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 WeilLancet 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% firstname.lastname@example.org (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
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
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 Articles 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 Articles
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 Articles
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
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
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
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
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. References
23 Fraser M, Taleo G, Taleo F, et al. Evaluation of the program to
Michael E, Bundy DA, Grenfell BT. Reassessing the global
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24 Rajendran R, Sunish IP, Mani TR, et al. Impact of two annual
tools for the control/elimination of lymphatic ﬁlariasis.
single-dose mass drug administrations with diethylcarbamazine
Bull World Health Organ 1997; 75: 491–503.
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26 Stolk WA, Subramanian S, Oortmarssen GJ, Das PK, Habbema JD.
29 Xu B, Cui X, Zhang Y, et al. Studies on the tranmission potential
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treatment in Pondicherry, India: a simulation study. J Infect Dis
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Michael E, Malecela-Lazaro MN, Kabali C, Snow LC, Kazura JW.
27 Ismail MM, Jayakody RL, Weil GJ, et al. Long-term efﬁcacy of
Mathematical models and lymphatic ﬁlariasis control: endpoints
single-dose combinations of albendazole, ivermectin and
and optimal interventions. Trends Parasitol (in press).
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www.thelancet.com Vol 367 March 25, 2006
LANCASHIRE TEACHING HOSPITALS NHS FOUNDATION TRUST Compliance in prescribing for the initiation of new oral Proton Pump Inhibitors against local and trust guidelines for inpatients. By Sameer Patel Project Supervisor: Jean Holmes (Senior Pharmacist) Background Information Proton pump inhibitors ( PPI’s) act on inhibiting gastric secretions in parietal cells of the stomach. There
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