Hello everyone and welcome to this week's blog post. In this week's article, I will be discussing the disease lymphatic filariasis. I will first explore what the disease is, including its cause and symptoms, before moving on to explain its treatment options. I will then evaluate eradication efforts for this disease.
What is lymphatic filariasis?
Lymphatic filariasis is a painful, tropical disease which affects the lymphatic system. This causes the severe enlargements of parts of the body, resulting in severe pain and disability. Due to the implementation of programmes to eradicate the disease, around 597 million people no longer require prophylactic drugs to protect them from the disease. Nevertheless, lymphatic filariasis threatens 893 million people in 49 countries across the world.
Lymphatic filariasis is considered a neglected tropical disease. These diseases are a group of diseases, caused by bacteria and parasites, which affect more than one billion people globally. As these diseases are most prevalent in the poorest societies, they are incredibly destructive, often causing physical and mental impairments which prevent adults from going to work and children from going to schools. Consequently, these diseases greatly impact the development of these countries and trap their residents in a cycle of poverty.
Moreover, as these diseases almost solely affect poor communities, pharmaceutical governments are hesitant to invest in cures for these diseases, as it is very unlikely that this would be profitable. Further, governments of these areas often don't have enough funds to allocate to research these diseases.
What causes lymphatic filariasis?
Lymphatic filariasis is an infectious disease which is caused by a range of microscopic nematode worms, including Wuchereria bancrofti (responsible for around 90% of cases), Brugia malayi and Brugia timori. They are transmitted by bites from infected mosquitos. The species of mosquito which transmits this disease is dependent on the region. For example, the Aedes aegypti mosquito (which also transmits malaria) is the vector for lymphatic filariasis in Africa and many Pacific islands, while the Culex quinquefasciatus mosquito is the vector for the disease in many urban and semi-urban areas in the Americas.
The mosquito becomes infected by biting an infected human. When it does so, it ingests contaminated blood which contains millions of immature larvae. These larvae then develop in the mosquitos' blood, forming mature larvae, which are then transferred to humans when bitten by the infected mosquito. These larvae are first deposited on the skin, however, they quickly enter the body and travel to the lymphatic system, where they develop into adult nematode worms. These adult worms then produce millions of immature larvae, which contaminate the blood and can infect another mosquito.
Once the adult worms accumulate in lymphatic vessels and lymph nodes, they block the flow of lymph (a mixture of proteins and tissue fluid which weren't collected by the capillaries) through these passages. As a result, this lymph tissue accumulates in tissues, especially in the lower half of the body.
What are the symptoms of lymphatic filariasis?
Most cases of lymphatic filariasis do not present with any external symptoms, however, even in asymptomatic cases, the disease can still cause damage to the lymphatic system, immune system and the kidneys.
In more severe cases, lymphatic filariasis develops into a chronic condition. This is because the lymphatic system is so blocked, that most of the lymph fluid remains in tissues and can't be transported back to the heart. In these cases, symptoms include lymphoedema (tissue swelling) and, in men, hydrocele (swelling of the scrotum).
Furthermore, as the lymphatic system is compromised, immune cells can't travel around the body as easily, so opportunistic infections are more common. These infections often target the skin, resulting in elephantiasis, which is where the skin on the patient's limb thickens.
How can lymphatic filariasis be treated?
There are many different medications which can be used in the treatment of lymphatic filariasis. In the United States, diethylcarbamazine (DEC) is used for the treatment of this disease. In the past, it was thought that a 12-day treatment regimen was needed, however, evidence suggests that a 1-day regimen is just as effective. This is very good news for treating the disease in developing countries as, since the disease can be treated with a single dose, the cost of treatment is much less. In addition, lymphedema can be treated by exercises, compressive garments and complete decongestive therapy. Further, surgery can also be used in the treatment of hydrocele.
One of the reasons that the symptoms of filariasis are so bad is due to the microbiome of the worms. There are many parasitic worms which infect humans, however, the ones which cause filariasis are the most debilitating. This is because they contain Wolbachia bacteria. Wolbachia is a symbiont to these nematode worms and, without this bacteria, these worms can't complete their life cycle.
These bacteria also help these worms trigger severe disease in humans as, when the worms die, they release Wolbachia into the bloodstream. While these microbes can't infect cells, they still trigger an immune response, in addition to the one already triggered by the worms. According to Professor Mark Taylor, a parasitologist, it is the combination of these two immune responses which causes the severe symptoms of lymphatic filariasis.
Unfortunately, this also makes the disease much harder to treat as, if the adult worms are killed too quickly, then they release all of their bacteria at once, resulting in a huge immune response. Consequently, any treatment for filariasis must kill the worms slowly to avoid this reaction.
Nevertheless, we can use the fact that these worms contain Wolbachia to make the treatment more effective. After it had been discovered that Wolbachia is present in all of these worms, researchers tried treating lymphatic filariasis with antibiotics (e.g. doxycycline) that kill Wolbachia. This resulted in the first cure for the disease. Nonetheless, this treatment is not perfect, as it can't be used in children or pregnant women, hence diethylcarbamazine and other medications are used in its treatment today. Doxycycline and other antibiotics can still be used alongside these treatments, as they make them more effective.
According to the World Health Organisation, the best treatment for lymphatic filariasis is treating entire communities in endemic regions, so that the worms and their larvae in asymptomatic carriers of the disease are eradicated and thus can't spread to other people.
To that end, the World Health Organisation launched the Global Programme to Eliminate Lymphatic Filariasis in 2000, a preventative chemotherapy campaign in these areas that aimed to eradicate lymphatic filariasis through mass drug administration. This is where an annual dose of three medicines (ivermectin, diethylcarbamazine citrate and albendazole) are provided for all civilians in these regions. This type of treatment is incredibly effective as, since there is no known animal reservoir for this disease, if the worms are killed in humans, then the disease should be eradicated.
This programme has had major successes so far. Between 2000 to 2018, 7.7 billion treatments were delivered in 68 countries, which has considerably reduced transmission of the disease in these areas. As a result, according to the UN, 16 countries and territories have now eliminated lymphatic filariasis as a public health problem. In addition, 7 other countries have also severely reduced the spread of this disease.
While this type of treatment is still needed in 49 other countries, I would contend that given the success of eradication measures in other countries, it is possible to severely limit this disease. Nonetheless, complete eradication will be much harder as many rural areas lack the infrastructure required to distribute these medications yearly. Indeed, as of 2018, 15 countries participating in the WHO initiative were not able to deliver preventative chemotherapy in all endemic areas. If this is not achieved, then some of these worms will still be present and a resurgence of the disease would be possible.
Sources:
Yong, E. I contain multitudes (1st ed.).
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