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A fossil (from Classical Latin: fossilis, literally "obtained by digging")^[1] is any preserved remains, impression, or trace of any once-living thing from a past geological age. Examples include bones, shells, exoskeletons, stone imprints of animals or microbes, objects preserved in amber, hair, petrified wood, oil, coal, and DNA remnants. The totality of fossils is known as the fossil record.

Paleontology is the study of fossils: their age, method of formation, and evolutionary significance. Specimens are usually considered to be fossils if they are over 10,000 years old.^[2] The oldest fossils are around 3.48 billion years old^[3][4][5] to 4.1 billion years old.^[6][7] The observation in the 19th century that certain fossils were associated with certain rock strata led to the recognition of a geological timescale and the relative ages of different fossils. The development of radiometric dating techniques in the early 20th century allowed scientists to quantitatively measure the absolute ages of rocks and the fossils they host.

There are many processes that lead to fossilization, including permineralization, casts and molds, authigenic mineralization, replacement and recrystallization, adpression, carbonization, and bioimmuration.

Fossils vary in size from one-micrometre (1 µm) bacteria^[8] to dinosaurs and trees, many meters long and weighing many tons. A fossil normally preserves only a portion of the deceased organism, usually that portion that was partially mineralized during life, such as the bones and teeth of vertebrates, or the chitinous or calcareous exoskeletons of invertebrates. Fossils may also consist of the marks left behind by the organism while it was alive, such as animal tracks or feces (coprolites). These types of fossil are called trace fossils or ichnofossils, as opposed to body fossils. Some fossils are biochemical and are called chemofossils or biosignatures.

Contents

• 1 Fossilization processes
  • 1.1 Permineralization
  • 1.2 Casts and molds
  • 1.3 Authigenic mineralization
  • 1.4 Replacement and recrystallization
  • 1.5 Adpression (compression-impression)
  • 1.6 Soft tissue, cell and molecular preservation
  • 1.7 Carbonization and coalification
  • 1.8 Bioimmuration
• 2 Types
  • 2.1 Index
  • 2.2 Trace
  • 2.3 Transitional
  • 2.4 Microfossils
  • 2.5 Resin
  • 2.6 Derived, or reworked
  • 2.7 Wood
  • 2.8 Subfossil
  • 2.9 Chemical fossils
• 3 Dating
  • 3.1 Estimating dates
  • 3.2 Limitations
• 4 Sites
  • 4.1 Lagerstätten
  • 4.2 Stromatolites
• 5 Astrobiology
• 6 Pseudofossils
• 7 History of the study of fossils
  • 7.1 Ancient civilizations
  • 7.2 Early modern explanations
  • 7.3 Linnaeus and Darwin
  • 7.4 After Darwin
  • 7.5 Modern era
• 8 Trading and collecting
• 9 Fossils as medicine
• 10 Gallery
• 11 See also
• 12 References
• 13 Further reading
• 14 External links

Fossilization processes

The process of fossilization varies according to tissue type and external conditions.

Permineralization

Permineralized bryozoan from the Devonian of Wisconsin.

Permineralization is a process of fossilization that occurs when an organism is buried. The empty spaces within an organism (spaces filled with liquid or gas during life) become filled with mineral-rich groundwater. Minerals precipitate from the groundwater, occupying the empty spaces. This process can occur in very small spaces, such as within the cell wall of a plant cell. Small scale permineralization can produce very detailed fossils.^[9] For permineralization to occur, the organism must become covered by sediment soon after death, otherwise the remains are destroyed by scavengers or decomposition.^[10] The degree to which the remains are decayed when covered determines the later details of the fossil. Some fossils consist only of skeletal remains or teeth; other fossils contain traces of skin, feathers or even soft tissues.^[11] This is a form of diagenesis.

Casts and molds

External mold of a bivalve from the Logan Formation, Lower Carboniferous, Ohio

In some cases, the original remains of the organism completely dissolve or are otherwise destroyed. The remaining organism-shaped hole in the rock is called an external mold. If this hole is later filled with other minerals, it is a cast. An endocast, or internal mold, is formed when sediments or minerals fill the internal cavity of an organism, such as the inside of a bivalve or snail or the hollow of a skull.^[12]

Authigenic mineralization

This is a special form of cast and mold formation. If the chemistry is right, the organism (or fragment of organism) can act as a nucleus for the precipitation of minerals such as siderite, resulting in a nodule forming around it. If this happens rapidly before significant decay to the organic tissue, very fine three-dimensional morphological detail can be preserved. Nodules from the Carboniferous Mazon Creek fossil beds of Illinois, USA, are among the best documented examples of such mineralization.^[13]

Replacement and recrystallization

Silicified (replaced with silica) fossils from the Road Canyon Formation (Middle Permian of Texas)

Recrystallized scleractinian coral (aragonite to calcite) from the Jurassic of southern Israel

Replacement occurs when the shell, bone, or other tissue is replaced with another mineral. In some cases mineral replacement of the original shell occurs so gradually and at such fine scales that microstructural features are preserved despite the total loss of original material. A shell is said to be recrystallized when the original skeletal compounds are still present but in a different crystal form, as from aragonite to calcite.^[14]

Adpression (compression-impression)

Compression fossils, such as those of fossil ferns, are the result of chemical reduction of the complex organic molecules composing the organism's tissues. In this case the fossil consists of original material, albeit in a geochemically altered state. This chemical change is an expression of diagenesis. Often what remains is a carbonaceous film known as a phytoleim, in which case the fossil is known as a compression. Often, however, the phytoleim is lost and all that remains is an impression of the organism in the rock—an impression fossil. In many cases, however, compressions and impressions occur together. For instance, when the rock is broken open, the phytoleim will often be attached to one part (compression), whereas the counterpart will just be an impression. For this reason, one term covers the two modes of preservation: adpression.^[15]

Soft tissue, cell and molecular preservation

Because of their antiquity, an unexpected exception to the alteration of an organism's tissues by chemical reduction of the complex organic molecules during fossilization has been the discovery of soft tissue in dinosaur fossils, including blood vessels, and the isolation of proteins and evidence for DNA fragments.^{[16][17][18][19]} In 2014, Mary Schweitzer and her colleagues reported the presence of iron particles (goethite-aFeO(OH)) associated with soft tissues recovered from dinosaur fossils. Based on various experiments that studied the interaction of iron in haemoglobin with blood vessel tissue they proposed that solution hypoxia coupled with iron chelation enhances the stability and preservation of soft tissue and provides the basis for an explanation for the unforeseen preservation of fossil soft tissues.^[20] However, a slightly older study based on eight taxa ranging in time from the Devonian to the Jurassic found that reasonably well-preserved fibrils that probably represent collagen were preserved in all these fossils and that the quality of preservation depended mostly on the arrangement of the collagen fibers, with tight packing favoring good preservation.^[21] There seemed to be no correlation between geological age and quality of preservation, within that timeframe.

Carbonization and coalification

Fossils that are carbonized or coalified consist of the organic remains which have been reduced primarily to the chemical element carbon. Carbonized fossils consist of a thin film which forms a silhouette of the original organism, and the original organic remains were typically soft tissues. Coalified fossils consist primarily of coal, and the original organic remains were typically woody in composition.

• 

  Carbonized fossil of a possible leech from the Silurian Waukesha Biota of Wisconsin.

• 

  Partially coalified axis (branch) of a lycopod from the Devonian of Wisconsin.

Bioimmuration

The star-shaped holes (Catellocaula vallata) in this Upper Ordovician bryozoan represent a soft-bodied organism preserved by bioimmuration in the bryozoan skeleton.^[22]

Bioimmuration occurs when a skeletal organism overgrows or otherwise subsumes another organism, preserving the latter, or an impression of it, within the skeleton.^[23] Usually it is a sessile skeletal organism, such as a bryozoan or an oyster, which grows along a substrate, covering other sessile sclerobionts. Sometimes the bioimmured organism is soft-bodied and is then preserved in negative relief as a kind of external mold. There are also cases where an organism settles on top of a living skeletal organism that grows upwards, preserving the settler in its skeleton. Bioimmuration is known in the fossil record from the Ordovician^[24] to the Recent.^[23]

Types

Examples of index fossils

Index

Main article: Index fossil

Index fossils (also known as guide fossils, indicator fossils or zone fossils) are fossils used to define and identify geologic periods (or faunal stages). They work on the premise that, although different sediments may look different depending on the conditions under which they were deposited, they may include the remains of the same species of fossil. The shorter the species' time range, the more precisely different sediments can be correlated, and so rapidly evolving species' fossils are particularly valuable. The best index fossils are common, easy to identify at species level and have a broad distribution—otherwise the likelihood of finding and recognizing one in the two sediments is poor.

Trace

Main article: Trace fossil

Trace fossils consist mainly of tracks and burrows, but also include coprolites (fossil feces) and marks left by feeding.^[25][26] Trace fossils are particularly significant because they represent a data source that is not limited to animals with easily fossilized hard parts, and they reflect animal behaviours. Many traces date from significantly earlier than the body fossils of animals that are thought to have been capable of making them.^[27] Whilst exact assignment of trace fossils to their makers is generally impossible, traces may for example provide the earliest physical evidence of the appearance of moderately complex animals (comparable to earthworms).^[26]

Coprolites are classified as trace fossils as opposed to body fossils, as they give evidence for the animal's behaviour (in this case, diet) rather than morphology. They were first described by William Buckland in 1829. Prior to this they were known as "fossil fir cones" and "bezoar stones." They serve a valuable purpose in paleontology because they provide direct evidence of the predation and diet of extinct organisms.^[28] Coprolites may range in size from a few millimetres to over 60 centimetres.

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  Cambrian trace fossils including Rusophycus, made by a trilobite

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  A coprolite of a carnivorous dinosaur found in southwestern Saskatchewan

• 

  Densely packed, subaerial or nearshore trackways (Climactichnites wilsoni) made by a putative, slug-like mollusk on a Cambrian tidal flat

Transitional

A transitional fossil is any fossilized remains of a life form that exhibits traits common to both an ancestral group and its derived descendant group. This is especially important where the descendant group is sharply differentiated by gross anatomy and mode of living from the ancestral group. Because of the incompleteness of the fossil record, there is usually no way to know exactly how close a transitional fossil is to the point of divergence. These fossils serve as a reminder that taxonomic divisions are human constructs that have been imposed in hindsight on a continuum of variation.

Microfossils

Microfossils about 1 mm

Microfossil is a descriptive term applied to fossilized plants and animals whose size is just at or below the level at which the fossil can be analyzed by the naked eye. A commonly applied cutoff point between "micro" and "macro" fossils is 1 mm. Microfossils may either be complete (or near-complete) organisms in themselves (such as the marine plankters foraminifera and coccolithophores) or component parts (such as small teeth or spores) of larger animals or plants. Microfossils are of critical importance as a reservoir of paleoclimate information, and are also commonly used by biostratigraphers to assist in the correlation of rock units.

Resin

The wasp Leptofoenus pittfieldae trapped in Dominican amber, from 20 to 16 million years ago. It is known only from this specimen.

Fossil resin (colloquially called amber) is a natural polymer found in many types of strata throughout the world, even the Arctic. The oldest fossil resin dates to the Triassic, though most dates to the Cenozoic. The excretion of the resin by certain plants is thought to be an evolutionary adaptation for protection from insects and to seal wounds. Fossil resin often contains other fossils called inclusions that were captured by the sticky resin. These include bacteria, fungi, other plants, and animals. Animal inclusions are usually small invertebrates, predominantly arthropods such as insects and spiders, and only extremely rarely a vertebrate such as a small lizard. Preservation of inclusions can be exquisite, including small fragments of DNA.

Derived, or reworked

See also: Zombie taxon

Eroded Jurassic plesiosaur vertebral centrum found in the Lower Cretaceous Faringdon Sponge Gravels in Faringdon, England. An example of a remanié fossil.

A derived, reworked or remanié fossil is a fossil found in rock that accumulated significantly later than when the fossilized animal or plant died. Reworked fossils are created by erosion exhuming (freeing) fossils from the rock formation in which they were originally deposited and their redeposition in a younger sedimentary deposit.

Wood

Petrified wood. The internal structure of the tree and bark are maintained in the permineralization process.

 

Polished section of petrified wood showing annual rings

Fossil wood is wood that is preserved in the fossil record. Wood is usually the part of a plant that is best preserved (and most easily found). Fossil wood may or may not be petrified. The fossil wood may be the only part of the plant that has been preserved: therefore such wood may get a special kind of botanical name. This will usually include "xylon" and a term indicating its presumed affinity, such as Araucarioxylon (wood of Araucaria or some related genus), Palmoxylon (wood of an indeterminate palm), or Castanoxylon (wood of an indeterminate chinkapin).

Subfossil

A subfossil dodo skeleton

The term subfossil can be used to refer to remains, such as bones, nests, or defecations, whose fossilization process is not complete, either because the length of time since the animal involved was living is too short (less than 10,000 years) or because the conditions in which the remains were buried were not optimal for fossilization. Subfossils are often found in caves or other shelters where they can be preserved for thousands of years. The main importance of subfossil vs. fossil remains is that the former contain organic material, which can be used for radiocarbon dating or extraction and sequencing of DNA, protein, or other biomolecules. Additionally, isotope ratios can provide much information about the ecological conditions under which extinct animals lived. Subfossils are useful for studying the evolutionary history of an environment and can be important to studies in paleoclimatology.

Subfossils are often found in depositionary environments, such as lake sediments, oceanic sediments, and soils. Once deposited, physical and chemical weathering can alter the state of preservation.

Chemical fossils

Chemical fossils, or chemofossils, are chemicals found in rocks and fossil fuels (petroleum, coal, and natural gas) that provide an organic signature for ancient life. Molecular fossils and isotope ratios represent two types of chemical fossils. The oldest traces of life on Earth are fossils of this type, including carbon isotope anomalies found in zircons that imply the existence of life as early as 4.1 billion years ago.

Dating

Estimating dates

Paleontology seeks to map out how life evolved across geologic time. A substantial hurdle is the difficulty of working out fossil ages. Beds that preserve fossils typically lack the radioactive elements needed for radiometric dating. This technique is our only means of giving rocks greater than about 50 million years old an absolute age, and can be accurate to within 0.5% or better. Although radiometric dating requires careful laboratory work, its basic principle is simple: the rates at which various radioactive elements decay are known, and so the ratio of the radioactive element to its decay products shows how long ago the radioactive element was incorporated into the rock. Radioactive elements are common only in rocks with a volcanic origin, and so the only fossil-bearing rocks that can be dated radiometrically are volcanic ash layers, which may provide termini for the intervening sediments.

Stratigraphy

Consequently, palaeontologists rely on stratigraphy to date fossils. Stratigraphy is the science of deciphering the "layer-cake" that is the sedimentary record. Rocks normally form relatively horizontal layers, with each layer younger than the one underneath it. If a fossil is found between two layers whose ages are known, the fossil's age is claimed to lie between the two known ages. Because rock sequences are not continuous, but may be broken up by faults or periods of erosion, it is very difficult to match up rock beds that are not directly adjacent. However, fossils of species that survived for a relatively short time can be used to match isolated rocks: this technique is called biostratigraphy. For instance, the conodont Eoplacognathus pseudoplanus has a short range in the Middle Ordovician period. If rocks of unknown age have traces of E. pseudoplanus, they have a mid-Ordovician age. Such index fossils must be distinctive, be globally distributed and occupy a short time range to be useful. Misleading results are produced if the index fossils are incorrectly dated. Stratigraphy and biostratigraphy can in general provide only relative dating (A was before B), which is often sufficient for studying evolution. However, this is difficult for some time periods, because of the problems involved in matching rocks of the same age across continents. Family-tree relationships also help to narrow down the date when lineages first appeared. For instance, if fossils of B or C date to X million years ago and the calculated "family tree" says A was an ancestor of B and C, then A must have evolved earlier.

It is also possible to estimate how long ago two living clades diverged, in other words approximately how long ago their last common ancestor must have lived, by assuming that DNA mutations accumulate at a constant rate. These "molecular clocks", however, are fallible, and provide only approximate timing: for example, they are not sufficiently precise and reliable for estimating when the groups that feature in the Cambrian explosion first evolved, and estimates produced by different techniques may vary by a factor of two.

Limitations

Some of the most remarkable gaps in the fossil record (as of October 2013) show slanting toward organisms with hard parts.

Organisms are only rarely preserved as fossils in the best of circumstances, and only a fraction of such fossils have been discovered. This is illustrated by the fact that the number of species known through the fossil record is less than 5% of the number of known living species, suggesting that the number of species known through fossils must be far less than 1% of all the species that have ever lived. Because of the specialized and rare circumstances required for a biological structure to fossilize, only a small percentage of life-forms can be expected to be represented in discoveries, and each discovery represents only a snapshot of the process of evolution. The transition itself can only be illustrated and corroborated by transitional fossils, which will never demonstrate an exact half-way point.

The fossil record is strongly biased toward organisms with hard-parts, leaving most groups of soft-bodied organisms with little to no role. It is replete with the mollusks, the vertebrates, the echinoderms, the brachiopods and some groups of arthropods.

Sites

Lagerstätten

Fossil sites with exceptional preservation—sometimes including preserved soft tissues—are known as Lagerstätten—German for "storage places". These formations may have resulted from carcass burial in an anoxic environment with minimal bacteria, thus slowing decomposition. Lagerstätten span geological time from the Cambrian period to the present. Worldwide, some of the best examples of near-perfect fossilization are the Cambrian Maotianshan shales and Burgess Shale, the Devonian Hunsrück Slates, the Jurassic Solnhofen limestone, and the Carboniferous Mazon Creek localities.

Stromatolites

Lower Proterozoic stromatolites from Bolivia, South America

Stromatolites are layered accretionary structures formed in shallow water by the trapping, binding and cementation of sedimentary grains by biofilms of microorganisms, especially cyanobacteria. Stromatolites provide some of the most ancient fossil records of life on Earth, dating back more than 3.5 billion years ago.

Stromatolites were much more abundant in Precambrian times. While older, Archean fossil remains are presumed to be colonies of cyanobacteria, younger (that is, Proterozoic) fossils may be primordial forms of the eukaryote chlorophytes (that is, green algae). One genus of stromatolite very common in the geologic record is Collenia. The earliest stromatolite of confirmed microbial origin dates to 2.724 billion years ago.

A 2009 discovery provides strong evidence of microbial stromatolites extending as far back as 3.45 billion years ago.

Stromatolites are a major constituent of the fossil record for life's first 3.5 billion years, peaking about 1.25 billion years ago. They subsequently declined in abundance and diversity, which by the start of the Cambrian had fallen to 20% of their peak. The most widely supported explanation is that stromatolite builders fell victims to grazing creatures (the Cambrian substrate revolution), implying that sufficiently complex organisms were common over 1 billion years ago.

The connection between grazer and stromatolite abundance is well documented in the younger Ordovician evolutionary radiation; stromatolite abundance also increased after the end-Ordovician and end-Permian extinctions decimated marine animals, falling back to earlier levels as marine animals recovered. Fluctuations in metazoan population and diversity may not have been the only factor in the reduction in stromatolite abundance. Factors such as the chemistry of the environment may have been responsible for changes.

While prokaryotic cyanobacteria themselves reproduce asexually through cell division, they were instrumental in priming the environment for the evolutionary development of more complex eukaryotic organisms. Cyanobacteria (as well as extremophile Gammaproteobacteria) are thought to be largely responsible for increasing the amount of oxygen in the primeval earth's atmosphere through their continuing photosynthesis. Cyanobacteria use water, carbon dioxide and sunlight to create their food. A layer of mucus often forms over mats of cyanobacterial cells. In modern microbial mats, debris from the surrounding habitat can become trapped within the mucus, which can be cemented by the calcium carbonate to grow thin laminations of limestone. These laminations can accrete over time, resulting in the banded pattern common to stromatolites. The domal morphology of biological stromatolites is the result of the vertical growth necessary for the continued infiltration of sunlight to the organisms for photosynthesis. Layered spherical growth structures termed oncolites are similar to stromatolites and are also known from the fossil record. Thrombolites are poorly laminated or non-laminated clotted structures formed by cyanobacteria common in the fossil record and in modern sediments.

The Zebra River Canyon area of the Kubis platform in the deeply dissected Zaris Mountains of southwestern Namibia provides an extremely well exposed example of the thrombolite-stromatolite-metazoan reefs that developed during the Proterozoic period, the stromatolites here being better developed in updip locations under conditions of higher current velocities and greater sediment influx.

Astrobiology

It has been suggested that biominerals could be important indicators of extraterrestrial life and thus could play an important role in the search for past or present life on the planet Mars. Furthermore, organic components (biosignatures) that are often associated with biominerals are believed to play crucial roles in both pre-biotic and biotic reactions.

On 24 January 2014, NASA reported that current studies by the Curiosity and Opportunity rovers on Mars will now be searching for evidence of ancient life, including a biosphere based on autotrophic, chemotrophic and/or chemolithoautotrophic microorganisms, as well as ancient water, including fluvio-lacustrine environments (plains related to ancient rivers or lakes) that may have been habitable.  The search for evidence of habitability, taphonomy (related to fossils), and organic carbon on the planet Mars is now a primary NASA objective.

Pseudofossils

Pseudofossils are visual patterns in rocks that are produced by geologic processes rather than biologic processes. They can easily be mistaken for real fossils. Some pseudofossils, such as geological dendrite crystals, are formed by naturally occurring fissures in the rock that get filled up by percolating minerals. Other types of pseudofossils are kidney ore (round shapes in iron ore) and moss agates, which look like moss or plant leaves. Concretions, spherical or ovoid-shaped nodules found in some sedimentary strata, were once thought to be dinosaur eggs, and are often mistaken for fossils as well.

History of the study of fossils

Gathering fossils dates at least to the beginning of recorded history. The fossils themselves are referred to as the fossil record. The fossil record was one of the early sources of data underlying the study of evolution and continues to be relevant to the history of life on Earth.  examine the fossil record to understand the process of evolution and the way particular species have evolved.

Ancient civilizations

Fossils have been visible and common throughout most of natural history, and so documented human interaction with them goes back as far as recorded history, or earlier.

There are many examples of paleolithic stone knives in Europe, with fossil echinoderms set precisely at the hand grip, going all the way back to Homo heidelbergensis and neanderthals. These ancient peoples also drilled holes through the center of those round fossil shells, apparently using them as beads for necklaces.

The ancient Egyptians gathered fossils of species that resembled the bones of modern species they worshipped. The god was associated with the hippopotamus, therefore fossilized bones of hippo-like species were kept in that deity's temples. Five-rayed fossil sea urchin shells were associated with the deity Sopdu, the Morning Star, equivalent of Venus in Roman mythology.

Ceratopsian skulls are common in the Dzungarian Gate mountain pass in Asia, an area once famous for gold mines, as well as its endlessly cold winds. This has been attributed to legends of both gryphons and the land of Hyperborea

Fossils appear to have directly contributed to the mythology of many civilizations, including the ancient Greeks. Classical Greek historian Herodotos wrote of an area near Hyperborea where gryphons protected golden treasure. There was indeed gold mining in that approximate region, where beaked Protoceratops skulls were common as fossils.

A later Greek scholar, Aristotle, eventually realized that fossil seashells from rocks were similar to those found on the beach, indicating the fossils were once living animals. He had previously explained them in terms of vaporous exhalations, which Persian polymath Avicenna modified into the theory of petrifying fluids (succus lapidificatus). Recognition of fossil seashells as originating in the sea was built upon in the 14th century by Albert of Saxony, and accepted in some form by most naturalists by the 16th century.

Roman naturalist Pliny the Elder wrote of "tongue stones", which he called glossopetra. These were fossil shark teeth, thought by some classical cultures to look like the tongues of people or snakes. He also wrote about the horns of Ammon, which are fossil ammonites, from whence the group of shelled octopus-cousins ultimately draws its modern name. Pliny also makes one of the earlier known references to toadstones, thought until the 18th century to be a magical cure for poison originating in the heads of toads, but which are fossil teeth from Lepidotes, a Cretaceous ray-finned fish.

The Plains tribes of North America are thought to have similarly associated fossils, such as the many intact pterosaur fossils naturally exposed in the region, with their own mythology of the thunderbird.

There is no such direct mythological connection known from prehistoric Africa, but there is considerable evidence of tribes there excavating and moving fossils to ceremonial sites, apparently treating them with some reverence.

In Japan, fossil shark teeth were associated with the mythical tengu, thought to be the razor-sharp claws of the creature, documented some time after the 8th century AD.

In medieval China, the fossil bones of ancient mammals including Homo erectus were often mistaken for "dragon bones" and used as medicine and aphrodisiacs. In addition, some of these fossil bones are collected as "art" by scholars, who left scripts on various artifacts, indicating the time they were added to a collection. One good example is the famous scholar Huang Tingjian of the South Song Dynasty during the 11th century, who kept a specific seashell fossil with his own poem engraved on it. In the West fossilized sea creatures on mountainsides were seen as proof of the biblical deluge.

In 1027, the Persian Avicenna explained fossils' stoniness in The Book of Healing:

If what is said concerning the petrifaction of animals and plants is true, the cause of this (phenomenon) is a powerful mineralizing and petrifying virtue which arises in certain stony spots, or emanates suddenly from the earth during earthquake and subsidences, and petrifies whatever comes into contact with it. As a matter of fact, the petrifaction of the bodies of plants and animals is not more extraordinary than the transformation of waters.

From the 13th century to the present day, scholars pointed out that the fossil skulls of Deinotherium giganteum, found in Crete and Greece, might have been interpreted as being the skulls of the Cyclopes of Greek mythology, and are possibly the origin of that Greek myth. Their skulls appear to have a single eye-hole in the front, just like their modern elephant cousins, though in fact it's actually the opening for their trunk.

Fossil shells from the cretaceous era sea urchin, Micraster, were used in medieval times as both shepherd's crowns to protect houses, and as painted fairy loaves by bakers to bring luck to their bread-making.

In Norse mythology, echinoderm shells (the round five-part button left over from a sea urchin) were associated with the god Thor, not only being incorporated in thunderstones, representations of Thor's hammer and subsequent hammer-shaped crosses as Christianity was adopted, but also kept in houses to garner Thor's protection.

These grew into the shepherd's crowns of English folklore, used for decoration and as good luck charms, placed by the doorway of homes and churches. In Suffolk, a different species was used as a good-luck charm by bakers, who referred to them as fairy loaves, associating them with the similarly shaped loaves of bread they baked.

Early modern explanations

More scientific views of fossils emerged during the Renaissance. Leonardo da Vinci concurred with Aristotle's view that fossils were the remains of ancient life. For example, da Vinci noticed discrepancies with the biblical flood narrative as an explanation for fossil origins:

If the Deluge had carried the shells for distances of three and four hundred miles from the sea it would have carried them mixed with various other natural objects all heaped up together; but even at such distances from the sea we see the oysters all together and also the shellfish and the cuttlefish and all the other shells which congregate together, found all together dead; and the solitary shells are found apart from one another as we see them every day on the sea-shores.

And we find oysters together in very large families, among which some may be seen with their shells still joined together, indicating that they were left there by the sea and that they were still living when the strait of Gibraltar was cut through. In the mountains of Parma and Piacenza multitudes of shells and corals with holes may be seen still sticking to the rocks...."

Ichthyosaurus and Plesiosaurus from the 1834 Czech edition of Cuvier's Discours sur les revolutions de la surface du globe

In 1666, Nicholas Steno examined a shark, and made the association of its teeth with the "tongue stones" of ancient Greco-Roman mythology, concluding that those were not in fact the tongues of venomous snakes, but the teeth of some long-extinct species of shark.

Robert Hooke (1635-1703) included micrographs of fossils in his Micrographia and was among the first to observe fossil forams. His observations on fossils, which he stated to be the petrified remains of creatures some of which no longer existed, were published posthumously in 1705.

William Smith (1769–1839), an English canal engineer, observed that rocks of different ages (based on the law of superposition) preserved different assemblages of fossils, and that these assemblages succeeded one another in a regular and determinable order. He observed that rocks from distant locations could be correlated based on the fossils they contained. He termed this the principle of faunal succession. This principle became one of Darwin's chief pieces of evidence that biological evolution was real.

Georges Cuvier came to believe that most if not all the animal fossils he examined were remains of extinct species. This led Cuvier to become an active proponent of the geological school of thought called catastrophism. Near the end of his 1796 paper on living and fossil elephants he said:

All of these facts, consistent among themselves, and not opposed by any report, seem to me to prove the existence of a world previous to ours, destroyed by some kind of catastrophe.

Interest in fossils, and geology more generally, expanded during the early nineteenth century. In Britain, Mary Anning's discoveries of fossils, including the first complete ichthyosaur and a complete plesiosaurus skeleton, sparked both public and scholarly interest.

Linnaeus and Darwin

Early naturalists well understood the similarities and differences of living species leading Linnaeus to develop a hierarchical classification system still in use today. Darwin and his contemporaries first linked the hierarchical structure of the tree of life with the then very sparse fossil record. Darwin eloquently described a process of descent with modification, or evolution, whereby organisms either adapt to natural and changing environmental pressures, or they perish.

When Darwin wrote On the Origin of Species by Means of Natural Selection, or the Preservation of Favoured Races in the Struggle for Life, the oldest animal fossils were those from the Cambrian Period, now known to be about 540 million years old. He worried about the absence of older fossils because of the implications on the validity of his theories, but he expressed hope that such fossils would be found, noting that: "only a small portion of the world is known with accuracy." Darwin also pondered the sudden appearance of many groups (i.e. phyla) in the oldest known Cambrian fossiliferous strata.

After Darwin

Since Darwin's time, the fossil record has been extended to between 2.3 and 3.5 billion years. Most of these Precambrian fossils are microscopic bacteria or microfossils. However, macroscopic fossils are now known from the late Proterozoic. The Ediacara biota (also called Vendian biota) dating from 575 million years ago collectively constitutes a richly diverse assembly of early multicellular eukaryotes.

The fossil record and faunal succession form the basis of the science of biostratigraphy or determining the age of rocks based on embedded fossils. For the first 150 years of geology, biostratigraphy and superposition were the only means for determining the relative age of rocks. The geologic time scale was developed based on the relative ages of rock strata as determined by the early paleontologists and stratigraphers.

Since the early years of the twentieth century, absolute dating methods, such as radiometric dating (including potassium/argon, argon/argon, uranium series, and, for very recent fossils, radiocarbon dating) have been used to verify the relative ages obtained by fossils and to provide absolute ages for many fossils. Radiometric dating has shown that the earliest known stromatolites are over 3.4 billion years old.

Modern era

The fossil record is life's evolutionary epic that unfolded over four billion years as environmental conditions and genetic potential interacted in accordance with natural selection.

The Virtual Fossil Museum

Paleontology has joined with evolutionary biology to share the interdisciplinary task of outlining the tree of life, which inevitably leads backwards in time to Precambrian microscopic life when cell structure and functions evolved. Earth's deep time in the Proterozoic and deeper still in the Archean is only "recounted by microscopic fossils and subtle chemical signals." Molecular biologists, using phylogenetics, can compare protein amino acid or nucleotide sequence homology (i.e., similarity) to evaluate taxonomy and evolutionary distances among organisms, with limited statistical confidence. The study of fossils, on the other hand, can more specifically pinpoint when and in what organism a mutation first appeared. Phylogenetics and paleontology work together in the clarification of science's still dim view of the appearance of life and its evolution.

Phacopid trilobite Eldredgeops rana crassituberculata. The genus is named after Niles Eldredge.

 

Crinoid columnals (Isocrinus nicoleti) from the Middle Jurassic Carmel Formation at Mount Carmel Junction, Utah

Niles Eldredge's study of the Phacops trilobite genus supported the hypothesis that modifications to the arrangement of the trilobite's eye lenses proceeded by fits and starts over millions of years during the Devonian. Eldredge's interpretation of the Phacops fossil record was that the aftermaths of the lens changes, but not the rapidly occurring evolutionary process, were fossilized. This and other data led Stephen Jay Gould and Niles Eldredge to publish their seminal paper on punctuated equilibrium in 1971.

Synchrotron X-ray tomographic analysis of early Cambrian bilaterian embryonic microfossils yielded new insights of metazoan evolution at its earliest stages. The tomography technique provides previously unattainable three-dimensional resolution at the limits of fossilization. Fossils of two enigmatic bilaterians, the worm-like Markuelia and a putative, primitive protostome, Pseudooides, provide a peek at germ layer embryonic development. These 543-million-year-old embryos support the emergence of some aspects of arthropod development earlier than previously thought in the late Proterozoic. The preserved embryos from China and Siberia underwent rapid diagenetic phosphatization resulting in exquisite preservation, including cell structures. This research is a notable example of how knowledge encoded by the fossil record continues to contribute otherwise unattainable information on the emergence and development of life on Earth. For example, the research suggests Markuelia has closest affinity to priapulid worms, and is adjacent to the evolutionary branching of Priapulida, Nematoda and Arthropoda.

Trading and collecting

Fossil trading is the practice of buying and selling fossils. This is many times done illegally with artifacts stolen from research sites, costing many important scientific specimens each year. The problem is quite pronounced in China, where many specimens have been stolen.

Fossil collecting (sometimes, in a non-scientific sense, fossil hunting) is the collection of fossils for scientific study, hobby, or profit. Fossil collecting, as practiced by amateurs, is the predecessor of modern paleontology and many still collect fossils and study fossils as amateurs. Professionals and amateurs alike collect fossils for their scientific value.

Fossils as medicine

Chagas disease
Other names	American trypanosomiasis
Photomicrograph of Giemsa-stained Trypanosoma cruzi
Pronunciation	/ˈtʃɑːɡəs/, Portuguese pronunciation: [ˈʃaɡɐs]
Specialty	Infectious disease
Symptoms	Fever, large lymph nodes, headache
Complications	Heart failure, enlarged esophagus, enlarged colon
Causes	Trypanosoma cruzi spread by kissing bugs
Diagnostic method	Finding the parasite, its DNA, or antibodies in the blood
Prevention	Eliminating kissing bugs and avoiding their bites
Medication	Benznidazole, nifurtimox
Frequency	6.2 million (2017)
Deaths	7,900 (2017)

Chagas disease, also known as American trypanosomiasis, is a tropical parasitic disease caused by Trypanosoma cruzi. It is spread mostly by b-y insects known as Triatominae, or "kissing bugs". The symptoms change over the course of the infection. In the early stage, symptoms are typically either not present or mild, and may include fever, swollen lymph nodes, headaches, or swelling at the site of the bite. After four to eight weeks, untreated individuals enter the chronic phase of disease, which in most cases does not result in further symptoms. Up to 45% of people with chronic infection develop heart disease 10–30 years after the initial illness, which can lead to heart failure. Digestive complications, including an enlarged esophagus or an enlarged colon, may also occur in up to 21% of people, and up to 10% of people may experience nerve damage.

T. cruzi is commonly spread to humans and other mammals by the bite of a kissing bug. The disease may also be spread through blood transfusion, organ transplantation, eating food contaminated with the parasites, and vertical transmission (from a mother to her baby). Diagnosis of early disease is by finding the parasite in the blood using a microscope or detecting its DNA by polymerase chain reaction. Chronic disease is diagnosed by finding antibodies for T. cruzi in the blood. It affects more than 150 types of animals.

Prevention focuses on eliminating kissing bugs and avoiding their bites. This may involve the use of insecticides or bed-nets. Other preventive efforts include screening blood used for transfusions. As of 2019, a vaccine has not been developed. Early infections are treatable with the medications benznidazole or nifurtimox, which usually cure the disease if given shortly after the person is infected, but become less effective the longer a person has had Chagas disease. When used in chronic disease, medication may delay or prevent the development of end–stage symptoms. Benznidazole and nifurtimox often cause side effects, including skin disorders, digestive system irritation, and neurological symptoms, which can result in treatment being discontinued. As of 2019, new drugs for Chagas disease are under development, and experimental vaccines have been studied in animal models.

It is estimated that 6.2 million people, mostly in Mexico, Central America and South America, have Chagas disease as of 2017, resulting in an estimated 7,900 deaths. Most people with the disease are poor, and most do not realize they are infected. Large-scale population migrations have carried Chagas disease to new regions, which now include the United States and many European countries.

The disease was first described in 1909 by Brazilian physician Carlos Chagas, after whom it is named. Chagas disease is classified as a neglected tropical disease.

Signs and symptoms

An acute Chagas disease infection with swelling of the right eye (Romaña's sign)

Chagas disease occurs in two stages: an acute stage, which develops one to two weeks after the insect bite, and a chronic stage, which develops over many years. The acute stage is often symptom-free. When present, the symptoms are typically minor and not specific to any particular disease. Signs and symptoms include fever, malaise, headache, and enlargement of the liver, spleen, and lymph nodes. Rarely, people develop a swollen nodule at the site of infection, which is called "Romaña's sign" if it is on the eyelid, or a "chagoma" if it is elsewhere on the skin. In rare cases (less than 1–5%), infected individuals develop severe acute disease, which can cause life-threatening fluid accumulation around the heart, or inflammation of the heart or brain and surrounding tissues. The acute phase typically lasts four to eight weeks and resolves without treatment.

Unless treated with antiparasitic drugs, individuals remain chronically infected with T. cruzi after recovering from the acute phase. Most chronic infections are asymptomatic, which is referred to as indeterminate chronic Chagas disease. However, over decades with chronic Chagas disease, 30–40% of people develop organ dysfunction (determinate chronic Chagas disease), which most often affects the heart or digestive system.

The most common manifestation is heart disease, which occurs in 14–45% of people with chronic Chagas disease. People with Chagas heart disease often experience heart palpitations and sometimes fainting due to irregular heart function. By electrocardiogram, people with Chagas heart disease most frequently have arrhythmias. As the disease progresses, the heart's ventricles become enlarged (dilated cardiomyopathy), which reduces its ability to pump blood. In many cases the first sign of Chagas heart disease is heart failure, thromboembolism, or chest pain associated with abnormalities in the microvasculature.

Also common in chronic Chagas disease is damage to the digestive system, particularly enlargement of the esophagus or colon, which affects 10–21% of people. Those with enlarged esophagus often experience pain (odynophagia) or trouble swallowing (dysphagia), acid reflux, cough, and weight loss. Individuals with enlarged colon often experience constipation, which can lead to severe blockage of the intestine or its blood supply. Up to 10% of chronically infected individuals develop nerve damage that can result in numbness and altered reflexes or movement. While chronic disease typically develops over decades, some individuals with Chagas disease (less than 10%) progress to heart damage directly after acute disease.

Signs and symptoms differ for people infected with T. cruzi through less common routes. People infected through ingestion of parasites tend to develop severe disease within three weeks of consumption, with symptoms including fever, vomiting, shortness of breath, cough, and pain in the chest, abdomen, and muscles. Those infected congenitally typically have few to no symptoms, but can have mild non-specific symptoms, or severe symptoms such as jaundice, respiratory distress, and heart problems. People infected through organ transplant or blood transfusion tend to have symptoms similar to those of vector-borne disease, but the symptoms may not manifest for anywhere from a week to five months. Chronically infected individuals who become immunosuppressed due to HIV infection can suffer particularly severe and distinct disease, most commonly characterized by inflammation in the brain and surrounding tissue or brain abscesses. Symptoms vary widely based on the size and location of brain abscesses, but typically include fever, headaches, seizures, loss of sensation, or other neurological issues that indicate particular sites of nervous system damage. Occasionally, these individuals also experience acute heart inflammation, skin lesions, and disease of the stomach, intestine, or peritoneum.

Cause

Life cycle and transmission of T. cruzi

Chagas disease is caused by infection with the protozoan parasite T. cruzi, which is typically introduced into humans through the bite of triatomine bugs, also called "kissing bugs". At the bite site, motile T. cruzi forms called trypomastigotes invade various host cells. Inside a host cell, the parasite transforms into a replicative form called an amastigote, which undergoes several rounds of replication. The replicated amastigotes transform back into trypomastigotes, which burst the host cell and are released into the bloodstream. Trypomastigotes then disseminate throughout the body to various tissues, where they invade cells and replicate. Over many years, cycles of parasite replication and immune response can severely damage these tissues, particularly the heart and digestive tract.

Transmission

Triatoma infestans, a common vector of T. cruzi

T. cruzi can be transmitted by various triatomine bugs in the genera Triatoma, Panstrongylus, and Rhodnius. The primary vectors for human infection are the species of triatomine bugs that inhabit human dwellings, namely Triatoma infestans, Rhodnius prolixus, Triatoma dimidiata and Panstrongylus megistus. These insects are known by a number of local names, including vinchuca in Argentina, Bolivia, Chile and Paraguay, barbeiro (the barber) in Brazil, pito in Colombia, chinche in Central America, and chipo in Venezuela. The bugs tend to feed at night, preferring moist surfaces near the eyes or mouth. A triatomine bug can become infected with T. cruzi when it feeds on an infected host. T. cruzi replicates in the insect's intestinal tract and is shed in the bug's feces. When an infected triatomine feeds, it pierces the skin and takes in a blood meal, defecating at the same time to make room for the new meal. The bite is typically painless, but causes itching. Scratching at the bite introduces the T. cruzi-laden feces into the bite wound, initiating infection.

In addition to classical vector spread, Chagas disease can be transmitted through food or drink contaminated with triatomine insects or their feces. Since heating or drying kills the parasites, drinks and especially fruit juices are the most frequent source of infection. This route of transmission has been implicated in several outbreaks, where it led to unusually severe symptoms, likely due to infection with a higher parasite load than from the bite of a triatomine bug.

T. cruzi can also be transmitted independent of the triatomine bug during blood transfusion, following organ transplantation, or across the placenta during pregnancy. Transfusion with the blood of an infected donor infects the recipient 10–25% of the time. To prevent this, blood donations are screened for T. cruzi in many countries with endemic Chagas disease, as well as the United States. Similarly, transplantation of solid organs from an infected donor can transmit T. cruzi to the recipient. This is especially true for heart transplant, which transmits T. cruzi 75–100% of the time, and less so for transplantation of the liver (0–29%) or a kidney (0–19%). An infected mother can also pass T. cruzi to her child through the placenta; this occurs in up to 15% of births by infected mothers. As of 2019, 22.5% of new infections occurred through congenital transmission.

Pathophysiology

Large scale anatomy of a heart damaged by chronic Chagas disease

In the acute phase of the disease, signs and symptoms are caused directly by the replication of T. cruzi and the immune system's response to it. During this phase, T. cruzi can be found in various tissues throughout the body and circulating in the blood. During the initial weeks of infection, parasite replication is brought under control by production of antibodies and activation of the host's inflammatory response, particularly cells that target intracellular pathogens such as NK cells and macrophages, driven by inflammation-signaling molecules like TNF-α and IFN-γ.

During chronic Chagas disease, long-term organ damage develops over years due to continued replication of the parasite and damage from the immune system. Early in the course of the disease, T. cruzi is found frequently in the striated muscle fibers of the heart. As disease progresses, the heart becomes generally enlarged, with substantial regions of cardiac muscle fiber replaced by scar tissue and fat. Areas of active inflammation are scattered throughout the heart, with each housing inflammatory immune cells, typically macrophages and T cells. Late in the disease, parasites are rarely detected in the heart, and may be present at only very low levels.

In the heart, colon, and esophagus, chronic disease also leads to a massive loss of nerve endings. In the heart, this may contribute to arrythmias and other cardiac dysfunction. In the colon and esophagus, loss of nervous system control is the major driver of organ dysfunction. Loss of nerves impairs the movement of food through the digestive tract, which can lead to blockage of the esophagus or colon and restriction of their blood supply.

Diagnosis

T. cruzi trypomastigotes seen in a blood smear

The presence of T. cruzi is diagnostic of Chagas disease. During the acute phase of infection, it can be detected by microscopic examination of fresh anticoagulated blood, or its buffy coat, for motile parasites; or by preparation of thin and thick blood smears stained with Giemsa, for direct visualization of parasites. Blood smear examination detects parasites in 34–85% of cases. Techniques such as microhematocrit centrifugation can be used to concentrate the blood, which makes the test more sensitive. On microscopic examination, T. cruzi trypomastigotes have a slender body, often in the shape of an S or U, with a flagellum connected to the body by an undulating membrane.

Alternatively, T. cruzi DNA can be detected by polymerase chain reaction (PCR). In acute and congenital Chagas disease, PCR is more sensitive than microscopy, and it is more reliable than antibody-based tests for the diagnosis of congenital disease because it is not affected by transfer of antibodies against T. cruzi from a mother to her baby (passive immunity). PCR is also used to monitor T. cruzi levels in organ transplant recipients and immunosuppressed people, which allows infection or reactivation to be detected at an early stage.

During the chronic phase, microscopic diagnosis is unreliable and PCR is less sensitive because the level of parasites in the blood is low. Chronic Chagas disease is usually diagnosed using serological tests, which detect immunoglobulin G antibodies against T. cruzi in the person's blood. The most common test methodologies are ELISA, indirect immunofluorescence, and indirect hemagglutination. Two positive serology results, using different test methods, are required to confirm the diagnosis. If the test results are inconclusive, additional testing methods such as Western blot can be used. T. cruzi antigens may also be detected in tissue samples using immunohistochemistry techniques.

Various rapid diagnostic tests for Chagas disease are available. These tests are easily transported and can be performed by people without special training. They are useful for screening large numbers of people and testing people who cannot access healthcare facilities, but their sensitivity is relatively low, and it is recommended that a second method is used to confirm a positive result.

T. cruzi can be isolated from samples through blood culture or xenodiagnosis, or by inoculating animals with the person's blood. In the blood culture method, the person's red blood cells are separated from the plasma and added to a specialized growth medium to encourage multiplication of the parasite. It can take up to six months to obtain the result. Xenodiagnosis involves feeding the person's blood to triatomine insects, then examining their feces for the parasite 30 to 60 days later. These methods are not routinely used, as they are slow and have low sensitivity.

Prevention

Bed nets can be used in endemic areas to prevent bites from triatomine bugs.

Efforts to prevent Chagas disease have largely focused on vector control to limit exposure to triatomine bugs. Insecticide-spraying programs have been the mainstay of vector control, consisting of spraying homes and the surrounding areas with residual insecticides. This was originally done with organochlorine, organophosphate, and carbamate insecticides, which were supplanted in the 1980s with pyrethroids. These programs have drastically reduced transmission in Brazil and Chile, and eliminated major vectors from certain regions: Triatoma infestans from Brazil, Chile, Uruguay, and parts of Peru and Paraguay, as well as Rhodnius prolixus from Central America. Vector control in some regions has been hindered by the development of insecticide resistance among triatomine bugs. In response, vector control programs have implemented alternative insecticides (e.g. fenitrothion and bendiocarb in Argentina and Bolivia), treatment of domesticated animals (which are also fed on by triatomine bugs) with pesticides, pesticide-impregnated paints, and other experimental approaches. In areas with triatomine bugs, transmission of T. cruzi can be prevented by sleeping under bed nets and by housing improvements that prevent triatomine bugs from colonizing houses.

Blood transfusion was formerly the second-most common mode of transmission for Chagas disease. T. cruzi can survive in refrigerated stored blood, and can survive freezing and thawing, allowing it to persist in whole blood, packed red blood cells, granulocytes, cryoprecipitate, and platelets. The development and implementation of blood bank screening tests has dramatically reduced the risk of infection during blood transfusion. Nearly all blood donations in Latin American countries undergo Chagas screening. Widespread screening is also common in non-endemic nations with significant populations of immigrants from endemic areas including the United Kingdom (implemented in 1999), Spain (2005), the United States (2007), France and Sweden (2009), Switzerland (2012), and Belgium (2013). Blood is tested using serological tests, typically ELISAs, to detect antibodies against T. cruzi proteins.

Other modes of transmission have also been targeted by Chagas disease prevention programs. Treating T. cruzi-infected mothers during pregnancy reduces the risk of congenital transmission of the infection. To this end, many countries in Latin America have implemented routine screening of pregnant women and infants for T. cruzi infection, and the World Health Organization recommends screening all children born to infected mothers to prevent congenital infection from developing into chronic disease. Similarly to blood transfusions, many countries with endemic Chagas disease screen organs for transplantation with serological tests.

There is no vaccine against Chagas disease. Several experimental vaccines have been tested in animals infected with T. cruzi and were able to reduce parasite numbers in the blood and heart, but no vaccine candidates had undergone clinical trials in humans as of 2016.

Management

A bottle of nifurtimox tablets

Chagas disease is managed using antiparasitic drugs to eliminate T. cruzi from the body and symptomatic treatment to address the effects of the infection. As of 2018, benznidazole and nifurtimox were the antiparasitic drugs of choice for treating Chagas disease, though benznidazole is the only drug available in most of Latin America. For either drug, treatment typically consists of two to three oral doses per day for 60 to 90 days. Antiparasitic treatment is most effective early in the course of infection: it eliminates T. cruzi from 50 to 80% of people in the acute phase, but only 20–60% of those in the chronic phase. Treatment of chronic disease is more effective in children than in adults, and the cure rate for congenital disease approaches 100% if treated in the first year of life. Antiparasitic treatment can also slow the progression of the disease and reduce the possibility of congenital transmission. Elimination of T. cruzi does not cure the cardiac and gastrointestinal damage caused by chronic Chagas disease, so these conditions must be treated separately. Antiparasitic treatment is not recommended for people who have already developed dilated cardiomyopathy.

Benznidazole is usually considered the first-line treatment because it has milder adverse effects than nifurtimox and its efficacy is better understood. Both benznidazole and nifurtimox have common side effects that can result in treatment being discontinued. The most common side effects of benznidazole are skin rash, digestive problems, decreased appetite, weakness, headache, and sleeping problems. These side effects can sometimes be treated with antihistamines or corticosteroids, and are generally reversed when treatment is stopped. However, benzidazole is discontinued in up to 29% of cases. Nifurtimox has more frequent side effects, affecting up to 97.5% of individuals taking the drug. The most common side effects are loss of appetite, weight loss, nausea and vomiting, and various neurological disorders including mood changes, insomnia, paresthesia and peripheral neuropathy. Treatment is discontinued in up to 75% of cases. Both drugs are contraindicated for use in pregnant women and people with liver or kidney failure. As of 2019, resistance to these drugs has been reported.

Complications

In the chronic stage, treatment involves managing the clinical manifestations of the disease. The treatment of Chagas cardiomyopathy is similar to that of other forms of heart disease. Beta blockers and ACE inhibitors may be prescribed, but some people with Chagas disease may not be able to take the standard dose of these drugs because they have low blood pressure or a low heart rate. To manage irregular heartbeats, people may be prescribed anti-arrhythmic drugs such as amiodarone, or have a pacemaker implanted. Blood thinners may be used to prevent thromboembolism and stroke. Chronic heart disease caused by Chagas is a common reason for heart transplantation surgery. Because transplant recipients take immunosuppressive drugs to prevent organ rejection, they are monitored using PCR to detect reactivation of the disease. People with Chagas disease who undergo heart transplantation have higher survival rates than the average heart transplant recipient.

Mild gastrointestinal disease can be treated symptomatically, such as by using laxatives for constipation, or taking a prokinetic drug like metoclopramide before meals to relieve esophageal symptoms. Surgery to sever the muscles of the lower esophageal sphincter (cardiomyotomy) is indicated in more severe cases of esophageal disease, and surgical removal of the affected part of the organ may be required for advanced megacolon and megaesophagus.

Epidemiology

Epidemiology of Chagas disease circa 2011: red is endemic countries where spread is through vectors; yellow is endemic countries where spread is occasionally through vectors; blue is non-endemic countries where spread is through blood transfusions

 

Disability-adjusted life years due to Chagas disease in 2016. Grey indicates no data. Otherwise, colors get increasingly dark red for each order of magnitude increase in DALY burden: 0, white. Up to 1,000 DALYs, yellow. 1,001 to 10,000 DALYs, orange. 10,001 to 100,000 DALYs, light red. Greater than 100,000 DALYs, dark red.

In 2017, an estimated 6.2 million people worldwide had Chagas disease, with approximately 162,000 new infections and 7,900 deaths each year. This resulted in a global annual economic burden estimated at US$7.2 billion, 86% of which is borne by endemic countries. Chagas disease results in the loss of over 800,000 disability-adjusted life years each year.

Chagas is endemic to 21 countries in continental Latin America: Argentina, Belize, Bolivia, Brazil, Chile, Colombia, Costa Rica, Ecuador, El Salvador, French Guiana, Guatemala, Guyana, Honduras, Mexico, Nicaragua, Panama, Paraguay, Peru, Suriname, Uruguay, and Venezuela. The endemic area ranges from the southern United States to northern Chile and Argentina, with Bolivia (6.1%), Argentina (3.6%), and Paraguay (2.1%) exhibiting the highest prevalence of the disease. In endemic areas, due largely to vector control efforts and screening of blood donations, annual infections and deaths have fallen by 67% and more than 73% respectively from their peaks in the 1980s to 2010. Transmission by insect vector and blood transfusion has been completely interrupted in Uruguay (1997), Chile (1999), and Brazil (2006), and in Argentina, vectorial transmission has been interrupted in 13 of the 19 endemic provinces. During Venezuela's humanitarian crisis, vectorial transmission has begun occurring in areas where it had previously been interrupted and Chagas disease seroprevalence rates have increased. Transmission rates have also risen in the Gran Chaco region due to insecticide resistance and in the Amazon basin due to oral transmission.

While the rate of vector-transmitted Chagas disease has declined throughout most of Latin America, the rate of orally transmitted disease has risen, possibly due to increasing urbanization and deforestation bringing people into closer contact with triatomines and altering the distribution of triatomine species. Orally transmitted Chagas disease is of particular concern in Venezuela, where 16 outbreaks have been recorded between 2007 and 2018.

Chagas exists in two different ecological zones: In the Southern Cone region, the main vector lives in and around human homes. In Central America and Mexico, the main vector species lives both inside dwellings and in uninhabited areas. In both zones, Chagas occurs almost exclusively in rural areas, where T. cruzi also circulates in wild and domestic animals. T. cruzi commonly infects more than 100 species of mammals across Latin America including opossums, armadillos, marmosets, bats, and various rodents, all of which can be infected by the vectors or orally by eating triatomine bugs and other infected animals.

Non-endemic countries

Though Chagas is traditionally considered a disease of rural Latin America, international migration has dispersed those suffering from the disease to numerous non-endemic countries, primarily in North America and Europe. As of 2020, approximately 300,000 infected people are living in the United States, about 30,000 to 40,000 of whom have Chagas cardiomyopathy. The vast majority of Chagas infections in the United States occur in immigrants from Latin America, but local transmission is possible. Eleven triatomine species are native to the United States and some southern states have persistent cycles of disease transmission between insect vectors and animal reservoirs, which include woodrats, possums, raccoons, armadillos and skunks. However, locally acquired infection is very rare: only 28 cases were documented from 1955 to 2015. As of 2013, the cost of treatment in the United States was estimated to be US$900 million annually (global cost $7 billion), which included hospitalization and medical devices such as pacemakers.

Chagas disease affects approximately 68,000 to 123,000 people in Europe as of 2019. Spain, which has a high rate of immigration from Latin America, has the highest prevalence of the disease. It is estimated that 50,000 to 70,000 Spanish people are living with the disease, which accounts for 75% of European cases. The prevalence of Chagas varies widely within European countries due to differing immigration patterns. Italy has the second highest prevalence, followed by the Netherlands, the United Kingdom, and Germany.

History

Carlos Chagas, in his laboratory at Instituto Oswaldo Cruz

T. cruzi likely circulated in South American mammals long before the arrival of humans on the continent. T. cruzi has been detected in ancient human remains across South America, from a 9000-year-old Chinchorro mummy in the Atacama Desert, to remains of various ages in Minas Gerais, to an 1100-year-old mummy as far north as the Chihuahuan Desert near the Rio Grande. Many early written accounts describe symptoms consistent with Chagas disease, with early descriptions of the disease sometimes attributed to Miguel Diaz Pimenta (1707), Luís Gomes Ferreira [pt] (1735), and Theodoro J. H. Langgaard (1842).

The formal description of Chagas disease was made by Carlos Chagas in 1909 after examining a two-year-old girl with fever, swollen lymph nodes, and an enlarged spleen and liver. Upon examination of her blood, Chagas saw trypanosomes identical to those he had recently identified from the hindgut of triatomine bugs and named Trypanosoma cruzi in honor of his mentor, Brazilian physician Oswaldo Cruz. He sent infected triatomine bugs to Cruz in Rio de Janeiro, who showed the bite of the infected triatomine could transmit T. cruzi to marmoset monkeys as well. In just two years, 1908 and 1909, Chagas published descriptions of the disease, the organism that caused it, and the insect vector required for infection. Almost immediately thereafter, at the suggestion of Miguel Couto, then professor of the Faculdade de Medicina do Rio de Janeiro [pt], the disease was widely referred to as "Chagas disease". Chagas' discovery brought him national and international renown, but in highlighting the inadequacies of the Brazilian government's response to the disease, Chagas attracted criticism to himself and to the disease that bore his name, stifling research on his discovery and likely frustrating his nomination for the Nobel Prize in 1921.

In the 1930s, Salvador Mazza rekindled Chagas disease research, describing over a thousand cases in Argentina's Chaco Province. In Argentina, the disease is known as mal de Chagas-Mazza in his honor. Serological tests for Chagas disease were introduced in the 1940s, demonstrating that infection with T. cruzi was widespread across Latin America. This, combined with successes eliminating the malaria vector through insecticide use, spurred the creation of public health campaigns focused on treating houses with insecticides to eradicate triatomine bugs. The 1950s saw the discovery that treating blood with crystal violet could eradicate the parasite, leading to its widespread use in transfusion screening programs in Latin America. Large-scale control programs began to take form in the 1960s, first in São Paulo, then various locations in Argentina, then national-level programs across Latin America. These programs received a major boost in the 1980s with the introduction of pyrethroid insecticides, which did not leave stains or odors after application and were longer-lasting and more cost-effective. Regional bodies dedicated to controlling Chagas disease arose through support of the Pan American Health Organization, with the Initiative of the Southern Cone for the Elimination of Chagas Diseases launching in 1991, followed by the Initiative of the Andean countries (1997), Initiative of the Central American countries (1997), and the Initiative of the Amazon countries (2004).

Research

Treatments

Fexinidazole, an antiparasitic drug approved for treating African trypanosomiasis, has shown activity against Chagas disease in animal models. As of 2019, it is undergoing phase II clinical trials for chronic Chagas disease in Spain. Other drug candidates include GNF6702, a proteasome inhibitor that is effective against Chagas disease in mice and is undergoing preliminary toxicity studies, and AN4169, which has had promising results in animal models.

A number of experimental vaccines have been tested in animals. Some approaches have used inoculation with dead or attenuated T. cruzi parasites or non-pathogenic organisms that share antigens with T. cruzi, such as Trypanosoma rangeli or Phytomonas serpens. DNA vaccination has also been explored. As of 2019, vaccine research has mainly been limited to small animal models, and further testing in large animals is needed.

Diagnostic tests

As of 2018, standard diagnostic tests for Chagas disease were limited in their ability to measure the response to antiparasitic treatment. Serological tests, for example, may remain positive for years after T. cruzi is eliminated from the body, and PCR may give false-negative results when parasitemia is low. Various potential biomarkers of treatment response are under investigation, such as immunoassays against specific T. cruzi antigens, flow cytometry testing to detect antibodies against different life stages of T. cruzi, and markers of physiological changes caused by the parasite, such as alterations in coagulation and lipid metabolism.

Another research area is the use of biomarkers to predict the progression of chronic Chagas disease. Serum levels of tumor necrosis factor alpha, brain and atrial natriuretic peptide, and angiotensin-converting enzyme 2, markers of heart damage and inflammation, have been found to correlate with the severity of Chagas cardiomyopathy. Endothelin 1 has been studied as a prognostic marker in animal models.

T. cruzi shed acute-phase antigen (SAPA), which can be detected in blood using ELISA or Western blot, has been used as an indicator of early acute and congenital infection. A novel assay for T. cruzi antigens in urine has been developed to diagnose congenital disease.

Parasitic worm

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Parasitic_worm 

Eggs of different species of parasitic worm.

Parasitic worms, also known as helminths, are large macroparasites; adults can generally be seen with the naked eye. Many are intestinal worms that are soil-transmitted and infect the gastrointestinal tract. Other parasitic worms such as schistosomes reside in blood vessels.

Some parasitic worms, including leeches and monogeneans, are ectoparasites - thus, they are not classified as helminths, which are endoparasites.

Parasitic worms live in and feed in living hosts. They receive nourishment and protection while disrupting their hosts' ability to absorb nutrients. This can cause weakness and disease in the host. Parasitic worms cannot reproduce entirely within their host's body; they have a life cycle that includes some stages that need to take place outside of the host. Helminths are able to survive in their mammalian hosts for many years due to their ability to manipulate the host's immune response by secreting immunomodulatory products. All parasitic worms produce eggs during reproduction. These eggs have a strong shell that protects them against a range of environmental conditions. The eggs can therefore survive in the environment for many months or years.

Many of the worms referred to as helminths are intestinal parasites. An infection by a helminth is known as helminthiasis, helminth infection, or intestinal worm infection. There is a naming convention which applies to all helminths: the ending "-asis" (or in veterinary science: "-osis") is added at the end of the name of the worm to denote the infection with that particular worm. For example, Ascaris is the name of a type of helminth, and ascariasis is the name of the infection caused by that helminth.

Taxonomy

Hookworms attached to the intestinal mucosa

 

Two pinworms

 

Image showing life cycle inside and outside of the human body of one fairly typical and well described helminth: Ascaris lumbricoides

Helminths are a group of organisms which share a similar form but are not necessarily related as part of evolution. The term "helminth" is an artificial term. There is no real consensus on the taxonomy (or groupings) of the helminths, particularly within the nematodes. The term "helminth" contains a number of phyla, many of which are completely unrelated. However, for practical considerations the term is currently used to describe four phyla with superficial similarities: Annelida (ringed or segmented worms), Platyhelminthes (flatworms), Nematoda (roundworms), and Acanthocephala (thorny-headed worms). The phylum Platyhelminthes includes two classes of worms of particular medical significance: the cestodes (tapeworms) and the trematodes (flukes and blood flukes), depending on whether or not they have segmented bodies.

There may be as many as 300,000 species of parasites affecting vertebrates, and as many as 300 affecting humans alone.

Helminths of importance in the sanitation field are the human parasites, and are classified as Nemathelminthes (nematodes) and Platyhelminthes, depending on whether they possess a round or flattened body, respectively.

Ringworm (dermatophytosis) is actually caused by various fungi and not by a parasitic worm.

Reproduction and life cycle

The lifetime of adult worms varies tremendously from one species to another but is generally in the range of 1 to 8 years (see following table). This lifetime of several years is a result of their ability to manipulate the immune response of their hosts by secreting immunomodulatory products.

Helminths can be either hermaphroditic (having the sex organs of both sexes), like tapeworms and flukes (not including the blood fluke), or have their sexes differentiated, like the roundworms. All helminths produce eggs (also called ova) for reproduction.

Eggs

Analysing for helminth eggs in samples of feces from a dry toilet in Kenya

 

Processed helminth eggs samples from a dry toilet in Kenya

Generally, thousands or even hundreds of thousands of eggs are produced each time the female worm deposits its eggs - a process called oviposition. There is a large variation in the number of eggs produced by different species of worm at one time; it varies in the range of 3,000 to 700,000. The frequency of egg deposition from an adult helminth is generally daily, and can occur up to six times per day for some Taenia species. Adult trematodes lay smaller numbers of eggs compared to cestodes or nematodes. However, the egg develops into a miracidia from which thousands of cercariae, or swimming larvae, develop. This means that one egg may produce thousands of adult worms. Helminth eggs remain viable for 1–2 months in crops and for many months in soil, fresh water, and sewage, or even for several years in feces, fecal sludge (historically called night soil), and sewage sludge - a period that is much longer compared to other microorganisms. Eggs can reach the soil when polluted wastewater, sewage sludge or human waste are used as fertilizer. Such soil is often characterized by moist and warm conditions. Therefore, the risk of using contaminated wastewater and sludge in agricultural fields is a real problem, especially in poor countries, where this practice is prevalent. Helminth eggs are regarded as the main biological health risk when applying sewage sludge, fecal sludge or fecal matter on agricultural soils. The eggs are the infective stage of the helminths’ life cycle for causing the disease helminthiasis.

Helminth eggs are resistant to various environmental conditions due to the composition of the egg shell. Each helminth egg species has 3 to 4 layers with different physical and chemical characteristics:

1. the 1 to 2 outer layers are formed of mucopolysaccharides and proteins,
2. the middle layers consist of chitinous material and serve to give structure and mechanical resistance to the eggs, and
3. the inner layer is composed of lipids and proteins and is useful to protect eggs from desiccation, strong acid and bases, oxidants and reductive agents as well as detergent and proteolytic compounds.

Due to this strong shell, helminth eggs or ova remain viable in soil, fresh water and sewage for many months. In feces, fecal sludge and sewage sludge they can even remain viable for several years. Helminth eggs of concern in wastewater used for irrigation have a size between 20 and 90 μm and a relative density of 1.06–1.23. It is very difficult to inactivate helminth eggs, unless temperature is increased above 40 °C or moisture is reduced to less than 5%. Eggs that are no longer viable do not produce any larvae. In the case of Ascaris lumbricoides (giant roundworm), which has been considered the most resistant and common helminth type, fertilized eggs deposited in soil are resistant to desiccation but are, at this stage of development, very sensitive to environmental temperatures: The reproduction of a fertilized egg within the eggshell develops at an environmental soil temperature about 25 °C which is lower than the body temperature of the host (i.e., 37 °C for humans). However, development of the larvae in the egg stops at temperatures below 15.5 °C, and eggs cannot survive temperatures much above 38 °C. If the temperature is around 25 °C, the infectiousness occurs after nearly 10 days of incubation.

Larvae

Larvae hatch from eggs, either inside or outside the host, depending on the type of helminth. For eggs in moist soil at optimal temperature and oxygen levels, the embryo develops into an infective larva after 2 to 4 weeks, named "second-stage larva". Once ingested by a host, this larva has the ability to get out of the egg, hatch in the small intestine and migrate to different organs. These infective larvae (or "infective eggs") may remain viable in soil for two years or longer.

The process of larval maturation in the host can take from about two weeks up to four months, depending on the helminth species.

Draft genomes for all categories of helminth have been sequenced in recent years and are available through the ParaSite sub-portal of WormBase.

Use in medicine

Parasitic worms have been used as a medical treatment for various diseases, particularly those involving an overactive immune response. As humans have evolved with parasitic worms, proponents argue they are needed for a healthy immune system. Scientists are looking for a connection between the prevention and control of parasitic worms and the increase in allergies such as hay-fever in developed countries. Removal of parasitic worms from areas is correlated with an increase in autoimmune disorders in those areas.  Parasitic worms may be able to damp down the immune system of their host, making it easier for them to live in the intestine without coming under attack. This may be one mechanism for their proposed medicinal effect.

One study suggests a link between the rising rates of metabolic syndrome in the developed worlds and the largely successful efforts of Westerners to eliminate intestinal parasites. The work suggests eosinophils (a type of white blood cell) in fat tissue play an important role in preventing insulin resistance by secreting interleukin 4, which in turn switches macrophages into "alternative activation". Alternatively-activated macrophages are important to maintaining glucose homeostasis (i.e., blood sugar regulation). Helminth infection causes an increase in eosinophils. In the study, the authors fed rodents a high-fat diet to induce metabolic syndrome, and then injected them with helminths. Helminth infestation improved the rodents' metabolism. The authors concluded:

Although sparse in blood of persons in developed countries, eosinophils are often elevated in individuals in rural developing countries where intestinal parasitism is prevalent and metabolic syndrome rare. We speculate that eosinophils may have evolved to optimize metabolic homeostasis during chronic infections by ubiquitous intestinal parasites….

Levels of infectiousness

Helminth eggs contained in wastewater, sewage sludge or human excreta are not always infectious, i.e. able to cause the disease helminthiasis. Fertilized eggs and unfertilized eggs can exist side by side. Unfertilized eggs are identifiable under the microscope by their elongated shape. No larvae can hatch from these kinds of eggs. Therefore, unfertilized eggs do not pose a danger to human health.

Sanitation

Removal versus inactivation in wastewater and sludge treatment

In order to physically remove (but not inactivate) helminth eggs from wastewater, processes that remove particles, such as sedimentation, filtration or coagulation-flocculation are employed. Therefore, waste stabilization ponds (lagoons), storage bassins, constructed wetlands, rapid filtration or upflow anaerobic sludge blanket (UASB) reactors can be used. These conventional wastewater treatment processes do not inactivate the helminth ova but only removes them from the wastewater and moves them to the sewage sludge.

Helminth ova cannot be inactivated with chlorine, UV light or ozone (in the latter case at least not with economical doses because >36 mg/L ozone are needed with 1 hour contact time).

Inactivation of helminth ova can be achieved in sewage sludge treatment where the temperature is increased over 40 °C or moisture is reduced to less than 5%. Best results can be obtained when both of these conditions are combined for an extended period of time. Details about the contact time under these conditions and other related environmental factors are generally not well-defined for every type of helminth egg species. Helminth eggs are considered highly resistant biological structures.

Indicator organism

Helminth eggs (or ova) are a good indicator organism to assess the safety of sanitation and reuse systems because they are the most environmentally resistant of all pathogens (viruses, bacteria, protozoa and helminths) and can in extreme cases survive for several years in soil. Therefore, the presence or absence of viable helminth eggs ("viable" meaning that a larva would be able to hatch from the egg) in a sample of dried fecal matter, compost or fecal sludge is often used to assess the efficiency of diverse wastewater and sludge treatment processes in terms of pathogen removal. In particular, the number of viable Ascaris eggs is often taken as an indicator for all helminth eggs in treatment processes as they are very common in many parts of the world and relatively easy to identify under the microscope. However, the exact inactivation characteristics may vary for different types of helminth eggs.

Diagnosis

Environmental samples

For the purpose of setting treatment standards and reuse legislation, it is important to be able to determine the amount of helminth eggs in an environmental sample with some accuracy. The detection of viable helminth eggs in samples of wastewater, sludge or fresh feces (as a diagnostic tool for the infection helminthiasis) is not straight forward. In fact, many laboratories in developing countries lack the right equipment or skilled staff required to do so. An important step in the analytical methods is usually the concentration of the eggs in the sample, especially in the case of wastewater samples. A concentration step may not be required in samples of dried feces, e.g. samples collected from urine-diverting dry toilets.

Human stool samples

For medical purposes, the exact number of helminth eggs is less important and therefore most diagnoses are made simply by identifying the appearance of the worm or eggs in feces. Due to the large quantity of eggs laid, physicians can diagnose using as few as one or two fecal smears. The Kato technique (also called the Kato-Katz technique) is a laboratory method for preparing human stool samples prior to searching for parasite eggs. Eggs per gram is a laboratory test that determines the number of eggs per gram of feces in patients suspected of having a parasitological infection, such as schistosomiasis.

Lymphatic filariasis

From Wikipedia, the free encyclopedia

 

 

Lymphatic filariasis
Other names	Elephantiasis tropica, elephantiasis arabum
Bellevue Venus; Oscar G. Mason's portrait of a woman with elephantiasis.
Specialty	Infectious disease
Symptoms	None, severe swelling of the arms, legs, breasts, or genitals
Causes	Filarial worms spread by mosquitos
Diagnostic method	Microscopic examination of blood
Prevention	Bed nets, mass deworming
Medication	Albendazole with ivermectin or diethylcarbamazine
Frequency	38.5 million (2015)

Lymphatic filariasis is a human disease caused by parasitic worms known as filarial worms. Most cases of the disease have no symptoms. Some people, however, develop a syndrome called elephantiasis, which is marked by severe swelling in the arms, legs, breasts, or genitals. The skin may become thicker as well, and the condition may become painful. The changes to the body have the potential to harm the person's social and economic situation.

The worms are spread by the bites of infected mosquitoes. Three types of worms are known to cause the disease: Wuchereria bancrofti, Brugia malayi, and Brugia timori, with Wuchereria bancrofti being the most common. These worms damage the lymphatic system. The disease is diagnosed by microscopic examination of blood collected during the night. The blood is typically examined as a smear after being stained with Giemsa stain. Testing the blood for antibodies against the disease may also permit diagnosis. Other roundworms from the same family are responsible for river blindness.

Prevention can be achieved by treating entire groups in which the disease exists, known as mass deworming. This is done every year for about six years, in an effort to rid a population of the disease entirely. Medications used include antiparasitics such as albendazole with ivermectin, or albendazole with diethylcarbamazine. The medications do not kill the adult worms but prevent further spread of the disease until the worms die on their own. Efforts to prevent mosquito bites are also recommended, including reducing the number of mosquitoes and promoting the use of bed nets.

In 2015 about 38.5 million people were infected. About 950 million people are at risk of the disease in 54 countries. It is most common in tropical Africa and Asia. Lymphatic filariasis is classified as a neglected tropical disease and one of the four main worm infections. The impact of the disease results in economic losses of billions of dollars a year.

Signs and symptoms

The most spectacular symptom of lymphatic filariasis is elephantiasis, a stage 3 lymphedema with thickening of the skin and underlying tissues. This was the first mosquito-borne disease to be discovered. Elephantiasis results when the parasites lodge in the lymphatic system and cause blockages to the flow of lymph. Infections usually begin in childhood.

The skin condition the disease causes is called "elephantiasis tropica" (also known as "elephantiasis arabum").

Elephantiasis mainly affects the lower limbs and various species of filarial worms tend to affect different parts of the body: Wuchereria bancrofti can affect the arms, breasts, legs, scrotum, and vulva (causing hydrocele formation), while Brugia timori rarely affects the genitals. Those who develop the chronic stages of elephantiasis are usually amicrofilaraemic and often have adverse immunological reactions to the microfilariae as well as the adult worms.

The subcutaneous worms present with skin rashes, urticarial papules, and arthritis, as well as hyper- and hypopigmentation macules. The related Onchocerca volvulus manifests itself in the eyes, causing "river blindness" (onchocerciasis), one of the leading causes of blindness in the world.

Serous cavity filariasis presents with symptoms similar to subcutaneous filariasis; it may also be associated with ascites following the severe inflammatory reaction in the lymphatics.

Elephantiasis leads to marked swelling of the lower half of the body and thickening of the skin, making it look like that of an elephant, a term called "pachyderm".

• 

  Drawn from the collection at the National Museum of Health and Medicine and shows the effect of elephantiasis in an historic context. Anatomical items: Left Leg, Scrotum.

• 

  Elephantiasis of the legs due to filariasis. Luzon, Philippines.

• 

  Man with massive scrotal elephantiasis, Tanzania, early 20th century

Causes

Life cycle of Wuchereria bancrofti, a parasite that causes lymphatic filariasis

Elephantiasis occurs in the presence of microscopic, thread-like parasitic worms such as Wuchereria bancrofti (the most common), Brugia malayi, and Brugia timori, all of which are transmitted by bites from infected mosquitoes. It is a type of helminth infection. Three types of worm cause the disease and damage the lymphatic system.

The disease itself is a result of a complex interplay between several factors: the worm, the endosymbiotic Wolbachia bacteria within the worm, the host's immune response, and the numerous opportunistic infections and disorders that arise. The adult worms only live in the human lymphatic system. The parasite infects the lymph nodes and blocks the flow of lymph throughout the body; this results in chronic lymphedema, most often noted in the lower torso (typically in the legs and genitals).

Diagnosis

The standard method for diagnosing active infection is by finding the microfilariae via microscopic examination. This may be difficult, as in most parts of the world, microfilariae only circulate in the blood at night. For this reason, the blood has to be collected nocturnally. The blood sample is typically in the form of a thick smear and stained with Giemsa stain. Testing the blood serum for antibodies against the disease may also be used.

Prevention

The present objective of prevention is the eradication of lymphatic filariasis, which is achievable since the disease has no known animal reservoir.

The World Health Organization recommends mass deworming—treating entire groups of people who are at risk with a single annual dose of two medicines, namely albendazole in combination with either ivermectin or diethylcarbamazine citrate. With consistent treatment, since the disease needs a human host, the reduction of microfilariae means the disease will not be transmitted, the adult worms will die out, and the cycle will be broken. In sub-Saharan Africa, albendazole (donated by GlaxoSmithKline) is being used with ivermectin (donated by Merck & Co.) to treat the disease, whereas elsewhere in the world, albendazole is used with diethylcarbamazine. As of 2019 WHO recommends prevention with a combination of ivermectin, diethylcarbamazine, and albendazole in areas were onchocerciasis does not occur. Transmission of the infection can be broken when a single dose of these combined oral medicines is consistently maintained annually for a duration of four to six years. Using a combination of treatments better reduces the number of microfilariae in blood. Avoiding mosquito bites, such as by using insecticide-treated mosquito bed nets, also reduces the transmission of lymphatic filariasis.

The Carter Center's International Task Force for Disease Eradication declared lymphatic filariasis one of six potentially eradicable diseases. According to medical experts, the worldwide effort to eliminate lymphatic filariasis is on track to potentially succeed by 2020.

For similar-looking but causally unrelated podoconiosis, international awareness of the disease will have to increase before elimination is possible. In 2011, podoconiosis was added to the World Health Organization's Neglected Tropical Diseases list, which was an important milestone in raising global awareness of the condition. The efforts of the Global Programme to Eliminate LF are estimated to have prevented 6.6 million new filariasis cases from developing in children between 2000 and 2007, and to have stopped the progression of the disease in another 9.5 million people who had already contracted it. Dr. Mwele Malecela, who chairs the programme, said: "We are on track to accomplish our goal of elimination by 2020." In 2010, the WHO published a detailed progress report on the elimination campaign in which they assert that of the 81 countries with endemic LF, 53 have implemented mass drug administration, and 37 have completed five or more rounds in some areas, though urban areas remain problematic.

Treatment

Anthelmintic

Treatments for lymphatic filariasis differ depending on the geographic location of the area of the world in which the disease was acquired. In sub-Saharan Africa, albendazole is being used with ivermectin to treat the disease, whereas elsewhere in the world, albendazole is used with diethylcarbamazine. Geo-targeting treatments is part of a larger strategy to eventually eliminate lymphatic filariasis by 2020.

Antibiotics

The antibiotic doxycycline is also effective in treating lymphatic filariasis. Its drawbacks over anthelmintic drugs are that it requires 4 to 6 weeks of treatment, should not be used in young children and pregnant women, and is photosensitizing, which limits its use for mass prevention. The parasites responsible for elephantiasis have a population of endosymbiotic bacteria, Wolbachia, that live inside the worm. When the symbiotic bacteria of the adult worms are killed by the antibiotic, they no longer provide chemicals which the nematode larvae need to develop, which either kills the larvae or prevents their normal development. This permanently sterilizes the adult worms, which also die within 1 to 2 years instead of their normal 10 to 14-year lifespan.

Vaccine

A vaccine is not yet available, but in 2013 the University of Illinois College of Medicine was reporting 95% efficacy in testing against B. malayi in mice.

Supportive treatments

Additionally, surgical treatment may be helpful for issues related to scrotal elephantiasis and hydrocele. However, surgery is generally ineffective at correcting elephantiasis of the limbs.

Epidemiology

Disability-adjusted life year for lymphatic filariasis per 100,000 inhabitants

 

  no data

  less than 10

  10-50

  50-70

  70-80

  80-90

  90-100

  100-150

  150-200

  200-300

  300-400

  400-500

  more than 500

Elephantiasis caused by lymphatic filariasis is one of the most common causes of disability in the world. A 2012 report noted that lymphatic filariasis affected 120 million people and one billion people at risk for infection. About 40 million people were disfigured or incapacitated by the disease in 2015. It is considered endemic in tropical and subtropical regions of Africa, Asia, Central and South America, and Pacific Island nations.

In areas endemic for podoconiosis, prevalence can be 5% or higher. In communities where lymphatic filariasis is endemic, as many as 10% of women can be afflicted with swollen limbs, and 50% of men can suffer from mutilating genital symptoms.

Filariasis is considered endemic in 73 countries; 37 of these are in Africa.

• Togo is the first Africa country to have been validated by the World Health Organization (WHO) as having eliminated LF as public health problem
• In the Americas, it is present in Brazil, Costa Rica, the Dominican Republic, Guyana, Haiti, Suriname, and Trinidad and Tobago.
• In Asia, it is present in Bangladesh, Cambodia, India, Indonesia, Laos, Malaysia, Maldives, the Philippines, Sri Lanka, Thailand, Timor-Leste, and Vietnam.
• In the Middle East, it was present only in Yemen until August 2019 when the World Health Organization (WHO) validated Yemen as having eliminated LF as public health problem
• In the Pacific region, it is endemic in American Samoa, the Cook Islands, Fiji, French Polynesia, Micronesia, Niue, Papua New Guinea, Samoa, Tonga, Tuvalu, and Vanuatu.

In many of these countries, considerable progress has been made towards elimination of filariasis. In July 2017, the World Health Organization (WHO) announced that the disease had been eliminated in Tonga. Elimination of the disease has also occurred in Cambodia, the Cook Islands, Egypt, Kiribati, Maldives, Marshall Islands, Niue, Palau, Sri Lanka, Thailand, Vanuatu, Viet Nam and Wallis and Fortuna. This list is constantly updates and adds on the China and South Korea that were among the first countries to eliminate LF, according to the WHO.

History

A man in Japan is helped to carry his enlarged scrotum

Lymphatic filariasis is thought to have affected humans for about 4000 years. Artifacts from ancient Egypt (2000 BC) and the Nok civilization in West Africa (500 BC) show possible elephantiasis symptoms. The first clear reference to the disease occurs in ancient Greek literature, wherein scholars differentiated the often similar symptoms of lymphatic filariasis from those of leprosy, describing leprosy as elephantiasis graecorum and lymphatic filariasis as elephantiasis arabum.

The first documentation of symptoms occurred in the 16th century, when Jan Huyghen van Linschoten wrote about the disease during the exploration of Goa. Similar symptoms were reported by subsequent explorers in areas of Asia and Africa, though an understanding of the disease did not begin to develop until centuries later.

In 1866, Timothy Lewis, building on the work of Jean Nicolas Demarquay [de] and Otto Henry Wucherer, made the connection between microfilariae and elephantiasis, establishing the course of research that would ultimately explain the disease. In 1876, Joseph Bancroft discovered the adult form of the worm. In 1877, the lifecycle involving an arthropod vector was theorized by Patrick Manson, who proceeded to demonstrate the presence of the worms in mosquitoes. Manson incorrectly hypothesized that the disease was transmitted through skin contact with water in which the mosquitoes had laid eggs. In 1900, George Carmichael Low determined the actual transmission method by discovering the presence of the worm in the proboscis of the mosquito vector.

Many people in Malabar, Nayars as well as Brahmans and their wives — in fact about a quarter or a fifth of the total population, including the people of the lowest castes — have very large legs, swollen to a great size; and they die of this, and it is an ugly thing to see. They say that this is due to the water through which they go, because the country is marshy. This is called pericaes in the native language, and all the swelling is the same from the knees downward, and they have no pain, nor do they take any notice of this infirmity.

— Portuguese diplomat Tomé Pires, Suma Oriental, 1512–1515.

Research directions

Researchers at the University of Illinois at Chicago (UIC) have developed a novel vaccine for the prevention of lymphatic filariasis. This vaccine has been shown to elicit strong, protective immune responses in mouse models of lymphatic filariasis infection. The immune response elicited by this vaccine has been demonstrated to be protective against both W. bancrofti and B. malayi infection in the mouse model and may prove useful in the human.

On September 20, 2007, geneticists published the first draft of the complete genome (genetic content) of Brugia malayi, one of the roundworms which causes lymphatic filariasis. This project had been started in 1994 and by 2000, 80% of the genome had been determined. Determining the content of the genes might lead to the development of new drugs and vaccines.

Diseases of affluence

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Diseases_of_affluence 

Diseases of affluence, previously called diseases of rich people, is a term sometimes given to selected diseases and other health conditions which are commonly thought to be a result of increasing wealth in a society. Also referred to as the "Western disease" paradigm, these diseases are in contrast to so-called "diseases of poverty", which largely result from and contribute to human impoverishment. These diseases of affluence have vastly increased in prevalence since the end of World War II.

Examples of diseases of affluence include mostly chronic non-communicable diseases (NCDs) and other physical health conditions for which personal lifestyles and societal conditions associated with economic development are believed to be an important risk factor — such as type 2 diabetes, asthma, coronary heart disease, cerebrovascular disease, peripheral vascular disease, obesity, hypertension, cancer, alcoholism, gout, and some types of allergy. They may also be considered to include depression and other mental health conditions associated with increased social isolation and lower levels of psychological well being observed in many developed countries. Many of these conditions are interrelated, for example obesity is thought to be a partial cause of many other illnesses.

In contrast, the diseases of poverty have tended to be largely infectious diseases, or the result of poor living conditions. These include tuberculosis, malaria, and intestinal diseases. Increasingly, research is finding that diseases thought to be diseases of affluence also appear in large part in the poor. These diseases include obesity and cardiovascular disease and, coupled with infectious diseases, these further increase global health inequalities.

Diseases of affluence started to become more prevalent in developing countries as diseases of poverty decline, longevity increases, and lifestyles change. In 2008, nearly 80% of deaths due to NCDs — including heart disease, strokes, chronic lung diseases, cancers and diabetes — occurred in low- and middle-income countries.

Main instances

According to the World Health Organization (WHO), the top 10 causes of deaths in high income/affluent countries in 2016 were from:

1. Ischemic heart diseases
2. Stroke
3. Alzheimer disease and other dementia
4. Trachea, bronchus and lung cancer
5. Chronic obstructive pulmonary disease
6. Lower respiratory infections
7. Colon and rectum cancers
8. Diabetes
9. Kidney diseases
10. Breast cancer

Except for the lower respiratory infections, all of them are non-communicable diseases. In 2016 WHO reported 56.9 million deaths worldwide, and more than half (54%), were due to the top causes of death previously mentioned.

Causes

Factors associated with the increase of these conditions and illnesses appear to be things that are a direct result of technological advances. They include:

• Less strenuous physical exercise, often through increased use of motor vehicles
• Irregular exercise as a result of office jobs involving no physical labor.
• Easy accessibility in society to large amounts of low-cost food (relative to the much-lower caloric food availability in a subsistence economy)
  • More food generally, with much less physical exertion expended to obtain a moderate amount of food
  • Higher consumption of vegetable oils and high sugar-containing foods
  • Higher consumption of meat and dairy products
  • Higher consumption of refined flours and products made of such, like white bread or white noodles
  • More foods which are processed, cooked, and commercially provided (rather than seasonal, fresh foods prepared locally at the time of eating)
• Prolonged periods of little activity
• Greater use of alcohol and tobacco
• Longer lifespans
  • Reduced exposure to infectious agents throughout life (this can result in a more idle and inexperienced immune system, as compared to an individual who experienced relatively frequent exposure to certain pathogens in their time of life)
• Increased cleanliness. The hygiene hypothesis postulates that children of affluent families are now exposed to fewer antigens than has been normal in the past, giving rise to increased prevalence of allergy and autoimmune diseases.

Diabetes mellitus

Diabetes is a chronic metabolic disease characterized by increase blood glucose level. Type 2 diabetes is the most common form of diabetes. It is caused by resistance to insulin or the lack of production of insulin. It is seen most commonly in adults. Type 1 diabetes or juvenile diabetes affects mostly children. This condition is due to little or lack of insulin production from the pancreas.

According to WHO the prevalence of diabetes has quadrupled from 1980 to 422 million adults.The global prevalence of diabetes has increased from 4.7% in 1980 to 8.5% in 2014. Diabetes has been a major cause for blindness, kidney failure, heart attack, stroke and lower limb amputation.

Prevalence in countries of affluence

The Centers of Disease Control and Prevention (CDC) released a report in 2015 indicating that more than 100 million Americans have diabetes or pre-diabetes. Diabetes was the seventh leading cause of death in United States in 2015. In developed countries like the United States, the risk for diabetes is seen in people with low socioeconomic status (SES). Socioeconomic status is defined by the education and the income level of a person. The prevalence of diabetes varies by education level. Of those diagnosed with diabetes:12.6% of adults had less than a high school education, 9.5% had a high school education and 7.2% had more than high school education.

Differences in diabetes prevalence are seen in the population and ethnic groups in USA. Diabetes is more common in non-Hispanic whites who are less educated and have a lower income. It is also more common in less educated Hispanics. The highest prevalence of diabetes is seen in the southeast, southern and Appalachian portion of the United States. In the United States the prevalence of diabetes is increasing in children and adolescents. In 2015, 25 million people were diagnosed with diabetes, of which 193,000 were children. The total direct and indirect cost of diagnosed diabetes in US in 2012 was $245 billion.

In 2009, the Canadian Diabetes Association (CDA) estimated that diagnosed diabetes will increase from 1.3 million in 2000 to 2.5 million in 2010 and 3.7 million in 2020. Diabetes was the 7th leading cause of death in Canada in 2015. Like United States, diabetes in more prevalent in the low socioeconomic group of people in Canada.

According to the International Diabetes Federation, more than 58 million people are diagnosed with diabetes in the European Union Region (EUR), and this will go up to 66.7 million by 2045. Similar to other affluent countries like America and Canada, diabetes is more prevalent in the poorer parts of Europe like Central and Eastern Europe.

In Australia according to self-reported data, 1 in 7 adults or approximately 1.2 million people had diabetes in 2014–2015. People who were living in remote or socioeconomically disadvantaged areas were 4 times more likely to develop type 2 diabetes as compared to non-indigenous Australians. Australia incurred $20.8 million in direct costs towards hospitalization, medication, and out-patient treatment towards diabetes. In 2015, $1.2 billion were lost in Australia's Gross Domestic Product (GDP) due to diabetes.

In these countries of affluence, diabetes is prevalent in low socioeconomic groups of people as there is abundance of unhealthy food choices, high energy rich food, and decreased physical activity. More affluent people are typically more educated and have tools to counter unhealthy foods, such as access to healthy food, physical trainers, and parks and fitness centers.

Risk factors

Obesity and being overweight is one of the main risk factors of type 2 diabetes. Other risk factors include lack of physical activity, genetic predisposition, being over 45 years old, tobacco use, high blood pressure and high cholesterol. In United States, the prevalence of obesity was 39.8% in adults and 18.5% in children and adolescents in 2015–2016. In Australia in 2014–2015, 2 out 3 adults or 63% were overweight or obese. Also, 2 out of 3 adults did little or no exercise. According to the World Health Organization, Europe had the 2nd highest proportion of overweight or obese people in 2014 behind the Americas.

In developing countries

According to WHO the prevalence of diabetes is rising more in the middle and low income countries. Over the next 25 years, the number of people with diabetes in developing countries will increase by over 150%. Diabetes is typically seen in people above the retirement age in developed countries, but in developing countries people in the age of 35-64 are mostly affected. Although, diabetes is considered a disease of affluence affecting the developed countries, there is more loss of life and premature death among people with diabetes in the developing countries. Asia accounts for 60% of the world's diabetic population. In 1980 less than 1% of Chinese adults were affected by diabetes, but by 2008 the prevalence was 10%. It is predicted that by 2030 diabetes may affect 79.4 million people in India, 42.3 million people in China and 30.3 million in United States.

These changes are the result of developing nations having rapid economic development. This rapid economic development has caused a change in the lifestyle and food habits leading to over-nutrition, increased intake of fast food causing increase in weight, and insulin resistance. Compared to the west, obesity in Asia is low. India has very low prevalence of obesity, but a very high prevalence of diabetes suggesting that diabetes may occur at a lower BMI in Indians as compared to the Europeans. Smoking increases the risk for diabetes by 45%. In developing countries around 50–60% adult males are regular smokers, increasing their risk for diabetes. In developing countries, diabetes is more commonly seen in the more urbanized areas. The prevalence of diabetes in rural population is 1/4th that of urban population for countries like India, Bangladesh, Nepal, Bhutan and Sri Lanka.

Cardiovascular disease

Cardiovascular disease refers to a disease of the heart and blood vessels. Conditions and diseases associated with heart disease include: stroke, coronary heart disease, congenital heart disease, heart failure, peripheral vascular disease, and cardiomyopathy. Cardiovascular disease is known as the world's biggest killer. 17.5 million people die from it each year, which equals 31% of all deaths. Heart disease and stroke cause 80% of these deaths.

Risk factors

High blood pressure is the leading risk factor for cardiovascular disease and has contributed to 12% of the cardiovascular related deaths worldwide. Other significant risk factors for heart disease include high cholesterol and smoking. 47% of all Americans have one of these three risk factors. Lifestyle choices, such as poor diet and physical inactivity, and excessive alcohol use can also contribute to cardiovascular disease. Medical conditions, like diabetes and obesity can also be risk factors.

Prevalence in countries of affluence

In the United States, 610,000 people die every year from heart disease which is equal to 1 in 4 deaths. The leading cause of death for both men and women in the United States is heart disease. In Canada, heart disease is the second leading cause of death. In 2014, it was the cause of death for 51,000 people. In Australia, heart disease is also the leading cause of death. 29% of deaths in 2015, had an underlying cause of heart disease. Heart disease causes one in four premature deaths in the United Kingdom and in 2015 heart disease caused 26% of all deaths in that country.

People of lower socio-economic status are more likely to have cardiovascular disease than those who have a higher socio-economic status. This inequality gap has occurred in developed countries because people who have a lower socio-economic status often face many of the risk factors of tobacco and alcohol use, obesity as well as having a sedentary lifestyle. Further social and environmental factors such as poverty, pollution, family history, housing and employment contribute to this inequality gap and to risk of having a health condition caused by cardiovascular disease. The increasing inequality gap between the higher and lower income populations continues in countries such as Canada, despite the availability of health care for everyone.

Alzheimer's disease and other dementias

Dementia is a chronic syndrome which is characterized by deterioration in the thought process beyond what is expected from normal aging. It affects the persons memory, thinking, orientation, comprehension, behavior and ability to perform everyday activity. There are many different forms of dementia . Alzheimer is the most common form which contributes to 60–70% of the dementia cases. Different forms of dementia can co-exist. Young onset dementia which occurs in individuals before the age of 65 contributes to 9% of the total cases. It is the major cause of disability and dependency among old people.

Worldwide, there are 50 million people who are suffering from dementia and every year 10 million new cases are being reported. The total number of people with dementia is projected to reach 82 million by 2030 and 152 million in 2050.

Prevalence in countries of affluence

According to CDC, Alzheimer is the 6th leading cause of death in U.S adults and 5th leading cause of death in adults over the age of 65. In 2014, 5 million Americans above the age of 65 were diagnosed with Alzheimer. This number is predicted to triple by the year 2060 and reach up to 14 million. Dementia and Alzheimer has been shown to go unreported on death certificates, leading to under representation of the actual mortality caused by these diseases. Between 2000 and 2015, mortality due to cardiovascular diseases has decreased by 11%, where as death from Alzheimer has increased by 123%. 1 in 3 people over the age of 65 die from Alzheimer or other forms of dementia. Furthermore, 200,000 individuals have been affected by young onset dementia. In United States, Alzheimer affects more women than men. It is twice more common in African-Americans and Hispanics than in whites. As the number of older Americans increases rapidly, the number of new cases of Alzheimer will rise too.

East Asia has the most people living with dementia (9.8 million) followed by Western Europe (7.5 million), South Asia (5.1 million) and North America (4.8 million). In 2016, the prevalence of Alzheimer was 5.05% in Europe. Like in United States, it is more prevalent in women than in men. In the European Union, Finland has the highest mortality among both men and women due to dementia. In Canada, over half a million people are living with dementia. It is projected that by 2031 the number will go up by 66% to 937,000. Every year 25,000 new cases of dementia are diagnosed.

Dementia is the second leading cause of death in Australia. In 2016, it was the leading cause of deaths in females. In Australia 436,366 people are living with dementia in 2018. 3 in 10 people over the age of 85 and 1 in 10 people over the age of 65 have dementia. It is the single greatest cause of disability in older Australians. Rates of dementia are higher for indigenous people. In people from the northern territory and western Australia the prevalence of dementia is 26 times higher in the 45–69 year old group and about 20 times greater in 60–69 year old group.

Risk factors in countries of affluence

The risk factors for developing dementia or Alzheimer's include age, family history, genetic factors, environmental factors, brain injury, viral infections, neurotoxic chemicals, and various immunological and hormonal disorders.

A new research study has found an association between the affluence of a country, hygiene conditions and the prevalence of Alzheimer in their population. According to the Hygiene Hypothesis, affluent countries with more urbanized and industrialized areas have better hygiene, better sanitation, clean water and improved access to antibiotics. This reduces the exposure to the friendly bacteria, virus and other microorganisms that help stimulate our immune system. Decreased microbial exposure leads to immune system that is poorly developed, which exposes the brain to inflammation as is seen in Alzheimer's disease.

Countries like the UK and France that have access to clean drinking water, improved sanitation facilities and have a high GDP show a 9% increase in Alzheimer's disease as opposed to countries like Kenya and Cambodia. Also countries like UK and Australia, where three quarters of their population lives in urban areas, have a 10% higher Alzheimer's rate than in countries like Bangladesh and Nepal where less than one tenth of their population live in urban areas.

Alzheimer's risk changes with the environment. Individuals from the same ethnic background living in an area of low sanitation will have a lower risk as compared to the same individuals living in an area of high sanitation who will be exposed to a higher risk of developing Alzheimer's. An African-American in U.S. has a higher risk of developing Alzheimer's as compared to one living in Nigeria. Immigrant populations exhibit Alzheimer disease rates intermediate between their home country and adopted country. Moving from a country of high sanitation to a country of low sanitation reduces the risk associated with the disease.

Mental illness

People who face poverty have more risks related to having a mental illness and also do not have as much access to treatment. The stressful events that they face, unsafe living condition and poor physical health lead to cycle of poverty and mental illness that is seen all over the world. According to the World Health Organization 76–85% of people living in lower and middle income countries are not treated for their mental illness. For those in higher-income counties, 35–50% of people with mental illness do not receive treatment. It is estimated that 90% of deaths by suicide are caused by substance use disorders and mental illness in higher income countries. In lower to middle income countries, this number is lower.

Prevalence of mental illness

One in four people have experienced mental illness at one time in their lives, and approximately 450 million people in the world currently have a mental illness. Those who are impoverished live in conditions associated with a higher risk for mental illness and, to compound the issue, do not have as much access to treatment. Stress, unsafe living conditions, and poor physical health associated with lack of sufficient income lead to a cycle of poverty and mental illness that is observed worldwide. Of all countries, India, China, and the United States have the highest levels of anxiety, depression and schizophrenia, according to the WHO. The proportion of people with depression is between 2% to 6%; Greenland, Australia, and the United States have the highest rates of this disorder. Of these three, the U.S. is reported to have the greatest rate of depression. In the U.S., approximately one in five adults has a mental illness, or 44.7 million people. In 2016, it was estimated that 268 million people in the world had depression.

Anxiety disorders, such as generalized anxiety, Obsessive Compulsive Disorder, and Post Traumatic Stress Disorder affected 275 million people worldwide in 2016. The global proportion of people affected by anxiety disorders is between 2.5–6.5%. Australia, Brazil, Argentina, Iran, the United States, and a number of countries in Western Europe appear to have a higher prevalence of anxiety disorders.

Cancer

Cancer is a generic term for a large group of disease which is characterized by rapid creation of abnormal cells that grow beyond their usual boundaries. These cells can invade adjoining parts of the body and spread to other organs causing metastases, which is a major cause of death. According to WHO, Cancer is the second leading cause of death globally. One in six deaths worldwide are caused due to cancer, accounting to a total of 9.6 million deaths in 2018.Tracheal, bronchus, and lung cancer is the leading form of cancer deaths across most high and middle-income countries.

Prevalence in countries of affluence

In United States, 1,735,350 new cases of cancer will be diagnosed in 2018. Most common forms of cancer are cancer of the breast, lung, bronchus, prostate, colorectal cancer, melanoma of skin, Non-Hodgkin's lymphoma, renal cancer, thyroid cancer and liver cancer. Cancer mortality is higher among men than in women. African-Americans have the highest risk of mortality due to cancer. Cancer is also the leading cause of death in Australia. The most common cancers in Australia are prostate, breast, colorectal, melanoma and lung cancer. These account for 60% of the cancer cases diagnosed in Australia.

Europe contains only 1/8 of the world population, but has around one quarter of the global cancer cases, with 3.7 million new cases each year. Lung, breast, stomach, liver, colon are the most common cancers in Europe. The overall incidences among different cancers vary across countries.

About one in two Canadians will develop cancer in their lifetime, and one in four will die of the disease. In 2017, 206,200 new cases of cancer were diagnosed. Lung, colorectal, breast, and prostate cancer accounted for about half of all cancer diagnoses and deaths.

Risk factors

High prevalence of cancer in high-income countries is attributed to lifestyle factors like obesity, smoking, physical inactivity, diet and alcohol intake. Around 40% of the cancers can be prevented by modifying these factors.

Allergies/autoimmune diseases

The rate of allergies around the world has risen in industrialized nations over the past 50 years. A number of public health measures, such as sterilized milk, use of antibiotics and improved food production have contributed to a decrease in infections in developed countries. There is a proposed causal relationship, known as the "hygiene hypothesis" that indicates that there are more autoimmune disorders and allergies in developed countries with fewer infections. In developing countries, it is assumed that the rates of allergies are lower than developed countries. That assumption may not be accurate due to limited data on prevalence. Research has found an increase in asthma by 10% in countries such as Peru, Costa Rica, and Brazil.