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Single-dose diethylcarbamazine in the control of periodic brugian filariasis in Peninsular Malaysia

Hakim SL, Vythilingam I, Marzukhi MI, Mak JW

Trans R Soc Trop Med Hyg, 1995 11 1;89(6):686-9.
PMID: 8594697

The study compared the effectiveness of a single dose of diethylcarbamazine (DEC) (6mg/kg) with the standard regimen of 6 doses (total 36 mg/kg) in mass chemotherapy for the control of brugian filariasis. Mass chemotherapy with single-dose DEC was instituted in one area and standard dose in the other and treatment was repeated after one year. Parasitological surveys were conducted before, and 3, 7 and 12 months after treatment. Pretreatment characteristics were not significantly different between the 2 treatment areas. There was a significant reduction in microfilaraemia prevalence rate from 24.7% to 14.7% at 12 months and to 6.8% at 19 months in the single dose area and from 22.8% to 9.6% at 12 months and to 2.7% at 19 months with the standard dose. Maximum reduction was at 7 months after treatment with both regimens. There was also significant progressive reduction in mean microfilarial density from 4.39 +/- 20.37 to 0.89 +/- 4.16 per 60 microL in the single-dose area and from 4.43 +/- 17.31 to 0.75 +/- per 60 microL in the standard dose area. There was a greater reduction of both microfilarial prevalence and density using the standard regimen but it was not statistically significant. Thus, a single dose of DEC is as effective as the standard dose in controlling periodic brugian filariasis.

Matched MeSH terms: Brugia malayi*
Fulltext Anopheles donaldi incriminated as a vector of periodic Brugia malayi in Grik, Perak, Malaysia

Vythilingam I, Hakim SL, Chan ST, Mak JW

Southeast Asian J. Trop. Med. Public Health, 1996 Sep;27(3):637-41.
PMID: 9185284

Studies were carried out to observe the species composition of mosquitos and to determine the vectors responsible for the transmission of filariasis in Grik, Perak, Malaysia. A total of 2,155 mosquitos belonging to 7 genera and 30 species were collected. Anopheles donaldi comprised 24.1% of the collection. Twelve out of 519 An. donaldi were infected with L3 larvae of Brugia malayi. The peak biting time was around 23.00-24.00 hours. The infective bites per month ranged from 0 to 6.3.

Matched MeSH terms: Brugia malayi*
Fulltext Pathology of lymphatic filariasis

Mak JW

International e-Journal of Science, Medicine & Education, 2012;6 Suppl:S80-86.
MyJurnal

Developing and adult worms of the human lymphatic filarial parasites (Wuchereria bancrofti,
Brugia malayi, and Brugia timori) are located mainly in the lymphatic system and occasionally in aberrant sites like subcutaneous and conjunctival cysts. Lymphatic
pathology ranging from dilatation of lymphatic channels and lymphangiectasia are detected on ultrasonography in apparently healthy, amicrofilaraemic, but filarial antigen positive individuals in endemic areas. Microfilariae are distributed in various organs and may be associated with immune mediated pathology at these sites; tropical pulmonary eosinophilia is characterized by intense immune mediated destruction of microfilariae in the lung parenchyma. In the spleen and other sites, nodular granulomatous lesions can occur where microfilariae are trapped and destroyed. The finding of Wolbachia endosymbionts in all stages of lymphatic filarial parasites has provided new insight on the adverse reactions
associated with anti-filarial chemotherapy. Inflammatory molecules mainly lipopolysaccharide (LPS)-like molecules released from endosymbionts on death of the
parasites are largely responsible for the adverse reactions encountered during anti-filarial chemotherapy. Prenatal tolerance or sensitization to parasite derived molecules can immune-modulate and contribute to both pathology and susceptibility/resistance to infection. Pathological responses thus depend not only on exposure to filarial antigens/infection, but also on host-parasiteendosymbiont factors and to intervention with antifilarial treatment. Treatment induced or host mediated death of parasites are associated with various grades of inflammatory response, in which eosinophils and LPS from endosymbionts play prominent roles, leading to death of the parasite, granulomatous formation, organization and fibrosis. The non-human primate (Presbytis spp.) model of
Brugia malayi developed for the tertiary screening of anti-filarial compounds has provided unique opportunities for the longitudinal study of the pathology associated with lymphatic filariasis. The pathology in this non-human primate model closely follows that seen in
human lymphatic filarial infections and correlates with clinical evidence of lymphatic pathology as detected with ultrasonography. These studies also show that successful treatment as detected by loss of motility and calcification of worms on ultrasonography is associated with reversal of early dilatations of lymphatic channels.

Matched MeSH terms: Brugia malayi
Fulltext Filariasis

Mak JW

Family Practitioner, 1982;5(3):23-26.

Brugia malayi and Wuchereria bancrofti infections cause lymphatic filariasis in Malaysia. About 2.5 million people live in endemic areas of filariasis, of whom 5% have microfilaraemia and probably twice as many are infected. There is a wide clinical spectrum of response to the infection. While some have asymptomatic microfilaraemia, others have episodic attacks of fever, lymphadenitis, retrograde lymphangitis and lymphoedema. Elephantiasis is a late complication. Tropical pulmonary eosinophilia and other forms of occult filariasis are due to hyper allergic reactions to microfilarial antigens. Parasitological and serological tests aid in confirming the clinical diagnosis. The drug of choice is diethylcarbamazine citrate.

Matched MeSH terms: Brugia malayi
Applicability of Brugia malayi immune antibody library for the isolation of a human recombinant monoclonal antibody to Echinococcus granulosus antigen B

Rahumatullah A, Ahmad A, Noordin R, Lai JY, Baharudeen Z, Lim TS

Exp Parasitol, 2020 Dec;219:108029.
PMID: 33096112 DOI: 10.1016/j.exppara.2020.108029

Echinococcus granulosus is a worldwide zoonotic infection that causes human cystic echinococcosis (CE) or hydatid disease. The present study describes the isolation and production of a monoclonal antibody against recombinant AgB protein using the developed Human AntibodY Disease ENhanced (HAYDEN)-Filariasis library. The DNA sequences of the isolated clones were analyzed, followed by gene analysis and binding assays. Clone E1 showed a full-length sequence and represents the IgHV5-LV3 antibody gene family. The antibody protein yield was satisfactory, and it reacted specifically against rAgB. The novel E1 protein is potentially useful for the development of an antigen detection assay for CE. The ability of the Brugia malayi immune antibody library to isolate antibodies against Echinococcus granulosus antigens highlights the broad coverage of immune antibody libraries.

Matched MeSH terms: Brugia malayi/genetics; Brugia malayi/immunology*
Delineation of BmSXP antibody V-gene usage from a lymphatic filariasis based immune scFv antibody library

Rahumatullah A, Ahmad A, Noordin R, Lim TS

Mol Immunol, 2015 Oct;67(2 Pt B):512-23.
PMID: 26277276 DOI: 10.1016/j.molimm.2015.07.040

Phage display technology is an important tool for antibody generation or selection. This study describes the development of a scFv library and the subsequent analysis of identified monoclonal antibodies against BmSXP, a recombinant antigen for lymphatic filariasis. The immune library was generated from blood of lymphatic filariasis infected individuals. A TA based intermediary cloning approach was used to increase cloning efficiency for the library construction process. A diverse immune scFv library of 10(8) was generated. Six unique monoclonal antibodies were identified from the 50 isolated clones against BmSXP. Analysis of the clones showed a bias for the IgHV3 and Vκ1 (45.5%) and IgHV2 and Vκ3 (27.3%) gene family. The most favored J segment for light chain is IgKJ1 (45.5%). The most favored D and J segment for heavy chain are IgHD6-13 (75%) and IgHJ3 (47.7%). The information may suggest a predisposition of certain V genes in antibody responses against lymphatic filariasis.

Matched MeSH terms: Brugia malayi/immunology*
Generation and selection of naïve Fab library for parasitic antigen: Anti-BmSXP antibodies for lymphatic filariasis

Omar N, Hamidon NH, Yunus MH, Noordin R, Choong YS, Lim TS

Biotechnol Appl Biochem, 2018 May;65(3):346-354.
PMID: 28833498 DOI: 10.1002/bab.1591

Phage display has been applied successfully as a tool for the generation of monoclonal antibodies (mAbs). Naive antibody libraries are unique as they are able to overcome several limitations associated with conventional mAb generation methods like the hybridoma technology. Here, we performed an in vitro selection and generation of Fab antibodies against Brugia malayi SXP protein (BmSXP), a recombinant antigen for the detection of lymphatic filariasis. We developed a naïve multi ethnic Fab antibody library with an estimated diversity of 2.99 × 109 . The antibody library was used to screen for mAbs against BmSXP recombinant antigen. Soluble monoclonal Fab antibodies against BmSXP were successfully isolated from the naïve library. The Fab antibodies obtained were expressed and analyzed to show its binding capability. The diversity obtained from a pool of donors from various ethnic groups allowed for a diverse antibody library to be generated. The mAbs obtained were also functional in soluble form, which makes it useful for further downstream applications. We believe that the Fab mAbs are valuable for further studies and could also contribute to improvements in the diagnosis of filariasis.

Matched MeSH terms: Brugia malayi/immunology*
Studies on filariasis in Malaya: the effect of diethylcarbamazine on Brugia malayi and B. pahangi in domestic cats

EDESON JF, LAING AB

Ann Trop Med Parasitol, 1959 Dec;53:394-9.
PMID: 13819289
Matched MeSH terms: Brugia malayi*
Fulltext Epidemiological screening of lymphatic filariasis among immigrants using dipstick colloidal dye immunoassay

Wan Omar A, Sulaiman O, Yusof S, Ismail G, Fatmah MS, Rahmah N, et al.

Malays J Med Sci, 2001 Jul;8(2):19-24.
PMID: 22893756

We have recently reported that a dipstick colloidal dye immunoassay (DIA) that detect parasite antigens in human serum is sensitive and specific for the diagnosis of active infection of lymphatic filariasis. Rabbit polyclonal antibodies (RbBmCAg) labelled with a commercial dye, palanil navy blue was used to detect filarial antigenemia among Indonesian and Bangladeshi immigrant workers (N= 630) at oil palm estates at Hulu Trengganu District, Peninsular Malaysia. Microfilaremia with Brugia malayi were detected in 51 (8.10 %) individuals, of which 42 (6.67 %) were among the Indonesians and 9 (1.98 %) among the Bangladeshis. Microfilaremia with Wuchereria bancrofti were detected in 33 (5.24 %) individuals of which 15 (2.38 %) were among the Indonesians and 18 (2.86 %) among the Bangladeshis workers. The DIA detected 96 (15.24 %) antigenemic cases which comprise of all the microfilaremic cases and 15 (2.38 %) amicrofilaremic cases. The amicrofilaremic cases with filarial antigenemia consisted of 9 (1. 43 %) Indonesians and 6 (0.95%) Bangladeshis. We have used 6 ul of the RbBmCAg and diluted (1:10) patients' sera per dipstick which make the DIA reagent conservative. The DIA is a rapid test and can be read in approximate 2 hours.. Additionally, coloured dots developed in the DIA can be qualitatively assessed visually for intensity. The DIA does not require sophisticated equipment or radioactivity, and therefore suitable for field application.

Matched MeSH terms: Brugia malayi
Fulltext Field demonstration of the usefulness of a model of 3D printed mosquito light trap made in Sabah

Shigeharu Sato, Tomonori Hoshi, Bumpei Tojo, Samson Yodot, Joni Jain

Malaysian Journal of Medicine and Health Sciences, 2019;15(106):80-80.
MyJurnal

Introduction: Collecting mosquitoes is essential for research in mosquito-borne diseases, but the light traps used for that purpose are expensive and often difficult to obtain around research fields. We designed a new 3D-printable mosquito light trap that can be made inexpensively anywhere where electricity is available (Hoshi et al, Scientific Reports, in press). In this study, we produced that trap in Sabah and demonstrated its usefulness in the field. Meth-ods: With a 3D printer, the main parts of the trap - body, lid, lamp stand and collection box - were printed in Kota Kinabalu using black polylactic acid (PLA) filaments purchased online. All other parts such as the computer fan and batteries were commercially available at local shops in Sabah. The parts were assembled into the complete units at Universiti Malaysia Sabah’s Rural Medical Education Centre (RMEC) in Sikuati, Kudat. Demonstration was performed at two sites in the Kudat district: RMEC campus and the premises of a local farm in Kampung Paradason. Results: The 3D traps collected 6 and 7 different species of mosquitoes at RMEC and Paradason sites, respectively. The numbers of mosquito species collected by the commercially-available CDC model-512 traps in parallel experiments were 2 (RMEC) and 10 (Paradason). The species collected by the 3D traps included Aedes albopictus (vector transmitting Dengue virus), Anopheles barbumbrosus (malaria), Culex quinquefasciatus (Wuchereria bancrofti, avian malaria, and arboviruses including Japanese encephalitis and Zika viruses) and Mansonia indiana (Brugia malayi). Conclu-sion: The 3D light trap which was produced in Sabah demonstrated its usefulness in the field tests performed in the Kudat district. This model can be used as an alternative to the rather expensive commercial light traps to collect the vector insects transmitting mosquito-borne diseases such as malaria, dengue, Japanese encephalitis, Zika fever and filariasis.

Matched MeSH terms: Brugia malayi
Detection of human filarial parasite Brugia malayi in dogs by histochemical staining and molecular techniques

Ambily VR, Pillai UN, Arun R, Pramod S, Jayakumar KM

Vet Parasitol, 2011 Sep 27;181(2-4):210-4.
PMID: 21620569 DOI: 10.1016/j.vetpar.2011.04.041

Human filariasis caused by Brugia malayi is still a public health problem in many countries of Asia including India, Indonesia, Malaysia and Thailand. The World Health Organization (WHO) has targeted to eliminate filariasis by the year 2020 by Mass annual single dose Diethylcarbamazine Administration (MDA). Results of the MDA programme after the first phase was less satisfactory than expected. Malayan filariasis caused by B. malayi is endemic in the south of Thailand where domestic cat serves as the major reservoir host. There is no report about the occurrence of B. malayi in dogs. The present work was carried out to find out the incidence of microfilariasis in dogs and also to detect the presence of human filarial infection in dogs, if any. One hundred dogs above 6 months of age presented to the veterinary college Hospital, Mannuthy, Kerala, with clinical signs suggestive of microfilariasis - fever, anorexia, conjunctivitis, limb and scrotal oedema - were screened for microfilariae by wet film examination. Positive cases were subjected to Giemsa staining, histochemical staining and molecular techniques. Results of the study showed that 80% of dogs had microfilariasis; out of which 20% had sheathed microfilaria. Giemsa and histochemical staining character, PCR and sequencing confirmed it as B. malayi. High prevalence of B. malayi in dogs in this study emphasized the possible role of dogs in transmission of human filariasis.

Matched MeSH terms: Brugia malayi/isolation & purification*
Comparative analysis of ITS1 nucleotide sequence reveals distinct genetic difference between Brugia malayi from Northeast Borneo and Thailand

Fong MY, Noordin R, Lau YL, Cheong FW, Yunus MH, Idris ZM

Parasitology, 2013 Jan;140(1):39-45.
PMID: 22917270 DOI: 10.1017/S0031182012001242

Brugia malayi is one of the parasitic worms which causes lymphatic filariasis in humans. Its geographical distribution includes a large part of Asia. Despite its wide distribution, very little is known about the genetic variation and molecular epidemiology of this species. In this study, the internal transcribed spacer 1 (ITS1) nucleotide sequences of B. malayi from microfilaria-positive human blood samples in Northeast Borneo Island were determined, and compared with published ITS1 sequences of B. malayi isolated from cats and humans in Thailand. Multiple alignment analysis revealed that B. malayi ITS1 sequences from Northeast Borneo were more similar to each other than to those from Thailand. Phylogenetic trees inferred using Neighbour-Joining and Maximum Parsimony methods showed similar topology, with 2 distinct B. malayi clusters. The first cluster consisted of Northeast Borneo B. malayi isolates, whereas the second consisted of the Thailand isolates. The findings of this study suggest that B. malayi in Borneo Island has diverged significantly from those of mainland Asia, and this has implications for the diagnosis of B. malayi infection across the region using ITS1-based molecular techniques.

Matched MeSH terms: Brugia malayi/classification*; Brugia malayi/genetics*
Use of antifilarial IgG4-ELISA to detect Brugia malayi infection in an endemic area of Malaysia

Rahmah N, Anuar AK, Ariff RH, Zurainee MN, A'shikin AN, Fadzillah A, et al.

Trop Med Int Health, 1998 Mar;3(3):184-8.
PMID: 9593356

OBJECTIVE: To evaluate the usefulness of antifilarial IgG4 antibody assay in detecting B. malayi infection in a filaria endemic area in Malaysia.
METHODS: A sandwich ELISA using B. malayi soluble antigen was employed to detect antifilarial IgG4 antibodies in serum samples of 330 individuals who comprised 88 healthy individuals from nonendemic areas, 15 B. malayi microfilaraemic cases, 22 individuals with soil-transmitted helminthiases, 9 elephantiasis cases and 196 residents from a B. malayi-endemic area. An O.D. value of > 0.420 at serum dilution of 1:400 was used as the cut-off point. This cut-off point was obtained by taking the mean optical density (0.252 + 4 S.E.) of 36 negative sera which had O.D. values greater than 0.1 at serum dilution of 1:400.
RESULTS: All 15 microfilaraemic persons were positive for antifilarial IgG4 antibody. Non-endemic normals, soil-transmitted helminth infected persons and chronic elephantiasis cases were negative for antifilarial IgG4 antibody. Of the 196 individuals from the filaria endemic area, 37 (18.8%) demonstrated presence of antifilarial IgG4 antibodies; and only eight individuals (4.1%) were positive for microfilariae. All eight microfilaraemic individuals were also positive for antifilarial IgG4 antibodies.
CONCLUSION: Antifilarial IgG4-ELISA could detect 4.6 times more positive cases than the microfilaria detection method. With appropriate cut-off values that eliminate cross-reactivities, this serological tool is very useful for Brugia malayi prevalence surveys and diagnosis.

Matched MeSH terms: Brugia malayi/immunology*; Brugia malayi/isolation & purification*
Fulltext The epidemiology and treatment of infection due to Brugia malayi

Edeson JFB

Bull World Health Organ, 1962;27(4-5):529-41.
PMID: 20604131

The author reviews the distribution, epidemiology, and treatment of filarial infection due to Brugia malayi, with special reference to Malaya. B. malayi infection in man is confined to the Far East between longitudes 75 degrees E and 140 degrees E and is essentially rural. The chief vectors are Mansonia spp., Anopheles hyrcanus group, A. barbirostris group, and Aëdes togoi. The epidemiological picture is complicated by the fact that B. malayi and other closely related species have now been found in several species of animals. The existence of an animal reservoir of infection might have important implications for filariasis control. As to the treatment of B. malayi infection, diethylcarbamazine has been found to reduce the microfilaria count and to kill the adult worms; the severe febrile reactions of microfilaria carriers to the initial doses of this drug may be reduced by administration of the steroid prednisolone.

Matched MeSH terms: Brugia malayi
Studies on filariasis in Malaya: the periodicity of the microfilariae of Brugia malayi and B. pahangi in animals

EDESON JF

Ann Trop Med Parasitol, 1959 Dec;53:381-7.
PMID: 13819292
Matched MeSH terms: Brugia malayi*
Studies on filariasis in Malaya: the periodicity of the microfilariae of Wuchereria malayi

TURNER LH, EDESON JF

Ann Trop Med Parasitol, 1957 Sep;51(3):271-7.
PMID: 13470766
Matched MeSH terms: Brugia malayi*
The design of target specific antibodies (scFv) by applying de novo workflow: Case study on BmR1 antigen from Brugia malayi

Khor BY, Lim TS, Noordin R, Choong YS

J Mol Graph Model, 2017 09;76:543-550.
PMID: 28811153 DOI: 10.1016/j.jmgm.2017.07.004

De novo approach was applied to design single chain fragment variable (scFv) for BmR1, a recombinant antigen from Bm17DIII gene which is the primary antigen used for the detection of anti-BmR1 IgG4 antibodies in the diagnostic of lymphatic filariasis. Three epitopes of the BmR1 was previously predicted form an ab initio derived three-dimensional structure. A collection of energetically favourable conformations was generated via hot-spot-centric approach. This resulted in a set of three different scFv scaffolds used to compute the high shape complementary conformations via dock-and-design approach with the predicted epitopes of BmR1. A total of 4227 scFv designs were generated where 200 scFv designs produced binding energies of less than -20 R.E.U with shape complementarity higher than 0.5. We further selected the design with at least one hydrogen bond and one salt bridge with the epitope, thus resulted in a total of 10, 1 and 19 sFv designs for epitope 1, 2 and 3, respectively. The results thus showed that de novo design can be an alternative approach to yield high affinity in silico scFv designs as a starting point for antibody or specific binder discovery processes.

Matched MeSH terms: Brugia malayi/immunology
Fulltext The structure and dynamics of BmR1 protein from Brugia malayi: in silico approaches

Khor BY, Tye GJ, Lim TS, Noordin R, Choong YS

Int J Mol Sci, 2014 Jun 19;15(6):11082-99.
PMID: 24950179 DOI: 10.3390/ijms150611082

Brugia malayi is a filarial nematode, which causes lymphatic filariasis in humans. In 1995, the disease has been identified by the World Health Organization (WHO) as one of the second leading causes of permanent and long-term disability and thus it is targeted for elimination by year 2020. Therefore, accurate filariasis diagnosis is important for management and elimination programs. A recombinant antigen (BmR1) from the Bm17DIII gene product was used for antibody-based filariasis diagnosis in "Brugia Rapid". However, the structure and dynamics of BmR1 protein is yet to be elucidated. Here we study the three dimensional structure and dynamics of BmR1 protein using comparative modeling, threading and ab initio protein structure prediction. The best predicted structure obtained via an ab initio method (Rosetta) was further refined and minimized. A total of 5 ns molecular dynamics simulation were performed to investigate the packing of the protein. Here we also identified three epitopes as potential antibody binding sites from the molecular dynamics average structure. The structure and epitopes obtained from this study can be used to design a binder specific against BmR1, thus aiding future development of antigen-based filariasis diagnostics to complement the current diagnostics.

Matched MeSH terms: Brugia malayi/metabolism*
Operational issues in the control of the vectors of Brugia

Chang MS

Ann Trop Med Parasitol, 2002 Dec;96 Suppl 2:S71-6.
PMID: 12625920

An estimated 13 million people in the Oriental Region have brugian filariasis. The filarial parasites that cause this disease exist in periodic and sub-periodic forms and are transmitted by four genera of mosquito: Anopheles, Mansonia and, less frequently, Coquillettidia and Ochlerotatus. In most endemic countries, control of the disease has been entirely based on chemotherapy, although house-spraying and use of insecticide-treated bednets can be quite effective against the vectors of nocturnally periodic Brugia malayi and B. timori. The vector-control methods that may be applied against the Mansonia mosquitoes that transmit the parasites causing sub-periodic brugian filariasis are reviewed here. Most of the conventional methods for controlling the immature, aquatic stages of mosquitoes have proved unsatisfactory against Mansonia. The reason is that, unlike the those of other genera, the larvae and pupae of Mansonia spp. are relatively immobile and obtain air not at the water surface but from the underwater roots, stems and leaves of floating plants to which the larvae and pupae attach. Removal of host plants can be very effective in reducing Mansonia productivity, whereas large-scale use of herbicides is restricted by the potential adverse effects on the ecosystem. Environmental management in water-development projects remains the best option.

Matched MeSH terms: Brugia malayi
Two microsatellite loci from Brugia malayi show polymorphisms among isolates from Indonesia and Malaysia

Underwood AP, Supali T, Wu Y, Bianco AE

Mol Biochem Parasitol, 2000 Mar 05;106(2):299-302.
PMID: 10699259
Matched MeSH terms: Brugia malayi/genetics*; Brugia malayi/isolation & purification

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