Talk:Yaws

Introduction

Yaws is a bacterial infection that enters through an open lesion and affects the skin, bones, and joints of its host if left untreated. This infection is caused by a microaerophilic spirochete bacterium, Treponema pallidum pertenue, which flourishes in tropical regions with poor living conditions, such as India, Africa, and South America. Yaws was nearly eradicated in the mid 1900s, but has recently become a major problem in many countries, specifically, India. The ecological, governmental, and social aspects of India and the nature of the microbe itself contribute to the spread of the disease. 

Description of Yaws

The symptoms of yaws usually appear in 3 stages: primary, secondary, and tertiary. The primary stage involves the entry and initial development of T. pallidum pertenue. The secondary stage is characterized by varying skin lesions and is highly infectious. Secondary lesions may go on to develop into tertiary stage, during which secondary lesions may come and go.

Primary stage:
After an incubation period of T. pallidum pertenue of approximately 3 weeks, the primary lesion (mother yaw) develops after a scratch, bite, or abrasion on exposed skin. The mother yaw develops a honey-brown crust and enlarges horizontally 1-5 cm in diameter. The crust hardens and then sloughs off and reveals a raspberry-like base. This raspberry-like base is filled with treponemes, making these lesions highly infectious. During this stage, infected persons may experience lymphadenopathy (swollen lymph nodes), fever, and joint pain. The mother yaw resolves spontaneously in 2-9 months, leaving an atrophic scar with central hypopigmentation and peripheral hyperpigmentation (10).

Secondary stage:
About 6-16 weeks after the primary stage, an eruption of skin lesions, bone lesions, and constitutional symptoms appears. The cutaneous lesions (daughter yaws) resemble the mother yaw but are smaller (up to 2 cm in diameter) and are usually located next to the mouth and nose. The daughter yaws expand, ulcerate, and excrete a fluid swarming with treponemes, which dries into a crust. These bumps on the skin surface can form thick, hyperkeratotic plaques that may become fissured or eroded. Macular and hyperkeratotic lesions on the palms of the hands and the soles of the feet (similar to lesions found in syphilis patients) may also be present. Infected persons may also experience painful osteopetrosis (bone hardening). Some of these early bone changes can be observed on radiographs. Manifestations during this stage are generally non-scarring and reversible. Patients may develop relapses for up to 5 years after the initial infection. The disease then enters a noninfectious latent period where patients do not exhibit any signs or symptoms (10).

Tertiary stage:
After 5-15 years of latency, a late stage develops and is characterized by destructive skin lesions, bone lesions, and possible neurological and ophthalmologic damage. Enlarging and painless subcutaneous nodules develop and undergo abscess formation, necrosis, and ulceration. Lesions have well-defined edges and an indurate base with granulation tissue and yellowish slough. The ulcers that develop in this stage may become infected and lead to devastating destruction of underlying structures. Furthermore, these ulcers may coalesce and form tracts that heal with keloid formation, which leads to crippling deformities and contractures (10).

Description of the microbe

Treponema pallidum subspecies pertenue, the causative agent of yaws, cannot be distinguished by means of histopathologic, serologic, immunologic or therapeutic methods from other treponemal bacteria such as Treponema pallidum subspecies pallidum, which causes syphilis and Treponema pallidum subspecies carateum, which causes pinta (16). These treponematoses are only differentiated by mode of transmission, and the clinical criteria and infection of laboratory animals and humans (16). However, a recent study discovered an antigenic difference established by a single amino acid residue at position 40 in the proteins, namely glutamine in TpF1 of subspecies pallidum and arginine in TyF1 of subspecies pertenue (8).

Treponema pallidum is a spirochete bacterium — spiral-shaped with outer and cytoplasmic membranes and a thin peptidoglycan layer. It has periplasmic flagella (or endoflagella), which lie in the periplasmic space and expand from both ends toward the middle of the organism. The flagellar filament has a sheath and core structure, and is composed of at least four major polypeptides (15). T. pallidum contains at least eight major membrane-associated lipoporoteins. The small number of intramembranous protein particles (~70 per mm2) in the outer membrane contributes to its unusual structure compared to other spirochetes and gram-negative bacteria that possess sevenfold the amount of protein. The sparsely distributed and uniformly sized outer membrane particles indicate that there are few different types of protein in the outer membrane. It is hypothesized that the low concentration of surface-exposed protein antigens decrease the reactivity of antibodies and immune cells enabling T. pallidum to avoid immune response, thus causing its pathogenesis (15).

T. pallidum was recently discovered to be a microaerophilic organism with a doubling time greater than 30 hours. Its slow growth and fastidious character in vivo and in vitro suggest that it may have metabolic limitations and growth requirements yet to be identified (15). However, previous studies indicate that it is capable of glucose metabolism and the synthesis of DNA, RNA, and protein. T. pallidum is a parasite and depends on host cells for protection against oxygen radicals because the bacterium need oxygen for metabolism but are highly susceptible to its toxicity (15).

Transmission of disease

Treponema pallidum subspecies pertenue is transmitted intradermally between humans by the transmission of puss through an open lesion. The puss contains treponemes, which enter the host through open abrasions of the skin or mucous membrane (17). Treponemes move through epithelial cells via the tight junctions between cells and invasively attach to fibronectin-coated surfaces on the extracellular matrix of host cells. Attachment to the fibronectin causes increased synthesis of fibroblasts in the cell (1). Antibodies in the circulating blood attach to antigens on the treponemes and ignite an inflammatory immune response that increases the swelling of the lesions (15).

Low concentration of antigen epitopes expressed on the cell surface of T. pertenue is the predicted cause of the pathogenesis of the bacteria because the limited amount of surface antigens decreases the likelihood of a host cell antibody recognizing the antigen (15). One-dimensional Radioimmunoprecipitation (RIP) confirmed that subspecies pertenue had a decreased amount of proteins expressed on the cell surface compared to subspecies pallidum (17).

The antigen that is thought to be immunodominant in T. pertenue is the 47-kDa antigen, which is present in all T. pallidum subspecies. Monoclonal antibodies 11E3 and 13C6 react with this antigen on the bacterial cell surface in the immune response against the bacteria. In comparison study between T. pallidum and T. pertenue, a binding assay and electron microscopy study were done and showed that the antigen was abundant on the cell surface of T. pallidum but had reduced presence on the surface of T. pertenue (12). This study indicated that the reduced presence of the 47-kDa antigen allowed for greater pathogenesis of the cell by reducing its ability to be recognized by host antibodies.

The contrast in the presence of the Immunoglobin M (IgM) and Immunoglobin G (IgG) antibodies in the immune system of neonate and adult guinea pigs indicates a greater risk of infection in children, which validates the prevalence of yaws in children under 15. In a study, adult guinea pigs expressed five times the amount of antibodies after exposure to T. pertenue compared to neonates. Additionally, the presence of antibodies was greatest in adults three to six weeks after infection, while neonates did not reach their peak presence until six to nine weeks after exposure (18).

While the limited presence of antigens aids the pathogenesis of the bacteria, the limited surface proteins also inhibit it. Specifically, the surface proteins P1 and P3, which are fibronectin-binding proteins, are very limited in presence on the cell surface. The absence of these proteins limits the number of host cells that the bacteria can bind to, therefore limiting the exposure of bacteria to the host cells. Fibronectin-binding surface proteins P2, P4, and P5 are not limited in their presence on the cell surface, however, which increases the pathogenesis and contributes to the effectiveness of the bacteria (14).

Many aspects of the pathogenesis of pertenue are still unknown and being studied, but the differences in the presence of antibodies, antigens, and other surface proteins provide some insight to the complex pathogenesis of this subspecies of T. pallidum.

Prevention

There are various antibiotics such as Tetracycline that can be administered for treating patients infected with yaws. However, the most prevalent drug used in treating any stage of yaws is penicillin G benzathine because its side effects are minimal compared to its counterparts (10). For instance, tetracycline can increase hypoprothrombinemic resulting in delayed clotting of the blood or may cause spontaneous bleeding. Penicillin G benzathine is considered as bactericidal because it affects cell wall biosynthesis during active growth. A single injection can kill the treponemes in a few minutes, while lesions are considered healed within almost a day (10). According to a study in the late 1900s, other treponemal diseases such as endemic syphilis (Treponema pallidum pallidum) are closely related to yaws in which there are no distinct differences in their antigenic and immunogenic properties. Also, bone lesions and joint lesions, which are frequent in yaws and endemic syphilis, show no distinct differences in appearance (6). Similarly, endemic syphilis can be treated with penicillin G benzathine.

Yaws in India

Yaws is particularly prevalent in the districts of Bengal, Travancore, Assam, Burma, and Ceylon (9). Sociological and geographical factors have caused a potential problem in this region of the world that has expanded to be sources of other predicaments economically and politically. Mass serological testing has revealed the highest number of cases that yaws has struck in areas around the world. India resulted in 25-30% positive for several different population groups tested for serological reactors (7). This has led to the search for solutions and medical responses to eradicate the spread of yaws.

Environmental factors revolve mainly around the moisture content and temperature in tropical and sub-tropical areas (7). High humidity specifically targets high moisture in the skin and an increase in skin infections from diseases and bacteria. High temperature has been observed especially in the areas of Burma and Assam, which falls within the isotherm of 80°F (9). However, during the winter season, where temperatures have fallen to approximately 65°F on average, yaws has a higher tendency to resemble syphilis in colder climates, where it may change its form and be nurtured (9). During the winter months, it is rare to see the painful lesions and the characteristic yellow-encrusted yaws on the skin that is usually occurs in warm, moist regions. These attributes are frequently mistaken as syphilitic. Yaws has also been found to be more prevalent in the hills of Assam than on the plains, where the altitude nears the 80°F isotherm. The hills have been detected at heights of 1,000 – 5,000 feet above sea level (9).

There is also an increase in the number of cases where rainfall is heavy in India, particularly during the rainy seasons. An increase in new cases and an increase in relapse cases are caused by the heavy rainfall of wet seasons, based on altitude and its soil characteristics. For instance, Burma has a close proximity to the sea and it approaches the 80°F isotherm. The soil is damp, and because of limited evaporation, water is unable to drain away the limestone that geologically forms. When limestone is present, there is very little vegetation, which becomes another contribution to high incidence of yaws. On the contrary, ample vegetation means scant formation of limestone (9).

In regards to the sociological aspect of India, 10.2% of the 30,000 cases of yaws in India assessed on a population of 1.25 million were Indian. Annually, about 5,000 cases are usually reported (9). Males are more dominant in catching the disease than females. Most cases were found in boys of ages between 5 and 14 years (9).

Economically, a lack of proper sanitation is a large issue in populations where there is a lower standard of living. Overcrowding in huts (2) becomes very common in large populations in India and poor personal hygiene is assumed to be one of the main causes of yaws. The prevalence of yaws can decline in these regions if clothes and shoes were worn more often, which would help maintain personal hygiene and sanitation (9). This serves as a protection barrier from being exposed directly to bacteria-rich objects, including exposure to open sores on infected people.

The availability of food is also scarce in India, which contributes to the low economic status and poor diet of the people. The diets are generally unbalanced: fresh fruit, vegetables, milk, and eggs are not readily available year-round. The water supply is also tainted by overuse, further contributing to poor hygiene (2). Malnutrition and poor sanitation play a major part in the proliferation of Yaws in India.

What is being done to address this problem

Include anything being done by the local government or groups as well as efforts by non-local groups.

What else could be done to address this problem

Are there solutions that could be successful but haven't been implemented due to political or economic reasons? Are there successful efforts in other countries? Are there reasons why these efforts may or may not be successful in the country you've focused on? etc. etc.

References

[Sample reference] Takai, K., Sugai, A., Itoh, T., and Horikoshi, K. "Palaeococcus ferrophilus gen. nov., sp. nov., a barophilic, hyperthermophilic archaeon from a deep-sea hydrothermal vent chimney". International Journal of Systematic and Evolutionary Microbiology. 2000. Volume 50. p. 489-500.

Edited by [insert your names here!], students of Rachel Larsen

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