Clinical Trial of Areca Nut Seed (Areca catechu L.

) Extract Tablets In Schoolchildren infested by Intestinal Worms in Mumbulsari sub-district Jember ABSTRACT *Utami, W.S., **Nuri, **Wicaksono, Y, ***Palupi, I.R, ***Gemawan, T Email: wiwien.dr@gmail.com *Lecturer in Faculty of Medicine, Jember University **Lecturer in Faculty of Pharmacy, Jember University ***Medical Students in Faculty of Medicine, Jember University

PREFACE Worm disease is a disease that can be suffered by all ages. Many people thinks not many human infected with this disease. But recent study shows how big chronic infection because of worms. According to WHO data, patients with worm disease counts 1 billion population of world, and 40-60% Indonesian population infected with worms. According to Millennium declaration, one disease that become big attention is soil transmitted helminthiasis, such as ascariasis, trichuriasis, dan ancylostomiasis (Molyneux, 2004). Worms can result in declining health, nutrition, intellectual and productivity of the patient and cost economically, because it causes loss of carbohydrates and protein and blood loss resulting in lower quality of human resources. In addition to inhibiting the development of physical, intellectual and labor productivity,it can lower the body's defenses so the patients become prone to other diseases (Supari, 2006). Ascariasis patient generally do not cause symptoms, but with a considerable number of worms (hyperinfection), especially in children will lead to malnutrition (Rasmaliah, 2001), whereas in tricuriasis patient, mild infections are asymptomatic. However, in severe infections, especially in children, there are symptoms of diarrhea which is often interspersed with dysentery syndrome and symptoms of anemia, weight loss and sometimes accompanied by rectus prolapse (Spears, 2007). As a result of hookworms infestation can cause anemia, impaired intellectual development (Haburchak, 2008). Indonesia is included in a tropical country so many parasites thrive in the cycle so it can easily infect humans (Istiqomah, 2007). Helminth infection is a chronic infection most common in toddlers and school age children (Faust and Russel, 1964). The results from worms survey in elementary schools in several provinces in the years 1986-1991 showed the prevalence of worms about 60% - 80% (Supari, 2006). Based on the results of research in Jember found that the prevalence of ascariasis and trichuriasis in Kalikotok slums and RSS Argopuro settlements (control group). The prevalence of ascariasis and trichuriasis at those

05) (Nurdian. Reinfection problems and low socioeconomic levels. prevalence remains high. parasitic worm egg contamination level is 52% in Suco villages and 68% at Lengkong village (Kurniawati. Besides.settlement respectively is 63% and 5% and 3% and 0% (p <0. while in the Lengkong village by 68%. lumbricoides. Eradication of helminth infection is not an easy thing to do. one of them is Areca (Areca catechu L.48%). Nut seed extract which has proven in vitro have ovisidal and vermisidal activity against Ascaris suum. The villages are village Mumbulsari. for traditional medicine can be used in health care.24%) (Eden. from 60 samples of elementary school students Kemiri 3 obtained 29 samples (48. In Subdistrict Mumbulsari. 2002). In another study in Jember. the test vermisidal activity in vivo in pigs infected with Ascaris suum. Jember.4 grams for 3 consecutive days to remove the worm Ascaris suum from pig intestine along with feces. therefore it is necessary to find an alternative drug for use in non-governmental organizations in combating this worm disease. the people know natural material (medicinal plants) that can be used to treat intestinal worms. catechu L. Blinding type that is used is a single blinding that is the subject did not know the treatment given. 2008).33) positive for helminth eggs. 2007). Suco and Lengkong (Armiyanti et al. This type of research study conducted is a clinical trial testing this with areca seed extract on people with intestinal worm infection in elementary school students in District Mumbulsari. and hookworms (17. resulting in the use of modern medicine still have problems. Usually drug often used to combat intestinal worm's life cycle is pirantel pamoate. The research was conducted using a controlled clinical trial design (controlled clinical trial) phase III with a parallel design.. 2003:43). Although it has been done with the treatment and eradication and others. According to research conducted by Herlina (2005:21) on the grounds of houses in the Suco and Lengkong village obtained the percentage of positive soil samples by 52% for eggs A. Furthermore. 2003). piperazin citrate and mebendazol. Jember.96%).) (Ahmad and Ismail. karang Kedawung. District of Mumbulsari is one district that most of the territory comprised of plantations. Ascaris lumbricoides eggs with the tallest percentage (68. PURPOSE AND METHOD The general objective of this study was to determine the results of clinical trials areca seed extract tablet (A. Kawang Rejo. . then it must go through a series of clinical trials in humans. The results show. Five of the seven villages in the district Mumbulsari is a plantation region.) of patients with helminth infections in sub Mumbulsari Jember. at a dose of 2. Subsequently areca seed extract tablet formulation and testing of acute toxicity in experimental animals (Nuri. while researchers know about it. Enterobius vermicularis (34. 2008).

Primary School pupils in grade 4 to 6 2. Not currently suffering from diseases that disrupt the oral medication 3. At the time of treatment. vomiting. The second sampling performed to evaluate the treatment and the number of eggs per gram after treatment. Not regularly taking medication / refusing to eat drug 2. University of Jember using Kato-Katz Treatment was done at worm positive subject. The first sampling conducted on all primary school students who are willing to follow the screening study in order to identify the presence of worm eggs in stool. After screening. Jember and identification of worm eggs are done at the Laboratory of Parasitology Faculty of Medicine. The second sampling after a worms positive sample given medication and wait up to 2 weeks. Incurred severe side effects such as diarrhea. In the last month did not receive an anthelmintic 4. 5. Exclusion criteria: 1. On stool examination found Ascaris lumbricoides eggs. subjects given the drug and a monitoring sheet that contains the identity. . did not participate in Stool examination in day 14 to-21 3. whereas group B as a control group given standard drugs. the positive for worms counted the number of worm eggs (egg per gram). namely pirantel pamoate. University of Jember. Study sample was selected according to the following criteria Inclusion criteria : 1. Stool samples obtained later be identified in the Laboratory of Parasitology Faculty of Medicine. Sampling was done twice. and 6. Sampling sites throughout the study was conducted in elementary schools in District Mumbulsari.The design of this research is true experimental design with the pre and post test comparing treatment groups to take measurements before and after treatment. when taking medication and side effects that may accompany (attached). The study population was primary school students grades 4. Separation of the randomized allocation of treatment is done using random number tables. stiff stomach and others Study sample who had signed informed consent were then divided into 2 groups: group A as a treatment group given areca seed extract tablet treatment.

subjects are required to submit back stool samples to monitor the treatment of and count the number of eggs per gram after treatment. Group B as the control group received standard treatment is pirantel pamoate capsules 10 mg / kg.33 8 100 SD Lengkong 1 SD Mumbulsari 1 SD Mumbulsari 2 SD Suco 1 SD Suco 4 SD Lampeji 1 SD 7 Karangkedawung 2 SD 8 Karangkedawung 3 Jumlah total Largest infestation of 75 pieces of samples was A.34 49.34 6. taken orally with a single dose. Group A as a treatment group received treatment with areca seed extract tablets therapeutic dose is 500 mg. Most numerous infestations is Karang Kedawung 2 elementary school. Group A received treatment with the preparation of traditional medicines that have been formulated that is selected tablet areca seed extract. The division was done randomly with an equal number of samples. After 2 weeks. A total of 75 samples or 16.46% positive for worm eggs from the 130 samples . Distribution of intestinal worm infestation in Primary Schools in District Mumbulsari can be seen in Table 1. while the infestation is at least 3.66 8 8 1.41% of them contain eggs or worms positive for intestinal worm infestation. No 1 2 3 4 5 6 Elementary school Total sample amount 39 43 46 86 29 42 130 42 457 Infestation positif amount 7 5 6 6 1 7 37 6 75 Ascaris lumbricoides infestation 4 5 6 6 1 4 23 4 53 Trichuris trichiura infestation 3 0 0 0 0 0 6 1 10 Hookworm infestation 0 0 0 0 0 3 8 1 12 Persentase (%) 9.4% is found on the Suco 4 elementary school.Treatment of the test groups were divided into 2 groups. followed by Hookworm infestation as many as 12 people or 16%. subjects Required taking the drug within 3 days in a row by 1 ½ tablets / day. A total of 37 pieces or 28. lumbricoides. A total of 53 people (71%) stools were examined containing Ascaris eggs. To evaluate the effectiveness of the drug used against intestinal worm infestation healing rate parameter (AP) or the cure rate (CR).33 9. Treatment for 3 consecutive days with the subject of children of primary school age from grade IV to grade VI. group B received the standard treatment Pirantel pamoate 10 mg / kg / oral / single dose. which is the amount of the percentage of patients who cured by not finding of helminth eggs in feces RESULTS The total number of samples obtained as many as 457 pieces of samples. and Trichuris trichiura as many as 10 people or 13%. .

Treatment with areca seed extract tablet sample number of 40 children.000 Tabel 3. Egg Reduction Rate on the subset A is greater than the subset b. so that 91.0000 Types of worms in the table shows the average Egg Reduction Rate on Ascaris and Hookworm are similar and different from the TT.0000 1.9510 1.6667 a 0.71% cure and egg reduction rate 94.TT Pirantel-Ascaris Pinang-Ascaris Pinang-Hookworm Piarantel-Hookworm Subset b 0.6667 0. Pirantel pamoate treatment with the number of samples of 35 children. a significance value of 0. To find out the specific differences in follow-up test conducted using Tukey HSD homogeneous subsets of tables that are useful to assess the dependent variable in the equation of worms types of factors and Average combinations factor Egg Reduction Rate as follows: Tabel 2. homogeneous subset table to drug combination and worm type combination Pirantel-TT Pinang.3%. P value> 0.2500 0.9467 1.05 then says that the average cure rate for each drug material is the same or treatment with areca seed extract tablets are able to heal patient with ascariasis in accordance with the standard treatment that used such as pirantel pamoate. after treatment there were four children in a positive ascariasis so the numbers of 85. Based on research data obtained.1%. after treatment there were two children in a positive ackariasis.9417 0.60% cure rate and egg reduction rate of 93. T homogeneous subset table to worm types Worm type TT Ascaris Hookworm Subset b 0. . the analysis was performed using non-parametric statistical test Chi-Square.5741 a 0.503 is obtained.

the drug pirantel elected to the majority of intestinal worm infestation. including parasitic species where they are targets for anthelmintic drugs (Kimber.hookworm. Pirantel pamoate is used in this study as a control group. so that the worms die in a state of spastic. Can be obtained that the average Egg Reduction Rate on the subset A larger than subset group b. the drug of first choice for treatment ascariasis (Elizabeth. trichuriasis and enterobiasis. While the combination of Areca-TT showed similarities with the second subset.The combination Pirantel-Ascaris. High cure rate with a single dose is 10mg/kgBB. 2005). DISCUSSION The success of therapy is influenced by many things. Nut seed extract can inhibit the secretion of cholinesterase. mild and temporary. as evidenced by preliminary tests prior to clinical trials (Nuri. PirantelHookworm Egg had an indifferent average reduction rate . In addition. Tablet extracts of areca nuts (Areca catechu L.1 to 1 mmol arecolin can inhibit the secretion of cholinesterase-induced activation of cholinergic receptors. 2008). Acetylcholine receptor agonist properties against intestinal nematode muscle cells. evidenced in a trial. Areca nuts (Areca catechu L.) contains alkaloids such as pyridine groups arecolin and arecaidine. Another thing that also influence the therapeutic efficacy of which the body's response to drugs that can vary from one person to another person. found that at doses of 0. Pirantel pamoate worms cause depolarization of the muscle and increase the frequency of the impulses. The importance of structure. This substance has a chemical structure similar to nicotine is known as acetylcholine receptor agonist muskarinis (Ghelardini. 2007) and also this study. Areca. Its use should be caution in patients with a history of heart disease because it can increase the SGOT (Elizabeth. Pirantel pamoate also inhibit the enzyme cholinesterase effect. but also ancylostosomiasis. . However. not only ascariasis. In mediating this effect by inhibiting the calcium influx without inhibiting the release of calcium of cytoplasm (Lim. Arecolin has the effect of the central nervous system depression and muscle paralysis caused by binding to acetylcholine receptors (Jaiswal. 2001). 2008). Ascaris-Areca. The use of this drug in pregnant women and aged less of two years is not recommended. Pirantel pamoate side effects are rare. In relation to genetic factors. have the potential to bind to the muscarinic and nicotinic receptors that can be used in anti helmintic. pharmacology and physiological LGICs have been fairly described in the model nematode. 2010).) has proven quite effective antelmintic activity. This can be caused by interactions between environmental factors and genetic factors. One of the most significant thing of course is the efficacy of the drug. these groups differ with Pirantel-TT. 2009). as in arecolin. Acetylcholine (ACh) is a neurotransmitter / neuromodulator in the nervous system of nematodes and induces its effects through interaction with both ligandgated ion channels (LGICs) and G protein-coupled receptors (GPCRs).

While the analysis results on the type of worm therapy subjects showed differences in the average egg reduction rate. This is consistent with the hypothesis that areca seed extract tablets have equal therapeutic results with pirantel pamoate. 2005). so if there is damage to the organ. This suggests that each type of worm infestation has certain sensitivity to a therapy. the severity of disease and lifestyle. 2005). so that one's response to the drug can be different from other people who may not have drug interactions. The existence of genetic expression differences between each individual will be able to give a different response to the fate of the drug in the body. People in a particular race for instance. Therefore. This is due to the liver is the place to metabolize the drug. Other environmental factors are not keeping up the habit while eating atatu hygiene after defecation (BAB). Analysis of research data found that administration of areca seed extract treatment is shown to have similarities with the standard drug administration pirantel pamoate. On Trichuris . Environmental factors include nutritional factors. and the kidney is one of the drug excretion sites of the body. This leads to the presence of drugs in the body become shortened (due to enlarged metabolism). This we can review the particular aspects of metabolism. According to research conducted by Gunawan (2010). Genetic polymorphism is a genetic variation that causes a difference in enzyme activity and capacity in carrying out its functions. Disease that often affects the body's response to drugs is a disease of the liver and kidneys. Other environmental factors are lifestyle factors. so the effect becomes smaller. causing reinfection ascariasis (Radji. The resulting enzyme capacity of each individual is different. On the type of worm Ascaris and Hookworm has therapeutic effectiveness of a better outcome than other types of worms TT. Other factors that influence besides genetic factors are environmental factors. Metabolic processes occur by the help of enzymes. in cases of intestinal worm infestation by Ascaris and Hookworm either single or both can use a areca nut and pirantel as an alternative therapy. other drugs factors which used together. Further analysis showed that the results of specific therapy on the type and Hookworm Ascaris worms have in common but both have different types of worms types of worms with TT.genetic polymorphisms is known term. Or conversely. and lifestyle factors. This is one of the spur of the differences in the body's response to the same drug. Presence of other drugs are used together can also interact with each other resulting in lower or alter the effects of other drugs. nutritional status at the nut is in a good nutritional status (83%). so the existence of the drug in the body increases and the effect becomes large or even toxic (Radji. may affect a person's response to the drug. it has a number of enzymes premetabolisme more than others due to genetic variation. it will affect the body's response to the drug. The enzyme is a protein that existence is the result of genetic expression (protein synthesis). In addition. other races have mutations in certain genes that cause the body's reduced ability to metabolize the drug.

Prevalensi Infeksi Cacing Tambang pada Penduduk Daerah Perkebunan di Kecamatan Mumbulsari. 2003.. CONCLUSION It was concluded that areca nut seed extract tablet (Areca catechu L. Dalam Farmakologi dan Terapi edisi 5. Jurnal Sains dan Teknologi. Craig & Fausts Clinical Parasitology. The pharmacology of cholinoceptors on the somatic muscle cells of the parasitic nematode Ascaris suum. the use of areca nut provide better therapeutic results than pirantel pamoate.1. 1991. dan Riyanti. E. 1964. Y.C. .& P. Meiyani. Colquhoun. “Antelmintik”. J Exp Biol. REFERENCES Armiyanti. No. 7th ed.E. R.2. Therapy using the areca nut gives egg reduction rate that is better than giving pirantel pamoate on worm Trichuris trichiura infestation while the worm Ascaris and Hookworm infestation given areca nut and pirantel pamoate therapy showed the same therapeutic results It is expected areca nut seed extract tablet (Areca catechu L. Maret 2003.) have showed antelmintic activity and is able to heal patient with intestinal worms infection is equivalent to the standard treatment used that is pirantel pamoate.trichiura infestation. Jul. I. Philadelphia: Lea 7 Febiger.2008. Faust.F. Russell.. ACKNOWLEDGMENTS This research can be done well on the Incentive Grants project for Research and Technology Ministry of Republic Indonesia (RI Kemenristek) in 2010. L. Elysabeth.) may be one alternative medicine intestinal worms infections in the future.158:509-30. Jakarta : Balai Penerbit FK UI. Vol.

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