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Eisai ATM Navigator Making health available worldwide

A Social Issue Neglected Tropical Diseases and Three Major Infectious Diseases

Mycetoma

<Picture of Mycetoma patient> CDC

Mycetoma is a serious inflammatory disease, which slowly and progressively destroys soft tissue. While most commonly seen on the feet, it can also occur on other parts of the body. It is caused by bacteria or fungus entering the body through a cut or wound and infecting the tissue beneath the skin. Although there are records of mycetoma dating back to ancient times, the first report in modern times came from the Indian town of Madura during the mid-19th century, so the disease was initially called “Madura Foot”. Most mycetoma patients are males between 20 and 40 years of age who are engaged in physically intensive labor, such as farming, in developing countries. Mycetoma was officially recognized as the 18th Neglected Tropical Disease at the World Health Assembly held in May 2016.

Causes of Infection

Disease Agent

Disease caused by bacteria (actinomycetoma) or fungi (eumycetoma)

<Microscopic view of bacteria Nocardia brasiliensis> CDC

<Microscopic view of fungi Madurella mycetomatis)> CDC

Vector

no known vector or animal reservoir

Mycetoma is divided into two subtypes based on the cause of the infection. It is known as Actinomycetoma if caused by bacterial infection and Eumycetoma if caused by fungal infection. In either case, there are multiple pathogens. Known bacterial pathogens are Nocardia brasiliensis, Actinomadura madurae and Streptomyces somaliensis. For fungal infections, there are over 20 types, but the most commonly observed is Madurella mycetomatis. Infection is caused by pathogens entering the body through a small wound, such as a thorn prick, and this is why there is a strong correlation between mycetoma patients and bare-footed laborers. Mycetoma is not contagious and cannot be passed from person to person.

Symptoms

Mycetoma usually progresses slowly, and is characterized by painless lesions under the skin which multiply and excrete fluid containing bacterial or fungal grains. While the initial infection is typically in the foot, it has been known to spread to the rest of the limb. Left untreated, it can lead to physical disabilities and deformities (leading to social discrimination) and a second infection of the same wound can result in death by blood poisoning. Since most endemic regions have poor medical infrastructure and health education, and due to the slow, painless nature of the symptoms, most patients don’t seek help until the disease is already advanced. At this stage, surgery or amputation are the only viable treatments.

<Picture of Mycetoma patient> CDC

Diagnosis and Treatment

Diagnostic Methods

Mycetoma can be diagnosed by microscopically examining surgical tissue biopsy or the fluid discharged by the lesions, however it is important to cultivate the organism to correctly identify the pathogen. DNA sequencing and various imaging technology are also options, but in most cases, endemic regions do not have access to these advanced tests. At present, there are no suitably simple diagnosis methods available.

 
Treatment

Besides removal of the infected area via surgery, there are medicinal treatments, but these differ depending on the pathogen. Actinomycetoma can be treated with antibiotics, and combination treatments of amikacin and co-trimoxazole have a >90% success rate. On the other hand, while azole anti-fungal drugs can be used to treat Eumycetoma, the success rate is only 25-35%, with a high likelihood of recurrence. As such, Eumycetoma is treated with both a lengthy course of anti-fungal drugs (over 12 months) and surgery. Ketoconazole (an oral agent) was originally an option, but this drug is now banned by the regulatory authorities in Europe and America (EMA, FDA) due to risk of liver toxicity. This leaves itraconazole as the only effective anti-fungal agent. This drug requires long-term adherence, side-effects may be a problem, and benefits are limited. Cost burdens are also an issue, with over 50% of patients stopping treatment midway. This often results in recurrence, with the patients ultimately needing surgery or amputation.

 

Prevention

There is still no viable method to control or prevent mycetoma. While complete suppression is difficult, it is possible to visit endemic regions and warn the inhabitants not to walk barefoot.

Regions at High Risk of Infection

While the organisms that cause mycetoma are found worldwide, tropical and subtropical zones in the “Mycetoma belt” (including the Bolivarian Republic of Venezuela, Chad, Ethiopia, India, Mauritania, Mexico, Senegal, Somalia, Sudan and Yemen) are most at risk.

Estimated Number of the People Infected

Mycetoma is not reportable by law, and since there is no surveillance system in place to gather information, the number of patients and outbreaks are unclear. According to a study published in 2013, which was based on 50 scientific reports from 1956 onwards, 8,763 cases were reported, of which 75% were from Mexico, Sudan and India. But since these reports only represent a single hospital per country, the actual figure is thought to be far higher.

Estimated Number of Deaths

There are no current estimates for the number of deaths due to mycetoma.

Initiatives by Pharmaceutical Companies and NGOs

Eisai

A research and development project relating to new treatments for eumycetoma was launched in collaboration with the international NPO, Drugs for Neglected Diseases initiative (DNDi), in September 2015. DNDi is conducting clinical trials in Sudan using Eisai’s anti-fungal agent E1224 (fosravuconazole).

References
WHO- Mycetoma, accessed February 13, 2017
http://www.who.int/buruli/mycetoma/en/
ISNTD Disease Brief, 'Mycetoma: The case for a new entrant to the WHO's list of Neglected Tropical Disease'; Mark Clark (April 2016)