Efficacy of a single dose albendazole chemotherapy on human intestinal helminthiasis among school children in selected rural tropical communities

Transcription

1 Volume 6 Issue 4 Jul-Aug 2013

2 ORIGINAL ARTICLE Efficacy of a single dose albendazole chemotherapy on human intestinal helminthiasis among school children in selected rural tropical communities Ekaette Godwin Edelduok, Felicia Nkechi Eke 1, Ngozi Evelyn Ezenwaji 1, Chinedu Ifeanyi Atama 1, Joseph Effiong Eyo 1 Department of Biological Sciences, Akwa Ibom State University, Ikot Akpaden, Mkpat Enin, Akwa Ibom State, 1 Department of Zoology and Environmental Biology, University of Nigeria, Nsukka, Enugu State, Nigeria ABSTRACT Introduction: The impact of chemotherapy on human intestinal helminthiasis among school children in semiurban tropical communities of Igbo-Eze South Local Government Area of Enugu State, South-Eastern Nigeria, was investigated. Materials and Methods: Stool samples were obtained from 1296 school children (ages 4-15 years) from six schools randomly selected from the study area. Helminth eggs were recovered from stool samples. Those infected were treated with single oral dose of 400 mg albendazole tablets and re-examined for helminth eggs 4 weeks posttreatment. Results: Out of 1296 school children examined, 106 (8.1%) of the children were signi icantly (P < 0.05) infected with human intestinal helminths thus: 64 (4.9%) with Ascaris lumbricoides, 33 (2.5%) with hookworm and 9 (0.7%) with Trichuris trichiura. Out of the 64 children infected with A. lumbricoides, there was a reduction in the prevalence of infection by 18.8%. Furthermore, out of the 33 children infected with hookworm, there was a reduction in the prevalence of infection by 15.1%. Out of the nine children infected with T. trichiura, there was a reduction in the prevalence of infection by 22.2%. Conclusion: These indings suggest intestinal helminth speci icity to the ef icacy of albendazole. Thus, further research into the development of more effective antihelminthic drugs is necessary. Key words: Albendazole, Ascaris lumbricoides, chemotherapy, hookworm, human intestinal helminthiasis, rural tropical communities, school children, Trichuris trichiura Introduction Human intestinal helminthiasis is among the most common infections afflicting humans in developing countries. They are one of the world s most important causes of retardation of physical and intellectual growth in children. [1,2] Between 500 million and 1 billion people are estimated to be infected annually world-wide. [3] According to Crompton [4] an estimated 1472 million persons harbor Ascaris lumbricoides, 1298 millions are infected with hookworm and about 1049 million with Trichuris trichiura. The global estimated prevalence of anemia in hookworm infection and of cognitive impairment in hookworm, Ascaris and Trichuris infections indicated that for each parasite, million persons may Access this article online Quick Response Code: Website: DOI: / be affected. [5] Thus, human intestinal helminthiasis constitutes an important public health problem. Human intestinal helminthiasis can be prevented and controlled through various measures. According to Crompton, [4] measures to control these infections should be aimed at reducing morbidity. Chemotherapy has been an important measure used in controlling human intestinal helminthiasis. [6,7] The approach used in chemotherapy is often the mass treatment of human populations with antihelminthic drugs, a process known as mass drug administration. [7] World Health Organization (WHO) is actively promoting the approach of using antihelminthic drugs in the community to lower the intensity of human intestinal helminthiasis. [7] Schoolage children can benefit at any time from appropriate antihelminthic treatment given to reduce the intensity of infections. [8,9] Human intestinal helminthiasis can be treated with different drugs depending on the parasite involved. The efficacy of mebendazole against soiltransmitted nematode infections has been reported to be high. [9] Other antihelminthic drugs recommended by WHO for the control of soil-transmitted nematodes include albendazole, levamisole and prattle. [7] However, there have been concerns about the sustainability of Correspondence: Prof. J. E. Eyo, Department of Zoology and Environmental Biology, University of Nigeria, Nsukka, Enugu State, Nigeria. joseph.eyo@unn.edu.ng Annals of Tropical Medicine and Public Health Jul-Aug 2013 Vol 6 Issue 4 413

3 deworming with antihelminthic drugs and the emergence of resistance. Thus, many of studies have been carried out to assess the impact of chemotherapy on human intestinal helminthiasis. [9-15] This notwithstanding, much still remains to be known about the impact of a single dose chemotherapy on human intestinal helminthiasis especially among infected children of Igbo- Eze South Local Government Area (LGA). Therefore, this study was carried out to investigate the impact of alblendazole chemotherapy on school children infected with human intestinal helminths in Igbo-Eze South LGA, Nigeria. Materials and Methods Study area The study was carried out in rural tropical communities in Igbo-Eze South LGA, Enugu State, Nigeria. The sampled communities were Ibagwa-Aka, Iheakpu-Awka, Iheaka, Ovoko, Itchi and Unadu. The headquarters of Igbo-Eze South LGA is at Ibagwa-Aka. Igbo-Eze South LGA is located between latitudes 7 19 East and 7 28 East and longitudes 7 00 North and 6 53 North. [16] The area is in the guinea savannah forest mosaic zone of Nigeria. The study area has two main seasons; the rainy and dry seasons. The rainy season usually starts in April and ends in September while the dry season usually starts in October and ends in March. The soil is moist and porous, which favors the survival of soil-transmitted helminths ova. The inhabitants of this area are mainly subsistent farmers and traders. There are 17 health centers in the area, with a General Hospital at Itchi. The total population of people in the study area is 75,368. [17] There are 44 primary schools with 14,994 pupils in the study area; 8860 males and 6134 females. [18] Each of the schools have six classes; primary 1-6. Selection of schools and pupils Six schools were used for this study. Primary schools in the study area were listed out and six schools were randomly selected (Township School 1, Ibagwa, Community Primary School 3, Itchi, Central School, Ovoko, Central School, Iheaka, Community Primary School 1, Unadu and Community Primary School, Iheakpu-Awka) using table of random numbers. From each of the six schools selected, 36 pupils were randomly sampled for the presence of helminth egg in fecal matter. Six pupils were selected from each class (classes 1-6) to make up a total of 36. This was done using the register of each class. When any selected pupil was absent, a pupil after the indicated one was sampled for replacement. A total of 1296 pupils were sampled at the end of 6 months (July-December 2005). Edelduok, et al.: Efficacy of albendazole on human intestinal helminthiasis 414 Annals of Tropical Medicine and Public Health Jul-Aug 2013 Vol 6 Issue 4 Ethical issues Informed oral consent was obtained from the pupil and headmasters/headmistresses of the schools. In addition, a meeting was held with the parents/guardians of the pupils, informing them of the importance of the study and seeking for their consent. Any pupil not willing to take part in the study was excluded. Pupils who were positive for human intestinal helminths were treated with appropriate antihelminthic drugs using trained nurses. The study was approved by the University of Nigeria Teaching Hospital Research Ethics Committee. Collection and examination of stool samples Stool samples were collected monthly for a period of 6 months. Each of the selected pupils was given a small bottle in which they collected their stool samples. The bottles were labeled with the pupil s name, age and sex. On collection of the stool samples, they were taken to the Parasitology and Public Health Laboratory, Department of Zoology and Environmental Biology, University of Nigeria, Nsukka, Enugu State, Nigeria for examination. At the laboratory, for the diarrheic stool samples, a drop of fresh physiological saline was placed on a slide. Using a tooth peak, a small amount of a stool sample was mixed with saline and examined under the microscope using first, the 10 objective followed by 40 objectives to identify the eggs. [19] For the non-diarrheic stool samples, the formolether concentration technique was employed. [19] Using a stick, 1 g of the stool sample mixed with physiological saline was put in a screw-cap bottle containing 4 ml of 10% formol water. The bottle was capped and mixed by shaking for about 20 s. Thereafter, the stool sample was sieved and the suspension collected in a beaker. The suspension was transferred to a tube and 3 ml of ether was added. The tube was stoppered and mixed by shaking for 1 min. Thereafter, the stopper was removed and centrifuged immediately at 3000 rpm for 1 min. After centrifuging, four layers were evident; the top layer of ether, thin layer of debris, formalin and sediment in the bottom with parasites. An applicator stick was used to loosen the layer of stool debris from the side of the tube. The ether, debris and formalin were then carefully poured off. The sediment was mixed, transferred to a slide and covered with a cover glass. The slide was examined under the microscope using first, the 10 objective followed by 40 objective to identify the eggs. [19,20] Infection was defined by the presence of eggs of human intestinal helminths in the stool samples. The number of pupils infected with human intestinal helminthiasis and the type of human intestinal helminths eggs observed were recorded. [19] Post-treatment monitoring Pupils found to be infected with intestinal helminths were administered with single oral doses of 400 mg

4 Edelduok, et al.: Efficacy of albendazole on human intestinal helminthiasis albendazole tablets. Their stool samples were collected again after 4 weeks post-treatment and examined for the presence or absence of intestinal helminths. Treatment was said to be effective when the parasites were not observed and ineffective when parasites were observed during the examination. [19,20] Data analysis Differences in the prevalence of infection were determined using the χ 2 test from the contingency tables. χ 2 test was also performed to compare the effectiveness of treatment on the different human intestinal helminths recorded during the study. The analysis was performed using Statistical Package for Social Sciences (SPSS) version 22.0 (IBM SPSS, IBM Corporation, Armonk, New York , USA). Results and Discussion Human intestinal helminthiasis is important health problems in the school-age population. This study has shown that human intestinal helminthiasis is prevalent among school children in the study area. Of the 1296 school children examined for human intestinal helminthiasis, 106 (8.1%) were infected thus; 64 (4.9%) were infected with A. lumbricoides, 33 (2.5%) were infected with hookworm, while 9 (0.7%) were infected with T. trichiura. However, within the infected group, the prevalence was 60.4%, 31.1% and 8.5% for A. lumbricoides, hookworm and T. trichiura infections, respectively [Table 1]. There was a significant difference in the prevalence of infections among the school children (P < 0.05). The higher prevalence of A. lumbricoides infection than hookworm and T. trichiura infections was consistent with some previous reports. [21,22] This finding has important health implications for morbidity and transmission rates. The treatment of school children who had intestinal helminths infections with single oral dose of 400 mg albendazole tablets led to reduction in the prevalence of intestinal helminth (18.8% for A. lumbricoides, 15.1% for hookworm and 22.2% for T. trichiura), but were largely not effective as exemplified by the high prevalence of post-treatment helminths (81.2% for A. lumbricoides, 84.9% for hookworm and 77.8% for T. trichiura) [Table 2]. In contrast with our study, reports of high efficacies of albendazole against human intestinal helminthiasis may be attributed to differences in geographical locations, climatic conditions and hygiene; which scored low among the sampled pupils. [23-27] Nevertheless, Hall and Nahar [28] had shown that single oral dose of 400 mg albendazole gave cure rate of less than 40.0% for A. lumbricoides and T. trichiura in children in Bangladesh. Moreover, the low cure rate of albendazole against trichuriasis (22.2%) observed in this study was consistent with that of Adams and others who Table 1: Prevalence of human intestinal helminths among school children in the study area Human intestinal helminths found Number examined Number infected Overall prevalence (%) Prevalence (%) within the infected group (106) A. lumbricoides Hookworm T. trichiura Total A. lumbricoides = ascaris lumbricoides, T. trichiura = trichuris trichiura Table 2: Effectiveness of treatment of infected children with drugs (single oral dose of 400 mg albendazole tablets) in the study area Infection Number infected and treated Efficacy of treatment Effective (%) Not effective (%) A. lumbricoides (18.8) 52 (81.2) Hookworm 33 5 (15.1) 28 (84.9) T. trichiura 9 2 (22.2) 7 (77.8) Total (15) 87 (67.0) A. lumbricoides = ascaris lumbricoides, T. trichiura = trichuris trichiura reported of low efficacy of a single dose of albendazole against trichuriasis. [14] Treatment failures recorded after 4 weeks of treatment may be attributed to re-infection, resistance of the parasites to drugs and decline in the efficacy of the drug. This signals the need for close monitoring of the performance of the drug against human intestinal helminth parasites in the area. Re-infection is usually an important factor in treatment. Elkins and others reported A. lumbricoides re-infection reaching 55% of pretreatment rates. [29] Quinnell and others reported of rates of hookworm re-infection reaching 80% of pretreatment rates, [30] while T. trichiura re-infection had been reported to reach 44% of pretreatment rates. [31] Similarly, Albonico et al. reported high rates of posttreatment re-infection for human intestinal helminths in areas of high endemicity. [32] It is possible that re-infection may have occurred due to poor sanitary conditions and lack of proper health education. [3,33] Despite re-infection however, regular treatment to reduce the worm burden consistently could prevent some of the morbidity associated with chronic infection. Furthermore, it is possible that the parasites may have developed resistance to the drug. This possibility needs to be explored; using methods such as the egg hatch assay [34] to assess the susceptibility of intestinal helminths to albendazole. Also, the possibility of combining this drug with another effective antihelminthic drug to prolong its useful therapeutic life should be explored. Albonico et al. noted that combination therapy with drugs with differing modes of action is an alternative strategy to improve efficacy Annals of Tropical Medicine and Public Health Jul-Aug 2013 Vol 6 Issue 4 415

5 and lower the risk of resistance. [13] Indeed, Mani et al. had reported high efficacy of co-administration of albendazole and diethylcarbamazine against geohelminthiasis, [35] while Belizario and others also reported high efficacy of a combination of albendazole and ivermectin and a combination of albendazole and diethylcarbamazine, against trichuriasis compared with a single dose of albendazole. [36] The use of new drugs in treating human intestinal helminthiasis should also be explored. Already, nitazoxanide, a nitroimidazole compound that is increasingly used in children with giardiasis and cryptosporidiosis, is being explored as a broad-spectrum antiparasitic agent with antihelminthic properties. [37] In randomized studies in China, tribendimidine, a drug with low toxicity and broad-spectrum activity against many human intestinal helminthiasis, was found to be equivalent to mebendazole and albendazole for the treatment of A. lumbricoides, T. trichiura and hookworm infections and was better than these drugs for N. americanus infection. [15] However, the implementation of these measures must take into account, cost considerations and affordability in view of the weak economic background of rural communities where the drug is mostly needed. This study has shown that human intestinal helminth was prevalent among school children in Igbo-Eze South LGA, Enugu State. Even though the treatment failures recorded in the study may have been due to re-infection, the possibility of a decline in the efficacy of albendazole in treating human intestinal helminthiasis and possibly, resistance of the parasites to the drug, should not be overlooked. Efforts at developing and testing new control tools should be intensified. Vaccination, which offers the possibility of a simple, single step for the interruption of infection, disease and transmission, should be explored. Further investigations on the efficacy of the different antihelminthic drugs against human intestinal helminthiasis are necessary since these drugs are widely used for preventive chemotherapy. Moreover, health education and improvement of sanitary conditions should be encouraged since chemotherapy alone cannot efficiently control the transmission of infections in the community. These efforts could lead to substantial reductions in the disease burdens due to human intestinal helminthiasis. Acknowledgement We are thankful to Chief and Mrs. Asuquo Ekpeyong, parents of the first author for partially funding the study. We are grateful to the head teacher, teaching staff and pupils of the various primary schools in Igbo-Eze South LGA, Enugu State, Nigeria for their various contributions during the study. We are also Edelduok, et al.: Efficacy of albendazole on human intestinal helminthiasis 416 Annals of Tropical Medicine and Public Health Jul-Aug 2013 Vol 6 Issue 4 thankful to the Department of Zoology and Environmental Biology, University of Nigeria for the provision of laboratory space, equipments and analytical packages for the study and Miss Nkechinyere Onah, Department of Zoology and Environmental Biology, for typing the manuscripts. There is no conflict of interest among the authors and with any organizations. References 1. Nokes C, Grantham-McGregor SM, Sawyer AW, Cooper ES, Bundy DA. Parasitic helminth infection and cognitive function in school children. Proc Biol Sci 1992;247: Drake LJ, Jukes MC, Stemberg RJ, Bundy DA. Geohelminth infections (ascariasis, trichuriasis and hookworm): cognitive and developmental impacts. Semi Pediatr Infect Dis 2000;11: Prevention and control of intestinal parasitic infections. Report of a WHO Expert Committee. World Health Organ Tech Rep Ser 1987;749: Crompton DW. How much human helminthiasis is there in the world? J Parasitol 1999;85: Murray CJ, Lopez AD. Global Burden of Disease and Injury. Global Health Statistics. USA: Harvard University Press; Savioli L, Bundy D, Tomkins A. Intestinal parasitic infections: A soluble public health problem. Trans R Soc Trop Med Hyg 1992;86: Report of the WHO Informal Consultation on the Use of Chemotherapy for the Control of Morbidity Due to Soil-Transmitted Nematodes in Humans. 29 th April to 1 st May WHO/CTD/SIP/96.2. Geneva: World Health Organization; Nwaorgu OC, Okeibunor J, Madu E, Amazigo U, Onyegegbu N, Evans D. A school-based schistosomiasis and intestinal helminthiasis control programme in Nigeria: Acceptability to community members. Trop Med Int Health 1998;3: Albonico M, Ramsan M, Wright V, Jape K, Haji HJ, Taylor M, et al. Soil-transmitted nematode infections and mebendazole treatment in Mafia Island schoolchildren. Ann Trop Med Parasitol 2002;96: Bennett A, Guyatt H. Reducing intestinal nematode infection: Efficacy of albendazole and mebendazole. Parasitol Today 2000;16: Albonico M, Bickle Q, Haji HJ, Ramsan M, Khatib KJ, Montresor A, et al. Evaluation of the efficacy of pyrantel-oxantel for the treatment of soil-transmitted nematode infections. Trans R Soc Trop Med Hyg 2002;96: Albonico M, Bickle Q, Ramsan M, Montresor A, Savioli L, Taylor M. Efficacy of mebendazole and levamisole alone or in combination against intestinal nematode infections after repeated targeted mebendazole treatment in Zanzibar. Bull World Health Organ 2003;81: Albonico M, Engels D, Savioli L. Monitoring drug effi cacy and early detection of drug resistance in human soil-transmitted nematodes: A pressing public health agenda for helminth control. Int J Parasitol 2004;34: Adams VJ, Lombard CJ, Dhansay MA, Markus MB, Fincham JE. Effi cacy of albendazole against the whipworm Trichuris trichiura A randomised, controlled trial. S Afr Med J 2004;94: Xiao SH, Hui-Ming W, Tanner M, Utzinger J, Chong W. Tribendimidine: A promising, safe and broad-spectrum anthelmintic agent from China. Acta Trop 2005;94: Igbo-Eze South LGA. Map of Igbo-Eze South LGA. Ibagwa-Aka: Igbo-Eze South Local Government Secretariat; NPC. Population Census of Nigeria. Enugu State, Nigeria: National Population Commission; SUBEB. Pupil Enrolment in Primary Schools. Enugu State, Nigeria: Statistics Unit, State Universal Basic Education Board; Cheesbrough M. District Laboratory Practice in Tropical Countries. Part 1. Cambridge, UK: Cambridge University Press; Ash L, Orihel T. Atlas of Human Parasitology. 4 th ed. USA: American Society of Clinical Pathologists; Taiwo AK, Agbolade OM. Intestinal helminthiasis among school children in Oru, Ogun State, Nigeria. Niger J Sci 2000;34:283-6.

6 Edelduok, et al.: Efficacy of albendazole on human intestinal helminthiasis 22. Adeyeba OA, Akinlabi AM. Intestinal parasitic infections among school children in a rural community, southwest Nigeria. Niger J Parasitol 2002;23: Chien FL, Foon KL, Hassan K. Effi cacy of albendazole against the three common soil-transmitted helminthiases. Trop Biomed 1989;6: Sinniah B, Chew PI, Subramaniam K. A comparative trial of albendazole, mebendazole, pyrantel pamoate and oxantel pyrantel pamoate against soil-transmitted helminthiases in school children. Trop Biomed 1990;7: Albonico M, Smith PG, Hall A, Chwaya HM, Alawi KS, Savioli L. A randomized controlled trial comparing mebendazole and albendazole against Ascaris, Trichuris and hookworm infections. Trans R Soc Trop Med Hyg 1994;88: Norhayati M, Oothuman P, Azizi O, Fatmah MS. Effi cacy of single dose albendazole on the prevalence and intensity of infection of soiltransmitted helminths in Orang Asli children in Malaysia. Southeast Asian J Trop Med Public Health 1997;28: Sacko M, De Clercq D, Behnke JM, Gilbert FS, Dorny P, Vercruysse J. Comparison of the effi cacy of mebendazole, albendazole and pyrantel in treatment of human hookworm infections in the southern region of Mali, West Africa. Trans R Soc Trop Med Hyg 1999;93: Hall A, Nahar Q. Albendazole and infections with Ascaris lumbricoides and Trichuris trichiura in children in Bangladesh. Trans R Soc Trop Med Hyg 1994;88: Elkins DB, Haswell-Elkins M, Anderson RM. The importance of host age and sex to patterns of reinfection with Ascaris lumbricoides following mass anthelmintic treatment in a South Indian fi shing community. Parasitology 1988;96: Quinnell RJ, Slater AF, Tighe P, Walsh EA, Keymer AE, Pritchard DI. Reinfection with hookworm after chemotherapy in Papua New Guinea. Parasitology 1993;106: Chan L, Bundy DA, Kan SP. Aggregation and predisposition to Ascaris lumbricoides and Trichuris trichiura at the familial level. Trans R Soc Trop Med Hyg 1994;88: Albonico M, Smith PG, Ercole E, Hall A, Chwaya HM, Alawi KS, et al. Rate of reinfection with intestinal nematodes after treatment of children with mebendazole or albendazole in a highly endemic area. Trans R Soc Trop Med Hyg 1995;89: Ukoli FM. Prevention and Control of Parasitic Diseases in Tropical Africa: the Main Issues. Ibadan, Nigeria: University Press PLC; Albonico M, Wright V, Ramsan M, Haji HJ, Taylor M, Savioli L, et al. Development of the egg hatch assay (EHA) for detection of antihelminthic resistance by human hookworms. Parasitologia 2002;44 Suppl 1: Mani TR, Rajendran R, Munirathinam A, Sunish IP, Md Abdullah S, Augustin DJ, et al. Effi cacy of co-administration of albendazole and diethylcarbamazine against geohelminthiases: A study from South India. Trop Med Int Health 2002;7: Belizario VY, Amarillo ME, de Leon WU, de los Reyes AE, Bugayong MG, Macatangay BJ. A comparison of the effi cacy of single doses of albendazole, ivermectin, and diethylcarbamazine alone or in combinations against Ascaris and Trichuris spp. Bull World Health Organ 2003;81: Gilles HM, Hoffman PS. Treatment of intestinal parasitic infections: A review of nitazoxanide. Trends Parasitol 2002;18:95-7. Cite this article as: Edelduok EG, Eke FN, Evelyn NE, Atama CI, Eyo JE. Effi cacy of a single dose albendazole chemotherapy on human intestinal helminthiasis among school children in selected rural tropical communities. Ann Trop Med Public Health 2013;6: Source of Support: Nil, Conflict of Interest: None declared. Annals of Tropical Medicine and Public Health Jul-Aug 2013 Vol 6 Issue 4 417