Effectiveness of four years mass drug administration in elimination of lymphatic filariasis in an Egyptian Village

The effectiveness of the Four Years MassThe effectiveness of the Four Years Mass
Drug Administration ofDrug Administration of
Diethylcarbamazine and Albendazole inDiethylcarbamazine and Albendazole in
Elimination of Lymphatic Filariasis in anElimination of Lymphatic Filariasis in an
Egyptian VillageEgyptian Village

INTRODUCTIONINTRODUCTION
--Lymphatic filariaisis is a major health problem inLymphatic filariaisis is a major health problem in
tropical and subtropical regions with at least 120tropical and subtropical regions with at least 120
million people are infected with the parasite inmillion people are infected with the parasite in
73 countries and over 40 million people have73 countries and over 40 million people have
overt clinical diseaseovert clinical disease
-LF remains today the second leading cause of a-LF remains today the second leading cause of a
permanent and long term disabilitypermanent and long term disability

Situation in EgyptSituation in Egypt
 Bancroftian filariasis has been endemic in EgyptBancroftian filariasis has been endemic in Egypt
for centuries with all the clinical manifestations.for centuries with all the clinical manifestations.
 The statue of a Pharaoh, created 4000 years ago,The statue of a Pharaoh, created 4000 years ago,
shows clear visible signs of the disease. Theshows clear visible signs of the disease. The
mummified body of Natsef-Amun, a priest atmummified body of Natsef-Amun, a priest at
Karnak in the times of Ramses XI proven afterKarnak in the times of Ramses XI proven after
3000 years by autopsy to have LF worms in the3000 years by autopsy to have LF worms in the
groin.groin.
 An estimated 250.000 people infected and 3.5An estimated 250.000 people infected and 3.5
million people at risk in 9 governorates in themillion people at risk in 9 governorates in the
Delta region.Delta region.

 Situation in EgyptSituation in Egypt
 Between 1950 and 1965 a large scale filariasisBetween 1950 and 1965 a large scale filariasis
control program was carried out in endemiccontrol program was carried out in endemic
areas. Although the decrease in the prevalenceareas. Although the decrease in the prevalence
was impressive, yet it was never reduced to Zerowas impressive, yet it was never reduced to Zero
in many of the endemic foci in Nile delta.in many of the endemic foci in Nile delta.
 Between 1985 and 1991 a study of sixBetween 1985 and 1991 a study of six
governorates of the Nile delta was carried outgovernorates of the Nile delta was carried out
and it revealed that the prevalence of lymphaticand it revealed that the prevalence of lymphatic
filariasis increases from less than 1% in 1965 tofilariasis increases from less than 1% in 1965 to
more than 20% in 1991more than 20% in 1991

Situation in EgyptSituation in Egypt
 The distribution of filariasis isThe distribution of filariasis is
predominantly focal; clusters of villagespredominantly focal; clusters of villages
with high prevalence are surrounded bywith high prevalence are surrounded by
others in which the disease is absent.others in which the disease is absent.
Theses villages are apparently similar andTheses villages are apparently similar and
only a few miles apart. Familialonly a few miles apart. Familial
aggregation of filariasis cases also haveaggregation of filariasis cases also have
been observed within individualbeen observed within individual
communitiescommunities

 The first announcement for the worldThe first announcement for the world
health assembly to encourage the idea ofhealth assembly to encourage the idea of
elimination of lymphatic filariasis waselimination of lymphatic filariasis was
issued in May 1997issued in May 1997
 This resolution has identified filariasis asThis resolution has identified filariasis as
one of only six “potentially eradicable”one of only six “potentially eradicable”
infectious diseases.infectious diseases.
 The epidemiological criteria to defineThe epidemiological criteria to define
achievement of the goal of elimination ofachievement of the goal of elimination of
the disease in certain area are often notthe disease in certain area are often not
specified in the WHA resolution 50.29 forspecified in the WHA resolution 50.29 for
the elimination of Lymphatic filariasis.the elimination of Lymphatic filariasis.

 The strategy of the Global ProgrammeThe strategy of the Global Programme
to Eliminate Lymphatic Filariasis hasto Eliminate Lymphatic Filariasis has
two components:two components:
 1- to stop the spread of infection (i.e.1- to stop the spread of infection (i.e.
interrupt transmission),interrupt transmission),
 2-and secondly, to alleviate the2-and secondly, to alleviate the
suffering of affected individuals (i.e.suffering of affected individuals (i.e.
morbidity control).morbidity control).

 To interrupt transmission, districts in whichTo interrupt transmission, districts in which
lymphatic filariasis is endemic must belymphatic filariasis is endemic must be
identified, and then community-wide massidentified, and then community-wide mass
treatment programmes implemented to treattreatment programmes implemented to treat
the entire at-risk population.the entire at-risk population.
 The elimination programme is based on once-The elimination programme is based on once-
yearly administration of single doses of twoyearly administration of single doses of two
drugs given together: albendazole plus eitherdrugs given together: albendazole plus either
diethylcarbamazine (DEC) or ivermectin,diethylcarbamazine (DEC) or ivermectin,
single-dose treatment must be carried out for 4-single-dose treatment must be carried out for 4-
6 years.6 years.

 Mass Drug Administration MDAMass Drug Administration MDA
The national program calls for repeatedThe national program calls for repeated
annual cycles of mass treatment withannual cycles of mass treatment with
single dose of Albendazole (400 mg)single dose of Albendazole (400 mg)
and DEC (6mg/kg) tablets. Childrenand DEC (6mg/kg) tablets. Children
under 2 years, pregnant women andunder 2 years, pregnant women and
people with severe underlying illnesspeople with severe underlying illness
are excluded.are excluded.

 Factors favouring the success of efforts toFactors favouring the success of efforts to
eliminate lymphatic Filariasiseliminate lymphatic Filariasis
Biological FactorsBiological Factors
 Humans are essential for the organism’s ‘life-cycle’; i.e.,Humans are essential for the organism’s ‘life-cycle’; i.e.,
the organism does not multiply freely in the environmentthe organism does not multiply freely in the environment
and has no significant non-human vertebrate host thatand has no significant non-human vertebrate host that
could serve as a reservoir for infection of humans.could serve as a reservoir for infection of humans.
 Different from many other vector-borne diseasesDifferent from many other vector-borne diseases
(e.g.,malaria, schistosomiasis, leishmaniasis), there is no(e.g.,malaria, schistosomiasis, leishmaniasis), there is no
amplification of the infection within the vector.amplification of the infection within the vector.
 Very important biological consideration for lymphaticVery important biological consideration for lymphatic
filariasis that favours its prospects for elimination is thatfilariasis that favours its prospects for elimination is that
prolonged exposure to the parasite (generally 3–6 months)prolonged exposure to the parasite (generally 3–6 months)
is required before infection is establishedis required before infection is established

 Technical factorsTechnical factors
 I-Available intervention (treatment) toolsI-Available intervention (treatment) tools
 To interrupt transmission of lymphatic filariasis it isTo interrupt transmission of lymphatic filariasis it is
necessary either to eliminate (or reduce to verynecessary either to eliminate (or reduce to very
low levels) the microfilaraemia in humans or tolow levels) the microfilaraemia in humans or to
control the mosquito vector effectively, the focus ofcontrol the mosquito vector effectively, the focus of
efforts to interrupt transmission has now shifted toefforts to interrupt transmission has now shifted to
treating infections in humanstreating infections in humans
 single-dose; once-yearly, treatment is extremelysingle-dose; once-yearly, treatment is extremely
effective in decreasing microfilaraemia.effective in decreasing microfilaraemia.

 Technical factorsTechnical factors
II-Available monitoring (diagnostic) tools:II-Available monitoring (diagnostic) tools:
 The development of assays to detect circulating antigenThe development of assays to detect circulating antigen
released by living adult parasites and remaining at stablereleased by living adult parasites and remaining at stable
levels in the circulation both day and night has opened uplevels in the circulation both day and night has opened up
many avenues related to surveillance and monitoring thatmany avenues related to surveillance and monitoring that
were almost completely closed before.were almost completely closed before.
 There are two monoclonal antibody-based assays forThere are two monoclonal antibody-based assays for
detecting circulating filarial antigen (CFA) now available,detecting circulating filarial antigen (CFA) now available,
one in an ELISA format (especially suitable for laboratoryone in an ELISA format (especially suitable for laboratory
analysis of samples collected in the field and the other in aanalysis of samples collected in the field and the other in a
card-test format (ICT) (suitable for evaluation either in thecard-test format (ICT) (suitable for evaluation either in the
laboratory or in the field.laboratory or in the field.
 Costs of control/elimination programmes ‘inexpensive’Costs of control/elimination programmes ‘inexpensive’
and easily ‘packaged’and easily ‘packaged’

 Examples of successful elimination already existExamples of successful elimination already exist
 None of the programmes using the newly available, optimalNone of the programmes using the newly available, optimal
tools for lymphatic filariasis elimination has yet been intools for lymphatic filariasis elimination has yet been in
existence long enough to record complete success,existence long enough to record complete success,
(anticipated to be 4–5 years for most endemic areas).(anticipated to be 4–5 years for most endemic areas).
 Active programmes based on DEC administration or vectorActive programmes based on DEC administration or vector
control eliminated bancroftian filariasis in Japan in recentcontrol eliminated bancroftian filariasis in Japan in recent
years and similar active programmes have also resulted inyears and similar active programmes have also resulted in
elimination of the infection from large parts of China,elimination of the infection from large parts of China,
Malaysia, Korea and certain islands of the Pacific.Malaysia, Korea and certain islands of the Pacific.

Aim of the workAim of the work
 To test the hypothesis that BancroftianTo test the hypothesis that Bancroftian
filariasis can be eliminated from anfilariasis can be eliminated from an
Egyptian village (Azizia village) byEgyptian village (Azizia village) by
four annual cycles of mass drugfour annual cycles of mass drug
administration with Albendazole andadministration with Albendazole and
DEC.DEC.

Subjects and MethodsSubjects and Methods
Type of studyType of study
AA Repeated SurveyRepeated Survey which consisted ofwhich consisted of 22
cross sectional studies after the third andcross sectional studies after the third and
fourth dose mass drug administration (yearfourth dose mass drug administration (year
2003-04). The pretreatment data was2003-04). The pretreatment data was
collected in the same manner before thecollected in the same manner before the
start of Mass Drug Administration MDA(yearstart of Mass Drug Administration MDA(year
2000) (3 cross sectional studies)2000) (3 cross sectional studies)

Site of studySite of study
Azizia village 50KMAzizia village 50KM
southeast ofsoutheast of
CairoCairo
Two sectorsTwo sectors
Kafr BahariKafr Bahari
Kafr KebliKafr Kebli
ReasonsReasons
Highly endemicHighly endemic
Pre treatment dataPre treatment data
Under MDAUnder MDA
Reached by day tripsReached by day trips

Village inhabitantsVillage inhabitants
 Ten percent of the households (500 individual from eachTen percent of the households (500 individual from each
sector (Kafr Kebli) and (Kafr Bahari) which would lead tosector (Kafr Kebli) and (Kafr Bahari) which would lead to
1000 inhabitant were checked two years successively1000 inhabitant were checked two years successively
2003-2004. The subjects were randomly selected each2003-2004. The subjects were randomly selected each
year, the houses were the sampling units (This study is notyear, the houses were the sampling units (This study is not
a follow up study or a cohort study). The collection of thea follow up study or a cohort study). The collection of the
sample occurred after the MDA by at least 6 months. MDAsample occurred after the MDA by at least 6 months. MDA
is distributed in September each year since 2000 and theis distributed in September each year since 2000 and the
collection of the sample for this study was accomplished incollection of the sample for this study was accomplished in
June to August each year.June to August each year.
-Each subject above 5 years in the household selected in the-Each subject above 5 years in the household selected in the
random sample undergone a Filariasisrandom sample undergone a Filariasis ICT card testICT card test
(Antigen detection) (CFA)(Antigen detection) (CFA)
-Collection of a venous sample in case the subject showed a-Collection of a venous sample in case the subject showed a
positive card test for evaluation ofpositive card test for evaluation of MFMF count.count.

School SurveySchool Survey
 Collection of a blood sample 0.5 ml of blood from aCollection of a blood sample 0.5 ml of blood from a
finger prick from all students of the first grade,finger prick from all students of the first grade,
second and fifth grade of the three schools thatsecond and fifth grade of the three schools that
are present in Azizia village Namely (Mohamedare present in Azizia village Namely (Mohamed
Farid , Moahmed Abdu, Azizia Primary school).Farid , Moahmed Abdu, Azizia Primary school).
The sample of blood taken from each student hadThe sample of blood taken from each student had
two tests applied first the BmM14 antibody testtwo tests applied first the BmM14 antibody test
and estimation of the hemoglobin percentage inand estimation of the hemoglobin percentage in
blood and first grade students samples hadblood and first grade students samples had
undergone an ICT card testing for detection ofundergone an ICT card testing for detection of
CFA.CFA.

KAP studyKAP study
 To assess the drug coverage ofTo assess the drug coverage of
MDAMDA
 Population response to MDAPopulation response to MDA
 Occurrence of Adverse eventsOccurrence of Adverse events
 Causes of not taking drugsCauses of not taking drugs

Fig.(1)Prevalence of Microfilaraemia andFig.(1)Prevalence of Microfilaraemia and
Antigenaemia Pre treatment (MDA) in the twoAntigenaemia Pre treatment (MDA) in the two
studied sectorsstudied sectors
11.7
19.2
10.4
15.3
13.1
23.4
0
5
10
15
20
25
30
%
Whole village KB KK
MF
AG

Fig.(2)Comparison between the different ageFig.(2)Comparison between the different age
categories as regards positivity of MF among thecategories as regards positivity of MF among the
whole population of Azizia village pre treatmentwhole population of Azizia village pre treatment
1.8
9.9
18.6
14.3
9.9 10.4
14.9
0
2
4
6
8
10
12
14
16
18
20
<10 11- 21- 31- 41- 51- 61>

Fig.(3)Comparison between the different ageFig.(3)Comparison between the different age
categories as regards positivity of Antigenaemiacategories as regards positivity of Antigenaemia
among the whole population of Azizia village preamong the whole population of Azizia village pre
treatmenttreatment
8.8
18.3
26
21.1 20.9
15.6 14.9
0
5
10
15
20
25
30
<10 11- 21- 31- 41- 51- 61>

Fig.(4)Comparison between the level ofFig.(4)Comparison between the level of
Antigenaemia along the course of MDA in AziziaAntigenaemia along the course of MDA in Azizia
village with its two sectorsvillage with its two sectors
19.2
5.9
2.4
15.3
5.1
1.3
23.4
6.6
3.7
0
5
10
15
20
25
Whole village KB KK
Pre
3rd year
4th year
*
* = P<0.01 Highly significant

Fig.(5)Comparison between the level of MicrofilaraemiaFig.(5)Comparison between the level of Microfilaraemia
along the course of MDA in Azizia village with its twoalong the course of MDA in Azizia village with its two
sectorssectors
11.7
1.6
0.3
10.4
1.4
0
13.1
1.8
0.6
0
2
4
6
8
10
12
14
Whole village KB KK
Pre
3rd year
4th year
*
* = P =0.05

Fig.( )MF and Antigen clearance after the thirdFig.( )MF and Antigen clearance after the third
dose of MDA in Azizia village and its two sectorsdose of MDA in Azizia village and its two sectors
86.3
69.2
86.5
66.7
86.2
71.8
0
10
20
30
40
50
60
70
80
90
100
%
Whole village KB KK
MF
AG

Fig.( )MF and Antigen clearance after the FourthFig.( )MF and Antigen clearance after the Fourth
dose of MDA in Azizia village and its two sectorsdose of MDA in Azizia village and its two sectors
97.4
87.5
100
91.5
95.4
84.2
75
80
85
90
95
100
%
Whole village KB KK
MF
AG

Fig.(6) Community Microfilarial load from preFig.(6) Community Microfilarial load from pre
mass drug administration to the 4mass drug administration to the 4thth
year afteryear after
MDAMDA
20.6
0.731
13.1
0
28.48
0.040.020
5
10
15
20
25
30
Pre MDA 3rd dose 4th dose
Whole village KB KK

Fig.(7) School survey antibodies BmM14Fig.(7) School survey antibodies BmM14
testing and Antigenaemia pre treatmenttesting and Antigenaemia pre treatment
18.4
10
0
2
4
6
8
10
12
14
16
18
20
%
Antibodies Antigenaemia

Fig. (8) Comparison between junior andFig. (8) Comparison between junior and
senior students as regards BmM14 antibodiessenior students as regards BmM14 antibodies
after the third year MDA 2003after the third year MDA 2003
Higher Percentage of positive antibodies among senior students (higher exposure
to L3
Grade Negative
No. %
Positive
No. %
First year 461 97.9 10 2.1
Second year 449 97.8 10 2.2
Fifth grade G5 394 93.4 28 6.6
X2
=17.1 P<0.01 Highly significant

Fig (9) Comparison between place of livingFig (9) Comparison between place of living
and antibodies positivity after the third yearand antibodies positivity after the third year
MDA 2003MDA 2003
Antibodies
Place of living
Negative
No. %
Positive
No. %
KB 165 99.4 1 0.6
KK 541 97.4 16 2.9
Other areas 204 98.6 3 1.4
X2
=3.7 P>0.05 not significant
Higher positivity among students living in KK compared to
other groups but this difference is not significant statistically
No significant difference between males and females

Fig (10) Comparison between junior andFig (10) Comparison between junior and
senior students as regards BmM14 antibodiessenior students as regards BmM14 antibodies
after the FOURTH year MDA 2004after the FOURTH year MDA 2004
Higher Percentage of positive antibodies among senior students (higher
exposure to L3
Grade Negative
No. %
Positive
No. %
First year G1 468 89.9 5 1.1
Second year G2 469 98.1 9 1.9
Fifth grade G5 365 92.2 31 7.8

Fig. (11) Comparison between place of livingFig. (11) Comparison between place of living
and antibodies positivity after the Foruth yearand antibodies positivity after the Foruth year
MDA 2004MDA 2004
Higher positivity among students living in KK compared to
other groups but this difference is not significant statistically
(higher transmission)
No significant difference between males and females
Antibodies
Place of living
Negative
No. %
Positive
No. %
KB 160 100 0 00 0
KK 542 98.0 11 2.0
Other areas 235 98.7 3 1.3
P>0.05 not significant

Fig.(12) Comparison between antigenaemia levelFig.(12) Comparison between antigenaemia level
pre treatment and after the fourth year ofpre treatment and after the fourth year of
treatmenttreatment
10
0.4
0
1
2
3
4
5
6
7
8
9
10
11
%
Pre treatment After 4th year
Decline in Antigenaemia level in first grade students is 96%

Fig.(13) MDA coverage after the third dose inFig.(13) MDA coverage after the third dose in
Azizia village (two sectors collectively) KAP studyAzizia village (two sectors collectively) KAP study
13%
87%
YES

Fig.(14)Comparison between the two sectors asFig.(14)Comparison between the two sectors as
regards taking of the drugs after the third doseregards taking of the drugs after the third dose
87.6
12.4
86.4
13.7
0
10
20
30
40
50
60
70
80
90
100
%
KB KK
Yes
No

Fig (15) Causes of not taking MDA in AziziaFig (15) Causes of not taking MDA in Azizia
VillageVillage
Cause of not taking the drug
No. %
Pregnancy 24 18.5
Breast feeding 10 7.7
Hate tablets 14 10.8
Fear of complications 19 14.6
Person is abroad or not at house 27 20.8
Distributing team didn’t deliver
the drug
14 10.8
Liver or chronic disease 1 0.76
Refusal (total rejection of the drug for
no reason)
21 16.2

Fig.(16)Adverse events among those who took theFig.(16)Adverse events among those who took the
drug (third dose)drug (third dose)
69.2
20.4
3.1 4.2 3.1
0
10
20
30
40
50
60
70
Dizziness Fatigue Fever Headache Nausea

Fig (16) Summary of the criteria forFig (16) Summary of the criteria for
elimination in the two sectors KB and KK ofelimination in the two sectors KB and KK of
Aziziza:Aziziza:
Criterion Kafr Bahari Kafr Kebli
1- MF <0.1% +ve -ve
2-AB in first grade
students <1%
+ve -ve
3- Mosquito pools < 1% -ve
11.8%
-ve
7.4%
Pre set criterion 0.1% MF
After the fourth dose MDA 0.3%

 It is concluded from this study that the AziziaIt is concluded from this study that the Azizia
village with its two sectors nearly reachedvillage with its two sectors nearly reached
elimination of Fialariasis.elimination of Fialariasis.
 KB has better results than KK which still needKB has better results than KK which still need
more efforts to reach elimination of Filariasismore efforts to reach elimination of Filariasis
hopefully after the fifth round of MDA.hopefully after the fifth round of MDA.
 Both sectors has reached a marked declineBoth sectors has reached a marked decline
compared to Pre Mass Drug Administrationcompared to Pre Mass Drug Administration
levels whichlevels which proves the successproves the success of theof the
Elimination programmeElimination programme in controllingin controlling
Lymphatic filariasis in one of the heavilyLymphatic filariasis in one of the heavily
infested villages all around the country.infested villages all around the country.

 One might also conclude that since the MassOne might also conclude that since the Mass
Drug Administration has brought about greatDrug Administration has brought about great
success in one of the heavily endemic village insuccess in one of the heavily endemic village in
Egypt (pretreatment level) that the other 179Egypt (pretreatment level) that the other 179
villages (Implementation units) with lowervillages (Implementation units) with lower
levels of infection could have reached betterlevels of infection could have reached better
results and reached the zero level of eliminationresults and reached the zero level of elimination
after the four years of MDA.after the four years of MDA.
 It is implied from this study that still theIt is implied from this study that still the
infection rate in mosquitoes is relatively highinfection rate in mosquitoes is relatively high
and more attention by the authorities for theand more attention by the authorities for the
vector control in both sectors in order to avoidvector control in both sectors in order to avoid
the resurgence of filariasis after the stopping ofthe resurgence of filariasis after the stopping of
the MDA rounds in Azizia village and otherthe MDA rounds in Azizia village and other
villages that could have high level of vectorvillages that could have high level of vector
transmission.transmission.

RecommendationsRecommendations
 Further study of both villages (sectors)Further study of both villages (sectors)
of Azizia in Giza governorate shouldof Azizia in Giza governorate should
be made after the fifth round of MDAbe made after the fifth round of MDA
which was given in September 2004 towhich was given in September 2004 to
compare the levels of infection withcompare the levels of infection with
the results after the fourth round ofthe results after the fourth round of
MDA and to confirm the completeMDA and to confirm the complete
elimination of Lymphatic Fialriasis inelimination of Lymphatic Fialriasis in
both sectors.both sectors.

 Active surveillance of Lymphatic FilariasisActive surveillance of Lymphatic Filariasis
should be implemented in Azizia villageshould be implemented in Azizia village
and other selected implementation units orand other selected implementation units or
sentinel sites for at least three years aftersentinel sites for at least three years after
the stoppage of MDA.the stoppage of MDA.
 Surveillance should be done in selectedSurveillance should be done in selected
villages (IUs) that had a high level ofvillages (IUs) that had a high level of
microfilaraemia as Azizia village or had amicrofilaraemia as Azizia village or had a
low coverage of MDA.low coverage of MDA.

 It is recommended also that more emphasis and studiesIt is recommended also that more emphasis and studies
should be done on the vector and vector control inshould be done on the vector and vector control in
Azizia village and other areas endemic for lymphaticAzizia village and other areas endemic for lymphatic
filariasis to document the interruption of transmissionfilariasis to document the interruption of transmission
of LF.of LF.
 The tools of this study should be implemented in theThe tools of this study should be implemented in the
detection of the level of infection and communitydetection of the level of infection and community
diagnosis in any village in Egypt.diagnosis in any village in Egypt.
 It is also recommended that the antibody testing(L3It is also recommended that the antibody testing(L3
antibodies) that was used in school to be made in theantibodies) that was used in school to be made in the
future as a rapid card test for detection of antibodyfuture as a rapid card test for detection of antibody
levels in school children which is a good indicator oflevels in school children which is a good indicator of
the level of transmission.the level of transmission.

Effectiveness of four years mass drug administration in elimination of lymphatic filariasis in an Egyptian Village

Effectiveness of four years mass drug administration in elimination of lymphatic filariasis in an Egyptian Village

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Effectiveness of four years mass drug administration in elimination of lymphatic filariasis in an Egyptian Village