Yaws
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Yaws is a tropical
infection An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dise ...
of the
skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other cuticle, animal coverings, such as the arthropod exoskeleton, have diffe ...
,
bone A bone is a Stiffness, rigid Organ (biology), organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red blood cell, red and white blood cells, store minerals, provid ...
s, and joints caused by the
spirochete A spirochaete () or spirochete is a member of the phylum Spirochaetota (), (synonym Spirochaetes) which contains distinctive diderm (double-membrane) gram-negative bacteria, most of which have long, helically coiled (corkscrew-shaped or s ...
bacterium Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
''
Treponema pallidum ''Treponema pallidum'', formerly known as ''Spirochaeta pallida'', is a spirochaete bacterium with various subspecies that cause the diseases syphilis, bejel (also known as endemic syphilis), and yaws. It is transmitted only among humans. It is ...
pertenue''. The disease begins with a round, hard swelling of the skin, in diameter. The center may break open and form an
ulcer An ulcer is a discontinuity or break in a bodily membrane that impedes normal function of the affected organ. According to Robbins's pathology, "ulcer is the breach of the continuity of skin, epithelium or mucous membrane caused by sloughing o ...
. This initial skin lesion typically heals after 3–6 months. After weeks to years, joints and bones may become painful,
fatigue Fatigue describes a state of tiredness that does not resolve with rest or sleep. In general usage, fatigue is synonymous with extreme tiredness or exhaustion that normally follows prolonged physical or mental activity. When it does not resolve ...
may develop, and new skin lesions may appear. The skin of the palms of the hands and the soles of the feet may become thick and break open. The bones (especially those of the nose) may become misshapen. After 5 years or more, large areas of skin may die, leaving scars. Yaws is spread by direct contact with the fluid from a lesion of an infected person. The contact is usually of a nonsexual nature. The disease is most common among children, who spread it by playing together. Other related treponemal diseases are
bejel Bejel, or endemic syphilis, is a chronic skin and tissue disease caused by infection by the ''endemicum'' subspecies of the spirochete ''Treponema pallidum''. Bejel is one of the "endemic treponematoses" (endemic infections caused by spiral-shaped ...
(''T. pallidum endemicum''), pinta (''T. carateum''), and
syphilis Syphilis () is a sexually transmitted infection caused by the bacterium ''Treponema pallidum'' subspecies ''pallidum''. The signs and symptoms of syphilis vary depending in which of the four stages it presents (primary, secondary, latent, an ...
(''T. p. pallidum''). Yaws is often diagnosed by the appearance of the lesions. Blood
antibody An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
tests may be useful, but cannot separate previous from current infections.
Polymerase chain reaction The polymerase chain reaction (PCR) is a method widely used to rapidly make millions to billions of copies (complete or partial) of a specific DNA sample, allowing scientists to take a very small sample of DNA and amplify it (or a part of it) t ...
is the most accurate method of diagnosis. No vaccine has yet been found. Prevention is, in part, done by curing those who have the disease, thereby decreasing the risk of transmission. Where the disease is common, treating the entire community is effective. Improving cleanliness and sanitation also decreases spread. Treatment is typically with
antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of ...
s, including:
azithromycin Azithromycin, sold under the brand names Zithromax (in oral form) and Azasite (as an eye drop), is an antibiotic medication used for the treatment of a number of bacterial infections. This includes middle ear infections, strep throat, pneumon ...
by mouth or benzathine penicillin by injection. Without treatment, physical deformities occur in 10% of cases. Yaws is common in at least 13 tropical countries as of 2012. Almost 85% of infections occurred in three countries—
Ghana Ghana (; tw, Gaana, ee, Gana), officially the Republic of Ghana, is a country in West Africa. It abuts the Gulf of Guinea and the Atlantic Ocean to the south, sharing borders with Ivory Coast in the west, Burkina Faso in the north, and To ...
,
Papua New Guinea Papua New Guinea (abbreviated PNG; , ; tpi, Papua Niugini; ho, Papua Niu Gini), officially the Independent State of Papua New Guinea ( tpi, Independen Stet bilong Papua Niugini; ho, Independen Stet bilong Papua Niu Gini), is a country i ...
, and
Solomon Islands Solomon Islands is an island country consisting of six major islands and over 900 smaller islands in Oceania, to the east of Papua New Guinea and north-west of Vanuatu. It has a land area of , and a population of approx. 700,000. Its capita ...
. The disease only infects humans. Efforts in the 1950s and 1960s by the
World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of h ...
decreased the number of cases by 95%. Since then, cases have increased, but with renewed efforts to globally eradicate the disease by 2020. In 1995, the number of people infected was estimated at more than 500,000. In 2016, the number of reported cases was 59,000. Although one of the first descriptions of the disease was made in 1679 by
Willem Piso Willem Piso (in Dutch Willem Pies, in Latin Gulielmus Piso, also called Guilherme Piso in Portuguese) (1611 in Leiden – 28 November 1678 in Amsterdam) was a Dutch physician and naturalist who participated as an expedition doctor in D ...
, archaeological evidence suggests that yaws may have been present among human ancestors as far back as 1.6 million years ago.


Signs and symptoms

Yaws is classified as primary, secondary, and tertiary; this is useful, but people often have a mix of stages. Within 9–90 days (but usually about 21 days) of infection, a painless but distinctive "mother yaw" nodule appears. Initially reddened and inflamed, it may become a
papilloma A papilloma (plural papillomas or papillomata) ('' papillo-'' + '' -oma'') is a benign epithelial tumor growing exophytically (outwardly projecting) in nipple-like and often finger-like fronds. In this context, papilla refers to the projection cre ...
, which can then become an
ulcer An ulcer is a discontinuity or break in a bodily membrane that impedes normal function of the affected organ. According to Robbins's pathology, "ulcer is the breach of the continuity of skin, epithelium or mucous membrane caused by sloughing o ...
, possibly with a yellow crust. Mother yaws are most commonly found on the legs and ankles, and are rarely found on the genitals (unlike syphilis) The mother yaw enlarges and becomes warty in appearance. Nearby "daughter yaws" may also appear simultaneously. This primary stage resolves completely, with scarring, within 3–6 months. The scar is often pigmented. File:10.1177 0956462414549036-fig3-Papilloma of primary yaws.jpg, Papilloma mother yaw File:Clinical presentation of skin NTDs tropicalmed-03-00120-g001 (cropped to yaws).jpg, Mother yaw nodule with central ulceration and a yellow crust File:10.1177 0956462414549036-fig2-Ulcer of primary yaws.jpg, Ulcerated mother yaw File:10.1177 0956462414549036-fig1-Ulcer of primary yaws.jpg, Ulcerated mother yaw File:10.1177 0956462414549036-fig8-Primary yaws, healed Lesion.jpg, Healed primary yaw lesion, showing pigmented scar The secondary stage occurs months to two years later (but usually 1–2 months later), and may thus begin when the mother yaw has not yet healed. It happens when the bacterium spreads in the blood and lymph. It begins as multiple, pinhead-like
papules A papule is a small, well-defined bump in the skin. It may have a rounded, pointed or flat top, and may have a dip. It can appear with a stalk, be thread-like or look warty. It can be soft or firm and its surface may be rough or smooth. Some h ...
; these initial lesions grow and change in appearance and may last weeks before healing, with or without scarring. Secondary yaws typically shows widespread skin lesions that vary in appearance, including "crab yaws" (areas of skin of abnormal colour) on the palms of the hands and soles of the feet (named for the crab-like gait they cause people with painful soles to assume). These may show
desquamation Desquamation occurs when the outermost layer of a tissue, such as the skin, is shed. The term is . Physiologic desquamation Keratinocytes are the predominant cells of the epidermis, the outermost layer of the skin. Living keratinocytes reside in ...
. These secondary lesions frequently ulcerate and are then highly infectious, but heal after 6 months or more. Secondary yaws affects the skin and bones. The most common bone-related problem is
periostitis Periostitis, also known as periostalgia, is a medical condition caused by inflammation of the periosteum, a layer of connective tissue that surrounds bone. The condition is generally chronic, and is marked by tenderness and swelling of the bone an ...
, an inflammation around the bone, often occurs in the bones of the fingers and the long bones of the lower arms and legs, causing swollen fingers and limbs. This causes pain at night and thickening of the affected bones (periostitis). About 75% of infected children surveyed in Papua New Guinea reported joint pain.
Swollen lymph nodes Edema, also spelled oedema, and also known as fluid retention, dropsy, hydropsy and swelling, is the build-up of fluid in the body's Tissue (biology), tissue. Most commonly, the legs or arms are affected. Symptoms may include skin which feels t ...
, fever, and malaise are also common. After primary and secondary yaws (and possibly, in some cases, without these phases), a latent infection develops. Within five years (rarely, within ten years) it can relapse and become active again, causing further secondary lesions, which may infect others. These relapse lesions are most commonly found around the armpits, mouth, and anus. File:Hypopigmented patches with overlying pink papules with central depressions.jpg, Secondary yaws begin as multiple small lesions. 10.1177 0956462414549036-fig4-Secondary yaws- multiple small ulcerative lesions.jpg, The small lesions grow. 10.1177 0956462414549036-fig5-Secondary yaws- maculo-papular lesions with scaling.jpg, Secondary lesions vary in appearance (see list of terms) File:Papulosquamous plaque and yellow-crusted nodules of secondary yaws on the leg (far view and close-up).jpg, Here two different appearances (papulosquamous plaque and yellow-crusted nodules) are seen in the same 10-year-old person (large-scale of both, close-up of nodules) File:Black-crusted erosion and surrounding hypopigmented patch on elbow.jpg, Hypopigmentation and an crusted erosion, elbow of a 5-year-old File:Large, hypopigmented patches topped with scaly pink and brown papules on the dorsa of feet and ankles.jpg, Secondary yaws; hypopigmented areas of skin topped with pink and brown
papule A papule is a small, well-defined bump in the skin. It may have a rounded, pointed or flat top, and may have a dip. It can appear with a stalk, be thread-like or look warty. It can be soft or firm and its surface may be rough or smooth. Some h ...
s, 9-year-old File:Plantar yaw with moist yellow crusted erosion overlying pink granulation tissue.jpg, Erosion on the sole of the foot, close-up ( large-scale). If deeper, it would be an ulcer File:Moist, thick yellow crusted pink papilloma, 9-year-old boy.jpg, Secondary yaws papilloma (same 9-year-old as pictures of feet) File:4150843630 bc699a7fa4 bPian.jpg, Secondary breakout in a Javanese child age of 12 years. Wax model File:Scars of yaws lesions on the legs of a female patient with a history of yaws skin lesions in childhood and positive non-treponemal and treponemal antibodies (latent yaws).jpg, Secondary yaws scars in an adult with childhood history of yaws
An estimated 10% of people with yaws formerly were thought to develop tertiary disease symptoms, but more recently, tertiary yaws has been less frequently reported. Tertiary yaws can include
gummatous A gumma (plural gummata or gummas) is a soft, non-cancerous growth resulting from the tertiary stage of syphilis (and yaws). It is a form of granuloma. Gummas are most commonly found in the liver (''gumma hepatis''), but can also be found in br ...
nodules. It most commonly affects the skin. The skin of the palms and soles may thicken (
hyperkeratosis Hyperkeratosis is thickening of the stratum corneum (the outermost layer of the epidermis, or skin), often associated with the presence of an abnormal quantity of keratin,Kumar, Vinay; Fausto, Nelso; Abbas, Abul (2004) ''Robbins & Cotran Patholo ...
). Nodules ulcerating near joints can cause tissue death. Periostitis can be much more severe. The shinbones may become bowed (saber shin) from chronic periostitis. Yaws may or may not have
cardiovascular The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, tha ...
or
neurological Neurology (from el, νεῦρον (neûron), "string, nerve" and the suffix -logia, "study of") is the branch of medicine dealing with the diagnosis and treatment of all categories of conditions and disease involving the brain, the spinal ...
effects; definitive evidence is lacking.


Rhinopharyngitis mutilans

Rhinopharyngitis mutilans, also known as gangosa, is a destructive ulcerative condition that usually originates about the
soft palate The soft palate (also known as the velum, palatal velum, or muscular palate) is, in mammals, the soft tissue constituting the back of the roof of the mouth. The soft palate is part of the palate of the mouth; the other part is the hard palate. ...
and spreads into the
hard palate The hard palate is a thin horizontal bony plate made up of two bones of the facial skeleton, located in the roof of the mouth. The bones are the palatine process of the maxilla and the horizontal plate of palatine bone. The hard palate spans ...
,
nasopharynx The pharynx (plural: pharynges) is the part of the throat behind the mouth and nasal cavity, and above the oesophagus and trachea (the tubes going down to the stomach and the lungs). It is found in vertebrates and invertebrates, though its struct ...
, and
nose A nose is a protuberance in vertebrates that houses the nostrils, or nares, which receive and expel air for respiration alongside the mouth. Behind the nose are the olfactory mucosa and the sinuses. Behind the nasal cavity, air next passes th ...
, resulting in mutilating
cicatrice A scar (or scar tissue) is an area of fibrous tissue that replaces normal skin after an injury. Scars result from the biological process of wound repair in the skin, as well as in other organs, and tissues of the body. Thus, scarring is a na ...
s, and outward to the face, eroding intervening
bone A bone is a Stiffness, rigid Organ (biology), organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red blood cell, red and white blood cells, store minerals, provid ...
,
cartilage Cartilage is a resilient and smooth type of connective tissue. In tetrapods, it covers and protects the ends of long bones at the joints as articular cartilage, and is a structural component of many body parts including the rib cage, the neck an ...
, and
soft tissues Soft tissue is all the tissue in the body that is not hardened by the processes of ossification or calcification such as bones and teeth. Soft tissue connects, surrounds or supports internal organs and bones, and includes muscle, tendons, ligam ...
. It occurs in late stages of yaws, usually 5 to 10 years after first symptoms of
infection An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dise ...
. This is now rare. Very rarely, yaws may cause
bone spurs An exostosis, also known as bone spur, is the formation of new bone on the surface of a bone. Exostoses can cause chronic pain ranging from mild to debilitatingly severe, depending on the shape, size, and location of the lesion. It is most commonl ...
in the upper jaw near the nose (gondou); gondou was rare even when yaws was a common disease. File:Medical diagnosis for the student and practitioner (1922) (14761746096).jpg, Deep ulceration occurs in tertiary yaws File:Medical diagnosis for the student and practitioner (1922) (14804596673).jpg, Severe tertiary yaws; gangosa File:Medical diagnosis for the student and practitioner (1922) p1117 (cropped to goundu).jpg, Goundu, a very rare yaws-caused deformity around the nose


Cause

The disease is transmitted by skin-to-skin contact with an infective lesion, with the bacterium entering through a pre-existing cut, bite, or scratch. Early (primary and secondary) yaws lesions have a higher bacterial load, thus are more infectious. Both papillomas and ulcers are infectious. Infectivity is thought to last 12–18 months after infection, longer if a relapse occurs. Early yaws lesions are often itchy, and more lesions may form along lines that are scratched. Yaws may be evolving less conspicuous lesions. Yaws is most common among children, who spread it by playing together. It is not thought to be transmitted from mother to child in the womb. Yaws is not a
venereal disease Sexually transmitted infections (STIs), also referred to as sexually transmitted diseases (STDs) and the older term venereal diseases, are infections that are spread by sexual activity, especially vaginal intercourse, anal sex, and oral se ...
. ''T. pallidum pertenue'' has been identified in nonhuman
primates Primates are a diverse order of mammals. They are divided into the strepsirrhines, which include the lemurs, galagos, and lorisids, and the haplorhines, which include the tarsiers and the simians (monkeys and apes, the latter including huma ...
( baboons,
chimpanzee The chimpanzee (''Pan troglodytes''), also known as simply the chimp, is a species of great ape native to the forest and savannah of tropical Africa. It has four confirmed subspecies and a fifth proposed subspecies. When its close relative th ...
s, and
gorilla Gorillas are herbivorous, predominantly ground-dwelling great apes that inhabit the tropical forests of equatorial Africa. The genus ''Gorilla'' is divided into two species: the eastern gorilla and the western gorilla, and either four or fi ...
s) and experimental
inoculation Inoculation is the act of implanting a pathogen or other microorganism. It may refer to methods of artificially inducing immunity against various infectious diseases, or it may be used to describe the spreading of disease, as in "self-inoculati ...
of human beings with a
simian The simians, anthropoids, or higher primates are an infraorder (Simiiformes ) of primates containing all animals traditionally called monkeys and apes. More precisely, they consist of the parvorders New World monkeys (Platyrrhini) and Catarrhi ...
isolate causes yaws-like disease. However, no evidence exists of cross-transmission between human beings and primates, but more research is needed to discount the possibility of a yaws animal reservoir in nonhuman primates.


Diagnosis

Most often the diagnosis is made clinically.
Dark field microscopy Dark-field microscopy (also called dark-ground microscopy) describes microscopy methods, in both light and electron microscopy, which exclude the unscattered beam from the image. As a result, the field around the specimen (i.e., where there is ...
of samples taken from early lesions (particularly ulcerative lesions) may show the responsible bacteria; the
spirochaetes A spirochaete () American and British English spelling differences#ae and oe, or spirochete is a member of the phylum (biology), phylum Spirochaetota (), (synonym Spirochaetes) which contains distinctive diderm bacteria, diderm (double-membr ...
are only 0.3 µm wide by 6–20 µm long, so light-field microscopy does not suffice. A microscopic examination of a biopsy of a yaw may show skin with clear epidermal hyperplasia (a type of skin thickening) and
papillomatosis Papillomatosis of skin is skin surface elevation caused by hyperplasia and enlargement of contiguous dermal papillae.Kumar, Vinay; Fausto, Nelso; Abbas, Abul (2004) ''Robbins & Cotran Pathologic Basis of Disease'' (7th ed.). Saunders. Page 1230. . ...
(a type of surface irregularity), often with focal
spongiosis Spongiosis is mainly intercellular edema (abnormal accumulation of fluid) in the epidermis,Kumar, Vinay; Fausto, Nelso; Abbas, Abul (2004) ''Robbins & Cotran Pathologic Basis of Disease'' (7th ed.). Saunders. Page 1230. . and is characteristic of ...
(an accumulation of fluid in specific part of the epidermis).
Immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...
cells,
neutrophil Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying in ...
s and
plasma cell Plasma cells, also called plasma B cells or effector B cells, are white blood cells that originate in the lymphoid organs as B lymphocytes and secrete large quantities of proteins called antibodies in response to being presented specific substan ...
s, accumulate in the skin, in densities that may cause microabscesses. Warthin–Starry or Levaditi silver stains selectively stain ''T. pallidum'', and direct and indirect
immunofluorescence Immunofluorescence is a technique used for light microscopy with a fluorescence microscope and is used primarily on microbiological samples. This technique uses the specificity of antibodies to their antigen to target fluorescent dyes to specif ...
and
immunoperoxidase Immunoperoxidase is a type of immunostain used in molecular biology, medical research, and clinical diagnostics. In particular, immunoperoxidase reactions refer to a sub-class of immunohistochemical or immunocytochemical procedures in which the ant ...
tests can detect
polyclonal antibodies Polyclonal antibodies (pAbs) are antibodies that are secreted by different B cell lineages within the body (whereas monoclonal antibodies come from a single cell lineage). They are a collection of immunoglobulin molecules that react against a ...
to ''T. pallidum''s. Histology often shows some spatial features which distinguish yaws from syphilis (syphilis is more likely to be found in the dermis, not the epidermis, and shows more
endothelial cell The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vessel ...
proliferation and
vascular The blood vessels are the components of the circulatory system that transport blood throughout the human body. These vessels transport blood cells, nutrients, and oxygen to the tissues of the body. They also take waste and carbon dioxide away f ...
obliteration). Blood-serum (serological) tests are increasingly done at the point of care. They include a growing range of treponemal and nontreponemal assays. Treponemal tests are more
specific Specific may refer to: * Specificity (disambiguation) * Specific, a cure or therapy for a specific illness Law * Specific deterrence, focussed on an individual * Specific finding, intermediate verdict used by a jury in determining the fina ...
, and are positive for any one who has ever been infected with yaws; they include the ''Treponema pallidum'' particle agglutination assay. Nontreponemal assays can be used to indicate the progress of an infection and a cure, and positive results weaken and may become negative after recovery, especially after a case treated early. They include the venereal disease research laboratory (
VDRL The Venereal Disease Research Laboratory test (VDRL) is a blood test for syphilis and related non-venereal treponematoses that was developed by the eponymous lab. The VDRL test is used to screen for syphilis (it has high sensitivity), whereas othe ...
; requires microscopy) and rapid plasma ( RPR; naked-eye result) tests, both of which
flocculate Flocculation, in the field of chemistry, is a process by which colloidal particles come out of suspension to sediment under the form of floc or flake, either spontaneously or due to the addition of a clarifying agent. The action differs from p ...
patient-derived
antibodies An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
with
antigens In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...
. Serological tests cannot distinguish yaws from the closely related
syphilis Syphilis () is a sexually transmitted infection caused by the bacterium ''Treponema pallidum'' subspecies ''pallidum''. The signs and symptoms of syphilis vary depending in which of the four stages it presents (primary, secondary, latent, an ...
; no test distinguishing yaws from syphilis is widely available. The two genomes differ by about 0.2%. PCR and
DNA sequencing DNA sequencing is the process of determining the nucleic acid sequence – the order of nucleotides in DNA. It includes any method or technology that is used to determine the order of the four bases: adenine, guanine, cytosine, and thymine. Th ...
can distinguish the two. There are also no common blood tests which distinguish among the four
treponematoses Treponematosis is a term used to individually describe any of the diseases caused by four members of the bacterial genus '' Treponema''. The four diseases are collectively referred to as treponematoses: * Syphilis (''Treponema pallidum pallidum'') ...
: syphilis (Treponema pallidum pallidum), yaws (Treponema pallidum pertenue), bejel (Treponema pallidum endemicum), and pinta (Treponema carateum). ''
Haemophilus ducreyi ''Haemophilus ducreyi'' is a fastidious gram-negative coccobacillus bacteria. It causes the sexually transmitted disease chancroid, a major cause of genital ulceration in developing countries characterized by painful sores on the genitalia. Ch ...
'' infections can cause skin conditions that mimic primary yaws. People infected with ''Haemophilus ducreyi'' lesions may or may not also have latent yaws, and thus may or may not test positive on serological tests. This was discovered in the mid-2010s. It seems that a recently diverged strain of ''Haemophilus ducreyi'' has evolved from being a sexually transmitted infection to being a skin ulcer pathogen that looks like yaws. Yaws has been reported in nonendemic countries.


Treatment

Treatment is normally by a single
intramuscular injection Intramuscular injection, often abbreviated IM, is the injection of a substance into a muscle. In medicine, it is one of several methods for parenteral administration of medications. Intramuscular injection may be preferred because muscles have ...
of long-acting
benzathine benzylpenicillin Benzathine benzylpenicillin, also known as benzathine penicillin G, is an antibiotic medication useful for the treatment of a number of bacterial infections. Specifically it is used to treat strep throat, diphtheria, syphilis, and yaws. It is a ...
, or less commonly by a course of other antibiotics, such as
azithromycin Azithromycin, sold under the brand names Zithromax (in oral form) and Azasite (as an eye drop), is an antibiotic medication used for the treatment of a number of bacterial infections. This includes middle ear infections, strep throat, pneumon ...
or
tetracycline Tetracycline, sold under various brand names, is an oral antibiotic in the tetracyclines family of medications, used to treat a number of infections, including Acne vulgaris, acne, cholera, brucellosis, plague (disease), plague, malaria, and sy ...
tablets. Penicillin has been the front-line treatment since at least the 1960s, but there is no solid evidence of the evolution of penicillin resistance in yaws. The historical strategy for the eradication of yaws (1952–1964) was: Benzathine benzylpenicillin requires a
cold chain A cold chain is a low temperature-controlled supply chain network. An unbroken cold chain is an uninterrupted series of refrigerated production, storage and distribution activities, along with associated equipment and logistics, which maintain qu ...
and staff who can inject it, and there is a small risk of
anaphylaxis Anaphylaxis is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of use of emergency medication on site. It typically causes more than one of the follow ...
. It was also not reliably available during the 2010s; there have been supply shortages. In the 2010s, a single oral dose of
azithromycin Azithromycin, sold under the brand names Zithromax (in oral form) and Azasite (as an eye drop), is an antibiotic medication used for the treatment of a number of bacterial infections. This includes middle ear infections, strep throat, pneumon ...
was shown to be as effective as intramuscular penicillin. Unlike penicillin, there is strong evidence that yaws is evolving
antibiotic resistance Antimicrobial resistance (AMR) occurs when microbes evolve mechanisms that protect them from the effects of antimicrobials. All classes of microbes can evolve resistance. Fungi evolve antifungal resistance. Viruses evolve antiviral resistance. ...
to azithromycin; there are two known mutations in the bacterium, each of which can cause resistance and make the treatment ineffective. This has threatened eradication efforts. Within 8–10 hours of penicillin treatment, bacteria can no longer be found in lesion biopsies. Primary and secondary lesions usually heal in 2–4 weeks; bone pain may improve within two days. If treated early enough, bone deformities may reverse and heal. Primary and secondary stage lesions may heal completely, but the destructive changes of tertiary yaws are largely irreversible. If lesions do not heal, or RPR test results do not improve, this may indicate treatment failure or re-infection; the treatment is typically repeated. WHO guidelines says that any presumed treatment failures at 4 weeks require macrolide resistance testing. File:Large, “moist cauliflower” papillomas on left axilla.jpg, Secondary yaws in the left armpit of a ten-year-old, 2020 File:Yaws papillomas on axilla significantly reduced in size 2 weeks and completely resolved 3-and-a-half months after one-dose azithromycin was taken.jpg, Same person, 2 weeks and 3.5 months after a single-dose azithromycin File:Yaws treatment.png, Before and two weeks after a single injection of benzathine penicillin, 1950s.


Epidemiology

Because ''T. pallidum pertenue'' is temperature- and humidity-dependent, yaws is found in humid tropical forest regions in
South America South America is a continent entirely in the Western Hemisphere and mostly in the Southern Hemisphere, with a relatively small portion in the Northern Hemisphere at the northern tip of the continent. It can also be described as the southe ...
,
Africa Africa is the world's second-largest and second-most populous continent, after Asia in both cases. At about 30.3 million km2 (11.7 million square miles) including adjacent islands, it covers 6% of Earth's total surface area ...
,
Asia Asia (, ) is one of the world's most notable geographical regions, which is either considered a continent in its own right or a subcontinent of Eurasia, which shares the continental landmass of Afro-Eurasia with Africa. Asia covers an area ...
and
Oceania Oceania (, , ) is a region, geographical region that includes Australasia, Melanesia, Micronesia, and Polynesia. Spanning the Eastern Hemisphere, Eastern and Western Hemisphere, Western hemispheres, Oceania is estimated to have a land area of ...
. About three quarters of people affected are children under 15 years of age, with the greatest incidence in children 6–10 years old. Therefore, children are the main reservoir of infection. It is more common in remote areas, where access to treatment is poorer. It is associated with poverty and poor sanitation facilities and personal hygiene. Worldwide, almost 85% of yaws cases are in Ghana, Papua New Guinea, and the Solomon Islands. Rates in sub-Saharan Africa are low, but tend to be concentrated in specific populations. , it is estimated that about 89 million people live in yaws-endemic areas, but data are poor, and this is likely an over-estimate. In the early 1900s, yaws was very common; in sub-saharan Africa, it was more frequently treated than malaria, sometimes making up more than half of treatments. Mass treatment campaigns in the 1950s reduced the worldwide
prevalence In epidemiology, prevalence is the proportion of a particular population found to be affected by a medical condition (typically a disease or a risk factor such as smoking or seatbelt use) at a specific time. It is derived by comparing the number o ...
from 50 to 150 million to fewer than 2.5 million; however, during the 1970s there were outbreaks in
South-East Asia Southeast Asia, also spelled South East Asia and South-East Asia, and also known as Southeastern Asia, South-eastern Asia or SEA, is the geographical south-eastern region of Asia, consisting of the regions that are situated south of mainland ...
, and there have been continued sporadic cases in South America. , it was unclear how many people worldwide were currently infected. From 2008 to 2012, 13 countries reported over 300,000 new cases to the WHO. There was no system for certifying local elimination of yaws, and it is not known whether the lack of reports from some countries is because they stopped having yaws cases or because they stopped reporting them. It is estimated that if there is not an active surveillance programme, there is less than a 1-in-2 chance that a country will successfully report yaws cases (if it gets them) in over three-quarters of countries with a history of yaws. These countries are thought to need international assistance to mount effective surveillance. Generally, yaws is not a
notifiable disease A notifiable disease is any disease that is required by law to be reported to government authorities. The collation of information allows the authorities to monitor the disease, and provides early warning of possible outbreaks. In the case of live ...
.


History

Examination of remains of ''
Homo erectus ''Homo erectus'' (; meaning "upright man") is an extinct species of archaic human from the Pleistocene, with its earliest occurrence about 2 million years ago. Several human species, such as '' H. heidelbergensis'' and '' H. antecessor' ...
'' from
Kenya ) , national_anthem = "Ee Mungu Nguvu Yetu"() , image_map = , map_caption = , image_map2 = , capital = Nairobi , coordinates = , largest_city = Nairobi , ...
, that are about 1.6 million years old, has revealed signs typical of yaws. The genetic analysis of the yaws causative bacteria—''Treponema pallidum pertenue''—has led to the conclusion that yaws is the most ancient of the four known ''Treponema'' diseases. All other ''Treponema pallidum'' subspecies probably evolved from ''Treponema pallidum pertenue''. Yaws is believed to have originated in tropical areas of Africa, and spread to other tropical areas of the world via immigration and the
slave trade Slavery and enslavement are both the state and the condition of being a slave—someone forbidden to quit one's service for an enslaver, and who is treated by the enslaver as property. Slavery typically involves slaves being made to perf ...
. The latter is likely the way it was introduced to
Europe Europe is a large peninsula conventionally considered a continent in its own right because of its great physical size and the weight of its history and traditions. Europe is also considered a Continent#Subcontinents, subcontinent of Eurasia ...
from
Africa Africa is the world's second-largest and second-most populous continent, after Asia in both cases. At about 30.3 million km2 (11.7 million square miles) including adjacent islands, it covers 6% of Earth's total surface area ...
in the 15th century. The first unambiguous description of yaws was made by the
Dutch Dutch commonly refers to: * Something of, from, or related to the Netherlands * Dutch people () * Dutch language () Dutch may also refer to: Places * Dutch, West Virginia, a community in the United States * Pennsylvania Dutch Country People E ...
physician
Willem Piso Willem Piso (in Dutch Willem Pies, in Latin Gulielmus Piso, also called Guilherme Piso in Portuguese) (1611 in Leiden – 28 November 1678 in Amsterdam) was a Dutch physician and naturalist who participated as an expedition doctor in D ...
. Yaws was clearly described in 1679 among African slaves by
Thomas Sydenham Thomas Sydenham (10 September 1624 – 29 December 1689) was an English physician. He was the author of ''Observationes Medicae'' which became a standard textbook of medicine for two centuries so that he became known as 'The English Hippocrate ...
in his
epistle An epistle (; el, ἐπιστολή, ''epistolē,'' "letter") is a writing directed or sent to a person or group of people, usually an elegant and formal didactic letter. The epistle genre of letter-writing was common in ancient Egypt as par ...
on
venereal diseases Sexually transmitted infections (STIs), also referred to as sexually transmitted diseases (STDs) and the older term venereal diseases, are infections that are spread by sexual activity, especially vaginal intercourse, anal sex, and oral s ...
, although he thought that it was the same disease as
syphilis Syphilis () is a sexually transmitted infection caused by the bacterium ''Treponema pallidum'' subspecies ''pallidum''. The signs and symptoms of syphilis vary depending in which of the four stages it presents (primary, secondary, latent, an ...
. The causative agent of yaws was discovered in 1905 by
Aldo Castellani Aldo Castellani, KCMG (8 September 1874 – 3 October 1971) was an Italian pathologist and bacteriologist A bacteriologist is a microbiologist, or similarly trained professional, in bacteriology -- a subdivision of microbiology that studies b ...
in ulcers of patients from
Ceylon Sri Lanka (, ; si, ශ්‍රී ලංකා, Śrī Laṅkā, translit-std=ISO (); ta, இலங்கை, Ilaṅkai, translit-std=ISO ()), formerly known as Ceylon and officially the Democratic Socialist Republic of Sri Lanka, is an ...
. The current English name is believed to be of Carib origin, from "yaya", meaning sore. Towards the end of the Second World War yaws became widespread in the North of Malaya under Japanese occupation. After the country was liberated, the population was treated for yaws by injections of arsenic, of which there was a great shortage, so only those with stage 1 were treated.


Eradication

A series of WHO yaws control efforts, which began shortly after creation of the WHO in 1948, succeeded in eradicating the disease locally from many countries, but have not lasted long enough to eradicate it globally. The Global Control of Treponematoses (TCP) programme by the WHO and the
UNICEF UNICEF (), originally called the United Nations International Children's Emergency Fund in full, now officially United Nations Children's Fund, is an agency of the United Nations responsible for providing Humanitarianism, humanitarian and Devel ...
launched in 1952 and continued until 1964. A 1953 questionnaire-based estimate was that there were 50–150 million yaws cases in 90 countries. The global prevalence of yaws and the other endemic treponematoses,
bejel Bejel, or endemic syphilis, is a chronic skin and tissue disease caused by infection by the ''endemicum'' subspecies of the spirochete ''Treponema pallidum''. Bejel is one of the "endemic treponematoses" (endemic infections caused by spiral-shaped ...
and pinta, was reduced by the Global Control of Treponematoses (TCP) programme between 1952 and 1964 from about 50 million cases to about 2.5 million (a 95% reduction). However, "premature integration of yaws and other endemic treponematoses activities into weak primary health-care systems, and the dismantling of the vertical eradication programmes after 1964, led to the failure to finish with the remaining 5% of cases" and led to a resurgence of yaws in the 1970s, with the largest number of case found in the Western Africa region. Following the cessation of this program, resources, attention and commitment for yaws gradually disappeared and yaws remained at a low prevalence in parts of Asia, Africa, and the Americas with sporadic outbreaks. With few cases, mainly affecting poor, remote communities with little access to treatment, yaws became poorly known, yaws knowledge and skills died out even among health professionals, and yaws eradication was not seen as a high priority. Although a single injection of long-acting penicillin or other
beta lactam A beta-lactam (β-lactam) ring is a four-membered lactam. A ''lactam'' is a cyclic amide, and ''beta''-lactams are named so because the nitrogen atom is attached to the β-carbon atom relative to the carbonyl. The simplest β-lactam possible is ...
antibiotic cures the disease and is widely available and the disease highly localised, many eradication campaigns ended in complacency and neglect; even in areas where transmission was successfully interrupted, re-introduction from infected areas occurred. Yaws eradication remained a priority in south-east Asia. In 1995, the WHO estimated 460,000 worldwide cases. In the Philippines, yaws stopped being listed as a
notifiable disease A notifiable disease is any disease that is required by law to be reported to government authorities. The collation of information allows the authorities to monitor the disease, and provides early warning of possible outbreaks. In the case of live ...
in 1973; as of 2020, it is still present in the country.
India India, officially the Republic of India (Hindi: ), is a country in South Asia. It is the seventh-largest country by area, the second-most populous country, and the most populous democracy in the world. Bounded by the Indian Ocean on the so ...
implemented a successful Yaws eradication campaign that resulted in the 2016 certification by the WHO that India was free of yaws. In 1996 there were 3,571 yaws cases in India; in 1997 after a serious elimination effort began the number of cases fell to 735. By 2003 the number of cases was 46. The last clinical case in India was reported in 2003 and the last latent case in 2006; certification by the WHO was achieved in 2016. In 2012 the WHO officially targeted yaws for eradication by 2020 following the development of orally administered azithromycin as a treatment, but missed that target. The Morges approach (named after
Morges Morges (; la, Morgiis, plural, probably ablative, else dative; frp, Môrges) is a municipality in the Swiss canton of Vaud and the seat of the district of Morges. It is located on Lake Geneva. History Morges is first mentioned in 1288 as ' ...
, Switzerland, where a meeting on it was held) involved mass treatment with
azithromycin Azithromycin, sold under the brand names Zithromax (in oral form) and Azasite (as an eye drop), is an antibiotic medication used for the treatment of a number of bacterial infections. This includes middle ear infections, strep throat, pneumon ...
. This was safe, but ran into problems with antibiotic resistance, and did not fully interrupt transmission. The discovery that oral antibiotic
azithromycin Azithromycin, sold under the brand names Zithromax (in oral form) and Azasite (as an eye drop), is an antibiotic medication used for the treatment of a number of bacterial infections. This includes middle ear infections, strep throat, pneumon ...
can be used instead of the previous standard, injected
penicillin Penicillins (P, PCN or PEN) are a group of β-lactam antibiotics originally obtained from ''Penicillium'' moulds, principally '' P. chrysogenum'' and '' P. rubens''. Most penicillins in clinical use are synthesised by P. chrysogenum using ...
, was tested on
Lihir Island Lihir Island (a.k.a. Niolam Island) is the largest island in the Lihir group of islands, 22 km long and 14.5 km wide, in Papua New Guinea's New Ireland Province. It consists of a complex of several overlapping basaltic stratovolcanoes r ...
from 2013 to 2014; a single oral dose of the macrolide antibiotic reduced disease prevalence from 2.4% to 0.3% at 12 months. The WHO now recommends both treatment courses (oral azithromycin and injected penicillin), with oral azithromycin being the preferred treatment. , there were 15 countries known to be endemic for yaws, with the recent discovery of endemic transmission in
Liberia Liberia (), officially the Republic of Liberia, is a country on the West African coast. It is bordered by Sierra Leone to Liberia–Sierra Leone border, its northwest, Guinea to its north, Ivory Coast to its east, and the Atlantic Ocean ...
and the
Philippines The Philippines (; fil, Pilipinas, links=no), officially the Republic of the Philippines ( fil, Republika ng Pilipinas, links=no), * bik, Republika kan Filipinas * ceb, Republika sa Pilipinas * cbk, República de Filipinas * hil, Republ ...
. In 2020, 82 564 cases of yaws were reported to the WHO and 153 cases were confirmed. The majority of the cases are reported from
Papua New Guinea Papua New Guinea (abbreviated PNG; , ; tpi, Papua Niugini; ho, Papua Niu Gini), officially the Independent State of Papua New Guinea ( tpi, Independen Stet bilong Papua Niugini; ho, Independen Stet bilong Papua Niu Gini), is a country i ...
and with over 80% of all cases coming from one of three countries in the 2010–2013 period: Papua New Guinea, Solomon Islands, and Ghana. A WHO meeting report in 2018 estimated the total cost of elimination to be US$175 million (excluding Indonesia). In the South-East Asian Regional Office of the WHO, regional eradication efforts are focused on the remaining endemic countries in this region (
Indonesia Indonesia, officially the Republic of Indonesia, is a country in Southeast Asia and Oceania between the Indian and Pacific oceans. It consists of over 17,000 islands, including Sumatra, Java, Sulawesi, and parts of Borneo and New Guine ...
and
East Timor East Timor (), also known as Timor-Leste (), officially the Democratic Republic of Timor-Leste, is an island country in Southeast Asia. It comprises the eastern half of the island of Timor, the exclave of Oecusse on the island's north-weste ...
) after
India India, officially the Republic of India (Hindi: ), is a country in South Asia. It is the seventh-largest country by area, the second-most populous country, and the most populous democracy in the world. Bounded by the Indian Ocean on the so ...
was declared free of yaws in 2016. Although yaws is highly localized and eradication may be feasible, humans may not be the only reservoir of infection.


References


External links

* {{Authority control Bacterium-related cutaneous conditions Syphilis Infectious diseases with eradication efforts Tropical diseases Wikipedia medicine articles ready to translate Wikipedia infectious disease articles ready to translate