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 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 (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 sequenced the genome of brugia malayi. identifying the genes of this organism might lead to development of new drugs and vaccines. 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, along with its prototype caenorhabditis briggsae. 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 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 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 bacteria and b. malayi is not fully understood. extrapolating from research done with wuchereria bancrofti, 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 lymphedema and blindness sometimes associated with b. malayi infections. in a study done by the university of bonn in ghana, doxycycline 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.