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Experimental infection of the leaf-monkeys, Presbytis cristata and Presbytis melalophos with subperiodic Brugia malayi

Mak JW, Choong MF, Lam PL, Suresh K

Acta Trop, 1990 May;47(4):223-6.
PMID: 1973024

The leaf-monkeys, Presbytis cristata and Presbytis melalophos, experimentally infected with subperiodic Brugia malayi, have been used for studies on the pathoimmunology of the infection and the screening of potential filaricides during the last 6-8 years, and considerable information on the pattern of microfilaraemia and adult worm recoveries have been obtained. The prepatent periods in 97 P. cristata and 45 P. melalophos, each infected with about 200 infective larvae, were similar, these being approximately 70 and 68 days respectively. Although all infected animals became microfilaraemic, the peak geometric mean count was much higher in P. cristata than in P. melalophos, this being 182.0 and 65.8 per ml blood respectively. Mean adult worm recovery expressed as the percentage of the infective dose was 4.7% and 2.5%, respectively. Most worms were recovered from the sacral nodes/thoracic duct or inguinal lymph nodes in these animals. In view of the higher worm recovery and the higher peak microfilaraemia attained, it is concluded that P. cristata is a better model for the infection than P. melalophos.

Matched MeSH terms: Elephantiasis, Filarial/parasitology*
Fulltext Antibodies to somatic L3 antigen not protective against Brugia malayi infection

Noordin R, Abdullah KA, Azahri NA, Ramachandran CP

Southeast Asian J. Trop. Med. Public Health, 1999 Dec;30(4):678-81.
PMID: 10928359

Western blot analysis of infective larvae (L3) antigen of Brugia malayi were performed on 200 sera from six groups of individuals: 36 samples from B. malayi microfilaremic individuals; 10 samples from individuals with elephantiasis; 50 and 20 samples from amicrofilaremic individuals in a B. malayi endemic area with no anti-filarial IgG4 antibodies (towards microfilaria and adult worm antigens) and samples with high titres of the anti-filarial IgG4 antibodies respectively; 50 samples from non-endemic normals and 34 samples from geohelminth-infected individuals. After protein transfer, PVDF membrane strips were successively incubated with blocking solution, human sera, monoclonal anti-human IgG4 antibody-HRP and developed with luminol chemiluminescence substrate. 28/36 (78%), 1/10 (10%) and 16/20(80%) of sera from individuals with microfilariae, elephantiasis and amicrofilaremic individuals with high titers of anti-filarial IgG4 antibodies respectively recognized L3 antigenic epitopes; the dominant and consistent antigenic bands were of approximately MW 43 kDa, 14 kDa, 15 kDa and 59 kDa. The rest of the sera were unreactive. This study showed that microfilaremics may or may not mount a notable antibody response to somatic L3 antigens, thus lending evidence that antibody response to this antigen is not protective against establishment of Brugia malayi infection.

Matched MeSH terms: Elephantiasis, Filarial/parasitology
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/parasitology
Experimental infection of the leaf-monkey, Presbytis cristata, with subperiodic Brugia malayi

Mak JW, Choong MF, Suresh K, Lam PL

Parasitol Res, 1990;76(8):689-91.
PMID: 2251244

Presbytis cristata monkeys infected through the inoculation of between 200 and 400 subperiodic Brugia malayi infective larvae (L3) in the right thigh, in both thighs or in the dorsum of the right foot were followed up for varying periods of up to about 8 months after infection. All 148 inoculated animals became patent, with mean prepatent periods being between 66 and 76 days. In animals injected in the thigh, the patterns of microfilaraemia were similar, there being a rapid rise in the geometric mean counts (GMCs) of microfilariae during the first 10-12 weeks of patency, which then plateaued at levels of greater than 1000/ml. Adult worm recovery, expressed as the percentage of the infective dose, was significantly higher in animals injected with 100 L3 in each thigh, being 9.4% as compared with 2.8%-4.8% in other groups. It is therefore recommended that animals should be injected with 100 L3 in each thigh and that the testing of potential filaricides in this model be carried out during the phase of rapid increase in microfilaraemia to ensure that any microfilaricidal effect can easily be detected.

Matched MeSH terms: Elephantiasis, Filarial/parasitology*
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
Zoonotic Brugia pahangi filariasis in a suburbia of Kuala Lumpur City, Malaysia

Tan LH, Fong MY, Mahmud R, Muslim A, Lau YL, Kamarulzaman A

Parasitol Int, 2011 Jan;60(1):111-3.
PMID: 20951228 DOI: 10.1016/j.parint.2010.09.010

Five local Malaysian patients with clinical manifestations consistent with lymphatic filariasis were referred to our medical centre between 2003 and 2006. Although no microfilariae (mf) were detected in their nocturnal blood samples, all were diagnosed to have lymphatic filariasis on the basis of clinical findings and positive serology results. PCR on their blood samples revealed that two of the patients were infected with Brugia pahangi, an animal filarial worm hitherto not known to cause human disease in the natural environment. All the patients were successfully treated with anti-filarial drugs: four patients were treated with a combination of diethylcarbamazine (DEC) and albendazole, and one with doxycycline. Four of them were residents of Petaling Jaya, a residential suburbia located 10 km southwest of Kuala Lumpur city, Malaysia. The fifth patient was a frequent visitor of the suburbia. This suburbia has no history or record of B. malayi infection. The most likely vector of the worm was Armigeres subalbatus as extensive entomological surveys within the suburbia revealed only adult females of this mosquito species were infected with B. pahangi larvae. Wild monkeys caught in the suburbia were free from B. pahangi mf, but domestic cats were mf positive. This suggests that infected cats might be the source of the zoonotic infection in the suburbia.

Matched MeSH terms: Elephantiasis, Filarial/parasitology*
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/parasitology*
Fulltext Laboratory Evaluation of a Rapid IgG4 Antibody Test (BLF Rapid™) for Bancroftian Filariasis

Noordin R, Yunus MH, Robinson K, Won KY, Babu S, Fischer PU, et al.

Am J Trop Med Hyg, 2018 12;99(6):1587-1590.
PMID: 30350768 DOI: 10.4269/ajtmh.18-0566

At the end phase of the Global Programme to Eliminate Lymphatic Filariasis, antibody testing may have a role in decision-making for bancroftian filariasis-endemic areas. This study evaluated the diagnostic performance of BLF Rapid™, a prototype immunochromatographic IgG4-based test using BmSXP recombinant protein, for detection of bancroftian filariasis. The test was evaluated using 258 serum samples, comprising 96 samples tested at Universiti Sains Malaysia (in-house) and 162 samples tested independently at three international laboratories in the USA and India, and two laboratories in Malaysia. The independent testing involved 99 samples from Wuchereria bancrofti microfilaria or antigen positive individuals and 63 samples from people who were healthy or had other infections. The in-house evaluation showed 100% diagnostic sensitivity and specificity. The independent evaluations showed a diagnostic sensitivity of 84-100% and 100% specificity (excluding non-lymphatic filarial infections). BLF Rapid has potential as a surveillance diagnostic tool to make "Transmission Assessment Survey"-stopping decisions and conduct post-elimination surveillance.

Matched MeSH terms: Elephantiasis, Filarial/parasitology
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/parasitology
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: Elephantiasis, Filarial/parasitology*
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/parasitology

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