Overview of the human filarial diseases.
Abstract
Filarial nematodes are parasitic worms transmitted by blood-feeding insects. Mainly found in tropical and subtropical areas of the developing world, diseases such as lymphatic filariasis and onchocerciasis represent major public health issues. With millions of people infected and billions at risk of infection, these diseases can stun economic growth and impair the life quality, hence the WHO classified both lymphatic filariasis and onchocerciasis as Neglected Tropical Diseases. The lesser known filarial disease loiasis is not only affecting millions of people, but represents a huge obstacle during mass drug administration programmes targeting other filarial diseases. Even less is known about mansonellosis, potentially the most widespread of the human filariases, but underestimated due to the lack of clinical symptoms. Large scale intervention as well as mass drug administration programmes are undertaken with the long term goal of eliminating the filarial diseases lymphatic filariasis and onchocerciasis. However, there is still neither a vaccination nor short term macrofilaricidal treatments available. The following chapter will encompass the different filarial diseases, the biology of the parasite and their vector, the epidemiology as well as pathology of the filariases, highlighting the impact of these diseases is still immense and further research in understanding and combating these diseases is needed.
Keywords
- Brugia
- filariasis
- ivermectin
- Loa loa
- loiasis
- lymphatic filariasis
- Mansonella
- mansonellosis
- neglected tropical diseases
- Onchocerca volvulus
- onchocerciasis
- parasitic diseases
- Wolbachia
- Wuchereria bancrofti
1. Introduction
Listed as a Neglected Tropical Disease (NTD) by the WHO, lymphatic filariasis (LF) is a debilitating infectious disease of the developing world. This disease is caused by three species of lymph-dwelling filarial nematodes,
1.1 Biology of the parasites
The three species of filarial nematodes causing LF are transmitted to its human host by different mosquito species.
Disease | Causative agent | Vector | Infection rate (estimations) | Geographical distribution |
---|---|---|---|---|
Lymphatic filariasis | 65 million | Africa, South and Southeast Asia, South America, Pacific Islands | ||
Onchocerciasis | 20.9 million | Sub-Saharan Africa, South America, Yemen | ||
Loiasis | 10 million | Western and Central Africa | ||
Mansonellosis | 114 million | Sub-Saharan African, Central and South America |
Species | Residency of adult worms | Size of adult worms | Microfilariae | Presence of | Major severe forms of pathology |
---|---|---|---|---|---|
Lymphatic vessels and lymph nodes; scrotal tissue | ♂4 cm ♀ 8–10 cm | Blood, nocturnal, sheathed, 244–296 μm | Yes | Lymphangitis, elephantiasis, hydrocele | |
Lymphatic vessels and lymph nodes | ♂ 1.3–2.3 cm ♀4.3–5.5 cm | Blood, nocturnal, sheathed, 177–230 μm | Yes | Lymphangitis, elephantiasis | |
Lymphatic vessels and lymph nodes | ♂ 1.3–2.3 cm ♀4.3–5.5 cm | Blood, nocturnal, sheathed, 177–230 μm | Yes | Lymphangitis, elephantiasis | |
Subcutaneous nodules | ♂ 2–5 cm, ♀ 33–70 cm | Skin (upper dermis), unsheathed, 220–360 μm | Yes | Blindness, dermatitis, Sowda | |
Subcutaneous tissue | ♂ 3–3.4 cm, ♀ 4–7 cm | Blood, diurnal, sheathed, 230–300 μm | No | Calabar swelling, Eye worm, Angioedema, | |
Dermal skin layer | ♂ 1.7 cm, ♀ 2.7 cm | Skin (upper dermis), unsheathed, 180–240 μm | ? | Mild dermatitis | |
Peritoneal, pleural, and pericardial cavity | ♂ 4.5 cm, ♀ 7–8 cm | Blood, unsheathed, 200 μm | Yes | Mainly asymptomatic | |
Peritoneal and pleural cavity | ♂ 2.6 cm, ♀ 3.2–6 cm | Blood and skin, unsheathed, 207–232 μm | Yes | Mainly asymptomatic |
1.2 Epidemiology
Currently, an estimated 858 million people live in 50 endemic countries [12, 13]. Of these, 65 million people are infected with LF. The majority of these infections, around 90%, are thereby caused by
1.3 Pathology
LF is a chronic and persistent disease, but the majority of infected individuals remain asymptomatic and do not develop clinical symptoms. However, LF can cause a broad spectrum of clinical manifestations including the most severe forms seen in patients with elephantiasis or hydrocele. The most common symptoms are lymphedema of the legs, lymphangitis, elephantiasis, and only in
2. Onchocerciasis
Another neglected tropical disease caused by a filarial nematode is onchocerciasis, also known as river blindness. This disease is caused through infections with
2.1 Biology of the parasite
The life cycle of
2.2 Epidemiology
As of 2017, 20.9 million individuals were infected with
2.3 Pathology
The vast majority of individuals infected with
3. Loiasis
Commonly known as the “African eye-worm”, the filarial nematode
3.1 Biology of the parasite
Like mentioned before, loiasis is caused by the tissue-dwelling nematode
3.2 Epidemiology
Loiasis is restricted to the rain forest areas of 12 countries of Western and Central Africa. These are namely Angola, Cameroon, the Central African Republic, Chad, the Republic of Congo and the Democratic Republic of Congo, Equatorial Guinea, Ethiopia, Gabon, Nigeria, Sudan and South Sudan [65]. Although large sections of these countries have low or no prevalence of loiasis, an estimated 14 million people reside in high-risk areas, where the prevalence of
3.3 Pathology
The majority of infected individuals remain asymptomatic. However, clinical symptoms of loiasis may take years to develop and due to the lack of severe pathology, this disease is even more neglected [68, 69, 70, 71]. One common clinical symptom is the Calabar swelling, a localized angioedema caused by transient subcutaneous swellings which mark the migratory course of the nematode [70]. Interestingly, only around 16% of endemic patients develop this symptom, which are usually located on the face, limbs or joints [27]. It is hypothesized that these swellings are a result of an allergic reaction to the migrating adult filariae or MF [71]. Associated symptoms also include local or disseminated pruritus, urticaria and restricted movement patterns. Symptoms usually resolve after 2–4 days, but they can persist or even reoccur [71].
4. Mansonellosis
Mansonellosis is caused by four different species of the nematode genus
4.1 Biology of the parasite
Mansonellosis is caused by four species of
4.2 Epidemiology
More than 600 million people live at high risk of infection with
4.3 Pathology
Generally, mansonellosis is not associated with severe clinical symptoms and is therefore not considered a public health problem. Infections with both
5. Current treatments and future perspectives
The United Nations Sustainable Development Goals and the WHO NTD road map 2021–2030 stated the goal of confirmed elimination of transmission for onchocerciasis and as a public health problem for LF by 2030. MDAs with ivermectin in combination with albendazole within Africa, or diethylcarbamazine (DEC) plus albendazole outside of Africa for LF and ivermectin alone for onchocerciasis were used. As mentioned above, the goal of eliminating LF by 2020 was missed by WHO’s GPELF. However, over 8 billion doses of the annual MDA treatments were distributed to more than 923 million people. The result is that 17 countries are currently under surveillance to confirm the elimination of LF transmission [18, 19, 103, 104]. The main intervention strategy for LF consists of annual, single dose MDAs with ivermectin plus albendazole or DEC plus albendazole targeting the MF stage. These treatments do not efficiently kill the adult worms, but removes MF from peripheral blood and inhibit MF release for a few months [105, 106]. A new approach for LF in areas that are that are not co-endemic for onchocerciasis and loiasis, is the now WHO-recommended MDA using a triple therapy. This therapy consists of a single dose of ivermectin (200 μg/kg), DEC (6 mg/kg) and albendazole (400 mg) [107]. The triple therapy was shown to reduce microfilaremia for more than 2 years and may have some macrofilaricidal efficacy. While the triple therapy can be seen as a game changer for LF, it is not recommended in co-endemic areas for onchocerciasis and loiasis. DEC can lead to severe adverse effects in onchocerciasis patients and
Targeting the
In contrast to LF and onchocerciasis, loiasis cannot be treated with anti-wolbachials such as doxycycline due to the lack of
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