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Reda M R Ramzy

Publications and source records attributed to Reda M R Ramzy.

15 recordsLinked to original sources

Diagnostic tools for filariasis elimination programs.

The ambitious and exciting Global Programme to Eliminate Lymphatic Filariasis (GPELF) is largely based on a strategy of mass drug administration (MDA) of repeated rounds of antifilarial medications to endemic populations around the world. Diagnostic tools are important to GPELF because they affect decisions regarding where to distribute MDA, how to measure its effects, how to define targets and endpoints for stopping MDA, and how to monitor populations for possible resurgence of filariasis transmission following suspension of MDA. This article reviews available diagnostic tests for filariasis and their potential use as tools for different phases of filariasis elimination programs.

Animals↗

Effect of yearly mass drug administration with diethylcarbamazine and albendazole on bancroftian filariasis in Egypt: a comprehensive assessment.

BACKGROUND: Egypt was one of the first countries to implement a national programme to eliminate lymphatic filariasis based on WHO's strategy of repeated rounds of mass drug administration (MDA) with diethylcarbamazine and albendazole (target population, 2.5 million in 181 localities). We assessed the effect of five yearly rounds of MDA on filariasis in four sentinel villages in Egypt. METHODS: We studied two areas with different infection rates before MDA: the Qalubyia study area had a low infection rate because of previous treatment with diethylcarbamazine; this was typical of most filariasis-endemic villages in Egypt before MDA. The Giza study area had a high baseline infection rate. We undertook repeated surveys in villages for treatment compliance and tests for microfilaraemia and circulating filarial antigenaemia, antibodies to filarial antigen Bm14 in schoolchildren, and infections in indoor-resting mosquitoes (assessed by PCR). FINDINGS: MDA compliance rates were excellent (>80%). In Giza after MDA, prevalence rates of microfilaraemia and circulating filarial antigenaemia fell from 11.5% to 1.2%, and from 19.0% to 4.8%, respectively (p<0.0001). Corresponding rates in Qalubyia fell from 3.1% to 0% and 13.6% to 3.1%, respectively (p<0.0001). Rates of antifilarial antibody and circulating filarial antigenaemia in schoolchildren (aged about 7-8 years), fell from 18.3% to 0.2% (p<0.0001) and from 10.0% to 0.4% (p<0.0001) in Giza, respectively, and from 1.7% to 0% and 1.7% to 0% (both p=0.13) in Qalubyia, respectively. Mosquito infection rates fell from 3.07% (95% CI 2.38-3.88) to 0.19% (0.08-0.38) in Giza and from 4.37% (3.07-5.99) to 0% (0-0.05) in Qalubyia. INTERPRETATION: MDA greatly affects variables related to infection (microfilaraemia and circulating filarial antigenaemia prevalence rates) and transmission (antifilarial antibodies in young children and mosquito infection rates). Our results suggest that after five rounds of MDA filariasis is likely to have been eliminated in most endemic localities in Egypt.

Albendazole↗

Bancroftian filariasis: effect of repeated treatment with diethylcarbamazine and albendazole on microfilaraemia, antigenaemia and antifilarial antibodies.

Diethylcarbamazine/albendazole (DEC/ALB) therapy is widely used in mass drug administration (MDA) programmes aimed at eliminating lymphatic filariasis. We studied the effects of repeated annual treatments with DEC/ALB on Wuchereria bancrofti microfilaraemia, filarial antigenaemia and IgG4 antibodies to Bm14 antigen. Fifty-seven subjects with asymptomatic microfilaraemia were treated with one or seven daily doses of DEC/ALB at time zero. All subjects were re-treated with single-dose DEC/ALB 12, 24 and 36 months later. The two treatment groups had comparable pre-treatment microfilaria counts. Multidose treatment cleared microfilaraemia more effectively than single-dose treatment. Filarial antigen levels decreased equally in both treatment groups. Total antigen clearance was observed in 29.6%, 52.0%, 63.6% and 79.5% of subjects at 12, 24, 36 and 48 months. These clearance rates are much higher than those observed in prior treatment trials with DEC or ivermectin. Antibody levels increased 4 weeks after treatment and then slowly decreased in most subjects. Antibody tests turned negative in 20%, 35%, 39.4% and 52.5% of treated subjects at 12, 24, 36 and 48 months post treatment. These results show that the studied parameters decline at different rates and to differing degrees following DEC/ALB treatment. These findings have important implications regarding strategies for monitoring the effects of MDA in populations.

Adolescent↗

A real-time PCR-based assay for detection of Wuchereria bancrofti DNA in blood and mosquitoes.

We developed and evaluated real-time polymerase chain reaction (PCR) assays for detecting Wuchereria bancrofti DNA in human blood and in mosquitoes. An assay based on detection of the W. bancrofti "LDR" repeat DNA sequence was more sensitive than an assay for Wolbachia 16S rDNA. The LDR-based assay was sensitive for detecting microfilarial DNA on dried membrane filters or on filter paper. We also compared real-time PCR with conventional PCR (C-PCR) for detecting W. bancrofti DNA in mosquito samples collected in endemic areas in Egypt and Papua New Guinea. Although the two methods had comparable sensitivity for detecting filarial DNA in reference samples, real-time PCR was more sensitive than C-PCR in practice with field samples. Other advantages of real-time PCR include its high-throughput capacity and decreased risk of cross-contamination between test samples. We believe that real-time PCR has great potential as a tool for monitoring progress in large-scale filariasis elimination programs.

Animals↗

Defining the cost of the Egyptian lymphatic filariasis elimination programme.

BACKGROUND: Lymphatic filariasis (LF) is targeted for global elimination. LF elimination programmes in different countries, including Egypt, are supported financially by national and international agencies. The national programme in Egypt is based on mass drug administration (MDA) of an annual dose of a combination of 2 drugs (DEC and albendazole) to all endemic villages. This study aimed primarily to estimate the Total and Government costs of two rounds of MDA conducted in Egypt in 2000 and 2001, the average cost per person treated, and the cost share of the different programme partners. METHODS: The Total costs reflect the overall annual costs of the MDA programme, and we defined Government costs as those expenditures made by the Egyptian government to develop, implement and sustain the MDA programmes. We used a generic protocol developed in coordination with the Emory Lymphatic Filariasis Support Center. Our study was concerned with all costs to the government, donors and other implementing parties. Cost data were retrospectively gathered from local, regional and national Ministry of Health and Population records. The total estimates for each governorate were based on data from a representative district for the governorate; these were combined with national programme data for a national estimate. RESULTS: The overall Total and Government costs for treating approximately 1,795,553 individuals living in all endemic villages in the year 2000 were USD 3,181,000 and USD 2,412,000, respectively. In 2001, the number of persons treated increased (29%) and the Total costs were USD 3,109,000 while Government costs were USD 2,331,000. In 2000, the average Total and Government costs per treated subject were USD 1.77 and USD 1.34, respectively, however, these costs decreased to USD 1.34 and USD 1.00, respectively in 2001. The coverage rate was 86.0% in 2000 and it increased to 88.0% in 2001. CONCLUSION: The Egyptian government provided 75.8% of all resources, as reflected in the Total cost estimates, and international agencies contributed the rest. Such data highlight both the commitment of the Egyptian government and the significance of the contributions of international bodies toward the LF elimination programme.

Journal Article↗

Effects of combined diethylcarbamazine and albendazole treatment of bancroftian filariasis on parasite uptake and development in Culex pipiens L.

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.

Adult↗

The evaluation of HLA-DRB1 antigens as susceptibility markers for unilocular cystic echinococcosis in Egyptian patients.

This is the first study dealing with the correlation between HLA antigens and cystic echinococcosis (CE) in Egyptian patients. The potential immunogenetic predisposition for susceptibility and resistance to unilocular echinococcosis was investigated by HLA-DRB1 typing; first by HLA-DRB1 amplification using PCR then using the allele-specific probing technique based on the reverse hybridization principle. The study was carried out on 35 patients with confirmed CE, and 100 apparently healthy individuals. A statistically significant positive association was found between HLA-DR3 and HLA-DR11 and the occurrence of CE. HLA-DR3 antigen was positively associated with the occurrence of isolated pulmonary cysts, multiple cysts, cysts >5 cm in size, non-cured disease and with a common radiological picture of hydatid cyst. A significant positive association of HLA-DR11 with the occurrence of cysts <5 cm in size was detected. This study demonstrates that carriers of DR-3 and DR-11 are at high risk for CE, and that those with DR-3 are more liable to complications.

Adolescent↗

Test strip detection of Wuchereria bancrofti amplified DNA in wild-caught Culex pipiens and estimation of infection rate by a PoolScreen algorithm.

Bancroftian filariasis is targeted for elimination in the Nile Delta of Egypt. Improved simple methods are needed for monitoring Wuchereria bancrofti infection in the mosquito vector and thereby the success of elimination programmes. We evaluated the performance of the SspI-PCR assay combined with a DNA Detection Test StripTM method and used the PoolScreen algorithm method for estimating mosquito infection rates. A total of 769 indoor-resting Culex pipiens were captured in 79 randomly selected houses from a filaria-endemic village in the Nile Delta of Egypt (24.4% antigenaemia and 8.6% microfilaraemia). Collected mosquitoes were pooled by house, and assayed by the SspI-PCR. Amplified parasite DNA was detected by both electrophoresis of agarose gel stained with ethidium bromide (EtBr) and by test strips. PCR based on EtBr and test strip methods identified 43 (54.4%) and 45 (56.9%) houses, respectively, as being filaria positive. The minimum mosquito infection rate, assuming one infected female/pool was 6.85% by the PCR test strips. Mosquito infection rate calculated by the PoolScreen2 algorithm software amounted to 8.1% [95% confidence interval 5.85, 10.47]. Because it is faster and safer, the PCR test strip is a practical tool, especially when combined with the PoolScreen algorithm method, for xenomonitoring the success of elimination programmes.

Algorithms↗

A randomized clinical trial comparing single- and multi-dose combination therapy with diethylcarbamazine and albendazole for treatment of bancroftian filariasis.

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.

Adult↗

Molecular characterization of Egyptian human and anima Echinococcus granulosus isolates by RAPD-PCR technique.

Five primers of known, but arbitrary nucleotide sequence (OPH-03, OPH-05, OPH-12, OPH-15, OPH-18) were used to detect genetic variability in Egyptian human, camel and pig E. granulosus isolates. OPH-03, OPH-05 & OPH-15 proved useful as genetic markers of strain variation, while OPH-12 and OPH-18 allowed distinction at the genus level i.e. diversified from Cysticercus tenuicollis. OPH-03 was the most effective giving sharp distinct banding pattern and the least values of similarity coefficients. Some variations were detected within E. granulosus isolates from the same host. The level of heterogeneity was low in three of the human isolates, camel and pig strains. Individual variation was detectable within other 3 human isolates. Human and camel isolates were the most related pair, having similar patterns and the highest similarity coefficients. The study implies that human cases in Egypt are of the camel/dog strain, and camels are important hosts for the transmission of human hydatidosis.

Animals↗

Duplex Doppler sonographic assessment of the effects of diethylcarbamazine and albendazole therapy on adult filarial worms and adjacent host tissues in Bancroftian filariasis.

We used duplex Doppler sonography to assess effects of diethylcarbamazine and albendazole therapy (DEC/ALB) on adult Wuchereria bancrofti in vivo. The study was performed in clinically normal Egyptian adults with blood microfilaria counts > 80/mL. Motile adult worms were observed before treatment in dilated scrotal lymphatic vessels in 28 of 36 men (78%) and over the proximal extremities in 5 of 22 women (23%). Most worm nests were inactivated in the months following treatment (90% at 12 months). Circulating filarial antigen levels (a marker for living adult worms) also fell dramatically following treatment. Some men had intrascrotal calcifications and/or non-palpable hydroceles detectable by ultrasound before they were treated. New hydroceles and intrascrotal calcifications appeared after treatment in many cases. However, most of these were transient and of no clinical significance. Prevelance rates for hydrocele and intrascrotal calcifications 24 months after treatment were essentially the same as those prior to treatment. These results show that DEC/ALB is highly active against adult W. bancrofti. They also suggest that host responses to dying adult worms are important in the pathogenesis of filarial hydroceles.

Adult↗

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.

This study examined relationships between blood microfilaria (MF) counts and parasite uptake and maturation in Culex pipiens fed on Egyptian volunteers with bancroftian filariasis. Uptake of MF and production of infective larvae (L3) were more closely correlated with MF counts in finger prick blood than in venous blood. Only a minority of ingested MF developed into L3. Few MF were ingested, and very few L3 were produced by mosquitoes that fed on infected subjects who were amicrofilaremic by 50 microL thick blood smear; the contribution of such carriers to filariasis transmission in Egypt is probably negligible. These results suggest that filariasis elimination programs should aim to achieve MF smear rates of zero. Single-dose diethylcarbamazine therapy reduced MF counts by 87.9% 6-7 months after treatment; similar reductions were observed for MF uptake, MF/mosquito, infectivity, and L3/mosquito. Thus, single-dose diethylcarbamazine had a major impact on MF ingestion and L3 production by mosquitoes.

Animals↗

Recent advances in molecular diagnostic techniques for human lymphatic filariasis and their use in epidemiological research.

Diagnosis of lymphatic filariasis for epidemiological studies is an area of science that has been greatly modernized over the last two decades. Recent developments and the introduction of new technologies have led to the replacement of traditional diagnostic methods that were insensitive, tedious and often impractical with molecular biology techniques that have considerable potential for field use. This paper reviews some of these major new techniques and the applications of molecular diagnosis in the field of lymphatic filariasis.

Animals↗

Schistosoma mansoni and Schistosoma haematobium: identification and characterization of glycoconjugate antigens in the hemolymph of infected vector snails.

Two carbohydrate epitopes were identified by monoclonal antibodies (KCS and E2) and characterized with respect to their immunoreactivity, monosaccharide structure, and location. Immunofluorescence demonstrated the presence of both epitopes on the surfaces of sporocysts, cercariae, and miracidia of Schistosoma mansoni, Schistosoma haematobium, and Schistosoma japonicum. However, spatial distribution and density of expression varied among species and developmental stages, and neither epitope was detectable on adult worm surfaces. Both glycans were found in the hemolymph of infected, but not uninfected, intermediate snail hosts. The presence of epitopes in hemolymph, as well as in schistosome eggs, is species-specific for KCS, recognizing only S. mansoni, and partly specific for E2, which reacted predominantly with S. haematobium. Immunoaffinity purification of target antigens for KCS and E2 from hemolymph of infected Biomphalaria and Bulinus, respectively, followed by carbohydrate composition analysis revealed a high content of fucose in both glycans. Methylation analysis demonstrated exclusively terminal fucose for the target antigen of KCS and terminal as well as internal fucose for the one of E2. Removal of terminal fucose abolished reactivity with both monoclonal antibodies. Both glycans are different from previously characterized schistosome carbohydrates. Their biological function(s) remain to be defined.

Animals↗

The impact of single-dose diethylcarbamazine treatment of bancroftian filariasis in a low-endemicity setting in Egypt.

This study was designed to evaluate the effect of a single dose of diethylcarbamazine (DEC, 6 mg/kg) on Wuchereria bancrofti infections in a low-endemicity setting in Egypt (microfilaremia, or MF, 3.7%, median MF 34/mL). Subjects with MF or filarial antigenemia were treated and restudied 1 year later. Treatment with DEC dramatically reduced blood MF counts, with clearance in 69% of subjects. Treatment also reduced filarial antigen levels, but low clearance rates suggest that some adult worms survived treatment in most patients. Mass treatment was administered in one village; 27 months later, MF prevalence had decreased 84% (from 4.9% to 0.8%). These results show that single-dose DEC treatment can have a major effect on MF prevalence rates and levels in low-endemicity settings. Although the World Health Organization advocates repeated multidrug regimens for filariasis elimination, mass treatment with DEC alone may be sufficient to interrupt transmission in areas with low infection intensities and prevalence rates.

Adolescent↗