Brugia malayi is a nematode (roundworm), one of three agents causing lymphatic filariasis in humans. Lymphatic filariasis, also known as elephantiasis, is a condition characterized by swelling of the lower limb. Two other causes of filaria of lymphatic filariasis are Wuchereria bancrofti and Brugia timori , both of which are different from B. malayi morphologically, symptomatically, and geographically.
B. malayi is transmitted by Mansonia mosquito and limited in South and Southeast Asia. It is one of the tropical diseases targeted for elimination by 2020 by the World Health Organization, which has spurred the development of vaccines and drugs, as well as new methods of vector control.
Video Brugia malayi
History of discovery
Identify different parasites
B. malayi was discovered in 1927 by the Dutch parasite expert Steffen Lambert Brug (1879-1946) (commonly known in scientific literature as S. Brug) while working in Indonesia. It's similar to other filarial wristworms Wuchereria bancrofti (later called Filaria (Microfilaria) bancrfoti ). But the new species of human filaria in North Sumatra is physiologically and morphologically different from the commonly found microfilariae of W. bancrofti in Jakarta. Based on their similarities and differences, the new species is named Filaria malayi . Although epidemiological studies identified Filaria malayi in India, Sri Lanka, China, North Vietnam, and Malaysia in the 1930s, Lichtenstein and Brug's hypothesis were not accepted until the 1940s, when Rao and Mapelstone identified two worms adults in India.
Based on similarities with W. bancrofti , Rao and Mapelstone propose to call the Wuchereria malayi parasite. After the discovery of new species such as W. pahangi (now B. treasure ) in 1956, and W. patei (now < i> B. patei ) in 1958, the scientific classification was revalued in 1960. Buckley proposed to divide the long genus of Wuchereria into two genera, Wuchereria and introducing Brugia just after the original inventor. Then Wuchereria contains only W. bancrofti , which has so far been found to only infect humans, and the genus Brugia contains B. malayi , which infects humans and animals, as well as other zoonotic species.
Identify various strains
In 1957, two human subspecies infecting B. malayi were discovered by Turner and Edeson in Malaysia based on observations of various patterns of microfilaria periodicity. Periodicity refers to a prominent peak in the microfilaria amount during the 24-hour interval when microfilariae is present and detected in the blood circulation. The basis of this phenomenon is still unknown.
- Nocturnal Periodicity: microfilariae is undetectable in the blood for most of the day, but microfilaria density peaks between midnight and 2 am every night.
- Nocturnal subposal: microfilariae present in the blood at all times, but appear at the greatest density between day and night.
Maps Brugia malayi
Transmission: vectors and reservoir
B. malayi is transmitted by mosquito vectors. The main mosquito vectors include Mansonia , Anopheles , and Aedes mosquitoes. The geographic distribution of such diseases depends on the appropriate mosquito breeding habitat.
- Nocturnal periodic forms are transmitted by Mansonia and some anopheles mosquitoes in open swamp and rice growing areas. These mosquitoes tend to bite at night and seem to only infect humans. Natural animal infections are rare and experimental animals do not resist infection.
- The nocturnal subperiodic form is transmitted by Mansonia in the forest swamps, where mosquitoes bite in the shade at all times. A natural zoonotic infection is common. Cats, dogs, monkeys, slow lorises, civet cat, and hamsters have all been experimentally infected with B. malayi from humans and can serve as important reservoirs.
The accumulation of many infective mosquito bites - several hundred to thousands - is needed to build the infection. This is because a competent mosquito usually only infects only a few infective L3 larvae (see Lifecycle), and less than 10% of larvae develop through all the necessary molting steps and develop into mature adult worms. So those most at risk for infection are individuals living in endemic areas - short-term travelers may not develop lymphatic filariasis.
Life cycle
The development and replication of B. malayi occurs in two separate phases: in the vector of mosquitoes and in humans. Both stages are critical to the parasitic life cycle.
Mosquitoes: Mosquitoes serve as biological vectors and intermediate hosts - necessary for developmental and transmission cycles B. malayi 4. Mosquitoes take a meal of human blood and digest microfilariae (egg shaped like a worm) that circulates in the human bloodstream.
5-7 In mosquitoes, the microfilariae releases the sheath, penetrates the midgut, and migrates to the thoracic muscle is an increase in microfilariae in size, molasses, and develops into infective larvae (L1 and L3) over a range of 7-21 days. No multiplication or sexual reproduction of microfilariae occurs in mosquitoes 8-1 The infective larvae (L3) migrate to the salivary glands, enter the trunk and flee to the human skin when the mosquito feeds the blood again.
Man: B. malayi has further development in human and sexual reproduction and egg production 1-2 Infective larvae (L3) actively penetrates the skin through the bite hole and develops into adulthood in the lymphatic system over a span of 6 months. Adult worms can survive in the lymphatic system for 5-15 years 3. Male and female adult worm pairs produce an average of 10,000 egg sheets (microfilaria) daily Microfilariae enter the bloodstream and show nocturnal periodicity and subperiodicity.
4. Other mosquitoes take blood meal and digest microfilariae. Infection depends on the mosquito that consumes blood food during periodic episodes - when microfilariae is present in the bloodstream.
Morphology
Adult
Adult worms resemble a typical nematode roundworm. Long and similar yarn, B. malayi and other nematodes only have longitudinal muscles and move in S-shape motion. Adults are usually smaller than adults W. bancrofti, though some adults have been isolated. Female adult worms (50 mm) larger than male worms (25 mm).
Microfilaria
B. malayi microfilariae has a length of 200-275Ã,Âμm and has a rounded anterior edge and a posterior pointed tip. Microfilaria sheathed, which is very attached with Giemsa. The actual envelope is the eggshell, a thin layer that surrounds the eggshell as microfilariae circulates in the bloodstream. Microfilariae retain the sheath until they are digested in the mosquito's midgut.
B. malayi microfilariae resembles W. bancrofti and Loa loa microfilariae with small differences that may be helpful in laboratory diagnosis. B. malayi microfilariae can be distinguished by the continuous row of nuclei found at the tail end. There are two terminal nuclei which are distinctly separated from other nuclei in the tail, whereas the tail W. bancrofti does not contain nuclei and loa loa microfilaria nuclei form a continuous sequence in the tail. B. malayi microfilariae also has a 2: 1 characteristic cephalic space ratio.
Symptoms
B. malayi is one of the causes of lymphatic filariasis, a condition characterized by infection and swelling of the lymphatic system. The disease is mainly due to the presence of worms in the lymphatic vessels and the inflammatory response generated from the host. The signs of infection are usually consistent with those seen in Bancroftian filariasis - fever, lymphadenitis, lymphangitis, lymphoedema, and secondary bacterial infections - with some exceptions.
Lymphadenitis
Lymphadenitis, swollen lymph nodes, is a common symptom of many diseases. This is an early manifestation of filariasis, usually occurring in the inguinal area during B. malayi infection and may occur before the adult worm.
Lymphangitis
Lymphangitis is inflammation of lymphatic vessels in response to infection. This occurs early in the course of infection in response to worm development, skin changes, death, or bacterial and fungal infections. The affected lymphatic vessels become distended and tender, and the upper skin becomes erythematous and hot. The formation and ulceration of abscess from affected lymph nodes occasionally occurs during B. malayi infection, more often than in Bancroftian filariasis. Remnants of adult worms can sometimes be found in ulcer drainage.
Lymphedema (elephantiasis)
The most obvious sign of infection, elephantiasis, is an enlargement of the legs-usually the legs. A late complication of infection, elephantiasis is a form of lymphedema and is caused by recurrent inflammation of the lymphatic vessels. Repeated inflammatory reactions cause dilation of the vessels and thickening of affected lymphatic vessels, which may interfere with function. The lymphatic system usually serves to maintain fluid balance between tissue and blood and serves as an integral part of the immune system. Blockage of these blood vessels due to inflammatory induced fibrosis, dead worms, or granulomatous reactions can disrupt the normal fluid balance, thus causing swelling of the extremities. Elephantiasis resulting from B. malayi infection usually affects the distal portion of the extremities. Unlike Bancroftian filariasis, B. malayi rarely affects the genitals and does not cause funiculitis, orchitis, epididymitis, hydrocele, or chyluria, a condition more frequently observed with Bancroftian infection.
Secondary bacterial infection
Secondary bacterial infection is common in patients with filariasis. Immune function is impaired due to lymphatic damage other than lymph node ulceration and abscess exposure and circulatory disorders because elephantiasis can cause bacterial or secondary fungal infections. Elephantiasis, in addition to the physical burden of swollen limbs, can be a very damaging condition given the bacterial infection. Part of the "Strategy for Eliminating Filariasis" WHO is targeting a hygiene promotion program to reduce the suffering of affected individuals (see Prevention Strategy).
However, clinical manifestations of infection vary and depend on several factors, including the host immune system, the dose of infection, and the difference in parasitic strain. Most infections appear asymptomatic, but vary from individual to individual. Individuals living in endemic areas with microfilaremia may never present with clear symptoms, whereas in other cases, only a few worms can exacerbate a severe inflammatory response.
Human disease progression, however, is not well understood. Adults usually develop worse symptoms, given the long exposure time required for infection. Infection can occur during childhood, but the disease seems to take years to manifest. The incubation period for infection ranges from 1 month to 2 years and usually microfilariae appear before the obvious symptoms. Lymphedema can develop within six months and development of elephantiasis has been reported in one year of infection among refugees, who are more naïve in immunology. Men tend to develop worse symptoms than women.
Laboratory diagnosis
Inguinal lymph nodes that are soft or enlarged or swollen in the extremities may warn doctors or public health workers to become infected.
With precise laboratory equipment, microscopic examination of microfilaria differential morphology features in stained blood films can aid the diagnosis - in particular the tail check, the presence of the sheath, and the size of the cephalic space. Giemsa staining will uniquely tarnish B. malayi pink sheath. However, finding microfilariae in a blood film can be difficult because of the nocturnal periodicity of some form of
Tests based on PCR are very sensitive and can be used to monitor both human infection and mosquito vectors. However, PCR testing is time-consuming, labor-intensive and requires laboratory equipment. Lymphatic filariasis mainly affects the poor, who live in areas without such resources.
ICT antigen card testing is widely used in the diagnosis of W. bancrofti, but commercial antigens from B. malayi are not widely available. However, new research developments have identified specific and sensitive recombinant (BmR1) antigens in detecting IgG4 antibodies against B. malayi and B. timori in enzyme-linked immunosorbent assays and tests a fast immunochromatographic dipstick (Brugia Rapid). However, it appears that immunoreactivity to these antigens varies in individuals infected with other filarial nematodes. This study has led to the development of two new rapid immunochromatographic IgG4 tape tests - WB rapid and panLF rapid - which detect Bancroftian filariasis and the three species of lymphatic filariasis, respectively, with high sensitivity and selectivity.
Management and therapy
The Global Alliance to Eliminate Lymphatic Filariasis was launched by the World Health Organization in 2000 with two main goals: 1) to disrupt transmission and 2) to reduce the suffering of affected individuals. Mass drug treatment programs are a key strategy for disrupting parasite transmission, and morbidity management, focusing on cleanliness, improving the quality of life of infected individuals.
Drugs
The goal of a community-based effort is to remove microfilariae from the blood of an infected person to prevent transmission to mosquitoes. This is mainly done through the use of drugs. Treatment for B. malayi infection is similar to Bancroftian filariasis. Diethylcarbamazine has been used in a mass-drug program as an effective microphillarathidal drug in several locations, including India. While diethylcarbamazine tends to cause adverse reactions such as fever and immediate weakness, it is not known to cause long-term adverse drug effects. It has been proven to kill adult worms and microfilariae. In Malaysia, the dose of diethylcarbamazine (6 mg/kg weekly for 6 weeks, 6 mg/kg daily for 9 days) reduces microfilaria to 80% for 18-24 months after treatment without mosquito control. The number of microfilariae slowly returns months after treatment, requiring several doses of the drug over time to achieve long-term control. However, it is not known how many years of mass drug administration is needed to eliminate transmission. there were several cases of diethylcarbamazine resistance confirmed in 2007.
Single doses of two drugs (albendazole-diethylcarbamazine and albendazole-ivermectin) have been shown to eliminate 99% microfilariae for a year after treatment and help to improve elephantiasis during the 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 bacteria in the life cycle of B. malayi and other nematodes, new drug efforts have targeted endobacterium. Tetracycline, rifampicin, and chloramphenicol have been effective in vitro by interfering with the development of larvae and microfilariae development. Tetracycline has been shown to cause reproductive abnormalities and embryogenesis in adult worms, resulting in worm infertility. Clinical trials have demonstrated the decreased efficacy of Wolbachia and microfilariae on onchocerciasis and W. bancrofti of infected patients. These antibiotics, while acting on a slightly more indirect route, promise antifilarial drugs.
Hygiene
Secondary bacterial infections are often observed with lymphatic filariasis. Rigorous hygiene practices, including washing with soap and water every day and cleaning germs can help heal infected surfaces, and slow down and potentially reverse the damage to existing tissues. Promoting hygiene is essential for lymphatic filariasis patients considering the immune and lymphatic systems are damaged and can help prevent suffering and disability.
Prevention strategy
Vaccines
Currently there is no licensed vaccine to prevent lymphatic filariasis. However, recent studies have produced vaccine candidates with good results in animal experiments. A glutathione-S-transferase, a detoxifying enzyme in the isolated parasite of Setaria cervi , the parasite of filaria bovin, reduces Vector control
Vector control has been effective in virtually eliminating lymphatic filariasis in some areas, but vector control combined with chemotherapy yields the best results. It is recommended that 11 to 12 years of effective vector control can eliminate lymphatic filariasis. Success methods of B. malayi vector control include residual spraying using DDT and insecticide treated bed nets. Mansonia larvae attach their respiratory tubes to roots and underwater plants to survive. While chemical larvicides provide only partial control, crop removal may prevent vector development, but also potential adverse effects on the aquatic environment. Lymphatic filariasis vector control is negligible compared with far more established efforts to control malaria and dengue vector vectors. Integrated vector control methods should be applied in areas where the same mosquito species is responsible for the transmission of some pathogens.
Epidemiology
B. malayi infects 13 million people in south and southeast Asia and is responsible for nearly 10% of the total cases of world lymphatic filariasis. B. malayi endemic or potentially endemic infections in 16 countries, where most common in southern China and India, but also in Indonesia, Thailand, Vietnam, Malaysia, the Philippines and South Korea. The distribution of B. malayi overlaps with W. bancrofti in this region, but does not co-exist with B. timori . The focus of regional endemicity is determined in part by the mosquito vector (see Transmission).
Genome describes
In 2007, scientists ranked the genome of Brugia malayi . Identifying the genes of these organisms can lead to the development of new drugs and vaccines.
To decipher the genome, "The entire Shotgun Sequencing Genome" is performed. The genome was found to be about 90-95 megabases in size. The sequencing results were then compared with the reference nematodes Caenorhabditis elegans, together with the prototype of Caenorhabditis briggsae . These two free-living nematodes are included in the study and are important for several reasons:
- compare genomes using C. elegans are allowed to identify similar associations in genes
- researchers found genomic conservation in the absence of conservation at a more local gene level
- This indicates that the reset has occurred from time to time between C. elegans and B. malayi and allows researchers to identify genes or proteins specific to B. malayi
- This unique gene is significant because they can cause parasitism to be seen in B. malayi , and therefore are potential targets for future studies
- researchers found genomic conservation in the absence of conservation at a more local gene level
- gene relationship offers insight into the evolutionary trends of parasite genes that can yield clues to better explain their unique ability to survive for many years in humans
Potential for new drugs to treat B. malayi
The comparison of sequences between the two genomes allows for the mapping of C. elegans orthologs to B. malayi genes. Using orthological mapping (between C. Elegans and B.malayi ) and combining genomic and functional genomic data, including an existing RNAi genome screen for C. elegans , a potentially important gene within B. malayi can be identified. Scientists hope to target these genes as potential new targets for drug treatment. The longevity of this parasite complicates treatment because most of the existing drugs target the larvae and thus do not kill the adult worms. Drugs often have to be taken periodically for years, and worms can cause immense immune reactions when they die and release foreign molecules inside the body. Drug treatments for filariasis have not changed significantly in over 20 years, and with increased risk of resistance, there is an urgent need for the development of new anti-filaria 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 therapy.
- potential new drug targets include:
- molting
- nuclear receptor
- collagen and collagen processing
- neuronal signaling
- the B. malayi kinome
- depends on host ( B. malayi ) and endosymbiont ( Wolbachia ) metabolism
Potential new targets for drugs or vaccines can provide new opportunities for understanding, treating, and preventing elephantiasis.
Endangered Endosymbiotic relationship with Wolbachia
The relationship between the bacteria Genome used in transplant research
The use of other expectations for this research is in the field of transplant research. Since the B. malayi genome is the first parasite gene that has been sequenced, its implications on the mechanism of parasitism in humans are very important to understand. According to Alan L. Scott, Ph.D., a collaborator at Johns Hopkins University, understanding how certain parasites, like B. malayi , can adapt to humans, can produce medical benefits far beyond treating elephantiasis. According to the authors, "These worms can be in the host for many years and do not always cause disease, in fact the less the disease the individual has, the more the worms are in circulation.Now we know that the gene does not exist in humans we can target to control disease. "Some of the predicted proteins for these new genes look similar to the known immuno modulator proteins, immune system regulators, which indicate that they are involved in disabling the host's immune system to ensure that parasites remain undetected. This previously unknown knowledge of immune suppressants can also be used in organ transplants and to help treat autoimmune diseases.
According to the Filarial Genome Project undertaken by the Special Program for Research and Training of Tropical Diseases, the gene Brugia malayi MIF is expressed in all stages of the life cycle of the parasite, and the results show that > B. malayi MIF can interact with the human immune system during infection by altering the function of macrophages in an infected individual. The current study tested the hypothesis that MIF may be involved in reducing the host immune response to microfilariae. Understanding how this particular parasite has adapted to humans can help organ transplant researchers by figuring out how to prevent the immune system from invading the transplanted tissue.
Overall expectations for genome sequencing use
Genome information can lead to a better understanding of which genes are important for different processes in the life cycle of the parasite. It is possible to target this gene more specifically and disrupt its life cycle. Understanding how this particular parasite has adapted to humans can produce medical benefits far beyond treating elephantiasis, says collaborator Alan L. Scott, Ph.D., of Bloomberg School of Public Health at Johns Hopkins University. "Parasitic worms are very similar to foreign tissues that have been transplanted into the human body, but unlike the hearts of baboons or pig's kidneys, which the immune system quickly recognizes as foreign and resistant, the worms can survive for years in the body. do so, so maybe someday beneficial for transplant surgery, "explained Dr. Scott.
See also
- List of parasites (human)
- Tropical Eosinophilia
References
- This article is based on the public domain (US Government website) source of the Department of Health and Human Services/Centers for Disease Control: Filariasis
External links
- Brugia_life_cycle_and_adults_in_lymphatics video by R. Rao
- Brugia malayi at UMich
- Special Program for Research and Training of Tropical Diseases (TDR). "Functional analysis of Brugia malayi genes". 2004
- University of Pittsburgh. "The researchers reveal the genetic secret of a destructive human parasite". September 20, 2007.
- Hoerauf, Achim. "Targeting wolbachia, doxycycline reduces the pathology of lymphatic filariasis". 18, September 2006.
- Global Program of the World Health Organization to Eliminate Lymphatic Filariasis
- Global Alliance to Eliminate Lymphatic Filariasis
- Gideon Infectious Diseases Online
- Parasite Image Library, Centers for Disease Control
Source of the article : Wikipedia
0 Comments