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A Social Issue Neglected Tropical Diseases and Three Major Infectious Diseases

Lymphatic filariasis

< Appearance of a patient with elephantiasis > CDC

With this disease, people are infected via certain species of mosquito. These mosquitoes carry thread-like worms called filariae that cause a variety of clinical manifestations leading to temporary and permanent disability, including lymphedema of the limbs or genital lymphedema, and elephantiasis (where the legs and/or other body parts swell to resemble those of an elephant). Virtually all patients with lymphatic filariasis also sustain subclinical lymphatic damage. Statistics show that more than 120 million people in 73 tropical and subtropical countries are afflicted with this disease.

Causes of Infection

Disease Agent

Thread-like helminth known as filariae (including Wuchereria bancrofti, Brugia malayi, and B. timori)

< Microscopic view of Microfilariae, Wuchereria bancrofti > CDC

Vector

Mainly mosquitoes (Anopheles, Culex and Aedes)

< Mosquito(Photo:Culex quinquefasciatus) >
James Gathany
CDC

Lymphatic filariasis develops when the filariae transmitted to the human host via a mosquito parasitizes in the lymph system. There are three types of agents, but it is believed that 90–95% of all lymphatic filariasis is caused by W. bancrofti.
When a mosquito carrying infective filarial larvae bites a person, the larvae enter and migrate within the host’s body. Later, filariae migrate to the lymphatic vessels and develop to the adult stage, causing serious damage to the lymph system. Adult filariae subsequently give birth to thousands of larvae, known as microfilariae, inside the host. These microfilariae are also transferred to the mosquito as it sucks blood, setting off a cycle of further infection. In most cases, childhood infections will continue to develop into adulthood.

U.S. Centers for Disease Control and Prevention,
"Parasites - Lymphatic Filariasis." Accessed March 19, 2014,
http://www.cdc.gov/parasites/lymphaticfilariasis/biology_w_bancrofti.html

Symptoms

During the acute stages of the disease, patients may exhibit characteristic symptoms such as cold chills and spasms commonly associated with fever. Other than these signs, however, there is hardly any indication during the early stages of infection, making many of those infected unaware that they may indeed be afflicted with the disease. As infected children grow up, they may experience fever attacks associated with lymphangitis and lymphadenitis, which in time causes circulation lesions of lymph fluid leading to such diseases as lymphedema (which includes elephantiasis and genital edema).

< Appearance of a patient with elephantiasis > CDC

Lymphedema

While lymphedema mostly develops on the legs, it can also develop on the arms, breasts, and genitalia. A decline in lymphatic function makes it difficult for the body to fight infections from other bacteria, eventually leading to elephantiasis.

 
Elephantiasis

Lymphedema advances rapidly and is associated with acute pain, fever, cold chills, and deformation of infected areas of the body.

 

Diagnosis and Treatment

Diagnostic Methods

There are two ways to diagnose lymphatic filariasis.
One is verification of the presence or absence of microfilariae in the blood using a microscope. Since microfilariae generally move to peripheral blood at night, blood drawing must be done at night.
The other method is a serological test (antibody titers in blood serum). Whichever method is used, there have been a number of cases where lymphedema nevertheless developed several years after a patient was found negative, underscoring the difficulty of accurately diagnosing lymphatic filariasis.

 
Treatment

Anthelmintics and other drugs for the treatment of lymphatic filariasis include diethylcarbamazine (DEC), albendazole, and ivermectin. Of these three, the most effective against both microfilariae and adult worms with the fewest side effects is DEC.
It is possible, however, that lymphedema and elephantiasis continue to develop even after the filariae are destroyed. Basic measures to prevent the symptoms from getting worse include sanitizing the swollen area and exercising to improve the flow of lymph fluid.

 

Prevention

The most effective preventive measure against lymphatic filariasis is to avoid mosquito bites. It is best to wear long-sleeved shirts and long pants and to apply a mosquito repellent to exposed skin. Mosquito nets over bedding and other sleeping areas are also effective. Once infected with lymphatic filariasis, the patient’s immunity weakens and this leads to susceptibility to other infectious diseases. It is therefore important to maintain hygiene in the home.
To prevent epidemics of lymphatic filariasis, WHO (World Health Organization) recommends community-wide, mass drug administration (MDA) of DEC as well as albendazole tablets or albendazole and ivermectin tablets once a year for four to six years in infected regions. Lymphatic filariasis must also be eliminated from the entire community at once since the disease can be re-transmitted soon after via mosquitoes.

Regions at High Risk of Infection

The risk of contracting lymphatic filariasis has been confirmed in 73 countries and territories in tropical and subtropical areas of Asia, Africa, the western Pacific, the Caribbean, and Latin America. Of these regions, approximately 65% of those infected live in Southeast Asia and 30% in Africa. The remainder of this population live scattered throughout the world’s other tropical and subtropical areas.

Infected Area Map

Estimated Number of Infected People

According to data released by the World Health Organization (WHO) in 2016, more than 947 million in 54 countries face the risk of lymphatic filaria infection, while it was estimated that more than 120 million people were infected in 2000.

Estimated Number of the Deaths

While lymphatic filariasis rarely causes death, it weakens the immune system, meaning that patients are also susceptible to other diseases.

Initiatives by Pharmaceutical Companies and NGOs

The elimination of lymphatic filariasis was officially adopted in a resolution at the 1997 World Health Assembly. Furthermore, the Pacific Programme to Eliminate Lymphatic Filariasis (PacELF) was launched by WHO in 1999 with the aim of eliminating lymphatic filariasis in 22 Pacific countries by 2010, and the Global Programme to Eliminate Lymphatic Filariasis (GPELF) was launched in 2000 to eliminate lymphatic filariasis by 2020.
In January 2012, pharmaceutical companies and health organizations from several countries assembled to issue a joint announcement, the London Declaration, aiming to eliminate neglected tropical diseases (NTDs), including lymphatic filariasis, by 2020. Each signatory to this declaration is now striving to accomplish this goal. Under these circumstances and as of 2013, the following pharmaceutical companies have formed partnerships with WHO pledging to eliminate lymphatic filariasis. To introduce some of the representative cases:

Global Alliance to Eliminate Lymphatic Filariasis (GAELF)

This is a public-private sector partnership where WHO as well as pharmaceutical companies (GlaxoSmithKline (GSK), Merck and Co. Inc, Eisai, etc.) donate or provide medicines to eliminate lymphatic filariasis. With the goal of having a world without lymphatic filariasis, each organization also offers grants and expertise.

Eisai

Under the London Declaration to eliminate NTDs, Eisai began manufacturing DEC since 2013, which it supplies for free to at-risk populations via WHO. The overall goal is to donate 2.2 billion DEC tablets to 250 million people in 26 countries and territories (as of October 2013) by 2020.

GlaxoSmithKline (GSK)

In 1998, GSK made a commitment to donate to WHO as much albendazole as needed until lymphatic filariasis (LF) is eliminated globally as a public health problem. GSK announced in 2010 the expansion of its commitment to WHO with a pledge to additionally donate up to 400 million albendazole tablets each year to fight soil-transmitted helminth infections in school age children. Since the start of GSK’s commitments to fight the two diseases, GSK has donated over 5 billion albendazole tablets to 61 countries implementing LF elimination activities and to 55 countries implementing deworming activities.

Merck & Co. Inc. (MSD)

In 1998, MSD expanded its MECTIZAN® Donation Program to include the prevention of LF in African countries where the disease coexists with onchocerciasis (river blindness). Through this commitment, MSD will supply free MECTIZAN® (ivermectin) directly to various countries for an indefinite period until lymphatic filariasis is successfully eliminated. (MECTIZAN® has been targeted at countries where there is river blindness or a combination of lymphatic filariasis and river blindness). Since 1998, MSD has donated more than 900 million treatments with MECTIZAN® for lymphatic filariasis in Africa and Yemen.

Johnson & Johnson

In 2012, Johnson & Johnson committed to the reformulation, pre-clinical and clinical development of flubendazole as a potential macrofilaricide. Originally created by Janssen Pharmaceutica as an anthelmintic, a new bioavailable formulation may be used to treat the adult filariae that cause river blindness and lymphatic filariasis. If pre-clinical development proves successful, Johnson & Johnson will also seek regulatory approval of the compound for the two neglected tropical diseases.

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/