Doi:10.1016/s0140-6736(06)68426-2

Articles
Effect of yearly mass drug administration with
diethylcarbamazine and albendazole on bancroftian
filariasis in Egypt: a comprehensive assessment
Reda M R Ramzy, Maged El Setouhy, Hanan Helmy, Ehab S Ahmed, Khaled M Abd Elaziz, Hoda A Farid, William D Shannon, Gary J Weil Lancet 2006; 367: 992–99
Background Egypt was one of the first countries to implement a national programme to eliminate lymphatic filariasis
See Comment page 966
based on WHO’s strategy of repeated rounds of mass drug administration (MDA) with diethylcarbamazine and
Research and Training Centre
albendazole (target population, 2·5 million in 181 localities). We assessed the effect of five yearly rounds of MDA on
on Vectors of Diseases, Ain
filariasis in four sentinel villages in Egypt.
Shams University, Cairo, 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
Prof H A Farid PhD); and
for treatment compliance and tests for microfilaraemia and circulating filarial antigenaemia, antibodies to filarial
Washington University School
antigen Bm14 in schoolchildren, and infections in indoor-resting mosquitoes (assessed by PCR).
of Medicine, St Louis, MO, USA
Findings MDA compliance rates were excellent (Ͼ80%). 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 (pϽ0·0001).
Corresponding rates in Qalubyia fell from 3·1% to 0% and 13·6% to 3·1%, respectively (pϽ0·0001). Rates of
antifilarial antibody and circulating filarial antigenaemia in schoolchildren (aged about 7–8 years), fell from 18·3% to
0·2% (pϽ0·0001) and from 10·0% to 0·4% (pϽ0·0001) 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%
[email protected]
(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.
Introduction
on WHO’s strategy for global elimination of lymphatic Lymphatic filariasis (caused by the mosquito-borne filariasis.2,5 This programme was one of the first to be nematodes Wuchereria bancrofti and Brugia malayi) is a initiated. The plan called for mass drug administration major public-health problem in many tropical and (MDA) in all known filariasis-endemic areas5 with yearly subtropical regions. Recent reports have estimated that at cycles of single-dose diethylcarbamazine (6 mg/kg least 120 million people are infected with these parasites bodyweight) and albendazole (fixed dose of 400 mg).
in 83 countries and that more than 40 million people MDA was distributed by local health teams on a house- have overt clinical disease (mostly hydroceles, to-house basis, with directly observed ingestion of the lymphoedema, and elephantiasis).1,2 Bancroftian filariasis drugs when possible. Pregnant women and children accounts for more than 90% of this disease burden.
younger than 2 years were excluded from MDA. The Bancroftian filariasis, caused by W bancrofti, has been programme was supported by a broad-based publicity endemic in Egypt for centuries.3 The infection was campaign, and excellent MDA coverage rates were thought to have been eliminated as a public-health problem in the 1960s, as a result of widespread diethyl- We assessed the effect of five rounds of MDA on carbamazine citrate treatment and intensive use of filariasis endemicity and transmission in sentinel villages residual insecticides for malaria control. However, included in the Egyptian PELF. A secondary goal of our relaxation of these efforts was followed by resurgence of study was to explore the value of different methods for filariasis in the 1980s, with an estimated 250 000 people monitoring the effect of MDA and for assessing progress infected by 1990 and 2·5 million people at risk in eight in national treatment programmes for filariasis. governorates, mostly in the Nile river delta region (lowerEgypt) and in Giza.4 The Egyptian Ministry of Health and Population Study participants and procedures
initiated a national programme to eliminate lymphatic This study was reviewed by and received ethics approval filariasis (PELF) in September, 2000, which was based from institutional review boards at Washington www.thelancet.com Vol 367 March 25, 2006
Articles
University School of Medicine and at Ain Shams NSW, Australia) were used for the first three surveys, University. We undertook three types of surveys in four and Filariasis Now cards (Binax, Portland, ME, USA) sentinel villages that were included in the Egyptian were used for surveys after MDA rounds 3, 4, and 5.
PELF. These types included: village surveys to assess Study participants with positive results from filariasis MDA compliance, filarial antigenaemia prevalence rates, antigen tests were tested for microfilaraemia by and microfilaraemia prevalence rates; school surveys to membrane filtration of 1 mL of venous blood taken detect antibodies to a recombinant filarial antigen between 2100 h and 0100 h, as previously described.6 We (Bm14) in primary schoolchildren; and mosquito defined the prevalence rate of microfilaraemia as the surveys to determine mosquito infection rates. number of people with microfilaremia divided by the The village surveys were done in two different regions number of people tested for filarial antigenaemia. This of Egypt that had different infection prevalence rates value slightly underestimates the true microfilaria before MDA was initiated (ie, pre-MDA). Two of the four prevalence rate, because the sensitivity of the antigen study villages (adjacent villages of Kafr Tahoria and card test in microfilaria carriers (as detected by mem- Tahoria) are located about 35 km northeast of Cairo, brane filter) is about 95%.7,8 We also calculated commu- Egypt, in the Qalubyia Governorate. These villages had nity microfilaraemia loads as an overall measure of low microfilaraemia prevalence rates before the first the microfilaraemia present in study communities.
round of MDA, and many residents had been previously Community microfilaraemia loads were calculated as: treated with diethylcarbamazine before MDA. Thus, the (the antilog of the [sum of log(Xϩ1)/N])Ϫ1, where X is villages in Qalubyia were fairly typical of filariasis- the microfilaraemia count in affected individuals, and N endemic villages in Egypt just before initiation of the is the number of people screened for infection by national PELF. The other two study villages (adjacent villages of Kafr El Bahary and Kafr El Qebly) are located Most PELFs worldwide detect microfilaraemia by the about 40 km southwest of Cairo in the Giza examination of thick smears of blood taken at night. To Governorate. The Giza villages had very little treatment verify that we did not miss smear-positive individuals by for filariasis before MDA, and they had the highest testing only those with positive circulating filarial known rates of microfilaraemia prevalence in Egypt just antigenaemia tests, we tested all participants for microfilaraemia after the fifth round of MDA by The study was done in randomly selected households.
microscopic examination of Giemsa-stained thick blood Villages were mapped and houses were numbered. We films prepared with 50 ␮L finger-prick blood samples used a computer to generate random numbers every year, and sampled houses with these numbers. We School surveys were done in primary schools that studied about 500 people older than 4 years in served the study villages. Written consent was not 100 houses every year in Kafr El Bahary, Kafr El Qebly, obtained from parents or guardians; the procedure of and Tahoria villages; about 250 people in 50 houses were obtaining consent from school headmasters and school studied every year in the smaller village of Kafr Tahoria.
physicians and assent from children was approved by These repeated cross-sectional surveys were done before both IRBs in accordance with NIH guidelines. We the first round of MDA and about 7–10 months after obtained finger-prick blood samples (300 ␮L) from assenting children in grade 1 (aged about 7 years) and Field teams consisting of a physician, a technician, and grade 5 (about age 11 years). Children in grades 1 and 2 a local health worker visited houses in the evening. After (grade 2 children aged about 8 years) were tested after obtaining verbal informed consent (written informed MDA rounds 1, 3, 4, and 5; results for these young consent was waived by the institutional review board children were combined and are reported as grade 1.
[IRB], according to guidelines from the National Grade 5 children were tested before MDA and after all Institute of Health [NIH]), the teams recorded MDA rounds apart from round 1. We stored plasma demographic and MDA compliance information on samples at Ϫ20ºC before antibody testing. Plasma IgG4 preprinted forms. Parents provided treatment histories antibodies to Bm14 were detected by ELISA, as for their children. Compliance rates in study villages previously described.10 Previous studies have shown that were estimated by dividing the number of study this test is sensitive and specific for infection or heavy participants in survey households who reported having taken diethylcarbamazine and albendazole in the Mosquitoes were collected for molecular xeno- previous round of MDA by the total number of study monitoring (detection of nucleic acid from a pathogen in participants who lived in these houses. To assess arthropod vectors) in the same houses as those sampled endemicity, we measured microfilaraemia and filarial in the village surveys for microfilaraemia and filarial antigenaemia. Finger-prick blood samples were antigenaemia. Mosquitoes were obtained before the first obtained for detection of W bancrofti antigenaemia round of MDA and about 8–11 months after every (circulating filarial antigenaemia) with rapid-format card subsequent round. Every house was visited once per tests. AMRAD ICT filariasis cards (French’s Forest, week for 4 or 5 consecutive weeks. Houses were visited www.thelancet.com Vol 367 March 25, 2006
Articles
Number of study
Microfilaraemia
Community microfilaraemia
Circulating filarial antigenaemia
participants tested
prevalence rate (95% CI)
load (95% CI)
prevalence rate (95% CI)
Giza study area
Pre-MDA
Qalubiya study area
Pre-MDA
Numbers in first column refer to number of MDA rounds that had taken place before blood samples were taken. Table 1: Effect of MDA on filariasis infection variables
late at night, and indoor-resting mosquitoes were taken by aspiration by trained field workers. Fed and gravid Culex Treatment compliance rates for our survey samples pipiens mosquitoes were pooled by house. Parasite DNA (combined data for all four villages) were 86·7%, 95·5%, was detected in mosquito pools by PCR as described in 90·1%, and 88·8% for rounds 1–4 of MDA, respectively.
detail elsewhere.13 Pools with more than 25 mosquitoes Village-specific compliance rates were 80% or higher were divided for PCR analysis. Mosquito infection rates (the Egyptian PELF target) in all cases, and was (maximum likelihood with 95% CIs) were calculated with consistent with high coverage rates reported by the Egyptian Ministry of Health and Population for thenational PELF. Statistical analysis
Data entry was undertaken with EpiInfo software
(version 6),15 with field limits and double data entry. We did all statistical analyses using SAS 9.1 for Windows procedures PROC MIXED and PROC GLIMMIX. Data were analysed separately for Giza and Qalubyia study areas. Mixed model analyses (fit with household as therandom effect) were calculated for prevalence rates of circulating filarial antigenaemia and microfilaraemia and for community microfilaraemia loads, to assess the significance of changes in these variables over time. These models were fit independently for Giza and Qalubyia.
House numbers were treated as the random effects. We estimated mean values from the mixed models, andcalculated the 95% CIs assuming a normal distribution. A Qalubyia
linear contrast was used to assess the significance ofdifferences in filariasis variables after the fourth and fifth rounds of MDA. Percentage changes from pre-MDAvalues were calculated and plotted to visually display the effect of MDA on different variables over time. Role of the funding source
The sponsor of the study reviewed the study protocol toensure compliance with good clinical practice standards.
Otherwise, the sponsor had no role in the study design, data collection, data analysis, data interpretation, orwriting of the report. The corresponding author had fullaccess to all the data in the study and had final Figure 1: Relative effect of MDA on filariasis infection variables in (A) Giza
and (B) Qalubyia study areas
responsibility for the decision to submit the manuscript Data shown are percentage relative to baseline values measured pre-MDA, at www.thelancet.com Vol 367 March 25, 2006
Articles
Table 1 shows data for microfilaraemia variables before and after every MDA round. Overall, all variables showed significant decreases from pre-MDA to round 5 children tested prevalence rate (% [95% CI]) (pϽ0·0001). Changes between rounds 4 and 5 were not Giza study area
significant by linear contrast. Pre-MDA microfilaraemia prevalence rates and community microfilaraemia loads were much higher in Giza than in Qalubyia (table 1).
Pre-MDA microfilaria counts in affected individuals in Giza and Qalubyia did not differ significantly (geometric mean 42·9, median 45·5 [IQR 9·5–154·5] vs 30·6, 38·0 Qalubyia study area
[9·0–128·0]; Mann-Whitney U test, p=0·33). Microfilaraemia rates fell sharply in both study areas after MDA, and only three microfilaria carriers were identified in Qalubyia villages after the second round of MDA. Similar declines were recorded for community microfilaraemia loads, with reductions of 73% after Numbers in first column refer to number of MDA rounds that had taken place before blood samples were taken. ND=not done MDA round 1 and 91% after round 5 in the high- (antibody testing was not done for grade 5 children after MDA round 1).
prevalence Giza study area (figure 1). Microfilaraemia Table 2: Effect of MDA on antifilarial antibody prevalence rates in primary schoolchildren
rates decreased more rapidly in the Qalubyia study areawhere baseline infection rates were lower than those inGiza.
in grade 1 children in Qalubyia were both 1·7%.
All study participants studied after the fifth round of Antibody prevalence rates in grade 1 and 5 children from MDA had thick smear examinations for micro- Giza and grade 5 children from Qalubyia fell filaraemia. Four (0·3%) of 1062 smears from Giza study significantly from pre-MDA to round 5 (pϽ0·0001); the participants were positive, but none of the 764 smears change in grade 1 children from Qalubyia was not from Qalubyia study participants was positive. All four significant (p=0·13) because of the low baseline rate and study participants with microfilaraemia by blood smear had positive test results for circulating filarialantigenaemia. Pre-MDA prevalence rates of circulating filarial antigenaemia in Qalubyia villages were much higher than corresponding microfilaraemia rates (table 1). This difference probably shows the effect of previous selectiveand mass diethylcarbamazine treatment campaigns in these villages,16 which cleared microfilaraemia from many residents without completely clearing antige- naemia. Antigenaemia rates fell more slowly than microfilaraemia rates after MDA (figure 1). Anti- genaemia rates fell more rapidly in the less heavily infected Qalubyia villages than in the Giza villages.
Antigen prevalence rates fell by 16% and 75% in Giza Qualubyia
villages and by 35% and 77% in Qalubyia villages after rounds 1 and 5 of MDA, respectively.
The ratio of microfilaraemia prevalence rate to circulating filarial antigenaemia prevalence rate was 0·58 in Giza villages before MDA. This ratio was 0·25 or less after MDA round 3. The ratio before MDA was 0·22 in Qalubyia villages, indicating previous treatment in this area; the ratio fell further after MDA. Pre-MDA antibody prevalence rates were higher in the Giza village schools than in the Qalubyia schools (23·8% vs 7·38%; pϽ0·0001) and higher in grade 5 than grade 1children (table 2). The pre-MDA antibody prevalence Figure 2: Relative effect of MDA on filariasis transmission variables in (A) Giza
rate for grade 1 children in Giza was significantly higher and (B) Qalubyia study areas
than the corresponding prevalence rate for circulating Data shown are percentage relative to baseline values measured pre-MDA, round 0. Antibody testing was not done for grade 5 children after MDA round 1.
filarial antigenaemia (18·3 vs 10·0%, respectively, Grade 1 children are aged 7–8 years, and grade 5 children are aged about pϽ0·0001). Pre-MDA antibody and antigenaemia rates www.thelancet.com Vol 367 March 25, 2006
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Discussion
Number of
Number of
Mosquitoes/pool
Mosquito infection rate
mosquitoes tested pools tested
(maximum likelihood %, 95% CI)
Our study has shown that five rounds of MDA with Giza study area
diethylcarbamazine and albendazole greatly affected various measures of filariasis endemicity and trans- mission in sentinel Egyptian villages with varying baseline infection rates. These villages seem to be on track to achieve filariasis elimination after five or six yearly rounds of MDA. If these sentinel villages are Qalubyia study area
typical of communities included in the Egyptian PELF, the national programme will probably be successful. The Global Programme to Eliminate Lymphatic Filariasis (GPELF) calls for selective diagnosis of sentinel groups to identify and map endemic areas and for at least five effective yearly rounds of MDA with one Numbers in first column refer to number of MDA rounds that had taken place before blood samples were taken. of the new, single-dose combination treatmentregimens for all individuals living in endemic areas.2,17,18 Table 3: Effect of MDA on mosquito infection rates
Since lymphatic filariasis is inefficiently transmittedand since human beings are the only mammalian host Rates of circulating filarial antigenaemia in grade 1 for the parasites in most endemic areas, the goal of children after MDA round 5 were 0·4% in Giza and 0% in MDA is to interrupt transmission by reducing the Qalubyia, respectively. Antibody prevalence rates for grade reservoir of microfilaraemia to levels lower than that 1 children in Qalubyia schools fell to zero after three needed for sustained transmission. Current targets for rounds of MDA (figure 2). Rates fell more rapidly for grade 1 and 5 children in Qalubyia, where baseline human microfilaraemia prevalence rates to less than 1% by infection rates were lower than those in Giza. The thick smear and the reduction of infection rates in volatility in relative antibody rates for years 1–3 shown in children born after the start of MDA to less than 0·1% figure 2 is due to a low baseline antibody rate in grade 1 (indicated by microfilaraemia or antigen testing).18 children from Qalubyia, which indicates that large When GPELF was initiated in 2000, the knowledge samples of children are needed to get accurate estimates base for the programme was thin in several important for antibody prevalence rates when prevalence rates are areas, and as a working hypothesis, the strategy needed low. Antibody rates in grade 1 Giza schoolchildren to be tested in the field. The prime question was decreased after every MDA round; after round 5, the whether MDA would actually work in large-scale antibody rate in these students was only 1% of the baseline programmes. There was also uncertainty regarding the value (table 2, figure 2). Antibody rates fell less sharply in best methods for monitoring the effect of MDA and for grade 5 Giza schoolchildren than in grade 1 Giza children.
establishing endpoints or targets for PELFs. By the end However, the antibody rate for grade 5 children in Giza of 2004, 38 countries had initiated national PELFs, and after four rounds of MDA was much lower than the rate in more than 76·5 million people received combination the same cohort of children when they were grade 1 MDA that year.19 Some of the early countries to adopt students, before the first round of MDA (7·8% vs 18·3%, the programme, including Egypt, have already com- pϽ0·0001). This result suggests that decreases in antibody pleted five rounds of MDA. Thus, issues such as MDA rates in children after MDA indicate both reduced exposure efficacy, monitoring strategies, and endpoints are now to filariasis and clearance of antibodies in some of the very high priorities for GPELF and for national PELF children who were antibody-positive before MDA. Mosquito infection rates in Giza and Qalubyia were Several publications have described effects of repeated similar at baseline, before MDA (table 3, figure 2). This MDA rounds in community-based studies with single- finding was unexpected, because pre-MDA micro- dose diethylcarbamazine (alone or in combination with filaraemia prevalence was much higher in Giza than in albendazole or ivermectin) on lymphatic filariasis Qalubyia. The mosquito infection rate in the Giza study endemicity.20–22 Reports from India and Vanuatu have area decreased significantly by 43% after the first MDA shown effects of two rounds of diethylcarbamazine with round and by 94% after five rounds of MDA. The albendazole on prevalence rates of circulating filarial mosquito infection rate in Qalubyia fell more sharply than antigenaemia.23,24 Here, we report the effects of repeated that recorded in Giza, with a 94% reduction after MDA rounds of a GPELF-recommended MDA regimen in the round 1 and a 100% reduction after MDA rounds 3 and 5 context of a national PELF. Our study also uses compre- (table 3). Similar to antigenaemia rates, mosquito infec- hensive monitoring (ie, use of several complementary tion rates fell more rapidly in Qalubyia (where baseline diagnostic methods to assess the endemicity and human infection rates were lower) than those in Giza transmission of lymphatic filariasis) to investigate the www.thelancet.com Vol 367 March 25, 2006
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The first objective of our study was to test the after five rounds of MDA. However, our 5-year results in hypothesis that bancroftian filariasis can be eliminated the Giza study area (microfilaraemia at about 1%, from communities by yearly cycles of MDA with antigenaemia at about 5%) suggest that five MDA diethylcarbamazine and albendazole. The Giza villages rounds with good coverage might not be sufficient to had unusually high baseline levels of filariasis eliminate filariasis in areas with high baseline infection endemicity for Egypt, whereas the Qalubyia villages had rates. Systematic non-compliance with MDA could have low baseline rates that were more typical of filariasis- contributed to this unsatisfactory result (unpublished endemic villages in Egypt before the PELF. Our data data). The Egyptian Ministry of Health and Population strongly suggest that five rounds of MDA eliminated will conduct a sixth round of MDA in selected localities, filariasis in the Qalubyia study area. This assertion is including the Giza study villages, early in 2006. based on the absence of microfilaraemia carriers Filarial antigen prevalence rates fell more slowly than (indicated by the stringent method of membrane microfilariae rates after MDA. This result is consistent filtration), the absence of antifilarial antibodies in grade with clinical trials that have shown diethylcarbamazine 1 schoolchildren, and the absence of infected mosqui- and albendazole to be more effective against micro- toes by PCR. Continuing studies will assess the filariae than against adult W bancrofti.6,27 However, importance of persistently low prevalence rates of prevalence rates of circulating filarial antigenaemia fell circulating filarial antigenaemia after suspension of to very low levels in study villages after several years of MDA. MDA also substantially reduced infection and effective MDA. If filarial antigen tests are to be used to transmission variables toward elimination targets in the monitor PELFs, baseline antigenaemia rates should be determined before the first round of MDA, and antigen Computer simulations have indicated that the number surveys should not be repeated until at least 6 months of treatment rounds needed to eliminate filariasis after the second or third round of MDA. Some depends largely on treatment coverage, drug efficacy, authorities are not content to rely exclusively on and baseline endemicity.25,26 Excellent MDA coverage, antigenaemia prevalence as an endpoint for PELFs; they the effective drug regimen, and generally low baseline require microfilaraemia prevalence data also. Our infection rates are all favourable factors for the Egyptian results support the strategy of using antigenaemia tests PELF. Results from the Giza and Qalubyia study areas to screen for potential microfilaraemia carriers after suggest that residual infection and transmission rates in MDA. All our study participants who had micro- the 181 localities in the Egyptian PELF were probably filaraemia by thick smear after MDA had positive reduced to very low levels after five rounds of MDA.
Filariasis was probably eliminated in most of these Our study has added new information on the ratio of localities, although this hypothesis needs to be tested. microfilaraemia to antigenaemia prevalence, mentioned The second major objective of our study was to test by Faris and colleagues,31 who reported ratios of 0·5 and and validate different methods for assessing the 0·64 in an untreated population when microfilaraemia progress of filariasis elimination in communities. We was detected by thick smear or by membrane filtration, followed two measures of endemicity: microfilaraemia respectively. We recorded a similar ratio before MDA (the parasite’s transmission stage from human beings to round 1 in the previously untreated Giza study area, with mosquitoes and the primary target of MDA) and filarial ratios decreasing after MDA. Current GPELF protocols antigenaemia (a marker for viable adult filarial worms).7 recommend surveys using blood taken at night to As expected, microfilaraemia prevalence rates fell monitor the effect of MDA on microfilaraemia and sharply in response to MDA. However, one problem antigen testing to guide decisions about when to stop with the following of such rates is that falls in rates can MDA.19 Although additional data are needed from other be transient, but this issue seems to be less of a problem endemic areas to confirm our findings, results from with diethylcarbamazine and albendazole treatment Egypt suggest that an antigenaemia prevalence rate of less than 2% (after a vigorous MDA programme) corresponds to a microfilaraemia prevalence rate of less microfilaraemia load, which indicates changes in both than 0·5% by filter (with lower rates probably detected by thick blood smear). We are not aware of any evidence The minimum prevalence of microfilaraemia needed showing that Culex or Anopheles mosquitoes can sustain for sustainable transmission of bancroftian filariasis by filariasis transmission with this range of micro- Culex mosquitoes is not firmly established.28 Reports from China29 suggest that residual filarial infections We investigated the effect of MDA on two variables disappeared without further intervention after preva- related to filariasis transmission, namely mosquito lence rates fell to less than 1% (indicated by thick infection rates and antifilarial antibody rates in school- smear). Other findings have suggested that PELFs children. Our xenomonitoring approach focused on should aim for prevalence rates no higher than 0·5%.30 indoor-resting mosquitoes (that had recently fed on Most endemic areas in Egypt probably achieved this goal human blood) as published elsewhere.14,32 PCR is much www.thelancet.com Vol 367 March 25, 2006
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more sensitive than dissection with microscopy for Anonymous. The global elimination of lymphatic filariasis: the detecting filarial parasites in mosquitoes.13 This added story of Egypt. Geneva: World Health Organization, 2003.
sensitivity is especially important when infection rates El Setouhy M, Ramzy R, Ahmed E, et al. A randomized clinical trialcomparing single- and multi-dose combination therapy with fall to low levels after MDA. Additional studies are diethylcarbamazine and albendazole for treatment of bancroftian needed to define mosquito infection rates that can be filariasis. Am J Trop Med Hyg 2004; 70: 191–96.
Weil GJ, Lammie PJ, Weiss N. The ICT filariasis test: a rapid-format antigen test for diagnosis of bancroftian filariasis. The present study has also shown the value of Parasitol Today 1997; 13: 401–04.
following antibody rates in young children to assess Ramzy RM, Helmy H, el-Lethy AS, et al. Field evaluation of a rapid- changes in lymphatic filariasis transmission after MDA.
format kit for the diagnosis of bancroftian filariasis in Egypt. East
Mediterr Health J 1999; 5: 880–87.
As with antigen testing, antibody rates can take several Remme J, Ba O, Dadzie K, Karam M. A force-of-infection model for years to fall to low levels, but our study has shown that onchocerciasis and its applications in the epidemiological rates can fall and approach zero after several years of evaluation of the Onchocerciasis Control Programme in the Volta
River basin area. Bull World Health Organ 1986; 64: 667–81.
effective MDA. Positive antibody tests in young children Ramzy RM, Helmy H, Faris R, Gad AM, Chandrashekar R, indicate recent exposure or transmission of the parasite.
Weil GJ. Evaluation of a recombinant antigen-based antibody assay Conversely, very low antibody rates show that filariasis for diagnosis of bancroftian filariasis in Egypt. transmission has been largely interrupted. We believe Ann Trop Med Parasitol 1995; 89: 443–46.
11 Chandrashekar R, Curtis KC, Ramzy RM, Liftis F, Li B-W, Weil GJ.
that antibody testing can complement molecular Molecular cloning of Brugia malayi antigens for diagnosis of xenomonitoring to monitor changes in filariasis lymphatic filariasis. Mol Biochem Parasitol 1994; 64: 261–74.
12 Lammie P, Weil G, Rahmah N, et al. Recombinant antigen based assays for the diagnosis and surveillance of lymphatic filariasis—a Contributors
multicenter trial. Filaria J 2004; 3: 9.
R M R Ramzy was the coprincipal investigator for the project. He 13 Ramzy R, Farid H, Kamal H, et al. A polymerase chain reaction- planned the project, participated in data analysis, and co-wrote the based assay for detection of Wuchereria bancrofti in human blood paper. M El Setouhy undertook the epidemiology analysis, served and Culex pipiens. Trans R Soc Trop Med Hyg 1997; 91: 156–60.
as the data manager, and did data analysis. H Helmy directed the 14 Helmy H, Fischer P, Farid H, Bradley M, Ramzy R. Test strip serological testing, cosupervised PCR studies, and did data analysis.
detection of Wuchereria bancrofti amplified DNA in wild-caught H A Farid supervised the entomology and diagnostic parasitology Culex pipiens and estimation of infection rate by a PoolScreen work, cosupervised PCR studies, and participated in data analysis. algorithm. Trop Med Int Health 2004; 9: 158–63.
E S Ahmed and K M Abd Elaziz did the village and school studies 15 Dean AG, Dean JA, Coulombier D, et al. Epi Info, version 6: a word and participated in data analysis. W D Shannon was the project processing, database, and statistics program for epidemiology onmicrocomputers. Atlanta, GA: Centers for Disease Control and statistician; he participated in planning the study and in data analysis.
G J Weil was the principal investigator for the project. He planned 16 Ramzy RM, el-Setouhy M, Helmy H, et al. The impact of the project, participated in data analysis, and co-wrote the paper. single-dose diethylcarbamazine treatment of bancroftian filariasis Conflict of interest statement
in a low-endemicity setting in Egypt. Am J Trop Med Hyg 2002; We declare that we have no conflict of interest. The filariasis antigen 67: 196–200.
card tests in this study use reagents licensed from Barnes-Jewish 17 Molyneux D, Neira M, Liese B, Heymann D. Elimination of Hospital, an affiliation of G J Weil. All royalties from sales of this test lymphatic filariasis as a public health problem: setting the scene for are donated to the Barnes-Jewish Hospital Foundation, a registered elimination. Trans R Soc Trop Med Hyg 2001; 94: 589–91.
18 WHO. Monitoring and epidemiological assessment of the programme to eliminate lymphatic filariasis at implementation unit Acknowledgments
level. Report no WHO/CDS/CPE/CEE/2005.50. Geneva: World We thank the field research teams and laboratory staff at the Research and Training Center for Vectors of Diseases at Ain Shams University for 19 World Health Organization. Global programme to eliminate their technical assistance; Elizabeth S Higgs at the US National Institute lymphatic filariasis. Wkly Epidemiol Rec 2005; 80: 202–12.
of Health for providing valuable advice and encouragement; and the late 20 Bockarie MJ, Tisch DJ, Kastens W, et al. Mass treatment to Prof Rifky Faris, who helped to plan this study. This work was supported eliminate filariasis in Papua New Guinea. N Engl J Med 2002; by a grant from the National Institutes of Health, AI-35855. IRBs at the 347: 1841–48.
Washington University School of Medicine and at Ain Shams University 21 de Rochars MB, Kanjilal S, Direny AN, et al. The Leogane, Haiti reviewed and approved this project including consent procedures demonstration project: decreased microfilaremia and program costs according to NIH requirements and US federal guidelines (Department after three years of mass drug administration. Am J Trop Med Hyg of Health and Human Services, Office of Protection from Research Risks 2005; 73: 888–94.
OPRR, later renamed Office for Human Research Protections, OHRP).
22 Simonsen PE, Meyrowitsch DW, Mukoko DA, et al. The effect of The regulations provide for waiver of written informed consent under repeated half-yearly diethylcarbamazine mass treatment on certain conditions (http://ohsr.od.nih.gov/guidelines/45cfr46.html; Wuchereria bancrofti infection and transmission in two East African communities with different levels of endemicity. paragraphs 46.116.c, 46.116.d, and 46.117.c2). Am J Trop Med Hyg 2004; 70: 63–71.
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