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A Social Issue Neglected Tropical Diseases and Three Major Infectious Diseases

Buruli Ulcer

<Appearance of Buruli ulcer> Wikimedia

Buruli ulcer, which mainly forms ulcers on human’s hands and feet, is an infectious disease epidemic in tropical and subtropical regions. Left untreated, necrosis can reach bones, causing disfiguration. It can be treated without surgery by using drugs at the early stages of infection.
At least 33 countries with tropical, subtropical and temperate climates have reported Bruli ulcer in Africa, South America and Western Pacific regions. In 2015, 2037 new cases were reported in 13 countries.

Causes of Infection

Disease Agent

Mycobacterium ulcerans

Vector

It is believed aquatic insects, mosquitoes, biting/stinging arthropods (insects, crustaceans, spiders, centipedes, etc.)

Host spider
James Gathany
CDC

The agent of Buruli ulcer is a bacterium called M.ulcerans. M. ulcerans belongs to the family of bacteria that causes leprosy and tuberculosis. M. ulcerans gets underneath the skin from a wound or insect bite and, occasionally, reaches bones. M. ulcerans produces a toxin called mycolactone, which destroys cellular tissue and impairs the immune system. Although the infection route has not been confirmed, it is believed that aquatic insects, mosquitoes, and biting/stinging arthropods (insects, crustaceans, spiders, centipedes, etc.) are the host or vector.

Symptoms

Symptoms of Buruli ulcer go through two stages: active and inactive.

<Appearance of Buruli ulcer> Wikimedia

Active Stage

There are both pre-ulcer and ulcer symptoms. When Buruli ulcer first develops, white nodules called papules appear underneath the skin. The area around these papules becomes thick and dark-colored (non-ulcerative symptoms). These symptoms appear mainly on hands, feet and legs. On rare occasions, an edema appears on the face. In many cases, these symptoms are not accompanied by pain.
If left untreated, however, ulcer symptoms develop, advancing to destroy a wide range of skin and soft tissue, as papules develop into large ulcers. When these begin to affect bones, limbs may be disfigured or a functional deficiency may occur (ulcer symptoms). In areas where Buruli ulcer is epidemic, more than 70% of the patients show ulcer symptoms.

 
Inactive Stage

This is the stage when past infections leave star-shaped scars on the skin. In some cases, aftereffects may also appear.

 

Diagnosis and Treatment

WHO (World Health Organization) recommends early treatment with a combination of streptomycin or amikacin (both antibiotics should be administered through intramuscular injection) and rifampicin for eight weeks. Recent clinical tests have revealed that treatment with this combination is highly effective during the early stages and the percentage of patients who are completely cured without undergoing surgical operation is high. Moreover, the risk of reinfection after treatment is close to zero.
When symptoms progress, surgery may be necessary to excise necrotic tissue, reconstruct disfigurations, or graft skin. After a surgical operation, dry skin and fissures are liable to develop from lesions easily damaged by sunlight. After operating, precautions such as moisture retention, massage and pressure bandages are also necessary.

For pregnant women

Taking into consideration the adverse effects on unborn child, a combination of rifampicin and clarithromycin, or rifampicin and moxifloxacin, is recommended.

 
For HIV/AIDS patients

Buruli ulcers in HIV/AIDS patients progress much faster than those of other patients due to their immune system being compromised. For simultaneous infections of Buruli ulcer and HIV, patients are likely to develop several lesions in addition to osteomyelitis. When a patient is infected with both Buruli ulcer and HIV, it is recommended that treatment follow the same guidelines as double infection of tuberculosis and HIV.

 

Prevention

A vaccine to prevent infection from Buruli ulcer is still at the research stage. Currently, a specific vaccine known as the BCG vaccine is used for short-term prevention.
To minimize symptoms and impairment, it is important to provide health education to local people and promote early diagnosis. As of 2013, there was no diagnostic method for Buruli ulcer available for medical facilities and, therefore, diagnosis is carried out in the laboratory. A common diagnostic method is via polymerase chain reaction (PCR) to identify specific DNA. The PCR method is the most reliable test, delivering results within 48 hours.

Regions at High Risk of Infection

Generally speaking, Buruli ulcer is epidemic in areas where there has been some kind of environmental change observed such as deforestation or mining exploration.
Cases of Buruli ulcer have been reported in at least 33 countries with tropical, subtropical and temperate climates in Africa, South America and Western Pacific regions. The majority of cases are reported from West and Central Africa, including Benin, Cameroon, Côte d’Ivoire, the Democratic Republic of the Congo and Ghana. In recent years Australia has been reporting a higher number of cases.

Estimated Number of Infected People

It is difficult to specify the number of patients because there has not been enough research conducted on this disease and it is difficult to diagnose its symptoms accurately. Buruli ulcer is found in at least 33 countries, and in 15 of these 33 countries, between 5,000 and 6,000 cases are reported every year.

Estimated Number of Deaths

It is assumed that the mortality rate has declined due to better diagnoses and earlier-stage treatment. While the exact number of deaths caused by Buruli ulcer is unknown, it is rare for Buruli ulcer to be the direct cause of death. On the other hand, even when fully recovered, many patients are left with functional impairment.

Initiatives by Pharmaceutical Companies and NGOs

In 1998, WHO, governments of endemic countries and NGOs began working to address Buruli ulcer. At the time, an organization for research and elimination of Buruli ulcer called the Global Buruli Ulcer Initiative (GBUI) was established with financial assistance from the Nippon Foundation. Later, in May 2004, the World Health Assembly adopted a resolution stating that monitoring and control of Buruli ulcer should be improved and research and treatment should be accelerated. The assembly also endorsed the combined administration of rifampicin and streptomycin as a treatment for the disease.
In 2009, government from African countries affected by Buruli ulcer together with health and medical organizations met to adopt the Cotonou Declaration, which announced that signatories would commit to taking the necessary measures to fully implement the WHO-recommended strategy for Buruli ulcer control.
In 2012, as part of the London Declaration, WHO announced that it would begin developing an oral antibiotic treatment for Buruli ulcer that would be available by 2015. WHO aims to reach a 70% treatment rate in all epidemic countries by 2020 through the use of antibiotics.

Sanofi

In 2001, Sanofi began a collaboration with WHO to combat Buruli ulcer and four other NTDs, namely, African sleeping sickness, leishmaniasis, Chagas’ disease and endemic treponematosis. This collaboration has been renewed in 2006 and 2011. From 2001 through 2016, Sanofi will have contributed US$75 million in financial support and drug donations to help eliminate these diseases. In places where Buruli ulcer is endemic such as Togo and Benin, Sanofi has supported programs to improve awareness of Buruli ulcer, train medical professionals, promote early diagnosis and provide rehabilitation for patients in collaboration with local health agencies and health organizations.

References
WHO- Neglected Tropical Diseases, accessed March 19, 2014,
http://www.who.int/neglected_diseases/mediacentre/factsheet/en/
CDC- Neglected Tropical Diseases, accessed March 19, 2014,
http://www.cdc.gov/globalhealth/ntd/diseases/