Relationships Between Wuchereria Bancrofti Microfilaria Counts in Human Blood and Parasite Uptake and Maturation in Culex Pipiens, With Observations on the Effects of Diethylcarbamazine Treatment on These Parameters

Farid, Hoda A.; Hammad, Ragaa E.; Soliman, Doaa A.; Setouhy, Maged A. El; Ramzy, Reda M. R.; Weil, Gary J.

doi:10.4269/ajtmh.2003.68.286

Cited by 12 publications

(12 citation statements)

References 25 publications

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“…As a consequence, the efficacy of a vaccine against filarial infections is likely to depend on how well it disrupts parasite immune evasion mechanisms. Given that the maintenance and transmission of filarial infections requires very few adult parasites [11] and that our previous work suggests that they are able to increase their fecundity in response to host immune attack [12], any intervention strategy should be assessed by its ability to suppress the transmissible stages, the microfilariae. Not only is this critical to reducing disease transmission, but in onchocerciasis microfilariae are the main cause of pathology.…”

Section: Introductionmentioning

confidence: 99%

Deletion of Parasite Immune Modulatory Sequences Combined with Immune Activating Signals Enhances Vaccine Mediated Protection against Filarial Nematodes

et al. 2012

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BackgroundFilarial nematodes are tissue-dwelling parasites that can be killed by Th2-driven immune effectors, but that have evolved to withstand immune attack and establish chronic infections by suppressing host immunity. As a consequence, the efficacy of a vaccine against filariasis may depend on its capacity to counter parasite-driven immunomodulation.Methodology and Principal FindingsWe immunised mice with DNA plasmids expressing functionally-inactivated forms of two immunomodulatory molecules expressed by the filarial parasite Litomosoides sigmodontis: the abundant larval transcript-1 (LsALT) and cysteine protease inhibitor-2 (LsCPI). The mutant proteins enhanced antibody and cytokine responses to live parasite challenge, and led to more leukocyte recruitment to the site of infection than their native forms. The immune response was further enhanced when the antigens were targeted to dendritic cells using a single chain Fv-αDEC205 antibody and co-administered with plasmids that enhance T helper 2 immunity (IL-4) and antigen-presenting cell recruitment (Flt3L, MIP-1α). Mice immunised simultaneously against the mutated forms of LsALT and LsCPI eliminated adult parasites faster and consistently reduced peripheral microfilaraemia. A multifactorial analysis of the immune response revealed that protection was strongly correlated with the production of parasite-specific IgG1 and with the numbers of leukocytes present at the site of infection.ConclusionsWe have developed a successful strategy for DNA vaccination against a nematode infection that specifically targets parasite-driven immunosuppression while simultaneously enhancing Th2 immune responses and parasite antigen presentation by dendritic cells.

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Section: Introductionmentioning

confidence: 99%

Deletion of Parasite Immune Modulatory Sequences Combined with Immune Activating Signals Enhances Vaccine Mediated Protection against Filarial Nematodes

et al. 2012

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“…8,9 Other studies have shown that mosquitoes fed on subjects with persistent, low-level microfilaremia following therapy ingest MF and produce infective filarial larvae. 10 The issue of treatment coverage must also be considered. No MDA program achieves complete coverage, and 80% coverage of eligible subjects (nonpregnant, more than two years of age, with no serious acute or chronic illness) is sometimes quoted as a goal for MDA programs; 11 actual coverage rates are often much lower than this.…”

Section: Introductionmentioning

confidence: 99%

A Randomized Clinical Trial Comparing Single- And Multi-Dose Combination Therapy With Diethylcarbamazine and Albendazole for Treatment of Bancroftian Filariasis

Setouhy¹,

Ramzy²,

Ahmed³

et al. 2004

The American Journal of Tropical Medicine and Hygiene

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The Global Program for Elimination of Lymphatic Filariasis calls for mass drug administration for endemic populations outside of sub-Saharan Africa with a single dose of diethylcarbamazine (DEC) and albendazole (Alb) annually for 4-6 years. Single-dose DEC/Alb dramatically reduces blood microfilaria (MF) counts, but most treated subjects fail to completely clear MF after a single dose. A more effective regimen might reduce the number of years required for elimination programs. We performed a randomized clinical trial in Egyptian adults with asymptomatic microfilaremia to compare treatment with seven daily doses of oral DEC (6 mg/kg) and Alb (400 mg) with a single dose of the same combination. We also studied the effect of re-treatment with single-dose DEC/Alb 12 months after the first treatment course. Multi-dose DEC/Alb was significantly more effective than single-dose therapy for reducing and clearing microfilaremia (mean reduction in MF/ml relative to pretreatment counts at 12 months, 99.6% versus 85.7%, with complete clearance in 75% versus 23.1%). The two regimens had similar activity against adult filarial worms, as indicated by serial ultrasound assessments. Neither regimen resulted in complete clearance of filarial antigenemia. There was no difference in adverse events, which were mild to moderate. Blood microfilaria and parasite antigen clearance rates increased following re-treatment. Multi-dose DEC/Alb may be a useful option for filariasis elimination programs, especially in the first year (when enthusiasm for mass drug administration and coverage rates are high), to quickly reduce community MF loads and transmission rates.

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“…pipiens mature to the infective stage (L3). 11 We found that while Cx. pipiens sometimes ingest MF when they feed on infected subjects with negative 50 L thick blood smears, such feedings produce very few L3.…”

Section: Introductionmentioning

confidence: 72%

“…pipiens. 11 The present project studied people with higher MF counts who were treated with two different DEC/ALB treatment regimens; subjects were restudied on multiple occasions over 12 months following treatment. A number of groups have reported effects of DEC/ALB on microfilaremia and adult worms in bancroftian filariasis.…”

Section: Discussionmentioning

confidence: 99%

Effects of Combined Diethylcarbamazine and Albendazole Treatment of Bancroftian Filariasis on Parasite Uptake and Development in Culex Pipiens L.

Farid¹,

Hammad²,

Hassan³

et al. 2005

The American Journal of Tropical Medicine and Hygiene

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We studied effects of combined diethylcarbamazine (DEC) and albendazole (ALB) treatment on Wuchereria bancrofti microfilaria (MF) uptake and development of infective larvae (L3) in Culex pipiens. Consenting Egyptian adults with microfilaremia (MF > 300/mL) were treated with one or seven daily doses of DEC/ALB. Laboratory-reared mosquitoes were fed on subjects before and after treatment. MF uptake and infectivity (assessed by mosquito dissection) were reduced by 89.6% and 82.9%, respectively, 12 months after single-dose treatment and by 96.2% and 99.7%, respectively, after multi-dose treatment. The L3:mosquito ratio decreased by 88% to 0.082 after single-dose treatment and by 99.8% to 0.001 after multi-dose treatment. If high coverage rates can be achieved for several annual cycles, mass drug administration (MDA) with DEC/ALB has the potential to decrease transmission to unsustainable levels and eliminate filariasis in populations. Multi-dose MDA (especially in the first year) might interrupt transmission with fewer cycles than single-dose treatment.

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Relationships Between Wuchereria Bancrofti Microfilaria Counts in Human Blood and Parasite Uptake and Maturation in Culex Pipiens, With Observations on the Effects of Diethylcarbamazine Treatment on These Parameters

Cited by 12 publications

References 25 publications

Deletion of Parasite Immune Modulatory Sequences Combined with Immune Activating Signals Enhances Vaccine Mediated Protection against Filarial Nematodes

Deletion of Parasite Immune Modulatory Sequences Combined with Immune Activating Signals Enhances Vaccine Mediated Protection against Filarial Nematodes

A Randomized Clinical Trial Comparing Single- And Multi-Dose Combination Therapy With Diethylcarbamazine and Albendazole for Treatment of Bancroftian Filariasis

Effects of Combined Diethylcarbamazine and Albendazole Treatment of Bancroftian Filariasis on Parasite Uptake and Development in Culex Pipiens L.

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