by certain pathological changes. Both the exocrine and endocrine functions of the pancreas are damaged during pancreatitis [67, 85, 86].
\nPersistent hypertension develops in the duodenum, stomach, esophagus, and biliary system on the background of chronic duodenal stasis [61], creating the favorable conditions for secondary infections (Escherichia coli, staphylococci, yeast-like fungi, and others) [60].
\nThe liver fluke invasion has a negative effect in the mother-placenta-fetus system [87], increasing the probability of gestoses and miscarriage [88].
\nThe involvement of gastrointestinal tract affects digestion and absorption, leading to dysmetabolic sensitization. As a consequence, allergic skin lesions are developed, including urticarial rash in the early phase and chronic hives with exacerbation periods and remissions in the late phase [85, 86]. The urticarial rash rather frequently transforms into papular and vesicular rash. In some cases, hives can follow a hemorrhagic pattern owing to release of erythrocytes, which fall apart and form pigment spots [61, 79, 89].
\nThe host immunopathological response is the cause underlying the dystrophy and necrosis of the epithelium of biliary tract and pancreatic ducts [79, 89, 90].
\nThe sclerotic processes leading to the development of chronic hepatitis are prevalent in the late phase. Superinvasion and reinvasion lead to development of an active hepatitis as a result of an immune inflammation in the liver [61, 68, 91].
\nComplications of opisthorchiasis most frequently develop in the chronic stage. This disease belongs to the group of carcinogenic helminthiases [55, 59, 92, 93]. Liver tumors [55, 57, 94] as well as stomach, pancreas, and breast tumors most frequently develop on the background of liver fluke superinvasion [95, 96].
\nThe carcinogenesis on the background of opisthorchiasis involves multifactorial mechanisms comprising inflammatory, mechanical, and secretory-excretory processes [84, 97].
\nIn case of superinvasion, maritae provide a sustainable basis of the food substrate—permanent proliferation and differentiation of liver and pancreatic stem cells as well as the stem cells in the organs beyond their ecological niche [55].
\nAn overt inflammation determines a constant response as the regenerative cell proliferation [55, 98].
\nActivated macrophages and polymorphonuclear leukocytes produce reactive oxygen species, proteolytic enzymes, proinflammatory cytokines, and growth factors. Reactive oxygen and nitrogen species and oxysterol production play the decisive role in the disturbance of the function of proto-oncogenes, the DNA regions the abnormalities in which induce cancer transformation of liver cells [45, 66]. As a result, adjacent cells are altered, and an active regeneration of injured tissues is triggered [97, 99].
\nMaritae interfere with the bile outflow in a purely mechanical manner. The stagnant bile in the ducts interacts with free radicals to form endogenous carcinogens, which has a mutagenic effect on the DNA of cholangiocytes [100, 101]. Eggs can penetrate to the periductal tissues via the ulcerations at the sites of liver fluke sucking and cause there a granulomatous inflammation [93]. The liver fluke excretory and secretory antigens (by themselves or via the interaction with free radicals) initiate cell proliferation during a liver fluke superinvasion [57] and display direct cytotoxic and mutagenic effects [96, 98, 102, 103, 104].
\nHemozoin, a liver fluke pigment, is able to induce a carbonyl (extracellular) stress [105, 106]. A long-term injury of cholangiocytes and a mitogenic effect of growth factors are the cause underlying the complications, such as epithelial hyperplasia, periductal fibrosis, and strictures, and cysts of bile ducts followed by cholestasis, as well as lead to development of cholangiocarcinoma [80, 84, 105, 107, 108].
\nMorphologically, up to 80% of all tumors in opisthorchiasis cases are cholangiocarcinomas [109]. The risk of cholangiocarcinoma development correlates with the duration and intensity of liver fluke invasion [109, 110, 111]. The external factors enhancing cholangiocarcinoma development in opisthorchiasis cases are alcohol (demonstrated for Opisthorchis viverrini) and food nitrosamines (independent risk factor), especially in the endemic regions [98, 112, 113].
\nIn 1970–2005, 1170 patients underwent surgery because of the complications of opisthorchiasis, which accounts for 24.6% of the total opisthorchiasis cases (4756). The patients with cholangiocholecystitis (70.3%), cholecystopancreatitis (18.4%), and hepatocholecystitis (11.3%) received a conservative treatment. A repeated invasion was observable in the overwhelming majority of patients; most of the opisthorchiasis cases (75%) were of the working age with the overall age range of 21–87 years [114].
\nOpisthorchiasis is complicated by liver abscesses, ascending cholangitis, hepatitis, and gastric and duodenal ulcers [115]. Frequently met surgical complications of opisthorchiasis are opisthorchiasis pancreatitis, observed in 16% cases [115]. A dangerous complication of opisthorchiasis cysts in the liver is abscesses and their rupture followed by bile peritonitis [114].
\nThe prevention measures against opisthorchiasis comprise in the following:
\ndetection and treatment of opisthorchiasis cases in the disease focus;
dehelminthization of domestic carnivores; and
protection of water bodies from feces, proper keeping of the areas of settlements, use of sewage containers in river vessels, decontamination of sewage, and prohibition of using the content of outhouse latrines for fertilization of vegetable gardens [63].
The degree of human protection is determined by the level of their knowledge about the measures ensuring the invasion prevention and their sanitary culture [64].
\nThe personal precautions mainly reduce to good cooking practices in fish processing, which ensures fish disinfection [63]. A special attention must be paid to teaching the population to properly process fish at home [64].
\nThe disinfection is attained by thermal treatment, freezing, smoking, and salting [58].
\nThe fishes with a weight of up to 1 kg must be frozen at a temperature of −28°C for 41 h or at −35°C for 10 h. In a household refrigerator, metacercariae retain viability for over 1 month [64].
\nFish (in the case of a large individual, cut into pieces of no more than 2 cm) should be stewed for at least 20 min from the moment of boiling or fried as small flattened pieces (or minced) for 20 min in a large volume of oil. Fish pies must be kept in the oven (200°C) for at least 60 min [63].
\nFish salting requires at least 2 weeks (2 kg salt per 10 kg fish; [64]). Before cold smoking, fish is disinfected by either salting or freezing [63].
\nHot smoking requires a temperature of 70–80°C for 2–2.5 h [64].
\nThe preservation meeting the Codex Alimentarius rules also guarantees safety from the liver fluke metacercariae [58].
\nIt is always necessary to carefully wash your hands and kitchen utensils after processing raw fish [64].
\nIt is strongly recommended to avoid consumption of raw fish, weakly or shortly salted fish, or raw minced fish as well as the frozen fish as stroganina (cut into thin slices), and other local variants of raw frozen fish as well as freshly caught fish in any home-made slightly salted, smoked, or dried variants prepared without observing the described technologies and by unknown persons [63].
\nUnfortunately, insufficient attention has been recently paid to education of population, which naturally resulted in an increase in the number of opisthorchiasis cases [116].
\nThe activity of epizootic process in Western Siberia depends on the parameters of water regime in this territory. The vastness of the Western Siberian floodplains increases from south northward as well as the regular pattern, volume, and duration of spring floods; duration of summer-fall floods in the floodplains; and good water heating [57, 64]. The Western Siberian rivers are rather slow, with a long freeze-up period, preventing aeration, and winter deficiency in oxygen. Poor soil draining and excessive moistening enhance an abundance of water in the region and an increased number of floodplain water bodies, favorable for the development of Bithyniidae mollusk population [57].
\nIn addition, large-scale hydrotechnical engineering activities (construction of channels, cascade artificial water reservoirs, dead dams without byways, and littering of water bodies with household and construction waste) create favorable conditions for mollusk development [57, 64].
\nWater and soil contamination with the liver fluke eggs significantly contribute to sustainable circulation of the opisthorchiasis agent in natural biocenoses; the liver fluke eggs have been detected in 1.13 ± 0.1% of the soil samples, 15.4 ± 0.9% of wastewater and silt samples, and 1.34 ± 0.2% of water from water bodies. The intensity of wastewater and sediment seeding with liver fluke eggs was maximal and varied from 2000 to 4000 eggs/m3; this value for the soil specimens was significantly lower, 0–40 eggs/kg soil. Because of poor disinvasion efficiency, the wastewater discharged into water bodies remains uncontaminated, thereby maintaining the circulation of this pathogen in nature [57, 117].
\nA high level of population infection with opisthorchiasis is aggravated by social factors, namely, a decrease in population living standards and an increase in the share of fish and home-made fish products in the diet of the inhabitants of the cities and villages adjacent to rivers. Population buys fish in shops or unofficial markets or harvests it by themselves. In particular, 52% of opisthorchiasis cases bought the fish in unofficial markets; 34% of them were infected as a result of amateur fishing; and 14.0% received the fish shipped from a northern part of the region [57].
\nThe main risk factors of opisthorchiasis are a high infection rate of the cyprinid fish species and the eating behavior pattern, i.e., prevalence in insufficiently disinfected fish in the common diet; in addition, the cyprinid fish is typically accessible to population, as is demonstrated by all-year-round fishing. In particular, over half (58.36 ± 2.81%) of the questioned subjects were amateur fishermen, and 41.44 ± 3.33% of them have their own fishing gear (nets, dragnets, etc.). This explains why the cohort of fishermen, water transportation workers, amateur fishermen, and their family members form the risk group with the maximum infection rate in the epicenter of the Ob-Irtysh opisthorchiasis focus. In the Khanty-Mansiysk Autonomous Okrug, the opisthorchiasis rate in the most important risk groups—buoy keepers and motor fishing fleet workers with their families—amounts to 75.6 ± 2.7 and 67.8 ± 3.8%, respectively [57]. In the southern part of the focus, the infection rate of the Tobolsk fish processing plant workers was 78 ± 0.3%; of the amateur fishermen in the Tobolsk raion, 36.6 ± 3.2%; and of the persons constantly involved in fishing in the Tyumen raion, 30.8 ± 3.8 and 50.0 ± 8.1% [57].
\nA high risk of opisthorchiasis is characteristic of the socially vulnerable cohorts, which eat the fish products conditionally approved as fit for human consumption, processed and prepared without taking into account the good cooking practice [57, 118, 119, 120]. In many households, weakly salted (in particular, large batches of ungutted fish salted in barrels), undercooked, freshly frozen, and freshly harvested cyprinid fish are the common all-year-round component of their diet. Infection can take place when testing minced fish “for salt” and accidental ingestion of liver fluke larvae from hands or kitchen utensils during fish processing. Children can be infected when cooking fish broth by themselves, making a kind of barbecue, or eating fresh fish [64, 85]. A high invasion rate of the indigenous northern population in Siberia is determined by the local tradition of eating stroganina, sliced frozen raw fish [64].
\nPopulation has little knowledge about the prevention measures. Only 27.93 ± 4.25% of the adult population is aware of the thermal processing practice, and 7.74 ± 1.31% knows the proper rules for fish salting and drying [57]. As has been shown, 89.0% of the opisthorchiasis cases either neglected the good fish cooking and salting practice or do not know them at all, and 1% of the infected subjects consume raw fish (stroganina) [57].
\nThe effect of urbanization on the epidemic process is rather ambiguous [57]. One of the factors of an autogenic impact on the function of parasitic liver fluke system is the migration of population. Migration “supplies” the cohorts with a high risk of infection and poorly or completely unaware of how to prevent the invasion (who eat the improperly cooked fish) to the territories with a high risk of opisthorchiasis. An increase in population enhances the decrease in its morbidity owing to “dilution” of the aboriginal population by a large influx of uninfected newcomers, involved in shift work or expeditions [57].
\nImprovement of the sanitary knowledge owing to development of the medical network and sanitary education activities at the locations of newcomer cohorts decreases the risk for opisthorchiasis [57].
\nLow rates of dehelminthization result in an increase in the number of infection sources. Human pollution of the habitat increases the risk of infection of the population. In particular, 90% of the opisthorchiasis subjects listed for regular medical check-up in the Khanty-Mansiysk Autonomous Okrug ignored the prescribed treatment [31]. In the city of Langepas (Khanty-Mansiysk Autonomous Okrug), the incidence of opisthorchiasis increased 1.2-fold because of the problems with providing the necessary drugs, refuse of the treatment, and ignore the therapy without any particular reason [121].
\nOpisthorchiasis is an anthropozoonous natural focal biohelminthosis caused by trematodes of O. felineus. Invasion has been recorded mainly in the Ob-Irtysh basin since 1891.
\nThe main source of opisthorchiasis caused by O. felineus is a person infected with opisthorchiasis, all fish-eating mammals (dogs, cats, foxes, muskrats, etc.) can also be the final hosts. In addition to human distributing up to 56.6% of invasive material, cats (15.8%), dogs (3.6%), and pigs (up to 0.9%) are assumed to be another source of infection [26]. Intermediate and additional hosts of O. felineus inhabit water bodies, and foci of opisthorchiasis are concentrated near rivers.
\nThe first intermediate host in the focus is freshwater mollusks, subclass Prosobranchiata, family Bithyniidae, genera Codiella and Opisthorchophorus. The mollusk invasion prevalence is very low, whereas the invasion intensity is very high. One mollusk lays up to 8000 cercariae [4, 5, 6, 7].
\nThe second intermediate host is fish of the family Cyprinidae. The prevalence of invasion of fish population ranges from 20 to 100%, while the invasion intensity varies from one to several hundred metacercariae (original data).
\nRussia has the highest incidence of this helminth. Natural foci of opisthorchiasis are located near the rivers Ob, Irtysh, Urals, Volga, Kama, Don, Dnieper, Severnaya Dvina, and Biryusa [32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42]. The world’s largest focus of opisthorchiasis is located in the Ob-Irtysh basin.
\nThe transmission mechanism of the infection fecal-oral route, and the transmission route is food. Infection occurs when a person eats raw or insufficiently thermally processed and freshly salted cyprinid fish, containing live larvae (metacercaria).
\nNatural susceptibility of people to opisthorchiasis is high. The population does not show durable immunity after curing. These helminths have adverse effects on human health, mainly affecting the hepatobiliary system and pancreas. Clinical manifestations of the acute phase of opisthorchiasis last from several days to 4–8 weeks or more, and the phase of chronic opisthorchiasis lasts 15–25 years or more. The duration of the incubation period (in the early phase of the disease) is 2–4 weeks (up to 6 weeks). Allergic reactions, mechanical, and neuroreflex effects of helminths play the main role in the pathogenesis of opisthorchiasis and cause biliary dyskinesia, temporary and complete cessation of bile flow, glandular proliferation in the epithelium of the biliary, and pancreatic ducts and other glandular organs. Pathological processes affect the liver (impaired secretion of enzymes and protein, reduced cholesterol synthesis, and antioxidant function of the liver), pancreas (impaired secretion of enzymes, including insulin), stomach and intestines (erosive gastritis and colitis), and skin (itching, cracks, and psoriasis). Severe complications of opisthorchiasis include biliary peritonitis, liver abscesses, liver cirrhosis, primary liver cancer (less commonly pancreas cancer), acute destructive pancreatitis, bronchial asthma, and diabetes mellitus. Due to the character of infection and a high degree of mutual adaptation of the host and the parasite, opisthorchiasis often proceeds latently (without clinical symptoms).
\nAmong people of various professions, fishermen, river fleet personnel, agricultural workers, and forest industry workers are primarily infected. In endemic areas, opisthorchiasis can be recorded at the age of 1–3 years. The infection rate attains its highest level by 25 years and keeps stable up to 50–60 years. The prevalence among the local population can reach 100% (original data).
\nThe most important prerequisites for an intensive epidemic process in these territories are natural and social factors:
abundance of rivers and lakes rich in fish and mollusks (the highest infection rate among population is recorded in territories with numerous flood meadows and former riverbeds and places where the floodplain is more developed);
hydrotechnical transformations;
intensive contamination of rivers and floodplain lakes by helminths’ eggs from permanent and temporary settlements, cities, etc. located on their banks;
prevalence of insufficiently disinfected fish in the diet and cyprinid fish consumed by the population;
specific ethnic or traditional behavior associated with food and nutrition that determines the nature of distribution and the infection rate among the population in endemic foci;
poor knowledge of preventive measures; and
infection is possible beyond these foci when exporting fish.
Simple personal preventive measures will contribute to prevention of opisthorchiasis.
\nThe optimal natural and climatic conditions together with social and economic factors create the favorable conditions for preservation of the world largest Ob-Irtysh focus of the opisthorchiasis caused by the trematode O. felineus.
\nThe work was supported by the Ministry of Education and Science of the Russian Federation (project no. 6.7525.2017/8.9), program for elevating the competitive ability of Tomsk State University, and Russian Science Foundation.
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