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  1. Pan LF-ELISA using BmR1 and BmSXP recombinant antigens for detection of lymphatic filariasis
    Abdul Rahman R, Hwen-Yee C, Noordin R
    Filaria journal, 2007;6:10.
    PMID: 17961264
    Anti-filarial IgG4 antibody has been shown to be a good marker for detection of lymphatic filaria infection. Previous studies demonstrated that anti-filarial IgG4 assay using BmR1 recombinant antigen was highly specific and sensitive for detection of brugian filariasis. For bancroftian filariasis, an equivalent assay employing recombinant antigen expressed from the ORF of SXP1 gene has been reported. In order to detect infections by all species of lymphatic filarial, BmR1 and BmSXP recombinant antigens were employed in the development of a pan LF-ELISA.
    Matched MeSH terms: Elephantiasis, Filarial
  2. Detection of circulating antigens and parasite specific antibodies in filariasis
    Abdullah WO, Oothuman P, Yunus H
    Southeast Asian J. Trop. Med. Public Health, 1993;24 Suppl 2:31-6.
    PMID: 7973943
    In Peninsular Malaysia, only Wuchereria bancrofti and Brugia malayi are reported to cause human filariasis. Brugia pahangi infects many of the same animal hosts as the zoonotically transmitted subperiodic B. malayi. There is a well-recognized need for improved diagnostic techniques for lymphatic filariasis. Parasite antigen detection is a promising new approach, and it will probably prove to be more sensitive and specific than clinical, microscopic and antibody-based serological methods. We recently generated monoclonal antibodies (MAb XC3) from in vitro culture products of adult B. pahangi (B.p. IVP). Filarial antigenemia was quantitated in various hosts including the sera from 6 Malaysian Aborigines with acute lymphatic filariasis. In hosts infected with brugian filariasis and dirofilariasis, antigenemia was scored ranging from 90 ng/ml to 960 ng/ml. None of the control animal and human sera had antigenemia above 90 ng/ml. In addition, MAb XC3 and B.p. IVP were applied in several seroepidemiological surveys among household cats in Kuala Selangor in order to correlate information gathered for future studies of possible cases of human infection. Out of the 81 cats surveyed, 10 (12.35%) and 5 (6.17%) were parasitologically positive for B. pahangi and B. malayi, respectively. However, 21 (25.92%) were antigenemia positive when serologically investigated with MAb XC3. Antifilarial antibodies to B.p. IVP by direct ELISA showed very high cross-reactivity with non-filarial gut worm infections. 16 (19.75%) cats had reciprocal titers ranging from 320 to 2,560. Only 1 (1.23%) cat from this group was antigenemic.
    Matched MeSH terms: Elephantiasis, Filarial/diagnosis*; Elephantiasis, Filarial/immunology; Elephantiasis, Filarial/parasitology
  3. Fulltext Ten-year analysis of Filariasis in east-coast Malaysia
    Ahmad Syaify B., Alamin M. D., Norafidah A. R.
    Malaysian Journal of Medicine and Health Sciences, 2019;15(106):83-83.
    MyJurnal
    Introduction:Lymphatic filariasis (LF) is a neglected tropical disease that can cause significant morbidity. In Malay-sia, National Programme for the Elimination of Lymphatic Filariasis started in 2001 with the initial target of achiev-ing Lymphatic Filariasis elimination status by 2018 but it has been revised to year 2020. Mass Drug Administration (MDA) Programme was performed from 2004 to 2008 in all endemic areas (Red Implementation Unit, IU) in Malay-sia including Terengganu state to stop disease transmission. Transmission Assessment Surveys (TAS) were conducted later on and for Terengganu, they were done in 2011 (TAS 1), 2015 (TAS 2) and 2017 (TAS 3) and had passed all the surveys based on critical cut off (CCO) point given. Methods: A cross sectional analysis of 10-year Terengganu filariasis records (2009-2018) was initiated in June 2019 using data source from eVekpro and filariasis cases line-list-ing. Results: Majority of filariasis cases in Terengganu were among males (n=147, 76.6%) with the highest number among 30-39 year-old age group (n=35, 18.2%). Majority of cases were Malaysian citizens (n=162, 84.4%) with main filariasis species identified were Brugia Malayi (n=149, 77.6%). The number of cases diagnosed was slightly higher from Green Implementation Unit area (n=102, 53.1%) compared to Red Implementation Unit area. Conclu-sion: The number of lymphatic filariasis cases among Terengganu citizens was below critical cut off point after the accomplishment of MDA programme and in accordance with the aim of lymphatic filariasis elimination status in Malaysia by 2020.
    Matched MeSH terms: Elephantiasis, Filarial
  4. Fulltext Lymphatic filariasis in Peninsular Malaysia: a cross-sectional survey of the knowledge, attitudes, and practices of residents
    Al-Abd NM, Nor ZM, Ahmed A, Al-Adhroey AH, Mansor M, Kassim M
    Parasit Vectors, 2014;7:545.
    PMID: 25428558 DOI: 10.1186/s13071-014-0545-z
    Lymphatic filariasis (LF) is a major cause of permanent disability in many tropical and sub-tropical countries of the world. Malaysia is one of the countries in which LF is an endemic disease. Five rounds of the mass drug administration (MDA) program have been conducted in Malaysia as part of the Global Program to Eliminate Lymphatic Filariasis (GPELF) by year 2020. This study investigated the level of awareness of LF and the MDA program in a population living in an endemic area of the country.
    Matched MeSH terms: Elephantiasis, Filarial/drug therapy; Elephantiasis, Filarial/epidemiology*
  5. Fulltext Recent advances on the use of biochemical extracts as filaricidal agents
    Al-Abd NM, Nor ZM, Al-Adhroey AH, Suhaimi A, Sivanandam S
    Evid Based Complement Alternat Med, 2013;2013:986573.
    PMID: 24298292 DOI: 10.1155/2013/986573
    Lymphatic filariasis is a parasitic infection that causes a devastating public health and socioeconomic burden with an estimated infection of over 120 million individuals worldwide. The infection is caused by three closely related nematode parasites, namely, Wuchereria bancrofti, Brugia malayi, and B. timori, which are transmitted to human through mosquitoes of Anopheles, Culex, and Aedes genera. The species have many ecological variants and are diversified in terms of their genetic fingerprint. The rapid spread of the disease and the genetic diversification cause the lymphatic filarial parasites to respond differently to diagnostic and therapeutic interventions. This in turn prompts the current challenge encountered in its management. Furthermore, most of the chemical medications used are characterized by adverse side effects. These complications urgently warrant intense prospecting on bio-chemicals that have potent efficacy against either the filarial worms or thier vector. In lieu of this, we presented a review on recent literature that reported the efficacy of filaricidal biochemicals and those employed as vector control agents. In addition, methods used for biochemical extraction, screening procedures, and structure of the bioactive compounds were also presented.
    Matched MeSH terms: Elephantiasis, Filarial
  6. Fulltext Assessing seroprevalence and associated risk factors for multiple infectious diseases in Sabah, Malaysia using serological multiplex bead assays
    Chan YL, Patterson CL, Priest JW, Stresman G, William T, Chua TH, et al.
    Front Public Health, 2022;10:924316.
    PMID: 36388287 DOI: 10.3389/fpubh.2022.924316
    BACKGROUND: Infectious diseases continue to burden populations in Malaysia, especially among rural communities where resources are limited and access to health care is difficult. Current epidemiological trends of several neglected tropical diseases in these populations are at present absent due to the lack of habitual and efficient surveillance. To date, various studies have explored the utility of serological multiplex beads to monitor numerous diseases simultaneously. We therefore applied this platform to assess population level exposure to six infectious diseases in Sabah, Malaysia. Furthermore, we concurrently investigated demographic and spatial risk factors that may be associated with exposure for each disease.

    METHODS: This study was conducted in four districts of Northern Sabah in Malaysian Borneo, using an environmentally stratified, population-based cross-sectional serological survey targeted to determine risk factors for malaria. Samples were collected between September to December 2015, from 919 villages totaling 10,100 persons. IgG responses to twelve antigens of six diseases (lymphatic filariasis- Bm33, Bm14, BmR1, Wb123; strongyloides- NIE; toxoplasmosis-SAG2A; yaws- Rp17 and TmpA; trachoma- Pgp3, Ct694; and giardiasis- VSP3, VSP5) were measured using serological multiplex bead assays. Eight demographic risk factors and twelve environmental covariates were included in this study to better understand transmission in this community.

    RESULTS: Seroprevalence of LF antigens included Bm33 (10.9%), Bm14+ BmR1 (3.5%), and Wb123 (1.7%). Seroprevalence of Strongyloides antigen NIE was 16.8%, for Toxoplasma antigen SAG2A was 29.9%, and Giardia antigens GVSP3 + GVSP5 was 23.2%. Seroprevalence estimates for yaws Rp17 was 4.91%, for TmpA was 4.81%, and for combined seropositivity to both antigens was 1.2%. Seroprevalence estimates for trachoma Pgp3 + Ct694 were 4.5%. Age was a significant risk factors consistent among all antigens assessed, while other risk factors varied among the different antigens. Spatial heterogeneity of seroprevalence was observed more prominently in lymphatic filariasis and toxoplasmosis.

    CONCLUSIONS: Multiplex bead assays can be used to assess serological responses to numerous pathogens simultaneously to support infectious disease surveillance in rural communities, especially where prevalences estimates are lacking for neglected tropical diseases. Demographic and spatial data collected alongside serosurveys can prove useful in identifying risk factors associated with exposure and geographic distribution of transmission.

    Matched MeSH terms: Elephantiasis, Filarial*
  7. 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: Elephantiasis, Filarial/prevention & control*; Elephantiasis, Filarial/transmission
  8. Fulltext Colonization of Mansonia dives Schiner in a field insectary
    Chang MS, Ho BC, Chan KL
    Southeast Asian J. Trop. Med. Public Health, 1991 Jun;22(2):229-34.
    PMID: 1683011
    Successful colonization of Mansonia dives, the principal vector of subperiodic Brugia malayi was established in a field insectary. Mean egg clusters laid on Eichhornia crassipes, Pistia stratiotes, Homalomena cordata and polystyrofoam strips were 12.0, 10.4, 9.5 and 13.7 respectively. However, the mean number of first instar larvae hatched from each egg cluster laid by females on the three plant substrates (range 51.1 to 58.6) was higher than that laid on the polystyrofoam strips (41.8). There were no significant differences in the success pupation and adult emergence rates among the three host plants used as attachment substrates. Adult emergence occurred at a mean of 10.8 days. The first adult emergence was observed at the 25th day after hatching and continued till the 50th day. The 50% mortality rates for the adults were estimated as 8 days for the males and 14 days for the females. The mean gonotrophic cycle ranged from 3.8 to 4.3 days with a mean of 4.04 days. 63.6% of Ma. dives females oviposited in a medium of rat dung and water. The mean incubation period of eggs ranged from 5.2 to 6.5 days with a mean of 5.7 days. The biology of Ma. dives and Ma. bonneae is briefly compared.
    Matched MeSH terms: Elephantiasis, Filarial/transmission
  9. Efficacy of diethylcarbamazine and pirimiphos-methyl residual spraying in controlling brugian filariasis
    Chang MS, Ho BC, Chan KL
    Trop. Med. Parasitol., 1991 Jun;42(2):95-102.
    PMID: 1680246
    A control programme against subperiodic brugian filariasis was implemented in three villages, (Kg. Ampungan, Kg. Sebangkoi and Kg. Sebamban) in Sarawak, Malaysia. In Kampong Ampungan, the mass administration of diethylcarbamazine (DEC-citrate) combined with residual house spraying of pirimiphos-methyl reduced microfilarial rate to 8% of the pre-treatment level and microfilarial density (MfD50) to 44% of the pre-treatment level over a period of four years. In Kampong Sebangkoi and Kampong Sebamban, where only mass DEC therapy was applied, the microfilarial rate and MfD50 declined distinctly in the second blood survey but increased gradually in two subsequent follow-up blood surveys. In Kg, Ampungan, we observed a significant reduction of infective biting rate (88.3%), infection rate (62.5%) and transmission potential (88.1%) of Mansonia bonneae at the fourth spray round. The corresponding reduction rates in Kg. Sebangkoi and Kg. Sebamban were 35.3%, 26.7%, 42.2% and 24%, 30.8% and 15.4% respectively. The biting density of the vector was reduced by 79.8% indoors and 31.8% outdoors at the sprayed village, while only a slight decrease in densities (17.9% indoors and 12.4% outdoors) was observed at the unsprayed village. Bioassay tests revealed that pirimiphos-methyl had a substantial fumigant effect on the vector. The integrated control measure in controlling subperiodic brugian filariasis is discussed.
    Matched MeSH terms: Elephantiasis, Filarial/drug therapy; Elephantiasis, Filarial/epidemiology; Elephantiasis, Filarial/prevention & control*
  10. Breeding-site productivity of the swamp forest mosquitoes Mansonia bonneae and Ma. dives in Sarawak, east Malaysia
    Chang MS, Jute N, Lah J
    Med Vet Entomol, 1988 Jan;2(1):19-28.
    PMID: 2908782
    Studies on larval population densities and adult emergence rates of the Brugian filariasis vectors Mansonia bonneae Edwards and Ma. dives Schiner were conducted in freshwater swamp forest bordering the Sadong River, Serian District, Sarawak, East Malaysia, during 1984-85. Three species of aquatic host-plants in the Family Araceae were identified as supporting immature stages of the Ma. bonneae/dives complex. Proportions of positive plants were 4.7%, 6.5% and 3.4% with 6.4 +/- 2.6, 7.3 +/- 2.8 and 10.1 +/- 1.1 larvae per positive plant, respectively, for the plant species Homalomena cordata Schott, H. rostrata Griffiths and Hydrostemma motleyi (Hook. f.) Mabberley. These data indicate no significant preferences between the three types of host-plant. Detailed monitoring of the host-plant H. cordata revealed no significant monthly fluctuations in larval density per plant nor the proportion of positive plants. 11.6% of larvae were Ma. dives and 88.4% were Ma. bonneae. Mean daily yields of Ma. bonneae/dives adults per square metre of H. cordata vegetated water surface were 0.45 males plus 0.57 females during the wet season (December-February) compared with 0.2 males plus 0.31 females during the dry season (June-August). Thus output of adults per plant was approximately halved, and suitable breeding areas were further reduced, during the dry season. By extrapolation from these rates, a crude mean estimate for productivity of Ma. bonneae/dives females is 1.6 million per hectare per annum in swamp forest habitats vegetated with any of the host-plants studied.
    Matched MeSH terms: Elephantiasis, Filarial/transmission*
  11. Fulltext Hematological changes in subperiodic Brugia malayi infection of the leaf-monkey, Presbytis cristata
    Choong MF, Mak JW
    Southeast Asian J. Trop. Med. Public Health, 1991 Jun;22(2):168-70.
    PMID: 1948274
    Hematological changes were monitored in the leaf-monkey, Presbytis cristata, infected experimentally with 200 subperiodic Brugia malayi infective larvae. Prepatent periods were 54-86 days and peak microfilarial geometric mean counts (GMCs) were 1324 per ml blood. Total leukocyte and differential counts were measured at pre-infection, and then at weakly intervals before and during patency. Blood eosinophil level increased to about thrice the initial level at 3 weeks post-infection and this was maintained for the next 13 weeks before it started to rise again, increasing to more than 5 times the initial level at 20 weeks post-infection. The observed pattern of eosinophilia is probably related to the level of microfilaremia and the destruction of microfilariae in the spleen. There was no significant change in the total leukocyte counts during the period of observation.
    Matched MeSH terms: Elephantiasis, Filarial/blood*; Elephantiasis, Filarial/parasitology
  12. Biochemical studies in Presbytis cristata infected with subperiodic Brugia malayi
    Choong MF, Mak JW
    Trop. Med. Parasitol., 1991 Mar;42(1):71-2.
    PMID: 1675809
    The Presbytis cristata--Brugia malayi model, now established as a reliable non-human primate model for the experimental screening of potential filaricides, was monitored at monthly intervals for changes in the liver and renal function tests and also for alkaline phosphatase levels during infection. Animals infected with 200-400 infective larvae became patient at 50-90 days post-infection and geometric mean microfilarial counts were above 1000 per ml from the fourth month onwards. There were no significant changes in the biochemical parameters monitored throughout the period of observation. This is an important observation as any changes seen in these parameters during experimental drug studies can be attributed to drug reaction or toxicity and this will be invaluable in decision making as to drug safety.
    Matched MeSH terms: Elephantiasis, Filarial/enzymology; Elephantiasis, Filarial/physiopathology*
  13. Simple blood-spot sampling with nested polymerase chain reaction detection for epidemiology studies on Brugia malayi
    Cox-Singh J, Pomrehn AS, Rahman HA, Zakaria R, Miller AO, Singh B
    Int J Parasitol, 1999 May;29(5):717-21.
    PMID: 10404266
    In the absence of a suitable Brugia malayi antigen detection assay, PCR remains one of the more sensitive alternatives to Giemsa-stained thick blood films for B. malayi detection. The need for refrigerated storage and transportation of blood has limited the use of PCR for large-scale epidemiology studies in remote endemic areas. Here we report simple finger-prick blood-spot collection, a one-tube DNA template extraction method and the development of a B. malayi-specific nested PCR assay. The assay was tested on 145 field samples and was positive for all 30 microscopy-positive samples and for an additional 13 samples which were microscopy-negative.
    Matched MeSH terms: Elephantiasis, Filarial/blood; Elephantiasis, Filarial/epidemiology; Elephantiasis, Filarial/parasitology*
  14. Does the morbidity management and disability prevention (MMDP) clinic serve the filarial lymphedema (FLE) patients' preeminent expectation?
    De Britto RLJ, Vijayalakshmi G, Boopathi K, Kamaraj P, Supriya VK, Yuvaraj J
    Trop Biomed, 2020 Mar 01;37(1):66-74.
    PMID: 33612719
    Advocacy and training on "Home care" for filarial lymphoedma (FLE) patients are provided through morbidity management and disability prevention (MMDP) clinic commonly known as filariasis clinic and clinical improvement is assessed by follow-up visits. While the physicians aim at reducing the recurrent ADL (coined as ADLA in 1997) episodes, the patients expect reduction in LE volume. The objective of the present study was to know whether the MMDP clinic serves the primary expectation of the FLE patients. LE patients who attended the clinic for at least four follow-up consultations and had LE volume measurements at three points of time during the one year period of observation were considered for analysis. Clinical assessment was done for LE grading and LE volume was measured by water displacement volumetry. Sixty-three patients who fulfilled the follow up criteria were included. It was observed that the median LE volume was 914ml (IQR 269 - 1935) at first visit of the observation period which reduced to 645ml (IQR 215- 1666) and 752ml (IQR 215 - 1720) at first and second follow-up visits respectively. Over all, in short span of one year, 21 of the 63 patients (33.3%) who visited MMDP clinic at least four times in a year were benefitted through the MMDP advocacy and the National filariasis control programme need to emphasise on the importance of follow up visits to FLE patients.
    Matched MeSH terms: Elephantiasis, Filarial/therapy*
  15. The effect of diethylcarbamazine citrate on incidence and recovery rates of Brugia malayi microfilaremia in Sabah, Malaysia
    Hiil JL, Kan SK, Parmar SS, Chan MK, Mak JW, Lim PK, et al.
    Am J Trop Med Hyg, 1988 May;38(3):582-8.
    PMID: 3275137
    Mass drug administration via 3 modes of delivery reduced the incidence and prevalence rates and intensity of Brugia malayi infection in 3 rural villages in the Bengkoka Peninsula, Sabah, in 1982-1983. A dosage of 6 mg diethylcarbamazine citrate (DEC-C)/kg body weight was administered either daily or weekly (total of 6 doses, 36 mg/kg body weight), and impact on B. malayi cases were comparable in the 3 villages. A total of 384 people participated in the DEC-C regimens, and all pregnant women and children under 2 years were excluded from the study. Bekessy's method of estimation of incidence and recovery rates was applied to data on B. malayi microfilaremia before drug administration. Treatment with DEC-C by any of the 3 modes of delivery drastically reduced the number of episodes of patent microfilaremia, incidence and prevalence, and median microfilarial density. Reduction was sustained for at least 18 to 24 months after treatment.
    Matched MeSH terms: Elephantiasis, Filarial/drug therapy*; Elephantiasis, Filarial/epidemiology
  16. Association of CTLA4 gene polymorphisms with lymphatic filariasis in an East Malaysian population
    Idris ZM, Miswan N, Muhi J, Mohd TA, Kun JF, Noordin R
    Hum Immunol, 2011 Jul;72(7):607-12.
    PMID: 21513760 DOI: 10.1016/j.humimm.2011.03.017
    Lymphatic filariasis (LF) is a parasitic disease caused by threadlike worms of the Brugia and Wuchereria species that live in the human lymphatic system. Regulatory T cells (Tregs) may play a key role in the pathogenesis of LF, and cytotoxic T-lymphocyte antigen-4 (CTLA4) expressed by Tregs is a potential candidate gene because it modulates T-cell activation. A case-control study was performed to establish a potential association of 5 CTLA4 gene promoter single nucleotide polymorphisms (SNPs; rs733618, rs11571316, rs5742909, rs231775, and rs16840252) with the occurrence of LF in an East Malaysian population (320 LF-infected individuals and 150 healthy controls). Polymorphisms were evaluated using TaqMan real-time polymerase chain reaction followed by direct sequencing. LF carriers of the rs733618 AG genotypes (p = 0.02) and those with combined minor allele G carriers (AG + GG; p = 0.01) exhibited a significantly decreased risk for LF. Among the asymptomatic amicrofilaremic cases, positive associations were reported for all genotypes and variants of rs733618 with odds ratios (ORs) ranging from 0.27 to 0.45. In the asymptomatic microfilaremic cases, marker rs231775 exhibited a significant decreased risk, with ORs ranging from 0.50 to 0.57. The study has identified SNPs in the CTLA4 promoter gene that may be functionally linked with susceptibility to LF.
    Matched MeSH terms: Elephantiasis, Filarial/genetics*
  17. Fulltext A randomized controlled trial of increased dose and frequency of albendazole with standard dose DEC for treatment of Wuchereria bancrofti microfilaremics in Odisha, India
    Kar SK, Dwibedi B, Kerketa AS, Maharana A, Panda SS, Mohanty PC, et al.
    PLoS Negl Trop Dis, 2015 Mar;9(3):e0003583.
    PMID: 25781977 DOI: 10.1371/journal.pntd.0003583
    Although current programmes to eliminate lymphatic filariasis have made significant progress it may be necessary to use different approaches to achieve the global goal, especially where compliance has been poor and 'hot spots' of continued infection exist. In the absence of alternative drugs, the use of higher or more frequent dosing with the existing drugs needs to be explored. We examined the effect of higher and/or more frequent dosing with albendazole with a fixed 300 mg dose of diethylcarbamazine in a Wuchereria bancrofti endemic area in Odisha, India. Following screening, 104 consenting adults were randomly assigned to treatment with the standard regimen annually for 24 months (S1), or annually with increased dose (800 mg albendazole)(H1) or with increased frequency (6 monthly) with either standard (S2) or increased (H2) dose. Pre-treatment microfilaria counts (GM) ranged from 348 to 459 mf/ml. Subjects were followed using microfilaria counts, OG4C3 antigen levels and ultrasound scanning for adult worm nests. Microfilarial counts tended to decrease more rapidly with higher or more frequent dosing at all time points. At 12 months, Mf clearance was marginally greater with the high dose regimens, while by 24 months, there was a trend to higher Mf clearance in the arm with increased frequency and 800 mg of albendazole (76.9%) compared to other arms, (S1:64%, S2:69.2% & H1:73.1%). Although higher and/or more frequent dosing showed a trend towards a greater decline in antigenemia and clearance of "nests", all regimens demonstrated the potential macrofilaricidal effect of the combination. The higher doses of albendazole did not result in a greater number or more severe side effects. The alternative regimens could be useful in the later stages of existing elimination programmes or achieving elimination more rapidly in areas where programmes have yet to start.
    Matched MeSH terms: Elephantiasis, Filarial/drug therapy*
  18. Fulltext Lymphatic pathology in asymptomatic and symptomatic children with Wuchereria bancrofti infection in children from Odisha, India and its reversal with DEC and albendazole treatment
    Kar SK, Dwibedi B, Das BK, Agrawala BK, Ramachandran CP, Horton J
    PLoS Negl Trop Dis, 2017 Oct;11(10):e0005631.
    PMID: 29059186 DOI: 10.1371/journal.pntd.0005631
    BACKGROUND: Once interruption of transmission of lymphatic filariasis is achieved, morbidity prevention and management becomes more important. A study in Brugia malayi filariasis from India has shown sub-clinical lymphatic pathology with potential reversibility. We studied a Wuchereria bancrofti infected population, the major contributor to LF globally.

    METHODS: Children aged 5-18 years from Odisha, India were screened for W. bancrofti infection and disease. 102 infected children, 50 with filarial disease and 52 without symptoms were investigated by lymphoscintigraphy and then randomized to receive a supervised single oral dose of DEC and albendazole which was repeated either annually or semi-annually. The lymphatic pathology was evaluated six monthly for two years.

    FINDINGS: Baseline lymphoscintigraphy showed abnormality in lower limb lymphatics in 80% of symptomatic (40/50) and 63·5% (33/52) of asymptomatic children. Progressive improvement in baseline pathology was seen in 70·8, 87·3, 98·6, and 98·6% of cases at 6, 12, 18, and 24 months follow up, while in 4·2, 22·5, 47·9 and 64·8%, pathology reverted to normal. This was independent of age (p = 0·27), symptomatic status (p = 0·57) and semi-annual/bi-annual dosing (p = 0·46). Six of eleven cases showed clinical reduction in lymphedema of legs.

    INTERPRETATION: A significant proportion of a young W. bancrofti infected population exhibited lymphatic pathology which was reversible with annual dosage of DEC and albendazole. This provides evidence for morbidity prevention & treatment of early lymphedema. It can also be used as a tool to improve community compliance during mass drug administration.

    TRIAL REGISTRATION: ClinicalTrials.gov No CTRI/2013/10/004121.

    Matched MeSH terms: Elephantiasis, Filarial/drug therapy*; Elephantiasis, Filarial/parasitology; Elephantiasis, Filarial/pathology*
  19. Purification of recombinant antigen BmSXP used in panLF rapid kit for lymphatic filariasis
    Khoo TK, Noordin R, Santhanam A
    Indian J Exp Biol, 2012 Apr;50(4):256-64.
    PMID: 22611913
    A rapid antibody detection test is very useful for the detection of lymphatic filariasis, especially for certification and surveillance of post-mass drug administration. panLF Rapid kit is suitable for this purpose since it can detect all species of lymphatic filaria. It is based on the detection of anti-filarial IgG4 antibodies that react with recombinant B. malayi antigens, BmR1 and BmSXP. There is an increase demand for the test due to its attributes of being rapid, sensitive and specific results, as well as its field-applicability. The main aim of this paper is to obtain high recovery and purity of recombinant antigen BmSXP via a modified method of immobilized metal affinity chromatography (IMAC). The highest product yield of 11.82 mg/g dry cell weight (DCW) was obtained when IMAC was performed using the optimized protocol of 10 mM imidazole concentration in lysis buffer, 30 mM imidazole concentration in wash buffer, and 10 column volume wash buffer containing 300 mM salt concentration. This gave a 54% protein recovery improvement over the manufacturer's protocol which recorded a product yield of only 7.68 mg/g DCW. The recovered BmSXP recombinant antigen showed good western blot reactivity, high sensitivity (31/32, 97%) and specificity (32/32, 100%) in ELISA, thus attesting to its good purity and quality.
    Matched MeSH terms: Elephantiasis, Filarial/immunology*
  20. 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: Elephantiasis, Filarial/parasitology
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