Filariasis
   HOME

TheInfoList



OR:

Filariasis is a filarial infection caused by parasitic
nematode The nematodes ( or ; ; ), roundworms or eelworms constitute the phylum Nematoda. Species in the phylum inhabit a broad range of environments. Most species are free-living, feeding on microorganisms, but many are parasitic. Parasitic worms (h ...
s (roundworms) spread by different vectors. They are included in the list of
neglected tropical diseases Neglected tropical diseases (NTDs) are a diverse group of tropical infections that are common in low-income populations in developing regions of Africa, Asia, and the Americas. They are caused by a variety of pathogens, such as viruses, bacteri ...
. The most common type is lymphatic filariasis caused by three species of '' Filaria'' that are spread by mosquitoes. Other types of filariasis are
onchocerciasis Onchocerciasis, also known as river blindness, is a disease caused by infection with the parasitic worm ''Onchocerca volvulus''. Symptoms include severe itching, bumps under the skin, and blindness. It is the second-most common cause of blindne ...
also known as ''river blindness'' caused by '' Onchocerca volvulus''; Loa loa filariasis (Loiasis) caused by '' Loa loa''; Mansonelliasis caused by three species of '' Mansonella'', and Dirofilariasis caused by two types of '' Dirofilaria''.


Epidemiology

In the year 2000, 199 million infection cases of lymphatic filariasis were predicted with 3.1 million cases in America and around 107 million in South East Asia, making up to 52% of the global cases coming from Bangladesh, India, Indonesia, and Myanmar combined. While the African nations that comprised around 21% of the cases showed a decrease in the trend over a period of 19 years from 2000 to 2018, studies still proved the global burden of infection to be concentrated in southeast Asia.


Cause

Eight known filarial worms have humans as a definitive host. These are divided into three groups according to the part of the body they affect: * Lymphatic filariasis is caused by the worms '' Wuchereria bancrofti'', '' Brugia malayi'', and '' Brugia timori''. These worms occupy the
lymphatic system The lymphatic system, or lymphoid system, is an organ system in vertebrates that is part of the immune system and complementary to the circulatory system. It consists of a large network of lymphatic vessels, lymph nodes, lymphoid organs, lympha ...
, including the lymph nodes; in chronic cases, these worms can lead to the syndrome of '' elephantiasis''. * Loiasis a subcutaneous filariasis is caused by '' Loa loa'' (the eye worm). '' Mansonella streptocerca'', and '' Onchocerca volvulus''. These worms occupy the layer just under the skin. ''O. volvulus'' causes river blindness. * Serous cavity filariasis is caused by the worms '' Mansonella perstans'' and '' Mansonella ozzardi'', which occupy the serous cavity of the
abdomen The abdomen (colloquially called the gut, belly, tummy, midriff, tucky, or stomach) is the front part of the torso between the thorax (chest) and pelvis in humans and in other vertebrates. The area occupied by the abdomen is called the abdominal ...
. '' Dirofilaria immitis'', the dog heartworm, rarely infects humans. These worms are transmitted by infected mosquitoes of the genera ''
Aedes ''Aedes'' (also known as the tiger mosquito) is a genus of mosquitoes originally found in tropical and subtropical zones, but now found on all continents except Antarctica. Some species have been spread by human activity: ''Aedes albopictus'', ...
, Culex, Anopheles'' and '' Mansonia.'' Recent evidence suggests that climate change has an influence in the spread of the parasitic disease and its vectors. Lymphatic filariasis has been the leading cause of permanent disfigurement and continues to be the second most common cause of long-term disability in the world, even after several efforts of curbing the problem.


Life cycle

''Wuchereria bancrofti'' (Wb) belonging to the family Onchocercidae, accounts for more than 90% of filarial infections worldwide. It completes its life cycle across two hosts, human beings are the definitive host while the mosquito is the intermediate host. The most common mosquito vectors that aid in transmission are Anopheles in Africa, ''Culex'' in America, ''Aedes'' and ''Mansonia'' in Asia (Zulfiqar et al., 2023). Female worms are ovoviviparous and can produce thousands of juveniles known as microfilariae, in infected humans. These are ingested by mosquitoes when they bite. The ingested microfilaria mature and eventually migrate to the insect proboscis from where they get injected into the human skin. Here they travel through the dermis to the lymph organs and further mature into male and female worm forms for the next 6 to 12 months and finally reproduce to complete the cycle. Individuals infected by filarial worms may be described as either "microfilaraemic" or "amicrofilaraemic", depending on whether microfilariae can be found in their peripheral blood. Filariasis is diagnosed in microfilaraemic cases primarily through direct observation of microfilariae in the peripheral blood.


Signs and symptoms

The most spectacular symptom of lymphatic filariasis is elephantiasisedema with thickening of the skin and underlying tissues—which was the first disease discovered to be transmitted by mosquito bites. Elephantiasis results when the parasites lodge in the
lymphatic system The lymphatic system, or lymphoid system, is an organ system in vertebrates that is part of the immune system and complementary to the circulatory system. It consists of a large network of lymphatic vessels, lymph nodes, lymphoid organs, lympha ...
. Cases of acute inflammatory filariasis manifest 5 to 7 day episodes of fever along with inflammation of
lymph nodes A lymph node, or lymph gland, is a kidney-shaped Organ (anatomy), organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphoc ...
. It is often accompanied by epididymitis and spermatic cord inflammation. Secondary bacterial infections are very common and are seen to be more severe in previously unexposed immigrants than in native residents. Chronic filarial disease develops gradually over the years. In most patients the lymphatic dilation does not present any physical symptoms. However, inflammatory responses to dying adult worms often lead to chronic lymphedema in the affected regions which then progresses to elephantiasis. ''W. bancrofti'' often causes hydrocele and scrotal elephantiasis. Moreover, disruption of lymphatic vessels or aberrant drainage of lymph fluid often leads to chyluria and chyloceles. Elephantiasis affects mainly the lower extremities, while the ears,
mucous membrane A mucous membrane or mucosa is a membrane that lines various cavities in the body of an organism and covers the surface of internal organs. It consists of one or more layers of epithelial cells overlying a layer of loose connective tissue. It ...
s, and
amputation Amputation is the removal of a Limb (anatomy), limb or other body part by Physical trauma, trauma, medical illness, or surgery. As a surgical measure, it is used to control pain or a disease process in the affected limb, such as cancer, malign ...
stumps are affected less frequently. However, different species of filarial worms tend to affect different parts of the body; '' Wuchereria bancrofti'' can affect the legs, arms,
vulva In mammals, the vulva (: vulvas or vulvae) comprises mostly external, visible structures of the female sex organ, genitalia leading into the interior of the female reproductive tract. For humans, it includes the mons pubis, labia majora, lab ...
, breasts, and scrotum (causing hydrocele formation), while '' Brugia timori'' rarely affects the genitals. Those who develop the chronic stages of elephantiasis are usually free from microfilariae (amicrofilaraemic), and often have adverse immunological reactions to the microfilariae, as well as the adult worms. The subcutaneous worms present with rashes, urticarial
papule A papule is a small, well-defined bump in the skin lesion, skin. It may have a rounded, pointed or flat top, and may have a umbilication, dip. It can appear with a Peduncle (anatomy), stalk, be thread-like or look warty. It can be soft or firm a ...
s, and arthritis, as well as hyper- and hypopigmentation macules. ''Onchocerca volvulus'' manifests itself in the eyes, causing "river blindness" (
onchocerciasis Onchocerciasis, also known as river blindness, is a disease caused by infection with the parasitic worm ''Onchocerca volvulus''. Symptoms include severe itching, bumps under the skin, and blindness. It is the second-most common cause of blindne ...
), one of the leading causes of blindness in the world. Serous cavity filariasis presents with symptoms similar to subcutaneous filariasis, in addition to abdominal pain, because these worms are also deep-tissue dwellers.


Diagnosis

Filariasis is usually diagnosed by identifying microfilariae on Giemsa stained, thin and thick blood film smears, using the "gold standard" known as the finger prick test. The finger prick test draws blood from the capillaries of the finger tip; larger veins can be used for blood extraction, but strict windows of the time of day must be observed. Blood must be drawn at appropriate times, which reflect the feeding activities of the vector insects. Examples are ''W. bancrofti'', whose vector is a mosquito; night is the preferred time for blood collection. ''Loa loa's'' vector is the deer fly; daytime collection is preferred. This method of diagnosis is only relevant to microfilariae that use the blood as transport from the lungs to the skin. Some filarial worms, such as ''M. streptocerca'' and ''O. volvulus'', produce microfilariae that do not use the blood; they reside in the skin only. For these worms, diagnosis relies upon skin snips and can be carried out at any time. In past, one of the first successes in the efforts to improve sensitivity and specificity of filarial diagnostic tests was identification of the repeated sequences in the parasite genome. The advancement in technologies like
polymerase chain reaction The polymerase chain reaction (PCR) is a method widely used to make millions to billions of copies of a specific DNA sample rapidly, allowing scientists to amplify a very small sample of DNA (or a part of it) sufficiently to enable detailed st ...
(PCR) led to the development of various assays that made large scale surveys of parasitic prevalence much easier. Filarial parasites are known to induce several immunoregulatory mechanisms like the activation of macrophages and T regulatory cells. It has been found that T regulatory cells play an essential role in how filarial worms modify the host immune response by producing immunoglobulin G4 (IgG4). A very high plasma content of IgG4 has been recorded in asymptomatic patients of LF. Thus, the newer assays measuring IgG4 responses to crude filarial extracts or using fractions of parasite extracts have a better overall specificity but are not efficient in discriminating microfilaremic from amicrofilaremic serum donors. Assays which measure circulating antigen are expected to be better at measuring active infection because only living worms secrete circulating antigen. As an attempt to come up with immunodiagnostic test kits for detection of circulating filarial antigen, numerous Antigens and
Antibodies An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as bacteria and viruses, including those that caus ...
specific to the parasites have been tested. An Og4C3 monoclonal antibody-based ELISA and an immunochromatographic ( ICT) card test using the same monoclonal antibody have been tested. However, these commercial assays have certain issues with respect to stability, cost and specificity in field applications. Moreover, it was seen that the ICT format showed 25% of microfilarial negative individuals as being positive for circulating filarial antigens. These commercial tests based on the above circulating antigens are also limited to successful detection of only adult bancroftian worms, making diagnosis only possible in later stages of infection when the therapeutics might no more show effect. A search for worm specific antigens was initiated where SXP-1 antigen was recognized to be specific for ''W.bancrofti'' filariasis. The antigen was identified after screening the cDNA library of adult worms with serum from both amicrofilaremic and microfilaremic patients.The native SXP-1 antigen was present in extracts of microfilariae and adult worms and were seen to be not specific to any lifecycle stage. To identify a W. bancrofti-specific antigen, pastor et al., used the Bm SXP gene to screen against the ''W.bancrofti'' Larval stage 3 cDNA library. This led to the identification of a cDNA sequence of ''W.bancrofti'' SXP-1 that encoded for a polypeptide with a predicted molecular weight of 20.8 kDa. Wb-SXP was found to be 85 percent identical to the BmSXP polypeptide and differed along the C terminal where the former had an extra 29 amino acid long extension. The WbSXP-1 variant, where a stop codon has been introduced at the amino acid position 153 has been shown to be widely distributed among different ''W.bancrofti'' populations. Searches carried out with available sequences from various worms revealed the presence of SXP-1 homologs in many other nematodes with substantial identities in sequence observed during pairwise comparisons. Some examples include O.volvulus (50% identity; Ov-SXP-1), Ascaris suum (43%; As-SXP-1), Loa loa (46%; Li-SXP-1), and ''C.elegans'' (29%; Ce-SXP-1).The presence of a number of invariant and conserved residues in all of these nematode-derived molecules suggests that Wb-SXP-1 is a member of a new protein family.


Treatment

The recommended treatment for people outside the United States is
albendazole Albendazole is a broad-spectrum antihelmintic and antiprotozoal agent of the benzimidazole type. It is used for the treatment of a variety of intestinal parasite infections, including ascariasis, pinworm infection, hookworm infection, trichuri ...
combined with ivermectin. A combination of diethylcarbamazine and albendazole is also effective. Side effects of the drugs include nausea, vomiting, and headaches. All of these treatments are microfilaricides; they have no effect on the adult worms. While the drugs are critical for treatment of the individual, proper hygiene is also required. One review study found that "there is good evidence" that albendazole itself does not contribute to the elimination of microfilaraemia or adult filarial worms, and thus is likely an unnecessary component of albendazole-ivermectin treatment. Diethylcarbamazine-medicated salt is effective in controlling lymphatic filariasis while maintaining its coverage at 90% in the community for six months. Different trials were made to use the known drug at its maximum capacity in absence of new drugs. In a study from India, it was shown that a formulation of albendazole had better anti-filarial efficacy than albendazole itself. In 2003, the common antibiotic
doxycycline Doxycycline is a Broad-spectrum antibiotic, broad-spectrum antibiotic of the Tetracycline antibiotics, tetracycline class used in the treatment of infections caused by bacteria and certain parasites. It is used to treat pneumonia, bacterial p ...
was suggested for treating elephantiasis. Filarial parasites have symbiotic bacteria in the genus '' Wolbachia'', which live inside the worm and seem to play a major role in both its reproduction and the development of the disease. This drug has shown signs of inhibiting the reproduction of the bacteria, further inducing sterility in the nematode. Clinical trials in June 2005 by the Liverpool School of Tropical Medicine reported an eight-week course almost eliminated microfilaraemia.


Society and culture


Research teams

In 2015 William C. Campbell and Satoshi Ōmura were co-awarded half of that year's
Nobel prize in Physiology or Medicine The Nobel Prize in Physiology or Medicine () is awarded yearly by the Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, acco ...
for the discovery of the drug avermectin, which, in the further developed form ivermectin, has decreased the occurrence of lymphatic filariasis.


Prospects for elimination

Filarial diseases in humans offer prospects for elimination by means of vermicidal treatment. If the human link in the chain of infection can be broken, then notionally the disease could be wiped out in a season. In practice it is not so simple, and there are complications in that multiple species overlap in certain regions and double infections are common. This creates difficulties for routine mass treatment because people with onchocerciasis in particular react badly to treatment for lymphatic filariasis.


Other animals

Filariasis can also affect domesticated animals, such as
cattle Cattle (''Bos taurus'') are large, domesticated, bovid ungulates widely kept as livestock. They are prominent modern members of the subfamily Bovinae and the most widespread species of the genus '' Bos''. Mature female cattle are calle ...
,
sheep Sheep (: sheep) or domestic sheep (''Ovis aries'') are a domesticated, ruminant mammal typically kept as livestock. Although the term ''sheep'' can apply to other species in the genus '' Ovis'', in everyday usage it almost always refers to d ...
, and dogs.


Cattle

* Verminous hemorrhagic dermatitis is a clinical disease in cattle due to ''Parafilaria bovicola''. * Intradermal onchocerciasis of cattle results in losses in
leather Leather is a strong, flexible and durable material obtained from the tanning (leather), tanning, or chemical treatment, of animal skins and hides to prevent decay. The most common leathers come from cattle, sheep, goats, equine animals, buffal ...
due to ''Onchocerca dermata'', ''O. ochengi'', and ''O. dukei''. ''O. ochengi'' is closely related to human ''O. volvulus'' ( river blindness), sharing the same vector, and could be useful in human medicine research. * ''Stenofilaria assamensis'' and others cause different diseases in Asia, in cattle and
zebu The zebu (; ''Bos indicus''), also known as indicine cattle and humped cattle, is a species or subspecies of Bos taurus, domestic cattle originating in South Asia. Zebu, like many Sanga cattle breeds, differs from taurine cattle by a fatty hump ...
.


Horses

* "Summer bleeding" is hemorrhagic subcutaneous nodules in the head and upper forelimbs, caused by '' Parafilaria multipapillosa'' (
North Africa North Africa (sometimes Northern Africa) is a region encompassing the northern portion of the African continent. There is no singularly accepted scope for the region. However, it is sometimes defined as stretching from the Atlantic shores of t ...
, Southern and
Eastern Europe Eastern Europe is a subregion of the Europe, European continent. As a largely ambiguous term, it has a wide range of geopolitical, geographical, ethnic, cultural and socio-economic connotations. Its eastern boundary is marked by the Ural Mountain ...
, Asia and South America).


Dogs

* Heart filariasis is caused by ''Dirofilaria immitis''.


See also

*
Ascariasis Ascariasis is a disease caused by the parasitic roundworm ''Ascaris lumbricoides''. Infections have no symptoms in more than 85% of cases, especially if the number of worms is small. Symptoms increase with the number of worms present and may in ...
*
Eradication of infectious diseases The Extinction, eradication of infectious diseases is the reduction of the prevalence of an Infection, infectious disease in the Earth, global Host (biology), host population to zero. Two infectious diseases have successfully been eradicated ...
* Helminthiasis * List of parasites (human) *
Neglected tropical diseases Neglected tropical diseases (NTDs) are a diverse group of tropical infections that are common in low-income populations in developing regions of Africa, Asia, and the Americas. They are caused by a variety of pathogens, such as viruses, bacteri ...
* Wolbachia pipientis


References


Further reading

* *


External links


Page from the "Merck Veterinary Manual" on "Parafilaria multipapillosa" in horses
{{Authority control Animal diseases Insect-borne diseases Helminthiases Tropical diseases Veterinary helminthology Parasitic diseases