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Home , Filariasis, Filarioidea, Loa loa, Mansonelliasis

FILARIAL DISEASES Aiming for rapid control and patient cure

Filariasis is a group of infectious diseases caused microfilariae in the body. Because of this, MDA by certain thread-like parasitic worms of the must be carried out repeatedly for many years helminth () family: lymphatic until the adult worms die out naturally and (LF, or ), (river blind- no longer produce new worms. For LF MDA, ness), (loiasis, or African eyeworm), and patients are treated once or twice a year for . LF and onchocerciasis have the 4-6 years, while for onchocerciasis, MDA must highest disease burdens of the filarial diseases. be done for 10 or more years. Infecting over 150 million people around the world Second, current drugs pose life-threatening side and placing a billion people at risk, particularly effects in the LF and onchocerciasis patients who in and , filariae are transmitted to are co-infected with Loa loa. A small percentage humans through the bites of and mosqui- of patients with Loa loa have very high levels of toes. While rarely fatal, filarial diseases inflict microfilariae, and treatment with current drugs life-long disabilities on patients, such as massively can result in the sudden, massive death of these swollen limbs and genitals; blindness; chronic, juvenile Loa loa worms that overwhelms the body debilitating pain, including regular acute attacks; and causes serious adverse reactions including severe, intense itching; disfigurement; and skin brain damage (encephalopathy) and kid- discoloration (‘leopard skin’), resulting in ney failure, both of which can be fatal. depression and social stigmatization. (2) Because of this side-effect risk, alone is the MDA with current drugs is con- second cause of chronic disabil- sidered unacceptable in areas ity worldwide. Generally, patients where the Loa loa prevalence with filaria are often incapacitated exceeds 20%.(3) by pain or poor limb function and Therefore, a drug that can kill thus cannot work or take care of the adult onchocerciasis and LF their families or themselves. Social worms (macrofilaricide) is needed. stigmatization because of their condition A new, safe, short-course macrofilaricidal often leads to abandonment, isolation, and lack drug could be used in individual patient treatment of support from others. In short, filarial diseases (case management) at the end of MDA (known slowly destroy the lives of patients who become as ‘mopping up’), when the incidence rate is infected – physically, economically, and socially. too low to justify initiating a new MDA round. It Control strategies for filarial diseases have for could also be used in screening and treatment decades revolved around mass drug adminis- programmes, which need to be scaled up, and in tration (MDA) of donated medicines, through low-endemic areas. It could ultimately be used in programmes such as the African Programme MDA programmes to help eliminate the disease for Onchocerciasis Control (APOC) and the Global in the community with just one or two rounds of Programme to Eliminate Lymphatic Filariasis MDA treatment: patients could be cured within (GPELF). These programmes have been in place 1-2 years, rather than potentially up to 12-15 for over 20 years and rely on MDA of safe anti- years. If sufficiently safe, the new drug would parasitic drugs: for onchocerciasis; enable the treatment of patients in areas ofLoa ivermectin, , and loa co-. (DEC) for LF. Through these programmes, WHO has set goals of eliminating LF (defined as 70% of countries verified free of LF and 30% engaged Ideal Target Product Profile in post-intervention surveillance activities) and for Filarial Diseases controlling onchocerciasis by 2020.(1) A new treatment for adults and children: However, shortcomings with the currently avail- able drugs call into question whether these > Macrofilaricide : Efficacious against the adult form of worms long-running filarial control strategies, which differ according to disease and are not active in > Oral, short-course treatment low-endemic areas, will truly wipe out filaria, > No side-effects following death of worms and whether all infected patients are adequately > Safe in pregnant and breastfeeding being identified and are receiving effective treat- women ment. First, current drugs kill mainly juvenile > Affordable worms (microfilariae), which are transmitted > Adapted to tropical climates (minimum via insect vectors, but do not kill adult worms three-year shelf-life) (macrofilariae), which continue to produce new

(1) Sustaining the drive to overcome the global impact of neglected tropical diseases: Second WHO report on neglected tropical diseases, World Health Organization, 2013. (2) Boussinesq M. (2006) Loiasis. Ann Trop Med Parasitol 100: 715‑31. (3) Boussinesq M. et al., (2001) Relationships between the prevalence and intensity of Loa loa infection in the Central province of Cameroon. Ann Trop Med Parasitol 95: 495-507. FILARIAL DISEASES

FACT SHEET

WHAT IS THE IMPACT OF worm that can live for 15 years in development of nodules, and skin onchocerciasis is also endemic (i.e. FILARIAL DISEASES? the human body. The disease is disfigurement and discoloration. African countries), or Onchocerciasis (river blindness): An contracted through the bite of an Chronic LF leads to lymphoedema diethylcarbamazine (DEC) in areas estimated 25 million people are infected female blackfly, which (tissue swelling, principally of the where onchocerciasis is not infected worldwide,(1) with 99% of transmits microfilarial worms legs and genitals), elephantiasis co-endemic (i.e. non-African cases in 31 African countries. Foci (larvae) from one person to another. (skin/tissue thickening), and countries). The antibiotic drug also occur in some areas of Latin After mating, a female worm massive fluid accumulation , while unsuitable for America (Brazil, Ecuador, releases about 1,000 new () in the testes. Patients use in MDA programmes because of Guatemala, Mexico, Venezuela) and microfilariae larvae per day. Larvae also suffer acute attacks of body its relatively long treatment Yemen.(2) Approximately 123 million develop into adult worms and settle pain. Physical disfigurement results duration (4-6 weeks), shows people are at risk of infection. into fibrous nodules in the human in social stigma, as well as financial promise for use in case Onchocerciasis is the world’s body close to the surface of the skin hardship from loss of income and management. second-leading infectious cause of or near the joints. increased medical expenses. LF and MDA drugs kill juvenile worms blindness.(3) The WHO estimates > LF is caused by Wuchereria onchocerciasis can cause immense (microfilariae), but not adult worms that about half a million people are bancrofti, transmitted to humans by socioeconomic burdens of isolation (macrofilariae). By killing blind due to onchocerciasis, and various species. When a and poverty. microfilariae, they can temporarily almost a million have different mosquito with infective larvae bites Loiasis leads to recurrent episodes prevent -borne transmission degrees of visual impairment. In a person, the parasites are of itchy swellings and to ‘eyeworm’, (until the adult worms produce endemic areas, children are deposited on the person’s skin and the visible migration of the adult more microfilariae larvae), and exposed from birth, and infection then enter the body. The larvae then worm across the surface of the eye, induce temporary sterilization of can lead to growth retardation and migrate to the lymphatic vessels which resolves after a few days but adult worms, preventing re- weight loss. where they develop into adult is itchy, painful, and causes light population with new microfilariae Lymphatic filariasis (LF; worms, damaging the lymphatic sensitivity. Subcutaneous migration for a few months. However, because elephantiasis): Over 120 million system. The worms live for 6 to of the worm causes tender, itching adult worms continue to live in the people are infected globally, with 8 years and produce millions of Calabar swelling, usually on the body, they eventually produce new about 40 million disfigured or larvae (microfilariae) that circulate limbs and near the joints. Other microfilariae, often before the next incapacitated by LF.(4) More than 1.4 in the blood. symptoms include generalized MDA, thus requiring repeated MDAs billion people in 73 countries are at > Loiasis is caused by Loa loa, the itching, muscle and joint pain, and for several years to decades until risk of infection. An estimated 25 adult worms of which can live for up fatigue. the adult worms die naturally. million men suffer genital disease, to 17 years, during which time they Ivermectin is safe and has been and over 15 million people have release millions of larvae into the WHAT ARE THE CURRENT used widely as a monotherapy in lymphoedema (swelling). The human body. These macrofilariae TREATMENTS AND THEIR MDA programmes for infection is usually acquired in migrate throughout the body just LIMITATIONS? onchocerciasis, killing the childhood, but its debilitating under the skin and sometimes Current treatments for microfilarial stage of the parasite. manifestations usually occur later cross into the subconjunctival tissue onchocerciasis and LF are based on However, in LF and onchocerciasis in life. After mental illness, LF is the of the eye where they can easily be mass drug administration (MDA) of patients co-infected with Loa loa, second most common cause of seen. They are transmitted through antiparasitic drugs through the sudden death of large numbers long-term disability worldwide. the repeated bites of deerflies (also programmes directed by the WHO. of Loa loa microfilariae following Loiasis (Loa loa; African eyeworm): known as mango flies or mangrove WHO recommends MDAs for treatment can lead to serious An estimated 14.4 million people flies). onchocerciasis at least once yearly adverse events, such as live in high-risk areas where Loa loa for 10-15 years, and for LF once encephalopathy, possibly resulting prevalence is >40%, and 15.2 million WHAT ARE THE SYMPTOMS? yearly for at least 5 years. The drugs in permanent brain damage and live in intermediate areas of 20-40% Onchocerchiasis causes eye lesions used in MDA programmes are death. Furthermore, reports of a prevalence. The number of people leading to visual impairment and ivermectin for onchocerciasis; and suboptimal response to ivermectin at high risk varies considerably permanent blindness. It also causes for LF, albendazole plus either by O. volvulus may be a sign of between countries. Patients intense itching, body pain, rashes, ivermectin in areas where developing resistance. infected with Loa loa only are not usually treated, but onchocerciasis and LF patients can be co-infected with Loa loa worms and, where such co-infection does exist, there WHAT IS DNDi DOING TO ADDRESS UNMET TREATMENT NEEDS? is significant risk of severe adverse events (SAEs) with ivermectin DNDi’s strategy is to develop a new drug with macrofilaricide (drug that kills adult worms) treatment. This limits the use of activity for use as a safe and field-adapted macrofilaricidal drug for patient case ivermectin in mass drug management and possibly later MDA. As a medium-term strategy, we are assessing administration (MDA) programmes emodepside, a potent antihelminthic drug currently used in combination with praziquantel to in co-endemic areas, and is an treat parasitic worms in cats and , as a potential clinical candidate to treat humans. impediment to achieving WHO elimination goals for LF and As a long-term strategy, DNDi is assessing additional opportunities through an active onchocerciasis. screening programme of drug compounds emanating from health/pharmaceutical /Sylvain Cherkaoui/Cosmos /Sylvain companies and academic institutions, with the goal of selecting one or two candidates to i HOW ARE FILARIAE move into clinical development. TRANSMITTED? The thin, thread-like parasitic roundworms (belonging to the By 2015, DNDi aims to develop for testing a new, short-course oral macrofilaricide drug superfamily of candidate, for use in case management and possibly later for MDA, and in regions DND credits: Photo - ) that cause filarial of LF and onchocerciasis co-infection with Loa loa. diseases are transmitted by flying insect vectors to humans:

> Onchocerciasis is caused by (1) http://www.cdc.gov/parasites/onchocerciasis/epi.html (2) http://www.who.int/mediacentre/factsheets/fs374/en/ (3) http:// , a parasitic www.who.int/blindness/partnerships/onchocerciasis_home/en/index.html (4) http://www.who.int/mediacentre/factsheets/fs102/en/

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