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.
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.
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.
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.
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.
The known filaricides, suramin and diethylcarbamazine citrate, were tested against subperiodic Brugia malayi infection in the leaf-monkey, Presbytis cristata. As expected, intravenous suramin at 10 mg/kg daily x 5 days or 17 mg/kg weekly x 5 weeks, did not show any microfilaricidal activity, but substantially reduced the recovery of live adult worms to 50.6% and 13.6% of controls respectively. Oral diethylcarbamazine citrate at 6 mg/kg daily x 6 or 10 days reduced final microfilarial counts to 30% of initial counts four weeks post-treatment and adult worm recovery was reduced to 4.5% and 0% of controls respectively. Although the antifilarial activity of these drugs against the infection in this non-human primate model appears to be similar to that seen in man, these results have to be confirmed using larger groups of animals.
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.
Introduction:Filariasis is an endemic infection in tropical and subtropical countries. The disease is caused by para-sites from the group filarodidae. Epidermolysis Bullosa, on the other hand is a group of rare genetic skin diseases that characterize by skin blister and erode facilely. Due to rarity of Epidermolysis Bullosa and uncommon occurrence of Filariasis, there is extremely limited case or paper reporting on safety profile of medication that are used to treat Filariasis patient with underlying Epidermolysis Bullosa.Serious adverse event that is anticipated in this cohort of patient are Stevens-Johnson syndrome and Mazotti reaction. Case description: Surveillance activity is necessary in high endemic localities in Sabah in order to control the spread of this mosquitoes-borne disease. The available tool is Brugia RapidTM kit, a test kit that detects filarial antibodies.A 13 year-old boy with underlying Epidemolysis Bullosa Simplex was detected during surveillance activities. It was further confirmed with night blood on microscopic slide that depicted high density of parasite (microfilaria count: 31). The WHO specifically exempted the following groups from the treatment - children under 5 years of age; pregnant women; and seriously ill individuals i.e. those who are having acute or chronic illness that makes them too sick or weak to get out of bed; and those with an illness who are life-dependent on medical intervention. This is because ingestion of the medications can result in adverse events due to the destruction of killed parasites. No guideline is available for treatment of lymphatic filariasis in rare genetic disorders. Conclusion: The recommended dosage for IDA is Ivermectin 3mcg/kg, Diethylcarbamazine 6mg/kg and Albendazole 400mg for positive patient yearly. Patient was admitted in hospital for observation treatment with the suggested dose. From the case study it shows it is safe to treat this cohort patient. However, it is advisable to treat such rare cases by case basis and in comparison to others where treatment is given in the community this patients should be treat in more control environment such in the hospital.
Introduction: : Lymphatic filariasis is a public health problem in Malaysia. In sub-district Tangkarason, Beluran the nine rounds of Mass Drug Administration (MDA) do not seem to work in reducing the microfilaria (Mf) prevalence below the 2% threshold that the World Health Organization (WHO) recommends for stopping MDA. The study aims to identify possible factors contributing to the transmission of lymphatic filariasis in the area. Methods: A total of 244 individuals from seven high risk localities, whom between the age of 19 and 99-year-old, were interviewed and tested for lymphatic filariasis antibody. The associated factors were analyzed using Chi-square test (Fisher exact test where applicable) and odds ratio (OR), and adjusted odds ratio (AOR) was estimated using logistic regression. Re-sults: The median age was 40-year-old (interquartile range: 30-53). The prevalence of brugian filariasis in the studied population was 31.1% (95% CI 0.25, 0.37). Prevalence of brugian filarial infection is higher in males than in females (34.6% vs. 27.4%, P = 0.219); and in older adults (≥ 56-year-old) than in young-and-middle-aged adults (46.3% vs 26.8%, P = 0.006). The older group is 2.4 times at higher odd of contracting the disease than the younger adults (95% CI 1.26, 4.38; P = 0.007). The prevalence of brugian filarial infection is higher among those who never receive pro-phylaxis treatment compared to those who had received medications (48.5% vs 28.4%, p = 0.021). Those who had received prophylaxis treatment have about 60% reduction in odd of lymphatic filariasis infection (OR 0.42; 95% CI 0.20, 0.89; P = 0.023). The proportion of the studied population who has outdoor jobs is 52.9%. The prevalence of brugian filarial is higher in this group compared to those with indoor jobs (38.0% vs 23.5%, p = 0.015). The older age group was significantly associated with brugian filarial infection after adjusting for other factors (AOR 3.20; 95% CI 1.63, 6.32). Conclusion: The older adults (≥ 56-year-old), those who never involved in MDA and those with outdoor jobs are associated with lymphatic filariasis infection in Beluran.
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.