MyMedR

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.

Helminthic infections among domestic dogs in and around Kuala Lumpur--a preliminary report

Ramachandran CP, Balasingam E, Lim BL

Med J Malaya, 1968 Mar;22(3):241.

PMID: 4234375

[Description of Onchocerca dewittei n. sp. (Filarioidea), parasite of Sus scrofa, in Malaysia (author's transl)]

Bain O, Ramachandran CP, Petter F, Mak JW

Ann Parasitol Hum Comp, 1977 7 1;52(4):471-9.

PMID: 931324

Onchocerca dewittei n. sp. was collected from a wild Boar at the metatarse level (tendons and subcutaneous connective tissue); it can be differentiated from other species by the female cuticle showing straight ridges which overlap in the lateral fields, and by its relatively thick microfilaria (length 228-247 mu and width 6-7 mu). This suidean Onchocerca displays some primitive characters such as straight ridges and persistency of ten pairs of caudal papillae in the male; but as a whole this species is undoubtedly more highly evolved than O. raillieti Bain, Müller and coll., 1976, a parasite of Equidae.

Parasitic disease among fishermen living on Penang Island. I. Helminthiases

Anuar K, Ramachandran CP, Paran TP

Med J Malaysia, 1978 Jun;32(4):321-7.

PMID: 732632

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.

Specificity and sensitivity of a rapid dipstick test (Brugia Rapid) in the detection of Brugia malayi infection

Rahmah N, Taniawati S, Shenoy RK, Lim BH, Kumaraswami V, Anuar AK, et al.

Trans R Soc Trop Med Hyg, 2002 1 31;95(6):601-4.

PMID: 11816429

A total of 753 serum samples from 6 institutions in 3 countries (Malaysia, Indonesia and India) were used to evaluate an immunochromatographic rapid dipstick test, Brugia Rapid, for diagnosis of Brugia malayi infection. The samples comprised sera from 207 microfilaria-positive individuals and 546 individuals from filaria non-endemic areas. The latter consisted of 70 individuals with soil-transmitted helminth infections, 68 with other helminth infections, 238 with protozoan infections, 12 with bacterial and viral infections and 158 healthy individuals. The dipstick is prepared with a goat anti-mouse antibody control line and a B. malayi recombinant-antigen test line. First, the dipstick is dipped into a well containing diluted patient serum, thus allowing specific anti-filarial antibody in the serum to react with the recombinant antigen. Then the dipstick is placed into an adjacent well containing reconstituted anti-human IgG4-gold. After 10 min, development of 2 red-purplish lines denotes a positive result and one line indicates a negative reaction. The overall results of the evaluation showed 97% sensitivity, 99% specificity, 97% positive predictive value and 99% negative predictive value. Brugia Rapid is thus a promising diagnostic tool for detection of B. malayi infection, and would be especially useful for the brugian filariasis elimination programme.

A recombinant antigen-based IgG4 ELISA for the specific and sensitive detection of Brugia malayi infection

Rahmah N, Lim BH, Khairul Anuar A, Shenoy RK, Kumaraswami V, Lokman Hakim S, et al.

Trans R Soc Trop Med Hyg, 2001 8 9;95(3):280-4.

PMID: 11490997

An IgG4 ELISA based on a novel recombinant antigen was evaluated for detection of Brugia malayi infection, using 2487 sera from various institutions: 2031 samples from Universiti Sains Malaysia, 276 blinded sera from 2 other institutions in Malaysia, 140 blinded sera from India and 40 blinded sera from Thailand. These sera were from various groups of individuals, i.e., microfilaraemics, chronic patients, endemic normals, non-endemic normals and individuals with other parasitic and bacterial infections. Based on a cut-off optical density reading of 0.300, the IgG4 ELISA demonstrated specificity rates of 95.6-100%, sensitivity rates of 96-100%, positive predictive values of 75-100% and negative predictive values of 98.9-100%. These evaluation studies demonstrated the high specificity and sensitivity of this test for the detection of active B. malayi infection. Thus, the IgG4 ELISA would be very useful as a tool in diagnosis and in elimination programmes for brugian filariasis.

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.

Experimental chemotherapy of lymphatic filariasis. A review

Mak JW, Navaratnam V, Ramachandran CP

Ann Trop Med Parasitol, 1991 Feb;85(1):131-7.

PMID: 1888210

An intense global collaborative effort under the leadership of the Steering Committee of the Filariasis Scientific Working Group of the Tropical Diseases Research Programme, World Health Organization, has brought together researchers, pharmaceutical chemists and clinicians in the development and search for antifilarial compounds which are more effective and more convenient to administer than diethylcarbamazine citrate, the current drug of choice for lymphatic filariasis. The Brugia spp.-rodent model has been used extensively for the primary screening and B. pahangi infections in the dog or cat for the secondary screening, of potential filaricides. Recently, the leaf-monkey (Presbytis spp.) infected with subperiodic B. malayi or Wuchereria kalimantani has been used for the tertiary evaluation and pharmacokinetic studies of compounds which have shown effectiveness in the primary and secondary screens. Both P. cristata and P. melalophos are extremely susceptible to subperiodic B. malayi infection, but the former is a better host as a higher peak microfilaremia and adult worm recovery rate were obtained. Although more than 30 potential filaricides have been evaluated in the tertiary screen, only a few compounds have shown some promise against lymphatic filariasis. CGP 20376, a 5-methoxyl-6-dithiocarbamic-S-(2-carboxy-ethyl) ester derivative of benzothiazole, had complete adulticidal and microfilaricidal activities against the parasite at a single oral dose of 20 mg kg-1. However, as the compound or its metabolites caused hepatotoxicity, its clinical use in the present formulation is not recommended.(ABSTRACT TRUNCATED AT 250 WORDS)

Brugia infections in man and animals: long-term observations on microfilaraemia and estimates of the efficiency of transmission from mosquito vector to definitive host

Wilson T, Ramachandran CP

Ann Trop Med Parasitol, 1971 Dec;65(4):525-46.

PMID: 4401424

A study on the prevalence of soil transmitted helminths among lettuce leaves sold in local markets in Penang, Malaysia

Anuar AK, Ramachandran CP

Med J Malaysia, 1977 Jun;31(4):262-5.

PMID: 562969

Selection of Culex pipiens fatigans for vector ability to the rural strain of Wuchereria bancrofti--a preliminary report

Thomas V, Ramachandran CP

Med J Malaya, 1970 Mar;24(3):196-9.

PMID: 4246801