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How the Pool Works
The Pool for Open Innovation against Neglected Tropical Diseases facilitates access to the compounds, technologies, and expertise that will help organizations conduct research on treatments for neglected diseases more efficiently and effectively.
There are two ways to participate in the Pool for Open Innovation: as a contributor and a user. For more information on how to get involved go to:
"We are delighted that Alnylam will join GSK in this important program by adding their unique RNAi technology to the patent pool. The more companies, academic institutions and foundations that join the pool, the more effective it will be."
With RNAi technology, we have the opportunity to treat disease and impact the lives of patients in a fundamentally new way by silencing disease-causing genes upstream of today's medicines.
Pool for Open Innovation
The Pool for Open Innovation against Neglected Tropical Diseases motivates innovative and efficient drug discovery and development by opening access to intellectual property or know-how in neglected tropical disease research.
The Pool for Open Innovation was established in February 2009 with the mission of motivating innovative and efficient drug discovery and development by opening access to intellectual property or know-how in neglected tropical disease product development. GlaxoSmithKline became the first major pharmaceutical company to propose a pool for neglected tropical disease in February 2009; Alnylam Pharmaceuticals joined the pool in July 2009 and BIO Ventures for Global Health was chosen as the administrator of the pool in January 2010. In January 2010, the Emory Institute for Drug Development and iThemba Pharmaceuticals joined the pool to access its know-how, experience, and intellectual property to accelerate its drug discovery initiatives for neglected tropical diseases. South Africa's Technology Innovation Agency (TIA) subsequently joined in May 2010 as the first government agency to access the Pool's resources in order to accelerate its efforts to grow the South African biotechnology sector and enhance the quality of life of those affected by neglected tropical diseases. In August 2010, The Medicines for Malaria Venture (MMV) became the first product development partnership (PDP) to contribute intellectual property to the Pool.
Intellectual property concerns have been at the heart of access to medicines. Intellectual property includes patents -- which give the owner a period of time to exclusively market a new product, and know-how—the accumulated experience that companies gain over time in working on new drugs. The Pool for Open Innovation makes thousands of patents and associated know-how accessible to qualified researchers working on drugs for neglected tropical diseases, allowing these researchers to take advantage of hundreds of millions of dollars of value accumulated in companies and universities.
The diseases targeted by the pool are the 16 diseases identified by the FDA for its own Neglected Tropical Diseases (NTD) initiative: tuberculosis, malaria, blinding trachoma, buruli ulcer, cholera, dengue/dengue haemorrhagic fever, racunculiasis, fascioliasis, human African trypanosomiasis, leishmaniasis, leprosy, lymphatic filariasis, onchocerciasis, schistosomiasis, soil transmitted helminthiasis, and yaws. The geographic focus of the pool will be the world's Least Developed Countries as identified by the United Nations and includes much of western and central Africa as well as several countries in Southeast Asia.
- Blinding trachoma
Trachoma is an infectious disease caused by an organism and usually occurs when the discharge from an infected person's eye is passed to another by way of hands, clothing, or flies. Children are the most susceptible to this disease because of their tendency to play and get dirty.
Trachoma is the leading cause of preventable blindness. It is estimated that 6 million people worldwide are blind due to trachoma and more than 150 million more are in need of treatment. Trachoma accounts for 15.5% of the global burden of blindness.
Trachoma occurs worldwide, most often in poor, rural communities within developing countries. The disease is easily preventable with the practice of good facial hygiene and environmental changes to produce cleaner living conditions. Although there is no vaccine, Trachoma is treatable with surgery to reverse the inward growth of the eyelashes and antibiotics.
Symptoms of trachoma include cloudy cornea, discharge from the eye, swelling of the lymph nodes just in front of the ears, swollen eyelids, and turned-in eyelashes.
Infection typically occurs during childhood and repeats over lifetime, eventually causing damage to the interior of the eyelid that forces the eyelashes to grow inward. The inward growth of the eyelashes results in rubbing on the front of the eye, damaging the cornea. The damage done to the cornea leads to severe vision loss and eventual blindness.
- Buruli ulcer
Buruli ulcer (BU) is an infectious disease caused by bacteria from the same family of bacteria that cause tuberculosis and leprosy. The bacteria produce a destructive toxin which causes tissue damage and inhibits immune response to the infected area. Human-to-human transmission has rarely been reported.
BU affects mainly poor rural communities located near still bodies of water; cases have also occurred following floods. Instances have been reported in 30 countries, mainly those with tropical and subtropical climates. Although BU has a low mortality rate, it is estimated that 7,000 people are infected with the disease annually.
It is one of the most common, and perhaps least understood major mycobacterial infection. Currently, there are six main research priorities that will lead to better understanding and prevention of BU. These research areas include mode of transmission, development of simple diagnostic tests, drug treatments and new treatment modalities, development of vaccines, social and economic studies, and studies to determine the incidence and prevalence.
Infection of BU leads to extensive destruction of the skin and soft tissue with the formation of large ulcers usually on the legs or arms. Ulcerations are generally painless unless complicated by a secondary infection. BU can destroy nerves, appendages, and blood vessels and can also invade bone tissue. The disease progresses without pain or fever, which may partially explain why infected persons often do not seek prompt treatment. Infected persons not treated early often suffer long-term functional disability, such as restriction of joint movements as well as the obvious cosmetic problems.
Cholera is an infectious disease caused by bacterial infection of the intestines. Cholera outbreaks are linked to crowded living conditions, inadequate or unprotected water supply, and poor sanitation; making developing countries highly vulnerable to this disease. The most common sources of cholera infection include surface and well water, raw or undercooked seafood, raw fruits and veggies, and grains.
It is estimated that 120,000 people die of cholera each year, with as many as 100 times more cases than officially reported. Cholera can be simply and successfully treated by immediate replacement of fluid and salts lost through diarrhea. Although antibiotics can shorten the course and diminish the severity of the illness, they are not as important as rehydration.
A recently developed oral vaccine for cholera is also available; however, improvements in water supply and sanitation represent the most sustainable approach to protecting against cholera.
Symptoms of cholera include abdominal cramps, dry mucus membranes or mouth, dry skin, excessive thirst, glassy or sunken eyes, lack of tears, lethargy, low urine output, nausea, rapid dehydration, rapid pulse, sunken "soft spots" in infants, vomiting, and sudden, watery diarrhea. Other complications of cholera include low blood sugar, low potassium levels, and kidney failure.
- Dengue fever
Dengue is the most common mosquito-borne viral disease, prominently transmitted by the female Aedes mosquito. Once a mosquito acquires the virus from an infected human, it is capable of transmitting the virus for the rest of its life-span.
Although dengue is rarely fatal, the deadly complication of dengue, dengue hemorrhagic fever (DHF), has a 6 to 30% death rate, with the most deaths occurring in children and young adults. It is estimated that DHF causes 22,000 deaths per year.
Dengue occurs in tropical and sub-tropical parts of the world. There are no specific antiviral medicines for dengue, but currently those infected are prescribed pain relievers to treat fever and pain.
Symptoms of dengue include severe flu-like symptoms ranging from a mild fever, to an incapacitating high fever with a severe headache, pain behind the eyes, muscles and joint pain, and rash.
DHF causes fever, abdominal pain, vomiting, bleeding, enlargement of the liver, and circulatory failure. During DHF, hemorrhagic manifestations occur after two to seven days. Complications include the tendency to bruise easily and other types of skin hemorrhages, bleeding nose or gums, and possible internal bleeding. Capillaries can become extremely permeable, allowing for fluid to escape from the blood vessels. This may lead to failure of the circulatory system, followed by death if the circulatory system is not corrected.
Dracunculiasis is a crippling infectious disease caused by a parasitic worm. The disease is transmitted exclusively by drinking contaminated water.
Although dracunculiasis is rarely fatal, death can occur through a secondary infection to the wound. To prevent a secondary infection, wounds are treated with tropical antibiotics.
Dracunculiasis affects people in rural, deprived, and isolated areas who depend on open water sources, like ponds, for drinking water. There is currently no vaccine or drugs available to prevent or heal the disease.
Drinking water becomes contaminated with the parasite when infected persons try to relieve the burning sensation by sticking the parasite infected part of the body in water. Once the female worm is submerged in water it releases hundreds of thousands of first-stage larvae into the body of water. The larvae are then ingested by tiny water fleas, which are then ingested by those who drink the contaminated water. The water fleas are digested by the stomach acids, leaving the parasite larvae to migrate through the intestinal wall. After 100 days, the male and female parasites mate. The male parasite dies and the female migrates down the muscle planes, and after nearly a year the female worm emerges, usually from the feet, with a uterus filled with larvae, repeating the cycle.
In dracunculiasis, as the parasite migrates through the infected person's subcutaneous tissues, it causes severe pain, especially in the joints. When the parasite emerges, from the feet in 90% of cases, it causes an intensely painful oedema, a blister and an ulcer accompanied by fever, nausea, and vomiting. A few days or even hours before the worm emerges the person may develop a fever, swelling, and pain in the area.
Fascioliasis is a parasitic infectious disease that can cause blockage of the bile ducts in the liver. Fascioliasis is a zoonosis, or a disease of animals that can be transmitted to humans. Susceptible hosts include main domestic animals like cattle, sheep, pigs, horses, donkeys, and others, and sylvatic animals such as hares, rabbits, and rodents. It is now also believed that human-to-human transmission can occur.
Fascioliasis cases are widespread throughout the world. It is estimated that between 2.4 and 17 million people are infected worldwide, and 180 million more are at risk.
The disease is transmitted through a fecal-oral route. Parasitic eggs are passed in feces of infected animals or humans and contaminate the water where they develop within snails. Snails then release mature larvae onto aquatic or semi-aquatic vegetation. Humans typically become infected by drinking contaminated water or using utensils or eating food washed with contaminated water. Fascioliasis can also be transmitted through the consumption of raw liver from infected sheep, goats, or cows.
The most common symptoms include fever, enlarged liver, malaise and weight loss, hives, cough, shortness of breath and/or chest pain, change in bowel habits, nausea, anorexia, vomiting, diarrhea, and/or jaundice, and abdominal pain. Human fascioliasis can be distinguished by four phases. The incubation phase is from the time of the ingestion of parasites to the visibility of the first symptoms, and may last from days to months. During the acute phase immature worms migrate through the liver. Symptoms include hemorrhage and inflammation and are usually severe, including fever, abdominal pain, respiratory disturbances, and skin rashes. The latent phase can last from months to years and most cases are asymptomatic. The chronic phase starts when the worms reach the bile duct. Symptoms during this phase are non-specific and usually mild; however, progressive inflammation can lead to more serious health problems.
- Human African trypanosomiasis
African trypanosomiasis is an infectious parasitic disease caused by protozoa parasites. The disease is transmitted to humans by infected tsetse flies, which acquire the infection through other infected humans or animals.
African trypanosomiasis currently affects more than 500,000 people, with more than 12,000 new cases developing every year. If left untreated, African trypanosomiasis is fatal, but the cure rate approaches 95 percent when those infected are treated with drugs that work inside the CNS.
There is no vaccine available for African trypanosomiasis. Most patients fully recover from African trypanosomiasis if treated during the first stage of the disease. However, the disease occurs mostly in remote rural areas where the health system is weak or nonexistent, making detection in the first stage difficult. Diagnosis is usually not made until the second, ultimately fatal stage when CNS manifestations develop.
There are two types of African trypanosomiasis. Trypanosoma brucei gambiense (TPG) is found in West and Central Africa, and represents 90% of African trypanosomiasis cases. This form of the disease is represented by chronic infection. Persons can be infected for months or years with no symptoms, but when symptoms do emerge the infected person is already in an advanced stage of the disease and the central nervous system (CNS) is already affected.
Trypanosoma brucei rhodesiense (TBR) is found in Eastern and Southern Africa and is represented by an acute infection. The first signs and symptoms of TBR appear after a few weeks or months. This form of the disease typically progresses rapidly and invades the CNS quickly.
There are also two phases of African trypanosomiasis. During the initial phase of the disease, the haemolymphatic phase, symptoms can include bouts of fever, headache, joint pain, and itching. Infected persons may also experience symptoms of extreme fatigue that can last for several years before the second phase of the disease, called the neurological phase, sets in. This longtime fatigue is why the disease is known as the "sleeping sickness".
The Neurological phase begins when the parasite crosses the blood/brain barrier and invades the CNS. This is generally when symptoms of the disease appear, including confusion, sensory disturbances, and poor coordination. Sleep cycle disturbance is also an important feature of African trypanosomiasis.
Leishmaniasis is an infectious parasitic disease with wide range of clinical symptoms. The disease is transmitted by the bite of a sandfly. Some types of these parasites can be transmitted through blood transfusions or contaminated needles. Congenital transmission, spread from pregnant woman to baby, has also been reported.
There are no vaccines or drugs to prevent infection. The best ways to prevent the disease are to wear protective clothing, insect repellant, bed nets, and place screens on doors and windows. With early treatment, the disease cure-rate is higher than 90%. If left untreated, death can occur in as quickly as three to 20 months. Approximately 80,000 people die from leishmaniasis each year.
Leishmaniasis occurs within the world's inter-tropical temperature regions, wherever the sandfly is found.
In leishmaniasis, a sandfly becomes infected with the parasite through biting an infected human. Then there is an incubation period of four to 25 days during which the parasite develops inside the sandfly. Once the sandfly feeds again, its painful sting infects the new victim with the parasite.
There are three forms of leishmaniasis. The cutaneous form of the disease normally produces skin ulcers on exposed parts of the body, such as the face, arms, and legs. The disease can produce a large number of lesions, sometimes up to 200, causing serious disability and leaving the patient permanently scarred. In the mucocutaneous form, lesions can lead to partial or full destruction of the mucous membranes of the nose, mouth, and throat cavities and surrounding tissues. The visceral form, also known as kala azar, is characterized by irregular bouts of fever, substantial weight loss, swelling of the spleen and liver, and anemia.
Leprosy is a chronic infection caused by bacteria. It affects the skin, nerves of the hands and feet, and can also cause problems in the eyes and nose. Leprosy is spread through long-term contact with an untreated person who has the disease, usually through coughing and sneezing. However, within two weeks of starting treatment an infected person is no longer contagious.
Currently, there is no vaccine for leprosy. The BCG (Bacille Calmette-Guerin) vaccine, used to prevent tuberculosis, provides some protection against leprosy, but is not often used to prevent the disease. Leprosy is a curable disease and treatment in early stages helps to avoid permanent disability. If left untreated, leprosy can cause progressive and permanent damage to skin, nerves, eyes, and limbs. People with long-term leprosy may lose use of hands and feet due to repeated traumatic injury because of lack of sensation due to nerve damage.
Multidrug therapy is recommended to treat leprosy; however medication cannot reverse any nerve damage that has already occurred. Leprosy is rarely fatal, but people with leprosy often suffer psychological and social problems due to the disfigurement and significant disability the disease can cause. It is estimated that 2.4 million people suffer from disabilities from leprosy and need ongoing care, with 300,000 new cases developing each year.
There are two variations of the disease, tuberculoid leprosy and lepromatous leprosy. Tuberculoid is milder than lepromatous and is characterized by skin discoloration. In this variation, fewer skin areas are affected and the disease is less contagious. A rash can develop that can eventually cause bacterial nerve damage.
The lepromatous variation is more common than the tuberculoid form. It is characterized by symmetric skin lesions, nodules, plagues, a thickened dermis, and nasal mucosa complications resulting in congestion and nose bleeds. In the lepromatous variation more skin areas are affected and the disease is more severe and contagious. People can also develop borderline leprosy, when they have features from both the Tuberculoid and Lepromatous variations.
- Lymphatic filariasis
Lymphatic filariasis, or Elephantiasis, is a parasitic and infectious tropical disease caused by one of three types of thread-like parasitic worms. The disease is transmitted through mosquito bites.
Lymphatic filariasis affects an estimated 120 million people in 80 countries throughout the tropics and subtropics, and approximately another 1.3 billion, 20% of the world's population, are at risk of acquiring the disease.
There is no vaccine for lymphatic filariasis. The best treatment for the disease is a combination of drugs to kill the parasite, skin care to prevent secondary infections, and elevation, exercises, and in some cases pressure bandages to reduce swelling.
Most people infected with lymphatic filariasis are asymptomatic and will never develop clinical symptoms. A small percentage of people will develop lymphedema, which is caused by irregular functioning of the lymph system. Lymphedema leads to fluid collection and swelling of the legs, arms, breast, and genitalia. Lymphedema can then lead to elephantiasis. Elephantiasis occurs in about 5% of cases and is characterized by the hardening and thickening of the skin caused by bacterial infections within the skin and lymph system. It leads to severe disfigurement, decreased mobility, and long-term disability.
In addition to these symptoms, there can also be internal damage to the kidneys and lymphatic system caused by the parasite. Although rarely fatal, the disease can also cause recurring infections, fever, severe inflammation of the lymph system, and a lung condition called tropical pulmonary eosinophilia.
Malaria is a parasitic infectious disease that is transmitted to people through the bites of infected mosquitoes. Malaria can also be transmitted through blood transfusions, organ transplants, or the shared use of contaminated needles or syringes. It can also be transmitted from mother to unborn baby before or during delivery. Malaria is not contagious and cannot be sexually transmitted.
Malaria is considered one of humanity's most serious parasitic infections. Each year, 350-500 million cases of malaria occur worldwide. If malaria is not treated promptly with effective medicines it can cause severe illness and is often fatal. Each year, more than 1 million people die of malaria, and a child dies of malaria every 30 seconds.
Malaria is found in tropical and subtropical regions. Approximately half the world's population is at risk for malaria, particularly those living in lower income areas.
There is no vaccine for malaria. Prevention measures focus on controlling the disease-carrying mosquito with the use of mosquito nets treated with long-term insecticides and indoor residual spraying of insecticides.
Initial symptoms of Malaria usually appear 10 to 15 days after the infected bite, and include fever, headache, chills, and vomiting. Other symptoms can include flu-like symptoms, muscle aches, lethargy, anemia, and jaundice. If not promptly treated, the falciparum variation can potentially cause kidney failure, seizures, mental confusion, coma, and death. In certain types pf malaria some parasites can lay dormant in the liver for months to four years, causing the disease to eventually recur (recurring malaria).
Onchocerciasis, or River Blindness, is a parasitic disease that is transmitted through the bites of black flies.
There is no vaccine or recommended drug to help prevent onchocerciasis. It is estimated that 17.7 million people are infected with the disease worldwide, and 99% of all cases are found in Africa. Approximately 270,000 of those infected suffer from blindness and another 500,000 have visual impairment.
In onchocerciasis, the parasites are transferred from an infected human to the female black fly through a bite. Over the course of one to three weeks the transferred parasite develops inside the black fly to form infective larvae. The larvae are then passed to another human through another bite. Once in a human, the larvae migrate to the subcutaneous tissue and slowly form into adult worms, completing the disease cycle.
An adult worm can live for 15 years in the human body. After mating, the female worm releases around 100 parasitic larvae a day in the surrounding subcutaneous skin tissue. The parasites can live in the human body for one to two years, and when they die they cause an inflammatory response that leads to skin rashes, lesions, intense itching, and skin depigmentation.
Over several years, severe dermatitis can occur. The skin can waste away and lose elasticity, giving the appearance of early aging. The parasites can also migrate to the eye where they cause inflammation and other complications. Over time the area becomes opaque, leading to impaired vision and eventually blindness. This is what gives the disease its common name, "River Blindness".
Schistosomiasis, or Bilharzias, is a parasitic infectious disease caused by parasitic worms. The disease is transmitted through contaminated freshwater where snails that carry the parasites live. Schistosomiasis can also be transmitted when the parasites penetrate the skin of persons who are wading, swimming, or bathing in the contaminated water. The freshwater becomes contaminated when infected people urinate or defecate in the water source.
There is no vaccine available for schistosomiasis. Next to malaria, schistosomiasis is considered humanity's most serious parasitic infection. Although schistosomiasis is rarely fatal, it can become a chronic illness that damages internal organs and causes cognitive deficiencies in children. The disease is most prevalent in rural areas in which standards of hygiene are low. More than 200 million people are infected worldwide.
Once the parasite penetrates human skin it matures in the lungs or liver and then migrates to the bladder, rectum, intestines, liver, portal venous system, spleen, or lungs causing inflammation or scarring. Parasitic eggs can become embedded in the tissues of the body, leading to the formation of granuloma. Once the disease progresses to the granuloma stage the damage is irreversible; it is possible to kill the parasite but not to repair the damage already done. Rarely, eggs are found in the brain or spinal cord and can cause seizures, paralysis, or spinal cord inflammation.
There are several variations of schistosomiasis, eastern, intestinal, and urinary. The type the infected has depends on the specific parasite that infects the individual and where it migrates to.
Within one to two months symptoms can include fever, chills, cough, and muscle aches, but most people have no symptoms at the early phase of the infection. Children who are repeatedly infected can develop anemia, malnutrition, and learning difficulties.
Complications of this disease can include bladder cancer, chronic kidney failure, chronic liver damage, an enlarged spleen, colon inflammation with bloody diarrhea, kidney and bladder obstruction, pulmonary hypertension, repeated blood infections can occur, right-sided heart failure, and seizures.
- Soil transmitted helminthiasis
Soil-transmitted helminthiasis, or intestinal worms, is a parasitic infectious disease caused by the ingestion of parasite eggs from contaminated soil or by penetration of the skin by larvae in the soil.
Soil-transmitted helminthiasis is associated with poverty, lack of sanitation, impaired hygiene, and overpopulation. It is estimated that 2 billion people worldwide are infected with this disease. It can become fatal due to anemia, vitamin A deficiency, and loss of appetite.
Soil-transmitted helminthiasis can be transmitted to humans through the ingestion of vegetables grown in the infected soil or by drinking water from sources near the infected soil. And most often young children contract the infection from lack of hand washing. For hookworms, the eggs also hatch into larvae which rest in the soil. If a person walks on the contaminated soil, the larvae can penetrate the skin, usually between the toes.
There are a wide range of symptoms including diarrhea, abdominal pain, and general malaise and weakness that may affect working and learning capacities, as well as impair physical growth.
Tuberculosis (TB) is a contagious disease that spreads through the air. When people cough, sneeze, talk, or spit they release TB germs, known as bacilli, into the air. A person only needs to inhale a small amount of bacilli to become infected. Left untreated, each person with active TB disease will infect on average between 10-15 people per year.
Approximately one-third of the world's population is currently infected with TB bacillus. Each year there are more than 8 million new cases of TB reported and almost 2 million TB related deaths. TB is a leading killer of people who are HIV infected due to their weakened immune defenses.
Bacille Calmette Guerin (BCG) is a vaccine for TB given throughout many parts of the world. BCG is especially effective in infants and children, but when administered the vaccine as a child people can still contract TB as an adult. There are currently several drugs to treat TB infections; however there are multiple strands of the disease that are drug-resistant.
TB most commonly affects the lungs, but can also involve almost any organ of the body. People infected with TB bacilli may not immediately become sick with the disease because the immune system blocks the TB bacilli, leaving the disease to lie dormant for years. When the immune system is weakened a person's chance of becoming sick increased.
When TB bacteria are inhaled they can multiply and cause a local lung infection, pneumonia, and then can spread to other parts of the body. The body's immune system stops the infection from spreading by forming scar tissue around the TB bacteria and isolating it from the rest of the body. Once the infection is contained, the disease is in an inactive state, latent TB, unless the body's immune system weakens and the bacteria can break through the scar tissue and become active again.
Symptoms of active TB are generally tiredness or weakness, weight loss, fever, and night sweats. If the infection in the lung worsens, further symptoms can include coughing, chest pain, coughing up of material from the lung, sputum and/or blood, and shortness of breath. If the infection spreads beyond the lungs the symptoms will depend on the organs involved.
Yaws is a chronic infection that affects mainly the skin, bone, and cartilage. It is transmitted primarily through direct skin contact with an infected person. Overcrowding, poor personal hygiene, and poor sanitation facilitate the spread of the disease.
The disease occurs mainly in poor communities in warm, humid, tropical areas of Africa, Asia and Latin America. Currently there is no global coordination to fight the disease.
Yaws can be completely eradicated from an area by giving penicillin or another appropriate antibiotic to everyone in the population, yet this may cost more than an impoverished country can afford. In the 1990's it was estimated that the global prevalence of yaws stood at 2.5 million, with 460,000 new cases each year.
There are four stages of Yaws. In the primary stage the appearance of the first, painless lesion occurs. This initial lesion usually heals without treatment after three to six months.
In the secondary stage, more lesions develop and the lymph nodes swell. These secondary lesions may be painless, or they may be filled with pus, burst, and ulcerate. The secondary stage may last for more than six months.
After the secondary stage comes the latent stage. During the latent stage the disease symptoms abate, although an occasional lesion may appear. Skin lesions may relapse for as long as five years after infection.
The fourth stage of Yaws is the tertiary stage. In this stage the disease can destroy areas of the skin, bones, and joints, and also deform them. The palms of the hands and soles of the feet tend to become thickened and painful. This late stage of yaws develops in 10% of cases, usually five to 10 years after the disease onset. Without treatment, multiple lesions will appear all over the body and can lead to chronic deformities of the legs, nose, palate, and upper jaw.