The effectiveness of the Four Years Mass The effectiveness of the Four Years Mass Drug Administration of Drug Administration of

Diethylcarbamazine and Albendazole in Diethylcarbamazine and Albendazole in Elimination of Lymphatic Filariasis in an Elimination of Lymphatic Filariasis in an

Egyptian VillageEgyptian Village

INTRODUCTIONINTRODUCTION

--Lymphatic filariaisis is a major health problem Lymphatic filariaisis is a major health problem in tropical and subtropical regions with at least in tropical and subtropical regions with at least 120 million people are infected with the parasite 120 million people are infected with the parasite in 73 countries and over 40 million people have in 73 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 disability permanent and long term disability

INTRODUCTIONINTRODUCTIONSituation in EgyptSituation in Egypt Bancroftian filariasis has been endemic in Egypt for Bancroftian filariasis has been endemic in Egypt for

centuries with all the clinical manifestations.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. The shows clear visible signs of the disease. The mummified body of Natsef-Amun, a priest at Karnak mummified body of Natsef-Amun, a priest at Karnak in the times of Ramses XI proven after 3000 years by in the times of Ramses XI proven after 3000 years by autopsy to have LF worms in the groin.autopsy to have LF worms in the groin.

An estimated 250.000 people infected and 3.5 million An estimated 250.000 people infected and 3.5 million people at risk in 9 governorates in the Delta region.people at risk in 9 governorates in the Delta region.

INTRODUCTIONINTRODUCTION Situation in EgyptSituation in Egypt Between 1950 and 1965 a large scale filariasis Between 1950 and 1965 a large scale filariasis

control program was carried out in endemic areas. control program was carried out in endemic areas. Although the decrease in the prevalence was Although the decrease in the prevalence was impressive, yet it was never reduced to Zero in impressive, yet it was never reduced to Zero in many of the endemic foci in Nile delta. many of the endemic foci in Nile delta.

Between 1985 and 1991 a study of six governorates Between 1985 and 1991 a study of six governorates of the Nile delta was carried out and it revealed that of the Nile delta was carried out and it revealed that the prevalence of lymphatic filariasis increases from the prevalence of lymphatic filariasis increases from less than 1% in 1965 to more than 20% in 1991less than 1% in 1965 to more than 20% in 1991

INTRODUCTIONINTRODUCTIONSituation in EgyptSituation in Egypt The distribution of filariasis is predominantly The distribution of filariasis is predominantly

focal; clusters of villages with high prevalence focal; clusters of villages with high prevalence are surrounded by others in which the disease are surrounded by others in which the disease is absent. Theses villages are apparently is absent. Theses villages are apparently similar and only a few miles apart. Familial similar and only a few miles apart. Familial aggregation of filariasis cases also have been aggregation of filariasis cases also have been observed within individual communities observed within individual communities

INTRODUCTIONINTRODUCTION The first announcement for the world The first announcement for the world

health assembly to encourage the idea health assembly to encourage the idea of elimination of lymphatic filariasis of elimination of lymphatic filariasis was issued in May 1997was issued in May 1997

This resolution has identified filariasis This resolution has identified filariasis as one of only six “potentially as one of only six “potentially eradicable” infectious diseases.eradicable” infectious diseases.

The epidemiological criteria to define The epidemiological criteria to define achievement of the goal of elimination achievement of the goal of elimination of the disease in certain area are often of the disease in certain area are often not specified in the WHA resolution not specified in the WHA resolution 50.29 for the elimination of Lymphatic 50.29 for the elimination of Lymphatic filariasis.filariasis.

INTRODUCTIONINTRODUCTION

The strategy of the Global Programme The strategy of the Global Programme to Eliminate Lymphatic Filariasis has to 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 the 2-and secondly, to alleviate the suffering of affected individuals (i.e. suffering of affected individuals (i.e. morbidity control). morbidity control).

INTRODUCTIONINTRODUCTION To interrupt transmission, districts in which To interrupt transmission, districts in which

lymphatic filariasis is endemic must be lymphatic filariasis is endemic must be identified, and then community-wide mass identified, and then community-wide mass treatment programmes implemented to treat treatment programmes implemented to treat the entire at-risk population. the entire at-risk population.

The elimination programme is based on The elimination programme is based on once-yearly administration of single once-yearly administration of single doses of two drugs given together: doses of two drugs given together: albendazole plus either albendazole plus either diethylcarbamazine (DEC) or ivermectin, diethylcarbamazine (DEC) or ivermectin, single-dose treatment must be carried single-dose treatment must be carried out for 4-6 years. out for 4-6 years.

INTRODUCTIONINTRODUCTION

Mass Drug Administration MDAMass Drug Administration MDA

The national program calls for repeated The national program calls for repeated annual cycles of mass treatment with annual cycles of mass treatment with single dose of Albendazole (400 mg) single dose of Albendazole (400 mg) and DEC (6mg/kg) tablets. Children and DEC (6mg/kg) tablets. Children under 2 years, pregnant women and under 2 years, pregnant women and people with severe underlying illness people with severe underlying illness are excluded. are excluded.

INTRODUCTIONINTRODUCTION Factors favouring the success of efforts to Factors favouring the success of efforts to

eliminate lymphatic Filariasiseliminate lymphatic Filariasis Biological FactorsBiological Factors Humans are essential for the organism’s ‘life-Humans are essential for the organism’s ‘life-

cycle’; i.e., the organism does not multiply freely in cycle’; i.e., the organism does not multiply freely in the environment and has no significant non-human the environment and has no significant non-human vertebrate host that could serve as a reservoir for vertebrate host that could serve as a reservoir for infection of humans.infection of humans.

Different from many other vector-borne diseases Different from many other vector-borne diseases (e.g.,malaria, schistosomiasis, leishmaniasis), there (e.g.,malaria, schistosomiasis, leishmaniasis), there is no amplification of the infection within the vector.is no amplification of the infection within the vector.

Very important biological consideration for Very important biological consideration for lymphatic filariasis that favours its prospects for lymphatic filariasis that favours its prospects for elimination is that prolonged exposure to the elimination is that prolonged exposure to the parasite (generally 3–6 months) is required before parasite (generally 3–6 months) is required before infection is established infection is established

INTRODUCTIONINTRODUCTION Technical factorsTechnical factors I-Available intervention (treatment) toolsI-Available intervention (treatment) tools To interrupt transmission of lymphatic filariasis it is To interrupt transmission of lymphatic filariasis it is

necessary either to eliminate (or reduce to very necessary either to eliminate (or reduce to very low levels) the microfilaraemia in humans or to low levels) the microfilaraemia in humans or to control the mosquito vector effectively, the focus of control the mosquito vector effectively, the focus of efforts to interrupt transmission has now shifted to efforts to interrupt transmission has now shifted to treating infections in humanstreating infections in humans

single-dose; once-yearly, treatment is extremely single-dose; once-yearly, treatment is extremely effective in decreasing microfilaraemia. effective in decreasing microfilaraemia.

INTRODUCTIONINTRODUCTION Technical factorsTechnical factors II-Available monitoring (diagnostic) tools:II-Available monitoring (diagnostic) tools:

The development of assays to detect circulating antigen The development of assays to detect circulating antigen released by living adult parasites and remaining at stable released by living adult parasites and remaining at stable

levels in the circulation both day and night has opened up levels in the circulation both day and night has opened up many avenues related to surveillance and monitoring that many avenues related to surveillance and monitoring that

were almost completely closed before. were almost completely closed before. There are two monoclonal antibody-based assays for There 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 laboratory one in an ELISA format (especially suitable for laboratory analysis of samples collected in the field and the other in a analysis of samples collected in the field and the other in a card-test format (ICT) (suitable for evaluation either in the card-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’

INTRODUCTIONINTRODUCTION

Examples of successful elimination already existExamples of successful elimination already exist

None of the programmes using the newly available, optimal None of the programmes using the newly available, optimal tools for lymphatic filariasis elimination has yet been in tools 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 vector Active programmes based on DEC administration or vector control eliminated bancroftian filariasis in Japan in recent control eliminated bancroftian filariasis in Japan in recent years and similar active programmes have also resulted in years 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 Bancroftian To test the hypothesis that Bancroftian

filariasis can be eliminated from an filariasis can be eliminated from an

Egyptian village (Azizia village) by Egyptian village (Azizia village) by

four annual cycles of mass drug four annual cycles of mass drug

administration with Albendazole and administration with Albendazole and

DEC.DEC.

Subjects and MethodsSubjects and Methods

Type of studyType of study

A A Repeated SurveyRepeated Survey which consisted of which consisted of 2 2 cross sectional studies after the third and cross sectional studies after the third and fourth dose mass drug administration (year fourth dose mass drug administration (year 2003-04). The pretreatment data was 2003-04). The pretreatment data was collected in the same manner before the collected in the same manner before the start of Mass Drug Administration MDA(year start of Mass Drug Administration MDA(year 2000) (3 cross sectional studies)2000) (3 cross sectional studies)

Subjects and MethodsSubjects and Methods

Site of studySite of study

Azizia village 50KM southeast Azizia village 50KM southeast of Cairoof Cairo

Two sectorsTwo sectorsKafr BahariKafr BahariKafr KebliKafr Kebli

ReasonsReasonsHighly endemicHighly endemicPre treatment dataPre treatment dataUnder MDAUnder MDAReached by day tripsReached by day trips

Subjects and MethodsSubjects and Methods

Village inhabitantsVillage inhabitants Ten percent of the households (500 individual from each sector Ten percent of the households (500 individual from each sector

(Kafr Kebli) and (Kafr Bahari) which would lead to 1000 (Kafr Kebli) and (Kafr Bahari) which would lead to 1000 inhabitant were checked two years successively 2003-2004. inhabitant were checked two years successively 2003-2004. The subjects were randomly selected each year, the houses The subjects were randomly selected each year, the houses were the sampling units (This study is not a follow up study or a were the sampling units (This study is not a follow up study or a cohort study). The collection of the sample occurred after the cohort study). The collection of the sample occurred after the MDA by at least 6 months. MDA is distributed in September MDA by at least 6 months. MDA is distributed in September each year since 2000 and the collection of the sample for this each year since 2000 and the collection of the sample for this study was accomplished in June to August each year.study was accomplished in 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 Filariasis random sample undergone a Filariasis ICT card testICT card test (Antigen (Antigen detection) (CFA)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 of positive card test for evaluation of MFMF count. count.

Subjects and MethodsSubjects and Methods

School SurveySchool Survey Collection of a blood sample 0.5 ml of blood Collection of a blood sample 0.5 ml of blood from a finger prick from all students of the first from a finger prick from all students of the first

grade, second and fifth grade of the three grade, second and fifth grade of the three schools that are present in Azizia village Namely schools that are present in Azizia village Namely

(Mohamed Farid , Moahmed Abdu, Azizia (Mohamed Farid , Moahmed Abdu, Azizia Primary school).Primary school).

The sample of blood taken from each student had two The sample of blood taken from each student had two tests applied first the BmM14 antibody test and tests applied first the BmM14 antibody test and

estimation of the hemoglobin percentage in blood and estimation of the hemoglobin percentage in blood and first grade students samples had undergone an ICT first grade students samples had undergone an ICT

card testing for detection of CFA.card testing for detection of CFA.

Subjects and MethodsSubjects and Methods

KAP studyKAP study To assess the drug coverage of To 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

RESULTSRESULTS

Fig.(1)Prevalence of Microfilaraemia and Fig.(1)Prevalence of Microfilaraemia and Antigenaemia Pre treatment (MDA) in the two Antigenaemia Pre treatment (MDA) in the two

studied sectorsstudied sectors

11.7

19.2

10.4

15.313.1

23.4

0

5

10

15

20

25

30

%

Whole village KB KK

MFAG

Fig.(2)Comparison between the different age Fig.(2)Comparison between the different age categories as regards positivity of MF among the categories 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 age Fig.(3)Comparison between the different age categories as regards positivity of Antigenaemia categories as regards positivity of Antigenaemia among the whole population of Azizia village pre among 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 of Fig.(4)Comparison between the level of Antigenaemia along the course of MDA in Azizia Antigenaemia 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 Microfilaraemia Fig.(5)Comparison between the level of Microfilaraemia along the course of MDA in Azizia village with its two along the course of MDA in Azizia village with its two

sectorssectors

11.7

1.60.3

10.4

1.4

0

13.1

1.80.6

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 third Fig.( )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

0102030

40506070

8090

100

%

Whole village KB KK

MF

AG

Fig.( )MF and Antigen clearance after the Fourth Fig.( )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

MFAG

Fig.(6) Community Microfilarial load from pre Fig.(6) Community Microfilarial load from pre mass drug administration to the 4mass drug administration to the 4thth year after year 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 BmM14 Fig.(7) School survey antibodies BmM14 testing and Antigenaemia pre treatmenttesting and Antigenaemia pre treatment

18.4

10

0

2

46

8

1012

1416

18

20

%

Antibodies Antigenaemia

Fig. (8) Comparison between junior and Fig. (8) Comparison between junior and senior students as regards BmM14 senior students as regards BmM14 antibodies after the third year MDA antibodies after the third year MDA

20032003

Higher Percentage of positive antibodies among senior students (higher exposure to L3

Grade NegativeNo. %

PositiveNo. %

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 Fig (9) Comparison between place of living and antibodies positivity after the living and antibodies positivity after the

third year MDA 2003third year MDA 2003

AntibodiesPlace of living

NegativeNo. %

PositiveNo. %

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 and Fig (10) Comparison between junior and senior students as regards BmM14 senior students as regards BmM14

antibodies after the FOURTH year MDA antibodies after the FOURTH year MDA 20042004

Higher Percentage of positive antibodies among senior students (higher exposure to L3

Grade NegativeNo. %

PositiveNo. %

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 Fig. (11) Comparison between place of living and antibodies positivity after the living and antibodies positivity after the

Foruth year MDA 2004Foruth year MDA 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

AntibodiesPlace of living

NegativeNo. %

PositiveNo. %

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 level Fig.(12) Comparison between antigenaemia level pre treatment and after the fourth year of pre treatment and after the fourth year of

treatmenttreatment10

0.4

0123456789

1011

%

Pre treatment After 4th year

Decline in Antigenaemia level in first grade students is 96%

Fig.(13) MDA coverage after the third dose in Fig.(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 as Fig.(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

0102030405060708090

100

%

KB KK

YesNo

Fig (15) Causes of not taking MDA in Fig (15) Causes of not taking MDA in Azizia VillageAzizia Village

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 0.76Refusal (total rejection of the drug for no reason)

21 16.2

Fig.(16)Adverse events among those who took the Fig.(16)Adverse events among those who took the drug (third dose)drug (third dose)

69.2

20.4

3.1 4.2 3.10

10

20

30

40

50

60

70

Dizziness Fatigue Fever Headache Nausea

Fig (16) Summary of the criteria for Fig (16) Summary of the criteria for elimination in the two sectors KB and KK elimination in the two sectors KB and KK

of Aziziza:of 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% -ve11.8%

-ve7.4%

Pre set criterion 0.1% MF

After the fourth dose MDA 0.3%

ConclusionConclusion

It is concluded from this study that the Azizia village It is concluded from this study that the Azizia village with its two sectors nearly reached elimination of with its two sectors nearly reached elimination of Fialariasis.Fialariasis.

KB has better results than KK which still need more KB has better results than KK which still need more efforts to reach elimination of Filariasis hopefully after efforts to reach elimination of Filariasis hopefully after the fifth round of MDA.the fifth round of MDA.

Both sectors has reached a marked decline compared to Both sectors has reached a marked decline compared to Pre Mass Drug Administration levels which Pre Mass Drug Administration levels which proves the proves the successsuccess of the of the Elimination programmeElimination programme in controlling in controlling Lymphatic filariasis in one of the heavily infested Lymphatic filariasis in one of the heavily infested villages all around the country.villages all around the country.

One might also conclude that since the Mass Drug One might also conclude that since the Mass Drug Administration has brought about great success in one of Administration has brought about great success in one of the heavily endemic village in Egypt (pretreatment the heavily endemic village in Egypt (pretreatment level) that the other 179 villages (Implementation units) level) that the other 179 villages (Implementation units) with lower levels of infection could have reached better with lower levels of infection could have reached better results and reached the zero level of elimination after the results and reached the zero level of elimination after the four years of MDA.four years of MDA.

It is implied from this study that still the infection rate in It is implied from this study that still the infection rate in mosquitoes is relatively high and more attention by the mosquitoes is relatively high and more attention by the authorities for the vector control in both sectors in order authorities for the vector control in both sectors in order to avoid the resurgence of filariasis after the stopping of to avoid the resurgence of filariasis after the stopping of the MDA rounds in Azizia village and other villages that the MDA rounds in Azizia village and other villages that could have high level of vector transmission.could have high level of vector transmission.

RecommendationsRecommendations Further study of both villages (sectors) Further study of both villages (sectors)

of Azizia in Giza governorate should of Azizia in Giza governorate should be made after the fifth round of MDA be made after the fifth round of MDA which was given in September 2004 to which was given in September 2004 to compare the levels of infection with compare the levels of infection with the results after the fourth round of the results after the fourth round of MDA and to confirm the complete MDA and to confirm the complete elimination of Lymphatic Fialriasis in elimination of Lymphatic Fialriasis in both sectors.both sectors.

RecommendationsRecommendations Active surveillance of Lymphatic Filariasis Active surveillance of Lymphatic Filariasis

should be implemented in Azizia village and should be implemented in Azizia village and other selected implementation units or other selected implementation units or sentinel sites for at least three years after the sentinel sites for at least three years after the stoppage of MDA.stoppage of MDA.

Surveillance should be done in selected Surveillance should be done in selected

villages (IUs) that had a high level of villages (IUs) that had a high level of microfilaraemia as Azizia village or had a microfilaraemia as Azizia village or had a low coverage of MDA.low coverage of MDA.

RecommendationsRecommendations It is recommended also that more emphasis and studies should It is recommended also that more emphasis and studies should

be done on the vector and vector control in Azizia village and be done on the vector and vector control in Azizia village and other areas endemic for lymphatic filariasis to document the other areas endemic for lymphatic filariasis to document the interruption of transmission of LF.interruption of transmission of LF.

The tools of this study should be implemented in the detection The tools of this study should be implemented in the detection of the level of infection and community diagnosis in any of the level of infection and community diagnosis in any village in Egypt.village in Egypt.

It is also recommended that the antibody testing(L3 It is also recommended that the antibody testing(L3

antibodies) that was used in school to be made in the future as antibodies) that was used in school to be made in the future as a rapid card test for detection of antibody levels in school a rapid card test for detection of antibody levels in school children which is a good indicator of the level of transmission. children which is a good indicator of the level of transmission.

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