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''Brugia malayi'' is a
filaria ''Filaria'' is a genus of nematodes belonging to the family Filariidae. The genus has cosmopolitan distribution. Species: *'' Filaria acutiuscula'' *'' Filaria bufonis'' *'' Filaria loliginis'' *'' Filaria martis'' *'' Filaria piscium'' ...
l (
arthropod Arthropods (, (gen. ποδός)) are invertebrate animals with an exoskeleton, a Segmentation (biology), segmented body, and paired jointed appendages. Arthropods form the phylum Arthropoda. They are distinguished by their jointed limbs and Arth ...
-borne)
nematode The nematodes ( or grc-gre, Νηματώδη; la, Nematoda) or roundworms constitute the phylum Nematoda (also called Nemathelminthes), with plant-Parasitism, parasitic nematodes also known as eelworms. They are a diverse animal phylum inhab ...
(roundworm), one of the three causative agents of
lymphatic filariasis Lymphatic filariasis is a human disease caused by parasitic worms known as filarial worms. Usually acquired in childhood, it is a leading cause of permanent disability worldwide. While most cases have no symptoms, some people develop a syndrome ...
in humans. Lymphatic filariasis, also known as
elephantiasis Elephantiasis is the enlargement and hardening of limbs or body parts due to tissue swelling. It is characterised by edema, hypertrophy, and fibrosis of skin and subcutaneous tissues, due to obstruction of lymphatic vessels. It may affect the geni ...
, is a condition characterized by swelling of the lower limbs. The two other filarial causes of lymphatic filariasis are ''
Wuchereria bancrofti ''Wuchereria bancrofti'' is a filarial (arthropod-borne) nematode (roundworm) that is the major cause of lymphatic filariasis. It is one of the three parasitic worms, together with '' Brugia malayi'' and '' B. timori'', that infect the lymphat ...
'' and '' Brugia timori'', which both differ from ''B. malayi'' morphologically, symptomatically, and in geographical extent. ''B. malayi'' is transmitted by '' Mansonia'' mosquitoes and is restricted to South and Southeast Asia. It is one of the tropical diseases targeted for elimination by the year 2020 by the
World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of h ...
, which has spurred vaccine and drug development, as well as new methods of vector control.


Signs and symptoms

''B. malayi'' is one of the causative agents of
lymphatic filariasis Lymphatic filariasis is a human disease caused by parasitic worms known as filarial worms. Usually acquired in childhood, it is a leading cause of permanent disability worldwide. While most cases have no symptoms, some people develop a syndrome ...
, a condition marked by infection and swelling of the lymphatic system. The disease is primarily caused by the presence of worms in the lymphatic vessels and the resulting inflammatory response of the host. Signs of infection are typically consistent with those seen in Bancroftian filariasis—fever,
lymphadenitis Lymphadenopathy or adenopathy is a disease of the lymph nodes, in which they are abnormal in size or consistency. Lymphadenopathy of an inflammatory type (the most common type) is lymphadenitis, producing swollen or enlarged lymph nodes. In cl ...
, lymphangitis,
lymphedema Lymphedema, also known as lymphoedema and lymphatic edema, is a condition of localized swelling caused by a compromised lymphatic system. The lymphatic system functions as a critical portion of the body's immune system and returns interstitial fl ...
, and secondary bacterial infection—with a few exceptions.


Lymphadenitis

Lymphadenitis Lymphadenopathy or adenopathy is a disease of the lymph nodes, in which they are abnormal in size or consistency. Lymphadenopathy of an inflammatory type (the most common type) is lymphadenitis, producing swollen or enlarged lymph nodes. In cl ...
, the swelling of the lymph nodes, is a commonly recognized symptom of many diseases. It is an early manifestation of filariasis, usually occurs in the inguinal area during ''B. malayi'' infection and can occur before the worms mature.


Lymphangitis

Lymphangitis is the inflammation of the lymphatic vessels in response to infection. It occurs early in the course of infection in response to worm development, molting, death, or bacterial and fungal infection. The affected lymphatic vessels become distended and tender, and the overlying skin becomes erythematous and hot. Abscess formation and ulceration of the affected lymph node occasionally occurs during ''B. malayi'' infection, more often than in Bancroftian filariasis. Remnants of adult worms can sometimes be found in the ulcer drainage.


Lymphedema

The most obvious sign of infection, elephantiasis, is the enlargement of the limbs–usually the legs. A late complication of infection, elephantiasis is a form of
lymphedema Lymphedema, also known as lymphoedema and lymphatic edema, is a condition of localized swelling caused by a compromised lymphatic system. The lymphatic system functions as a critical portion of the body's immune system and returns interstitial fl ...
and is caused by repeated inflammation of the lymphatic vessels. Repeated inflammatory reactions causes vessel dilation and thickening of the affected lymphatic vessels, which can compromise function. The lymphatic system normally functions to maintain fluid balance between tissues and the blood and serves as an integral part of the immune system. Blockage of these vessels due to inflammatory induced fibrosis, dead worms, or granulomatous reactions can interfere with normal fluid balance, thus leading to swelling in the extremities. Elephantiasis resulting from ''B. malayi'' infection typically affects the distal portions of the extremities. Unlike Bancroftian filariasis, ''B. malayi'' rarely affects genitalia and does not cause funiculitis, orchitis, epididymitis, hydrocele, or chyluria, conditions more often observed with Bancroftian infection.


Secondary bacterial infection

Secondary bacterial infection is common among patients with filariasis. Compromised immune function due to lymphatic damage in addition to lymph node ulcerations and abscesses exposure and impaired circulation due to elephantiasis can cause secondary bacterial or fungal infection. Elephantiasis, in addition to the physical burden of a swollen limb, can be a severely debilitating condition given bacterial infection. Part of the WHO's "Strategy to Eliminate Lymphatic Filariasis" targets hygiene promotion programs in order to alleviate the suffering of affected individuals (see Prevention Strategies).. However, clinical manifestations of infection are variable and depend on several factors, including host immune system, infectious dose, and parasite strain differences. Most infections appear asymptomatic, yet vary from individual to individual. Individuals living in endemic areas with microfilaremia may never present with overt symptoms, whereas in other cases, only a few worms can exacerbate a severe inflammatory response. The development of the disease in humans, however, is not well understood. Adults typically develop worse symptoms, given the long exposure time required for infection. Infection may occur during childhood, but the disease appears to take many years to manifest. The incubation period for infection ranges from 1 month to 2 years and typically microfilariae appear before overt symptoms. Lymphedema can develop within six months and development of elephantiasis has been reported within a year of infection among refugees, who are more immunologically naive. Men tend to develop worse symptoms than women.


Hosts

Hosts of ''B. malayi'' include
Southeast Asia Southeast Asia, also spelled South East Asia and South-East Asia, and also known as Southeastern Asia, South-eastern Asia or SEA, is the geographical United Nations geoscheme for Asia#South-eastern Asia, south-eastern region of Asia, consistin ...
n cats.


Cause


Life cycle

Development and replication of ''B. malayi'' occurs in two discrete phases: in the mosquito vector and in the human. Both stages are essential to the life cycle of the parasite. Mosquito: The mosquito serves as a biological vector and intermediate host – it is required for the developmental cycle and transmission of ''B. malayi''.
4. The mosquito takes a human blood meal and ingests microfilariae (worm-like sheathed eggs) that circulate in the human blood stream.
5-7 In the mosquito, the microfilariae shed sheaths, penetrate the midgut, and migrate to the thoracic muscles were the microfilariae increase in size, molt, and develop into infective larvae (L1 and L3) over a span of 7–21 days. No multiplication or sexual reproduction of microfilariae occurs in the mosquito.
8-1 The infective larvae (L3) migrate to the salivary glands, enter the proboscis and escape onto human skin when the mosquito takes another blood meal. Human: ''B. malayi'' undergoes further development in the human as well as sexual reproduction and egg production.
1-2 The infective larvae (L3) actively penetrate the skin through the bite hole and develop into adults in the lymphatic system over a span of 6 months. Adult worms can survive in the lymphatic system for 5–15 years.
3. The male and female adult worms mate and the females produce an average of 10,000 sheathed eggs (microfilaria) daily The microfilariae enter the blood stream and exhibit nocturnal periodicity and subperiodicity.
4. Another mosquito takes a blood meal and ingests the microfilariae. Infection depends on the mosquito taking a blood meal during a periodic episode – when microfilariae are present in the bloodstream.


Morphology


Adult

Adult worms resemble typical nematode roundworms. Long and threadlike, ''B. malayi'' and other nematode possess only longitudinal muscles and move in an S-shape motion. Adults are typically smaller than adult ''W. bancrofti'', though few adults have been isolated. Female adult worms (50 mm) are larger than male worms (25 mm).


Microfilariae

''B. malayi'' microfilariae are 200–275  µm in length and have a round anterior end and a pointed posterior end. The microfilariae are sheathed, which stains heavily with Giemsa. The sheath is actually the egg shell, a thin layer that surrounds the egg shell as the microfilariae circulates in the bloodstream. The microfilariae retain the sheath until they are digested in the mosquito midgut. ''B. malayi'' microfilariae resemble ''W. bancrofti'' and ''
Loa loa ''Loa loa'' is a filarial (arthropod-borne) nematode (roundworm) that causes ''Loa loa'' filariasis. ''Loa loa'' actually means "worm worm", but is commonly known as the "eye worm", as it localizes to the conjunctiva of the eye. ''Loa loa'' is ...
'' microfilariae with minor differences that can aid in laboratory diagnosis. ''B. malayi'' microfilariae can be distinguished by the noncontinuous row of nuclei found in the tip of the tail. There are two terminal nuclei that are distinctly separated from the other nuclei in the tail, whereas the tail of ''W. bancrofti'' contains no nuclei and ''Loa loa'' microfilariae nuclei form a continuous row in the tail. ''B. malayi'' microfilariae also have a characteristic cephalic space ratio of 2:1.


Spread

''B. malayi'' is transmitted by a mosquito vector. The principal mosquito vectors include ''Mansonia'', ''
Anopheles ''Anopheles'' () is a genus of mosquito first described and named by J. W. Meigen in 1818. About 460 species are recognised; while over 100 can transmit human malaria, only 30–40 commonly transmit parasites of the genus ''Plasmodium'', which c ...
'', and ''
Aedes ''Aedes'' is a genus of mosquitoes originally found in tropical and subtropical zones, but now found on all continents except perhaps Antarctica. Some species have been spread by human activity: ''Aedes albopictus'', a particularly invasive spe ...
'' mosquitoes. The geographical distribution of the disease is thus dependent on suitable mosquito breeding habitat. * The nocturnal periodic form is transmitted by ''Mansonia'' and some anopheline mosquitoes in open swamps and rice growing areas. These mosquitoes tend to bite at night and appear to only infect humans. Natural animal infections are rare and experimental animals do not retain infection. * The nocturnal subperiodic form is transmitted by ''Mansonia'' in forest swamps, where mosquitoes bite in the shade at any time. Natural zoonotic infections are common. Cats, dogs, monkeys, slow lorises, civet cats, and hamsters have all been successfully experimentally infected with ''B. malayi'' from man and may serve as important reservoirs. The accumulation of many infective mosquito bites – several hundreds to thousands – is required to establish infection. This is because a competent mosquito usually transmits only a few infective L3 larvae (see
Life cycle Life cycle, life-cycle, or lifecycle may refer to: Science and academia *Biological life cycle, the sequence of life stages that an organism undergoes from birth to reproduction ending with the production of the offspring * Life-cycle hypothesis ...
), and less than 10% of those larvae progress through all the necessary molting steps and develop into adult worms that can mate. Thus those at greatest risk for infection are individuals living in endemic areas—short term tourists are unlikely to develop lymphatic filariasis.


Diagnosis

Tender or enlarged inguinal lymph nodes or swelling in the extremities can alert physicians or public health officials to infection. With appropriate laboratory equipment, microscopic examination of differential morphological features of microfilariae in stained blood films can aid diagnosis—in particular the examination of the tail portion, the presence of a sheath, and the size of the cephalic space.
Giemsa staining Giemsa stain (), named after German chemist and bacteriologist Gustav Giemsa, is a nucleic acid stain used in cytogenetics and for the histopathological diagnosis of malaria and other parasites. Uses It is specific for the phosphate groups o ...
will uniquely stain ''B. malayi'' sheath pink. However, finding the microfilariae on blood films can be difficult because of the nocturnal periodicity of some forms of ''B. malayi''. PCR based assays are highly sensitive and can be used to monitor infections both in humans and the mosquito vectors. However, PCR assays are time-consuming, labor-intensive and require laboratory equipment. Lymphatic filariasis mainly affects the poor, who live in areas without such resources.. The ICT antigen card test is widely used in the diagnosis of ''W. bancrofti'', but commercial antigens of ''B. malayi'' have not been widely available. However, new research developments have identified a recombinant antigen (BmR1) that is both specific and sensitive in the detection of IgG4 antibodies against ''B. malayi'' and ''B. timori'' in an
enzyme-linked immunosorbent assay The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay uses a solid-phase type of enzyme immunoassay (EIA) to detect the presence ...
and an
immunochromatographic Affinity chromatography is a method of separating a biomolecule from a mixture, based on a highly specific macromolecular binding interaction between the biomolecule and another substance. The specific type of binding interaction depends on the ...
rapid dipstick (Brugia Rapid) test. However, it appears that immunoreactivity to this antigen is variable in individuals infected with other filarial nematodes. This research has led to the development of two new rapid immunochromatographic IgG4 cassette tests – WB rapid and panLF rapid – which detect Bancroftian filariasis and all three species of lymphatic filariasis, respectively, with high sensitivity and selectivity.


Prevention


Vaccines

There is currently no licensed vaccine to prevent lymphatic filariasis. However, recent research has produced vaccine candidates with good results in experimental animals. A glutathione-S-transferase, a detoxification enzyme in parasites isolated from '' Setaria cervi'', a bovine filarial parasite, reduced ''B. malayi'' adult parasite burden by more than 82% for 90 days after treatment.


Vector control

Vector control has been effective in virtually eliminating lymphatic filariasis in some regions, but vector control combined with chemotherapy produces the best results. It is suggested that 11 to 12 years of effective vector control may eliminate lymphatic filariasis.Remme J.H.F., Feenstra P., Lever P.R., Medici A., Morel C., Noma M., Ramaiah K.D., Richards F., Seketeli A., Schmunis G., van Brakel W.H., and Anna Vassall. Chapter 22. Tropical diseases targeted for elimination: Chagas disease, lymphatic filariasis, onchocerciasis, and leprosy. Book: Disease Control Priorities in Developing Countries. Successful methods of ''B. malayi'' vector control include residual house spraying using DDT and insecticide treated bednets. ''Mansonia'' larvae attach their breathing tubes to underwater roots and plants in order to survive. While chemical larvicides have only provided partial control, plant removal could prevent vector development, but also potential adverse effects on the aquatic environment. Lymphatic filariasis vector control is neglected in comparison to the far more established efforts to control malaria and dengue vectors. Integrated vector control methods should be applied in areas where the same mosquito species is responsible for transmitting multiple pathogens..


Management

The Global Alliance to Eliminate Lymphatic Filariasis was launched by the World Health Organization in 2000 with two primary goals: 1) to interrupt transmission and 2) to alleviate the suffering of affected individuals. Mass drug treatment programs are the main strategy for interrupting parasite transmission, and morbidity management, focusing on hygiene, improves the quality of life of infected individuals.


Drugs

A goal of community-based efforts is to eliminate microfilariae from the blood of infected individuals in order to prevent transmission to the mosquito. This is primarily accomplished through the use of drugs. The treatment for ''B. malayi'' infection is the same as for Bancroftian filariasis.
Diethylcarbamazine Diethylcarbamazine is a medication used in the treatment of filariasis including lymphatic filariasis, tropical pulmonary eosinophilia, and loiasis. It may also be used for prevention of loiasis in those at high risk. While it has been used for ...
has been used in mass treatment programs as an effective microfilaricidal drug in several locations, including India.Adinarayanan S, Critchley J, Das PK, Gelband H. Diethylcarbamazine (DEC)-medicated salt for community-based control of lymphatic filariasis. Cochrane Database of Systematic Reviews, 2007. While diethylcarbamazine tends to cause adverse reactions like immediate fever and weakness, it is not known to cause any long-term adverse drug effects. It has been shown to kill both adult worms and microfilariae. In Malaysia, diethylcarbamazine dosages (6 mg/kg weekly for 6 weeks; 6 mg/kg daily for 9 days) reduced microfilariae by 80% for 18–24 months after treatment in the absence of mosquito control. Microfilariae numbers slowly return many months after treatment, thus requiring multiple drug doses over time in order to achieve long-term control. However, it is not known how many years of mass drug administration is required to eliminate transmission. there have been any confirmed cases of diethylcarbamazine resistance as of 2007. Single doses of two drugs (albendazole-diethylcarbamazine and albendazole-ivermectin) have been shown to remove 99% of microfilariae for a year after treatment and help to improve elephantiasis during early stages of the disease. Ivermectin does not appear to kill adult worms but serves as a less toxic microfilaricide. Since the discovery of the importance of ''
Wolbachia ''Wolbachia'' is a genus of intracellular bacteria that infects mainly arthropod species, including a high proportion of insects, and also some nematodes. It is one of the most common parasitic microbes, and is possibly the most common reproduct ...
'' bacteria in the life cycle of ''B. malayi'' and other nematodes, novel drug efforts have targeted the endobacterium. Tetracyclines, rifampicin, and chloramphenicol have been effective in vitro by interfering with larvae molting and microfilariae development. Tetracyclines have been shown to cause reproductive and embryogenesis abnormalities in the adult worms, resulting in worm sterility. Clinical trials have demonstrated the successful reduction of ''Wolbachia'' and microfilariae in onchocerciasis and ''W. bancrofti'' infected patients. These antibiotics, while acting through a slightly more indirect route, are promising antifilarial drugs.


Hygiene

Secondary bacterial infection is often observed with lymphatic filariasis. Rigorous hygiene practices, including washing with soap and water daily and disinfecting wounds can help heal infected surfaces, and slow and potentially reverse existing tissue damage. Promoting hygiene is essential for lymphatic filariasis patients given the compromised immune and damaged lymphatic systems and can help prevent suffering and disability.


Epidemiology

''B. malayi'' infects 13 million people in south and southeast Asia and is responsible for nearly 10% of the world's total cases of lymphatic filariasis. ''B. malayi'' infection is endemic or potentially endemic in 16 countries, where it is most common in southern China and India, but it also occurs in Indonesia, Thailand, Vietnam, Malaysia, the Philippines, and South Korea. The distribution of ''B. malayi'' overlaps with ''W. bancrofti'' in these regions, but does not coexist with ''B. timori''. Regional foci of endemicity are determined in part by the mosquito vectors


History


Distinct parasite

''B. malayi'' was discovered in 1927 by the Dutch parasitologist Steffen Lambert Brug (1879–1946) (who is commonly known in the scientific literature as S.L. Brug) while working in Indonesia. It was similar to another filarial roundworm ''
Wuchereria bancrofti ''Wuchereria bancrofti'' is a filarial (arthropod-borne) nematode (roundworm) that is the major cause of lymphatic filariasis. It is one of the three parasitic worms, together with '' Brugia malayi'' and '' B. timori'', that infect the lymphat ...
'' (then called ''Filaria (Microfilaria) bancrofti''). But the new species of human filaria in North Sumatra was both physiologically and morphologically distinct from the ''W. bancrofti'' microfilariae commonly found in Jakarta. Based on their resemblance and differences, the new species was named ''Filaria malayi''. Despite epidemiological studies identifying ''Filaria malayi'' in India, Sri Lanka, China, North Vietnam, and Malaysia in the 1930s, Lichtenstein and Brug's hypothesis was not accepted until the 1940s, when Rao and Mapelstone identified two adult worms in India. Based on the similarities with ''W. bancrofti'', Rao and Mapelstone proposed to call the parasite ''Wuchereria malayi.'' After the discovery of new species such as ''W. pahangi'' (now '' B. pahangi'') in 1956, and ''W. patei'' (now ''B. patei'') in 1958, the scientific classification was reassessed in 1960. Buckley proposed to divide the old genus ''Wuchereria'', into two genera, ''Wuchereria'' and introduced a new ''Brugia'' after the original discoverer. Then ''Wuchereria'' contains only ''W. bancrofti'', which so far has been found to infect only humans, and the genus ''Brugia'' contains ''B. malayi'', which infects humans and animals, as well as other zoonotic species..


Different strains

In 1957, two subspecies of human infecting ''B. malayi'' were discovered by Turner and Edeson in Malaysia based on the observation of different patterns of microfilaria periodicity. Periodicity refers to a pronounced peak in microfilariae count during a 24‑hour interval when microfilariae are present and detectable in the circulating blood. The basis for this phenomenon remains largely unknown.. * Nocturnal periodicity: microfilariae are not detectable in the blood for the majority of the day, but the microfilarial density peaks between midnight and 2 AM nightly. * Nocturnal subperiodicity: microfilariae are present in the blood at all times, but appear at greatest density between noon and 8 PM.


Research

In 2007,
scientists A scientist is a person who conducts scientific research to advance knowledge in an area of the natural sciences. In classical antiquity, there was no real ancient analog of a modern scientist. Instead, philosophers engaged in the philosophica ...
sequenced In genetics and biochemistry, sequencing means to determine the primary structure (sometimes incorrectly called the primary sequence) of an unbranched biopolymer. Sequencing results in a symbolic linear depiction known as a sequence which suc ...
the
genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...
of ''Brugia malayi''. Identifying the
genes In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
of this organism might lead to development of new
drugs A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via inhalat ...
and
vaccines A vaccine is a biological preparation that provides active acquired immunity The adaptive immune system, also known as the acquired immune system, is a subsystem of the immune system that is composed of specialized, systemic cells and pro ...
. To decipher the genome, "Whole Genome Shotgun Sequencing" was performed. The genome was found to be approximately 90-95 megabases in size. The results of the sequencing were then compared to those of the reference nematode ''
Caenorhabditis elegans ''Caenorhabditis elegans'' () is a free-living transparent nematode about 1 mm in length that lives in temperate soil environments. It is the type species of its genus. The name is a blend of the Greek ''caeno-'' (recent), ''rhabditis'' (ro ...
'', along with its prototype ''
Caenorhabditis briggsae ''Caenorhabditis briggsae'' is a small nematode, closely related to ''Caenorhabditis elegans''. The differences between the two species are subtle. The male tail in ''C. briggsae'' has a slightly different morphology from ''C. elegans''. Other di ...
''. These two free-living nematodes were incorporated in the study and were important for several reasons: * comparing genomes using ''C. elegans'' allowed for the identification of similar linkages in genes ** the researchers found a genomic conservation with an absence of conservation at a more local gene level *** this demonstrated that rearrangements had occurred over time between the ''C. elegans'' and ''B. malayi'' and allowed researchers to identify genes or proteins that were specific to ''B. malayi'' *** these unique genes were significant because they could have led to the parasitism seen in ''B. malayi'', and therefore are potential targets for future studies * gene linkages offer insight into the evolutionary trend of parasitic genes that could yield clues to further explain their unique ability to successfully survive for many years in humans


New medications

Sequence comparisons between the two genomes allow for mapping of ''C. elegans''
orthologs Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a spec ...
to ''B. malayi'' genes. By using orthology mappings (between ''C. elegans'' and ''B.malayi'') and incorporating the extensive genomic and functional genomic data, including genome-wide RNAi screens that already exist for ''C. elegans'', potentially essential genes in ''B. malayi'' can be identified. Scientists are hoping to be able to target these genes as potential new targets for drug treatments. The longevity of this parasite complicates treatment because most existing drugs target the larvae and thus do not kill adult worms. The drugs often must be taken periodically for years, and the worms can cause a massive immune reaction when they die and releases foreign molecules in the body. Drug treatments for filariasis have not changed significantly in over 20 years, and with the risk of resistance rising, there is an urgent need for the development of new anti-filarial drug therapies. From the genome sequence, several metabolic pathways have been identified, containing dozens of gene products that may be helpful in the discovery of more targeted and effective drug therapies. * possible new drug targets include: ** molting ** nuclear receptors ** collagens and collagen processing ** neuronal signaling ** the ''B. malayi''
kinome In molecular biology, biochemistry and cell signaling the kinome of an organism is the complete set of protein kinases encoded in its genome. Kinases are usually enzymes that catalyze phosphorylation reactions (of amino acids) and fall into severa ...
** reliance on host (''B. malayi'') and endosymbiont (''Wolbachia'') metabolism These potential new targets for drugs or vaccines may provide new opportunities for understanding, treating and preventing elephantiasis.


Relationship with ''Wolbachia''

The relationship between the ''
Wolbachia ''Wolbachia'' is a genus of intracellular bacteria that infects mainly arthropod species, including a high proportion of insects, and also some nematodes. It is one of the most common parasitic microbes, and is possibly the most common reproduct ...
'' bacteria and ''B. malayi'' is not fully understood. Extrapolating from research done with ''
Wuchereria bancrofti ''Wuchereria bancrofti'' is a filarial (arthropod-borne) nematode (roundworm) that is the major cause of lymphatic filariasis. It is one of the three parasitic worms, together with '' Brugia malayi'' and '' B. timori'', that infect the lymphat ...
'', another nematode that causes filariasis, ''Wolbachia'' may aid in embryogenesis of the worm, be responsible for potent inflammatory responses from macrophages and filarial disease, and be linked to the onset of lyphedema and blindness sometimes associated with ''B. malayi'' infections. In a study done by the University of Bonn in Ghana,
doxycycline Doxycycline is a broad-spectrum tetracycline class antibiotic used in the treatment of infections caused by bacteria and certain parasites. It is used to treat bacterial pneumonia, acne, chlamydia infections, Lyme disease, cholera, typhus, an ...
effectively depleted ''Wolbachia'' from ''W. bancrofti''. It is likely that the mechanism of doxycycline is similar to that in other filarial species, i.e., a predominant blockade of embryogenesis, leading to a decline of microfilariae according to their half-life. This could render doxycycline treatment an additional tool for the treatment of microfilaria-associated diseases in Bancroftian filariasis, along with ''B. malayi'' fiariasis. The course of treatment with doxycycline could be much shorter as it would make the adult worm sterile in one shot rather than repeatedly have to target the replenished larvae that current treatments kill, and there would be fewer side effects for the infected individual.


Transplant research

Another hopeful use for the research is in the area of transplant research. Because the ''B. malayi'' genome is the first parasitic genome to have been sequenced, the implications on the mechanism of parasitism in humans are crucial to understand. According to Alan L. Scott, Ph.D., a collaborator at Johns Hopkins University, understanding how a particular parasite, such as ''B. malayi'', can adapt to humans, may yield medical benefits far beyond treating elephantiasis. According to the author, "This worm can reside in the host for years and not necessarily cause disease, in fact the less disease the individual has, the more worms there are in circulation. Now that we know those genes don't exist in humans we can target them to control disease." Some of the predicted proteins for these new genes appear similar to known immuno-modulator proteins, regulators of the immune system, suggesting that they are involved in deactivating the host's immune system to ensure the parasite remains undetected. Knowledge of these previously unknown immune suppressors could also be of use in organ transplants and to help treat autoimmune disease. According to the Filarial Genome Project being done by The Special Programme for Research and Training in Tropical Diseases, the ''Brugia malayi'' MIF gene is expressed in all life-cycle stages of the parasite, and results suggest that ''B. malayi'' MIF may interact with the human immune system during the course of infection by altering the function of macrophages in the infected individual. Studies are currently testing the hypothesis that MIF may be involved in reducing the host's immune response to the microfilariae. Understanding how this particular parasite has adapted to humans may help organ transplant researchers by figuring out how to prevent the immune system from attacking the transplanted tissue.


See also

*
List of parasites (human) Endoparasites Protozoan organisms Helminths (worms) Helminth organisms (also called helminths or intestinal worms) include: Tapeworms Flukes Roundworms Other organisms Ectoparasites References {{Portal bar, Bio ...
*
Tropical eosinophilia Tropical pulmonary eosinophilia (TPE, tropical eosinophilia, or Weingarten's syndrome), is characterized by cough, bronchospasm, wheezing, abdominal pain, and an enlarged spleen. Occurring most frequently in the Indian subcontinent and Southeast Asi ...


References

* The article is based on the
public domain The public domain (PD) consists of all the creative work A creative work is a manifestation of creative effort including fine artwork (sculpture, paintings, drawing, sketching, performance art), dance, writing (literature), filmmaking, ...
(U.S. Government website) sourc
US Dept. of Health and Human Services / Center for Disease Control: Filariasis


External links


Brugia_life_cycle_and_adults_in_lymphatics video by R. Rao




* ttp://www.physorg.com/news109517312.html University of Pittsburgh. "Researchers reveal genetic secrets of devastating human parasite". 20 September 2007.
Hoerauf, Achim. "Targeting wolbachia, doxycycline reduces pathology of lymphatic filariasis". 18, September 2006.

The World Health Organization's Global Program to Eliminate Lymphatic Filariasis

The Global Alliance to Eliminate Lymphatic Filariasis

Gideon Infectious Diseases Online


{{DEFAULTSORT:Brugia Malayi Parasitic nematodes of humans Insect-borne diseases Spirurida Nematodes described in 1927 Lymphatic filariasis