Jhs.pharm.or.jp

Journal of Health Science, 53(4) 443–449 (2007)
Responses to Albendazole Treatment for Hookworm
Infection in Ethnic Thai and Immigrant in West-central
Thailand
Malinee Thairungroj Anantaphruti,∗ Supaporn Nuamtanong, Dorn Watthanakulpanich,
Wanna Maipanich, Somchit Pubampen, Surapol Sanguankiat, Teera Kusolsuk,
Chatree Muennoo, and Jitra Waikagul
Department of Helminthology, Faculty of Tropical Medicine, Mahidol University, 420/6 Ratchawithi Road, Bangkok 10400, Thailand (Received March 16, 2007; Accepted May 18, 2007) Ethnic Thai and immigrant schoolchildren and villagers of Bo-ong, a village in Pilok sub-district, Thong Pha Phum District, Kanchanaburi Province, western Thailand, were investigated for helminth infections in September2003 and July 2004. Among the 143 schoolchildren, total cumulative hookworm prevalence in both surveys was58.7%, with 47.6% for Thais and 63.4% for immigrants, while among the 183 villagers, it was 69.4% (Thais:60.6%; immigrants: 75.0%). The efficacy of 400 mg single-dose albendazole among different hookworm-infectedracial/ethnic groups was analyzed 21 days’ post-treatment. Kato-Katz and polyethylene tube cultivation methodswere used for stool examination. Among the 211 hookworm-positive cases in both surveys, only 82 cases fromthe last survey were followed up. By Kato-Katz technique, for the schoolchildren and villagers combined, the curerate tended to be higher among the immigrants (65.0%) than the Thais (54.6%) (p = 0.445). By Sasa’s modifiedHarada-Mori culture technique, the cure rates also differed by racial grouping, and were higher (46.3%) among theimmigrants and lower (27.8%) among the Thais (p = 0.269). However, similar egg reduction rates were foundfor the two racial groups, at 96.0 and 92.6%, respectively. In addition, a higher intensity of hookworm infectiontolerated albendazole therapy, lower cure rates were obtained in moderate-to-heavy infections (56.3%) and higherrates for light infections (63.6%) among the total population. There were no significant differences in drug efficacyamong the 2 ethnic groups of Thai and immigrants (p > 0.05) in Kanchanaburi Province, Thailand.
Key words —— hookworm, albendazole, Thailand, Kanchanaburi, ethnic groups
INTRODUCTION
ing hookworm, with a recommended 400 mg sin-gle dose. Studies have shown high variability in Hookworm infection is a major soil-transmitted drug efficacy for hookworm and Trichuris infec- helminthiasis that causes health problems among tions in different regions. In Africa, where hook- the population, particularly children in poor com- worm infection is caused by Necator americanus, munities in developing countries. In Thailand, over- a single-dose treatment with albendazole was ef- all nationwide hookworm infection decreased from fective, with 78.8%6) and 56.8%7) cure rates in 40.6% in 1982, to 11.4% in 2001.1, 2) However, the over 1000 pupils in a number of primary schools prevalence was higher in southern Thailand than 3 weeks’ post-treatment. In China, albendazole is other parts of the country, where the prevalence in highly effective, with a 95.4% cure rate against 14 southern provinces in 1989 was 68.8%.3) Conse- hookworm infection caused by N. americanus and quently, in other parts of the country, especially in Ancylostoma duodenale (N. americanus: A. duode- remote areas, prevalence remains high.4, 5) nale ratio = 1 : 0.7) in adult populations in Hunan Albendazole, a benzimidazole anthelminthic, Province, when assessed by Kato-Katz technique has been widely used in large-scale treatment pro- 14 days’ post-treatment.8) In ancylostomiasis hook- grams for intestinal nematode infections, includ- worm, a high cure rate (92.2%) was obtained in 480patients aged 2–60 years,9) while an 87.2% cure rate ∗To whom correspondence should be addressed: Department of was reported in children aged 2–15 years.10) In Kan- Helminthology, Faculty of Tropical Medicine, Mahidol Univer- chanaburi Province, western Thailand, a number of sity, 420/6 Ratchawithi Road, Bangkok 10400, Thailand. Tel.
neighboring minority ethnic populations have mi- & Fax: +66-2643-5600; E-mail: [email protected] grated and settled along the Thai-Myanmar border schoolchildren of the village primary school and over several decades. This study aimed to evaluate villagers aged > 5 years. Two parasitological sur- the effective differences in treatment against hook- veys of both schoolchildren and villagers were car- worm infections for two main groups, immigrant ried out in September 2003 and July 2004. Stool and ethnic Thai schoolchildren and villagers in a boxes were distributed through the teachers to the remote area of western Thailand, using single-dose schoolchildren, and the village leader to the vil- lagers. All stool samples were examined by Kato-Katz technique11) and the level of intensity fol-lowed the World Health Organization (WHO) clas- MATERIALS AND METHODS
sification.12) All cases of helminthic infection weretreated with albendazole 400 mg single dose, ex- Characterization of the Study Areas and Popu-
cept those with Trichuris infection, who received it lation —— The study was carried out in Bo-ong,
for 3 consecutive days. Follow-up treatment was a village in Pilok Subdistrict, Thong Pha Phum performed only at the last survey, in July 2004, District, Kanchanaburi Province, west-central Thai- 21 days’ post-medication, when the stool contain- land. The village is located southwest of the wa- ers were distributed, and the feces of treated pa- ter basin of Vajiralongkorn Dam, close to the Thai- tients collected and re-examined by Kato-Katz tech- Myanmar border. It is a rural highland surrounded nique. Sasa’s modified polyethylene tube cultiva- by perennial water, and to the west, by heavy forest, tion technique was used for samples of pre-treated and a partial plain area. Communication to and from hookworm-positive cases, to detect filariform lar- nearby villages and the district centers is limited to vae.13, 14) Only hookworm-infected cases were as- boat or foot. There are approximately 800 residents, sessed for the curative efficacy of albendazole. The 70% of whom are immigrants. The majority of the egg-reduction rate (the ratio of egg-count per gram immigrants are Karen (90%), and the rest are Mon, of feces reduced from pre-treatment to post-treated Karang, Myanmar, and Laos. Between ethnic Thai levels) was also analyzed. Mixed hookworm- and and immigrant group, there are no obvious differ- Trichuris-infected cases were excluded from the ences of ethnical characteristics, food and cooking habits or occupational activities. However, the im- Statistical Analysis —— Two groups of the exam-
migrant group earned lower income and is laborious ined population, schoolchildren and villagers, were worker. There is no local health station; the health constituted by race—ethnic Thais and immigrants.
service for the villagers is at Thong Pha Phum Dis- Hookworm prevalence and cure rates after treat- trict Hospital. The climate of the area is tropical ment were used for comparison among the two pop- with hot, rainy, and dry seasons. The main occu- ulation groups. Associations among category vari- pations are rice and cassava agriculture, and fish- ables were tested by Fisher’ exact test.
ing. No house in the village had electricity or pipedwater. The village water supply was in a precari-ous condition, available via direct piping from the mountain to the village temple, where the residentsneeded to convey it independently. The water vol- Parasitic Infections in the Schoolchildren
ume during the dry season was inadequate. Houses The school had a total of 162 students (70 in the village were built of wood, roofed with cor- males; 92 females). Of these, 47 were Thais and rugated iron sheeting or thatch. A small number 115 immigrants; 88.3% (143/162) of the schoolchil- of houses had toilet facilities. The community had dren participated in stool examinations during the a branch of the municipal primary school, but no building or rooms for classes, so that the temple’s shown in Table 1. Prevalence is expressed as cu- multi-purposes open hall was arranged into class- mulative positives for helminth eggs in both sur- Parasitological Examination and Follow-up ——
soil-transmitted helminthic infections was 62.9%; The study was approved by the ethics commit- it was higher in immigrant schoolchildren (66.3%) tee of the Faculty of Tropical Medicine, Mahi- than Thais (54.8%). The higher pattern of preva- dol University and informed consent was obtained lence among immigrants was seen in all types of Table 1. Stool Results for Primary School Children and Villagers Aged 5–78 Years in Bo-ong, Pilok Subdistrict, Thong
Pha Phum District, Kanchanaburi Province, in September 2003 and July 2004, by Kato-Katz Technique a) Males 61, Females 82, b) Males 92, Females 87, Not specified 4, c) STH = Soil-transmitted helminths, d) p = 0.095, e) common parasite, occurring in 58.7% of the exam- dren and villagers showed a significant difference ined students, with 63.4% in immigrants and 47.6% in hookworm infection between these two groups, in Thais. No significant difference was found be- tween the Thai and immigrant groups for hookworminfection, p = 0.095. Trichuris infection was mod- Treatment Efficacy
erate, with 11.9% overall prevalence, and 12.9% in A total of 211 hookworm-positive cases of both immigrants and 9.5% in Thais. Ascaris was a mi- surveys, 52 villagers and 30 schoolchildren of the nor infection, in approximately 2% of cases. Taenia last survey, were enrolled for albendazole therapy eggs were found in 2.0% of immigrants, i.e., in two at 400 mg single dose and follow-up drug efficacy immigrant boys. A small number of schoolchildren were assessed at 21 days’ post-treatment.
had mixed infections with 2 or 3 kinds of helminths.
of the hookworm-infected cases (66; 80.5%) (22 Among the mixed infections, almost all cases were schoolchildren and 44 villagers) in the 82 follow- immigrant children; the most common combination up cohort had light-intensity infections. No heavy of helminths was hookworm and Trichuris. One infection was found in the schoolchildren, and only immigrant boy in grade 1 had triple mixed infec- one was found in each of the Thai and immigrant tions with hookworm, Trichuris and Ascaris (Data villager groups. Moderate infection was found in 2 Thai and 6 immigrant schoolchildren; and 3 eachof Thai and immigrant villagers (Fig. 1). The av- Parasitic Infections in the Villagers
erage number of eggs per gram (NEPG) of feces A total of 183 villagers (92 males; 87 females; in each intensity class is shown in Table 3. The 4 not specified) were enrolled for stool examina- stool results after albendazole administration are tion during the study. Approximately 60% (112) shown in Table 2. The immigrant villagers showed were immigrants and the rest, 40% (71), were a higher response to albendazole by Kato-Katz tech- nique and tended to had a higher cure rate (72.2%) schoolchildren, and the cumulative positive rates than the Thais (56.3%), p = 0.340. The schoolchil- for each parasitic infection among the immigrants dren showed a similar trend, higher (54.2%) for im- were higher than among the Thais. These included migrants than Thais (50.0%), p = 0.999. How- soil-transmitted helminths (STH) 75.9% and 60.6%; ever, the cure rates in the two groups of villagers hookworm 75.0% and 60.6%; Trichuris 12.5% and plus schoolchildren, immigrants (65.0%) and Thais 1.4%; Ascaris 5.4% and 0%; and Taenia 4.5% and (54.6%) did not differ significantly (p = 0.445).
1.4%, respectively (Table 1). Hookworm infection Seventy-two stool samples from 82 follow-up was the most prominent in both immigrants and patients were deemed sufficient for stool culture.
Thais, with an overall prevalence of 69.4%, which Cure rate assessed by coproculture was generally almost equaled that of STH (69.9%). There was a lower than by Kato-Katz technique. However, sim- slight significant difference in hookworm infection ilar result patterns were obtained; the immigrants, among the Thai and immigrant villager groups, p = either schoolchildren or villagers, showed better re- 0.048. Analysis of the combination of schoolchil- sponses to albendazole treatment than the Thais.
Fig. 1. Hookworm-infected Cases of Thai and Immigrant Schoolchildren and Villagers, Grouped by Intensity Class of Infection
Light: < 2000 EPG, Moderate: 2000–7000 EPG, Heavy: > 7000 EPG. EPG = egg per gram of feces.
Table 2. Efficacy of Albendazole 400 mg Single Dose Against Hookworm Infection in Primary
School Children and Villagers Aged > 10 Years in Bo-ong, Pilok Subdistrict, Thong PhaPhum District, Kanchanaburi Province, in September 2003 and July 2004, by Kato-Katzand Culture Techniques a) p = 0.999, b) p = 0.340, c) p = 0.445, d) p = 0.269.
The cure rates for immigrant schoolchildren and vil- light and 50.0% in moderate-plus-heavy infections.
lagers were 43.5 and 48.4%, respectively, whereas The overall cure rate in the studied population was those of the Thais were 33.3 and 25.0%. The over- all cure rate for the studied population, assessed by Albendazole induced a high-percentage reduc- fecal culture, was 41.7%. There was no signifi- tion in egg count (93.9%). The 2 groups of study cant difference in the cure rate for the immigrants subjects showed similar egg-reduction rates (ERR), (46.3%) and Thais (27.8%) (p = 0.269; Table 2).
at 96.0% for Thais and 92.6% for immigrants.
Cases with light-intensity infections had bet- Lower ERR for either Thais (84.1%) or immigrants ter responses to drug therapy, and a higher cure (80.4%) were obtained for light-intensity infections rate (63.6%) was obtained than the moderate-plus- than for moderate-plus-heavy infections (98%; Ta- heavy infections (56.3%). Consequently, the im- migrants responded well, with 66.0% in light and60.0% in moderate-plus-heavy infections, whereasthe Thais responded more poorly, with 56.3% in Table 3. Cure and Egg Reduction Rates (ERR) for Hookworm Infection Obtained after Albendazole Treatment, by
(a) In Thais and Immigrants (Schoolchildren plus villagers) (b) In the Studied Populations (Thais and Immigrants) of Schoolchildren (30) plus Villagers (52) DISCUSSION
To assess the efficacy of drug treatment, the type of diagnostic test is an important factor. The copro- Soil-transmitted helminthiases, particular hook- culture method is designed to diagnose nematode worm infection, are still highly prevalent in Thai- infections like hookworm, where the parasites give land. More than 50% of the studied population, ei- rise to a larval stage that dwells in the soil. This ther schoolchildren or villagers, were infected (Ta- method can detect larvae even in very light infec- ble 1), and the immigrant group had higher preva- tions. Marwi16) compared Katz’s modified Kato’s lence than the Thais. At baseline, these two groups thick-smear method with Harada-Mori culture for of patients showed a significant difference in hook- detecting hookworm infection and found a 78.8% worm prevalence which is the main infection under recovery rate for the former and 85.8% for the lat- study. After treatment with albendazole, the cure ter in 354 known hookworm-egg-positive stool sam- rates tended to be higher among the immigrants than ples. Our results for hookworm infection recovery the Thais, but were found to have no significant dif- after albendazole treatment agreed with the above ference. The significant difference in hookworm report. A higher recovery rate for hookworm larvae prevalence shifted to an insignificant difference af- by culture method was found than for hookworm ter albendazole therapy. However, our data indi- eggs by Kato-Katz technique. On the other hand, a cated no association between hookworm infection lower cure rate was obtained by culture method than and race. Nontasut et al. studies the treatment of trichuriasis with mebendazole and found insignifi- The initial intensity class of infection influences cantly different cure rates among two groups of pa- drug efficacy; cure rates declined with increasing in- tients, Thais and Karen, residing in different regions tensity of infection. Nontasut et al.17) reported cure of Thailand.15) Unfortunately, this study reported no rates varied from 66.6, 64.3, and 50.0% in light, statistical analysis of prevalence prior treatment in moderate, and heavy hookworm infections, respec- tively, with a 64.6% total cure rate for primary schoolchildren with an average age of 10 years.
W., Nuamtanong, S. and Pubampen, S. (2004) Similarly, in adult patients, a cure rate of 75.0% Soil-transmitted helminthiases and health behaviors with NEPG < 5000, and 50.0% with NEPG > 5000 among schoolchildren and community members in were recorded by Viravan et al.18) Our cure-rate re- a west-central border area of Thailand. Southeast sults agreed well with those investigators.
Asian J. Trop. Med. Public Health, 35, 260–266.
Albendazole produced substantial reductions in 5) Maipanich, W., Itiponpanya, N., Rojekittikhun, W., Siripanth, C., Pubampen, S., Sa-nguankiat, 96.6% was obtained in 29 aborigine (Orang Asli) S., Juntanavivat, C., Incheang, S. and Sukosol, T.
hookworm-infected patients 1–13 years old, and (2002) Intestinal parasitosis among hilltribe people 94.5% of 32 residents of rubber and oil-palm es- and soil contamination in Nan Province, Northern tates in Malaysia.19, 20) Moreover, Sitthichareonchai Thailand. J. Trop. Med. Parasitol., 25, 30–37.
et al.21) reported equal ERR (96.0%) in patients 6) Saathoff, E., Olsen, A., Kvalsvig, J. D. and with different NEPG of < 1000 and > 10000. Our Appleton, C. C. (2004) Patterns of geohelminth in-fection, impact of albendazole treatment and re- results, by contrast, showed higher ERR in NEPG > infection after treatment in schoolchildren from ru- 2000 (98.5%) than in NEPG < 2000 (81.5%).
ral KwaZulu-Natal/South-Africa. B. M. C. Infec- A wide variety of results have been obtained for tious Diseases, 4, 27–37.
drug efficacy of anthelminthics in hookworm infec- 7) Albonico, M., Smith, P. G., Hall, A., Chwaya, H.
tion. A number of factors could reflect variations in M., Alawi, K. S. and Savioli, L. (1994) A random- drug efficacy; we demonstrated type of diagnostic ized controlled trial comparing mebendazole and al- test and initial intensity class of infection. Although bendazole against Ascaris, Trichuris and hookworm different ethnic/racial populations showed some dif- infections. Trans. R. Soc. Trop. Med. Hyg., 88, 585–
ferent responses to albendazole, no significant dif- ferences were found in drug efficacy among the 2 8) Yu, S. H., Xu, L. Q. and Jiang, Z. X. (1997) ethnic groups, Thai and immigrant populations in Treatment of Soil-transmitted helminth infections by anthelmintics in current use. In Collected Paperson the Control of Soil-transmitted Helminthiases Acknowledgements
(Hayashi, S., Kobayashi, A., Kagei, N., Yasuraoka, main project supported financially by Mahidol Uni- K. and Hara, T., Eds.), vol. VI, The Asian Parasite versity research grants. Thanks are extended to Va- Control Organization, Tokyo, pp.190–196.
jiralongkorn Dam Electricity Generating Authority 9) Jagota, S. C. (1986) Albendazole, a broad-spectrum of Thailand for supporting accommodation during anthelmintic, in the treatment of intestinal nematode and cestode infection: a multicenter study in 480 pa-
tients. Clin. Ther., 8, 226–231.
10) Prasad, R., Mathur, P. P., Taneja, V. K. and Jagota, S.
REFERENCES
C. (1985) Albendazole in the treatment of intestinal
helminthiasis in children. Clin. Ther., 7, 164–168.
1) Preuksaraj, S., Jeradit, C., Sathitayathai, A., 11) Katz, N., Chaves, A. and Pelegrino, J. (1972) A sim- Kijvannee, S. and Leedonrusmi, T. (1982) Studies ple device for quantitative stool thick smear tech- on prevalence and intensity of intestinal helminthic nique in schistosomiasis mansoni. Rev. Inst. Med. infections in the rural population of Thailand 1980– Trop. Sao Paulo, 14, 397–400.
1981. Commun. Dis. J., 8, 245–269.
12) World Health Organization (WHO) (1987) Preven- 2) Ministry of Public Health, Thailand (2002) Report tion and control of intestinal parasitic infections. Re- of the evaluation on the helminthiasis control pro- port of a WHO Expert Committee, WHO Tech. Rep. gram in Thailand by the end of the 8th Health De- velopment Plan in the year 2001, Department of 13) Harada, Y. and Mori, O. (1955) A new method for Communicable Disease Control, Ministry of Public culturing hookworm. Yonaga Acta Med., 1, 177.
14) Sasa, M., Mitsui, G., Harinasuta, C. and Vajrasthira, 3) Charanasri, U., Jongsuksantikul, P. and Jeradit, C. (1965) A polyethylene tube culture method for C. (1989) Survey of intestinal helminthiasis in 14 diagnosis of parasitic infection by hookworm and southern provinces of Thailand. Commun. Dis. J., related nematodes. Jpn. J. Exp. Med., 35, 277–289.
15, 391–404.
4) Anantaphruti, M. T., Waikagul, J., Maipanich, Muennoo, C. (2000) Efficacy of multiple dose mebendazole against trichuriasis in Thai and Karen Public Health, 13, 654–657.
patients. Southeast Asian J. Trop. Med. Public 19) Norhayati, M., Oothuman, P., Azizi, O. and Fatmah, Health, 31, 460–462.
M. S. (1997) Efficacy of single dose albendazole 16) Marwi, M. A. (1979) Comparative efficacy of meth- on the prevalence and intensity of infection of soil- ods commonly used for diagnosis of soil-transmitted transmitted helminthes in Orang Asli children in helminths. Thesis for Master of Science (Tropical Malaysia. Southeast Asian J. Trop. Med. Public Medicine), Faculty of Tropical Medicine, Mahidol Health, 28, 563–569.
20) Ramalingam, S., Sinniah, B. and Krishnan, U.
17) Nontasut, P., Singhasivanon, V., Pharinyanuparp, V., (1983) Albendazole, an effective single dose, broad Chiamratana, B., Sanguankiat, S., Dekumyoy, P. and spectrum anthelmintic drug. Am. J. Trop. Med. Hyg., Setasuban, P. (1989) Effect of single dose albenda- 32, 984–989.
zole and single dose mebendazole on Necator amer- icanus. Southeast Asian J. Trop. Med. Public Health, Akarabovorn, P. (1984) Clinical trial of a 400 mg 20, 237–242.
dose of albendazole in hookworm infection in 18) Viravan, C., Migasena, S., Bunnag, D. and Chulalongkorn hospital. Chula. Med. J., Harinasuta, T. (1982) Clinical trial of albendazole in hookworm infection. Southeast Asian J. Trop. Med.

Source: http://jhs.pharm.or.jp/data/53(4)/53_443.pdf