ORIGINAL

Niger J Paed 2013; 40 (3): 217 –221

Ekenjoku AJ

Oringanje C

Meremikwu MM

Comparative efficacy of Levamisole,

Mebendalzole and Pyrantel

Pamoate against common intestinal

nematodes among children in

Calabar, South-South Nigeria

DOI:http://dx.doi.org/10.4314/njp.v40i3,3

Accepted: 18th December 2012

Abstract Introduction: Continued

endemicity of intestinal nema-

todes infestation in children in our

environment despite availability

of potent and safe anthelmintic

drugs is of public health interest.

Objective: This study assessed the

comparative efficacy of selected

anthelmintic drugs namely

the following anthelmintic drugs

(Mebendazole 500mg, Pyrantel

10mg/kg or Levamisole 2.5mg/

kg). The efficacy of the drugs was

determined by the level of clear-

ance of worm egg/ova from fresh

stool samples of the pupils on post

-treatment examination.

Result: The study showed the

three anthelmintic drugs display-

ing one hundred percent (100%)

efficacy in respect of Ascaris and

trichuris worms, but less so for

hookworm. Mebendazole dis-

played 90.48%, Pyrantel 45.16%)

and Levamisole (17.86%) efficacy

level against hookworm.

(

)

Oringanje C

Ekenjoku AJ, Meremikwu MM

Institute of Tropical Diseases Re-

search and Prevention, University

of Calabar Teaching Hospital PMB

1

278 Calabar, Nigeria

Mebendazole, pyrantel pamoate

and levamisole-against common

intestinal nematodes namely

Ascaris lumbricoides, Hookworm

(

Ancylostoma duodenale and

Necator americanus) and

Trichuris trichuria in children in

Calabar Municipality, South-

South Nigeria

Method: One hundred and thirty

eight pupils from four primary

schools in Ikot Ishie/Ikot Ansa

communities of Calabar with

worm infestation (Ascaris, hook-

worm and Trichuris including

mixed infestation) were random-

ized by simple balloting to one of

Conclusion: The overall result

indicates that Mebendazole was

the most efficacious agent against

the three common intestinal

worms.

Keywords: Anthelminthic, nema-

todes, children, Nigeria

Introduction

World Health Organization (WHO) in its concern for the

disease aims at eradication with chemotherapy and im-

proved and high-quality socio-cultural habits (personal

hygiene, environmental sanitation, good waste/sewage

disposal and portable water supply). C₆hemotherapy

forms the mainstay of control of infestation .

Intestinal helminthiasis is a recognized public health

problem, worse in the tropical and subtropical develop-

1

ing areas ; certain areas of Asia, Africa, and Latin

2

America . This may be related to the standard of living

and environmental hygiene. Ascaris lumbricoides,

Trichuris trichiura and hook worm (Ancylostoma duo-

denale and Necator americanus) are the most common

infections in human with an estimated global burden of

Mebendazole, Pyrantel pamoate and Levamisole are

recommended drugs against intestinal nematodes. The

6

current anthelmintic drugs have been in use for decades

3

,4

7

3

9 million disability-adjusted life years lost (DALYs) .

starting with Pyrantel pamoate in the 1960s . It is there-

The disease of intestinal helminthiasis has been

associated with some effects which manifest by many

symptoms and complications in growing children. These

effects include malnutrition, stunting of growth and

reduced cognitive ability, which in general hamper

fore important to assess the efficacy of the available

antihelmintic agents in current use from time to time.

The relevance of such assessment lies in the possibility

of development of resistance by these worms to these

8

agents, as already reported in animals .

5

optimal child growth and development .

Considering the rate of drug abuse and misuse in our

2

18

environment, it is worthwhile to assess the efficacy of

these drugs against these common intestinal worms. The

pattern of activity of each drug against the different

worms tested may be useful in future trials, choice of

treatment or anthelmintic drug policy, as is the case with

malaria treatment. This is also in keeping with, and pro-

vides data for, the current practice of “Evidence-based-

medicine”. The object of this study was to assess the

efficacy of three most commonly used anthelmintic

drugs in Nigeria namely, Mebendazole, Pyrantel

pamoate and Levamisole in school children identified

with intestinal nematodes (Ascaris lumbricoides, Ancy-

lostoma duodenale and Necator americanus and

Trichuris trichuria) in Calabar-Nigeria.

pupils were sent home with a letter to their parents em-

phasizing the importance of not administering any other

drug to the child during the period of the study and if

need be, should contact the trial physician whose num-

ber was written in the letter.

Post-treatment stool examination was again conducted

after one week using the same method used for the pre-

treatment stool examination and the end point was cure

rate (proportion of egg-positive at baseline, which be-

came egg-negative after treatment). Single stool analysis

was employ₁e₀d_-₁₃in this study and this has been shown to

be effective

. The results were recorded and analyzed

using Chi-squared statistics to observed if there will be a

significant different in the efficacy of the three drugs

against the different parasite.

Subjects and Method

Results

This open-label randomized comparative study was car-

ried out between November and December 2005 in

Calabar Municipality, Nigeria. Four hundred and forty

pupils were selected from four primary schools in Ikot

Ishie and Ikot Ansa community within the Local Gov-

ernment Area. Ethical clearance for the study was ob-

tained from the University of Calabar Teaching Hospital

Ethical Committee. The Cross River State Ministry of

Education gave formal approval and permission for the

study. Written informed consent was acquired from the

children’s parents or legal guardians to participate in the

study with emphasis made on voluntary participation

and possible withdrawal at any time during the study.

Children of parent who consented were given an empty

stool container, labeled with their names and class grade

and asked to return it with a fresh sample of stool the

next day.

Four hundred and forty pupils’ who met the inclusion

criteria: age between 4 and 12years (both males & fe-

males), residence within the community for 6 months

and above, written consent from parents/guardian and

ability to ingest tablet with water were enrolled for the

study. Two hundred and eighty four pupils returned with

their stool samples the next day and were screened for

intestinal nematode infestation. One hundred and thirty

eight (138) pupils were found to be infested with worms

giving an overall average of 48.59% worm infestation.

The distribution of the different type of worms is shown

in Table 1. Most children were diagnosed with hook-

worm infection (35.6%). The overall infection rates of

A. lumbricoides, T. trichuris and mixed infection are

26.1%, 6.7% and 16.5% respectively.

The sample was tested for intestinal nematode infesta-

tion by microscopic examination of fresh stool samples

Table 1: Distribution of helminthes

Type of

helminth

Number found

% number found

(N = 284)

9

using brine flotation method . The method is simple,

straight forward and suitable for field study. Samples

were analyzed with a time frame of 45 to 60 minutes

beyond which the adherent eggs/ova would sink down

Ascaris

74

26.1

Hookworm

Trichuris

Mixed

101

19

47

35.6

6.7

16.5

9

the solution . One hundred and thirty eight (138,

4

8.59%) of the screened population were identified with

various worms (Ascaris lumbricoides, Ancylostoma duo-

denale, Necator americanus and Trichuris trichuria) by

virtue of eggs/ova in stool.

Overall, 138 were infested; 49 pupils receiving Meben-

dazole (19 Ascaris, 38 Hookworm and 7 Trichuris); 47

recieving Pyrantel pamoate (31, 14 and 6 for Ascaris,

Hookworm and Trichuris respectively) and 42 received

Levamisole (24 Ascaris, 5 hookworm and 6 Trichuris).

The efficacy of the drugs is shown in table 2. The three

drugs showed 100% efficacy against Ascaris and

Trichuris, but less so against hookworm. Mebendazole,

however, displayed better efficacy (90.48%) than pyran-

tel pamoate (45.16%) and Levamisole (17.86%) against

hook worm. There was a significant difference between

the efficacies of the three anthelmintic drugs against

Hookworm (Xcal > Xtable). No adverse events were

observed on either of the drugs during the study period.

The infested pupils were randomly assigned to one of

the three treatment sch_Redules, of single dose of either

mebendazole (wormin brand) 500mg or pyprantel

R

pamoa_Rte (combantrin brand) 10mg/kg or Levamisole

(

levax brand) 2.5 mg/kg using simple balloting irre-

spective of polyparasitism or mono-infection. All the

treatments was ingested with water and given in the

school classrooms under direct observation of the study

personnel. Pupils were given the next dose above the

calculated dosage (mg/kg). Pupils were observed for

about 30 minutes after administration of drug and treat-

ment was repeated once if patient vomited within 30

minutes of drug administration. To ensure that other

types of anti-helminthics were not administered at home,

2

19

Table 2: Comparative efficacy of drugs on different worms

Efficacy of drugs against different worms*

Drug type

No. of pupils treated

Ascaris

Hookworm

Trichuris

Mebendazole

49

47

19/19(100%)

31/31(100%)

38/42(90.48%)

14/31(45.16%)

7/7(100%)

6/6(100%)

Pyrantel

pamoate

Levamisole

42

24/24(100%)

5/28(17.86%)

6/6(100%)

*Fractions represent the total number of worms cleared in each group and not number of individuals freed of worms

infestation.

Number Eligible = 440

Number screened = 284

1

sample

56 pupils did not return with stool

Number randomized = 138

Mebendazole = 49

Levamisole = 42

Lost to follow up = 0

Number analyzed = 42

Pyrantel Pamoate = 47

Lost to follow up = 0

Number analyzed = 49

Number analyzed = 47

Fig 1: Flow chart showing study participation and compliance

Discussion

absorption rate of 96.5 percent and Pyrantel Pamoate has

a low absorption rate.

This study showed a prevalence rate of intestinal

The three Levamisole, Mebendazole and Pyrantel

pamoate drugs were 100% effective against Ascaris and

Trichuris. The efficacy for Ascaris was comparable with

other stud₁ie₇s; a study from China reported cure rate of

over 95% and a review on antihelminths studies re-

nematodes of 48.59% which is comparable to 46.5%

reported by by Ikpeme in school age children in 2005

but lower a prevalence rate of 67.2% obtained by Mere-

mikwu et a_,l₁,₃ 1995 in preschool children in the same

1

community . The downward trend evident from these

18

ported cure rate of between 97.5 – 100% . This sug-

reports may be due to difference in age and changes in

living conditions. Improvement in socio-economic status

tends to lower the risk of worm infestation even though

this study was carried out in the rural area of Calabar

Municipality.

gests that despite widespread use of these drugs over the

past few decades, the worms have not developed resis-

tance against these drugs. However, the case differs with

Trichuris as studies in the past had reported variable

cure rate ranging from 22.2% to 86.8 for the three

14

1

9

drugs . Keiser and Utzinger in their review concluded

The prevalence of the each infection was 35.6%, 26.1%,

that the treatment of Trichuris with single oral doses of

6

.7% and 16.5% for Hookworm, Ascaris, Trichuris and

18

current anthelminths is unsatisfactory . Another study

polyparasitism respectively. It would have been ex-

pected that Ascaris have the greater prevalence due of its

mode of transmission but high rate of hookworm have

concluded that Pyrantel pamoate for Trichuris was inef-

17

ficacious . The low prevalence of Trichuris in this

study makes it difficult to draw any relevant conclusion.

1

5

also been restricted to areas with rural poverty .

In the case of hookworm, the efficacy of three drugs

varied remarkably. The efficacy of Levamisole, Pyrantel

pamoate and Mebendazole against hookworm was

The result of the comparative efficacy of three drugs

against the different worms showed a high efficacy rate

for Mebendazole across the three worms. This finding is

in agreement with observation of de Silva (1997) that

Mebendazole is highly effective against these common

nematodes with better higher activity against Ascaris

1

7.86%, 45.16% and 90.48% respectively. The drug

efficacies in T. trichiura infection were similar to those

reported in previous studies, with Mebendazole greatly

reducing the prevalence followed by Pyrant₁e₈l_,₁₉pamoate

1

6

than hookworm . This is surprising as Mebendazole is

poorly absorbed unlike Levamisole which has an oral

and Levamisole having a much smaller effect

.

Mebendazole is the only one of the three drugs that is

2

20

known to inhibit the development and growth of larval

stage of hookworm and Trichuris which may explain

the high efficacy of this compound against these

nematodes.

Authors Contributions

2

Ekenjoku AJ: participated effectively in the planning,

data collection and analysis, and writing of

the manuscript/paper, supervision of study.

Oringanje C: took part in sample analysis and prepara

tion of the manuscript.

Meremikwu MM: Contributed in the planning of the

study, preparation of protocol and of

the manuscript.

The number of pupils screened was far less than the

number registered. This was due to failure of the pupils

to return stool samples. Many of them returned consent

form signed by their parent but could not pass stool

before coming to school. Others forgot even the stool

already collected in the sample bottle at home. This

resulted in loss of many sample bottles even after

several visits to each school, hence limitation of sample

size. Another limitation is that monoparasitism and

polyparasitism was not separated during the

randomization process.

Conflict of Interest: None

Funding: None

Acknowledgements

The Primary School Board of Ministry of Education

Cross-River State for permission/authorization for the

study. Heads, teachers and pupils of the four primary

schools-Ishie primary school, Immaculate conception

primary school, Army day primary school and Nigerian

navy primary school all in Calabar municipality for their

zealous co-operation and participation in the study.

Mrs Philomena Ekenjoku, Chief nursing officer, General

hospital calabar, and Ugo Ekenjoku for assiduous task

of organization of pupils and data collection. Mrs Vivian

Asiegbu, the laboratory scientists for stool samples

analysis & microscopy, Felix Ekenjoku and Amara

Ekenjoku for computer typing of the manuscript.

Conclusion

The study assessed the efficacy of mebendazole, pyran-

tel and Levamisole against intestinal nematodes in

primary school pupils in a rural Nigeria community with

Mebendazole being the most effective anthelminthic

drug against the three commonest intestimal worms in

this community with efficacy exceeding 90% in all

cases. The result of this study supports the World Health

Organization (WHO) recommendation for the use of

mebendazole in the integrated management of childhood

infection, mass treatment programs and school health

1

5

program . Evidence from this study can influence

anthelmintic drug policy in this country as is the case

with malaria, in line with “evidence-based-medicine”,

and suggest clinical selectivity and choice of anthelmin-

tic drug in contemporary helminthic control programs.

Professor Akpan O.A (late), Professor of Pharmacology

(Deputy Provost, College of Medical Sciences,

University of Calabar) for supervising the study.

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