Community control of Ascaris lumbricoides in rural Oyo State, Nigeria: mass, targeted and selective treatment with levamisole

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1 Community control of Ascaris lumbricoides in rural Oyo State, Nigeria: mass, targeted and selective treatment with levamisole 291 S. O. ASAOLU 1, C. V. HOLLAND 2 * and D. W. T. CROMPTON 3 1 Department of Zoology, Obafemi Awolowo University, Ile-Ife, Nigeria 2 Department of Zoology, Trinity College, Dublin 2, Ireland 3 WHO Collaborating Centre for Ascariasis, Department of Zoology, University of Glasgow, Glasgow G12 8QQ, Scotland (Received 2 February 1991; revised 25 March 1991; accepted 25 March 1991) SUMMARY A study to compare effects of mass, targeted and selective chemotherapy with levamisole (Ketrax) as an action for the control of Ascaris lumbricoides was carried out in three communities in rural Oyo State, Nigeria. Selective treatment was applied in one village by treating the most heavily infected 20 % of the inhabitants, targeted treatment in the second village involved children aged 2-15 years, while mass treatment was offered to all inhabitants excluding infants under 1 year and pregnant women in the third village. Recommended doses of levamisole were given in the villages, as described above, at 3-monthly intervals during a period of 1 year. Prevalence and intensity (epg) of A. lumbricoides infection were determined immediately before and 3 months after the period of intervention using a modified Kato-Katz technique. In the selective treatment village, no significant differences were found between the pre- and post-treatment egg counts (mean( + s.d.) epg versus respectively) of A. lumbricoides in the total population. In the targeted treatment village, significant differences were recorded in pre- and post-treatment egg counts for the total population ( versus 2579±6529) among the children alone ( versus ) and among the untreated adults ( versus 4561 ± 8798). In the mass treatment village, significant differences in pre- and post-treatment egg count values were also recorded ( versus ). The intensity of Trichuris trichiura and hookworm infections among the villagers before and after intervention were not observed to have changed significantly regardless of selective, targeted or mass treatment. Key words: Ascaris lumbricoides, treatment tactics, mass, targeted, selective, intensity, levamisole. INTRODUCTION Recent research has focused on the public health significance of the soil-transmitted helminths, particularly in relation to nutritional morbidity in growing children (Stephenson, 1987; Taren & Crompton, 1989). The prevalence of these infections remains staggeringly high, with Ascaris lumbricoides infecting about a quarter of the world's population (Crompton, 1989). Safe, effective anthelmintic drugs have been developed and used widely, but national control programmes in developing countries are still relatively rare. This scarcity can be partially explained by the cost of such programmes in the relevant countries and the difficulties inherent in establishing heath care priorities (Walsh & Warren, 1979). Improvements in sanitation, safe and adequate water supplies, personal hygiene and the extension of health education are necessary partners to any chemotherapeutic regime but the implementation of such improvements is slow and depends on general economic development. * Reprint requests to Dr C. V. Holland. These practical problems have led to the suggestion of novel approaches to control- using alternative cost-effective strategies. It has become increasingly obvious that a control programme can only be effective if detailed information on the epidemiology of the infections at the local level can be obtained (Holland & Asaolu, 1990; Nwosu, 1983). The aim of the present study was to compare the effectiveness of three approaches to chemotherapeutic measures against common soil-transmitted helminth infections. These approaches are described as mass, targeted and selective treatment (Anderson & Medley, 1985; Anderson, 1989) and can be defined as follows. Mass treatment is a population level application in which all members of the community who so wish are treated, irrespective of age, sex, social characteristics or infection intensity. Targeted treatment involves a group application where membership of the group may be defined by age, sex, religion, occupation or other characteristic. Selective treatment concerns individual application where selection is based on the intensity of current or past infection. Ascaris lumbricoides was the primary focus of treatment in this Parasitology (1991), 103, Printed in Great Britain

2 . O. Asaolu, C. V. Holland and D. W. T. Crompton 292 study, but the impact of the treatment tactics on infections of Trichuris trichiura and hookworm was also investigated. MATERIALS AND METHODS Village selection Four similar villages were selected for the study. The three experimental villages, Alakowe, Iyanfoworogi and Akeredolu, are all located in Oranmiyan Local Government Area (LGA) of Oyo State, Nigeria. A fourth village, Iloba, which served as a control, is located in the adjoining Atakumosa LGA. Each village lies within km of the Obafemi Awolowo University Campus at Ile-Ife. The villages are isolated from each other with limited contact between them and there was no evidence of previous experience of control programmes for soil-transmitted helminths. Villages were selected on the basis of their co-operation and their similar socio-economic profile. Houses in the village are built of mudwall and roofed with corrugated galvanized iron sheets. There is no organized sewage disposal system and refuse and human faeces are dumped in the bush behind each house. Sources of water are from ponds and streams located near the village. Children attend the primary school located in their own village and their parents are subsistence and cocoa farmers. The nearest hospital is located at Ile-Ife. Annual rainfall in the region ranges from 1000 to 4000 mm and falls mainly between April and October. The average maximum and minimum daily temperatures were 32 and 20 C respectively and the vegetation is rain forest. Study design Introductory meetings were held in several villages during November and December The purpose of the programme was explained to as many inhabitants as possible in each village. The four study villages were selected on the basis of cooperation by majority consent. The villages are similar in terms of population size (see Table 1), socio-economic characteristics and location in relation to Ile-Ife. A house-to-house survey was undertaken in each village. Each household was allocated a number which was written on the front of the house and a list of inhabitants was compiled with details of name, age and sex and each person received an ID number. Pre-treatment faecal samples were collected from all willing participants from each of the four villages in January and February 1989 (see Table 1). Anthelmintic treatment with levamisole (Ketrax, CAPL/Lagos, I.C.I. Pharmaceuticals, U.K.) used according to the manufacturer's instructions, was provided to each experimental village at 3-monthly intervals in March 1989, June 1989, September 1989 and December 1989, according to the following procedure (see Table 1). (a) Selective treatment was provided at Alakowe. On the basis of the faecal samples collected in January and February 1989 the 20 % most heavily infected individuals were selected for treatment. This was based on eggs per gram of faeces (epg) of Ascaris lumbricoides. Of the 286 individuals who provided faecal samples, 176 (61-5 %) were infected with A. lumbricoides and 36 of the infected group were found to have faecal egg counts of at least epg (representing the top 20%). These individuals comprised the group for selective treatment, (b) Targeted treatment was provided at Iyanfoworogi with children aged from 2 to 15 years comprising the group for targeted treatment, (c) Mass treatment was provided at Akeredolu. All willing residents were treated, but infants under the age of 1 year and pregnant women were excluded, (d) Iloba village acted as a control with no treatment being provided on any of the four occasions. Levamisole is now one of the anthelmintic drugs recommended on the WHO list of essential drugs (WHO, 1990). In March 1990, a post-treatment faecal sample was collected from as many inhabitants as possible from each village and mass treatment was then offered in all four villages to all willing participants. Parasitological procedures Each stool was mixed thoroughly and a portion was fixed in 10% aqueous formaldehyde. Samples were examined in the laboratory by means of the modified Kato-Katz procedure (WHO, 1985) and, in addition to qualitative diagnosis, an indirect measure of helminth intensity was obtained by counting eggs (epg). Statistical methods Pre-treatment and post-treatment intensity was expressed as the mean eggs per gram of faeces (epg) ± the standard deviation. Percentage prevalence was also described for each village before and after treatment and error bars representing the 95 % confidence level and assuming the binomial distribution were constructed. The difference between the pre-treatment and post-treatment mean parasite intensity was assessed using a paired i-test on the log(x+l) transformed data (epg) for each village. One-way ANOVA was used to examine the relationship between host age and post-treatment intensity. Repeated measures ANOVA was also performed in order to compare the impact of the three treatment strategies on helminth intensity. The change in intensity (or the difference in intensity after treatment) was compared in this way. All statistical tests were done with the 95 %

3 Treatment tactics for Ascaris control 293 Table 1. Details of the participating populations in the four villages Village Iloba (Control) Alakowe (Selective) Iyanfoworogi (Target) Akeredolu (Mass) Population Household number Mean household size (±S.D.) No. of pre-treatment faecal samples Percentage participation Age class (years) ± % ± ± % ± % Table 2. Pre-treatment and post-treatment intensity of Ascaris lumbricoides among the inhabitants of the study villages Village n (%) Pre-treatment Post-treatment Paired t-value (P value) Iloba (control) Alakowe (selective) Iyanfoworogi (targeted) Akeredolu (mass) 288* (68-2)t 185 (65-0) 211 (61-1) 224 (55-1) 7542±11785J 6775 ± ± ± ± ± (P ^ ) 1-63 (P^ 01045) 901 (P< ) (P< 00001) * Number of individuals who provided pre-treatment and post-treatment faecal samples. f Sample size presented as percentage of individuals who provided pre-treatment faecal samples. Intensity expressed as mean epg ( + S.D.). Comparison of the 36 selected individuals who received treatment revealed a pre-treatment mean (n = 24) and a post-treatment value of (t = 11-24; P < ). value of confidence limit but because of the large number of i-tests performed the confidence level was adjusted to take account of this. Given the number of tests employed the confidence level was set at the 99-7 % level. RESULTS Pre-treatment results Co-operation, with regard to the collection of pretreatment faecal samples, was satisfactory, with the percentage of the village population who provided samples varying from 85-6 % in Alakowe to 68-2 % in Akeredolu (Table 1). The age distribution of the four villages is also shown in Table 1, the proportion of children in each village was similar ranging from 45-5 % (Iyanfoworogi) to 54 # 1 % (Alakowe). In the village which received selective treatment, 69-4 % of the heavily infected individuals were children and 3O - 5 % were adults. In addition, 5 of these individuals were from the same household and a further 8 households had 2 or 3 heavily infected individuals within them. The prevalences and intensities of A. lumbricoides, T. trichiura and hookworm at the start of the study, before the first dose of anthelmintic drug was given, are shown in Tables 2 and 3 for the participants in each village. The results of other investigations show that Necator americanus is the common species of hookworm in this part of Nigeria (see Oyerinde, 1978). Further details about the epidemiology and population biology of the study communities will be described elsewhere (Asaolu et al.; personal observations).

4 S. O. Asaolu, C. V. Holland and D. W. T. Crompton 294 Table 3. Pre-treatment and post-treatment intensity of Trichuris trichiura and hookworm sp. for the four villages Village Parasite Pre-treatment Post-treatment Iloba Alakowe Iyanfoworogi Akeredolu Trichuris Hookworm Trichuris Hookworm Trichuris Hookworm Trichuris Hookworm ± n c jo 80- > 60 i> g H IL (pre) IL (post AL (pre) AL (post) IY (pre) IY (post) AK (pre) AK (post) Villages Fig. 1. Percentage prevalence of Ascaris lumbricoides pre- and post-treatment in the four villages. The error bars represent the 95% confidence limits assuming a binomial distribution. IL, Iloba; AL, Alakowe; IY, Iyanfoworogi; AK, Akeredolu; pre, pre-treatment; post, post-treatment. Post-treatment results The effects of the different applications of chemotherapy were measured by comparing the pre- and post-treatment values for intensity (Tables 2 and 3). The comparisons were restricted to individuals from whom stool samples had been collected on both occasions (January/February 1989 and March 1990). The mean epg( + s.d.) of A. lumbricoides before and after treatment for each village are presented in Table 2. The percentage prevalence and the associated 95 % confidence limits for each village before and after treatment are shown in Fig. 1. The mean intensity of A. lumbricoides was reduced in the control village, Iloba, but not significantly so. In Alakowe, when the results from the 36 individuals who participated in the selective treatment are examined individually they show a very significant reduction in intensity after treatment, in contrast to the intensity value in the village as a whole (see Table 2). Of the 36 individuals originally selected, posttreatment samples were collected from 24. Of the 12 missing individuals, 6 left the village during the period of the study and the other 6 did not provide faecal samples. The inclusion of these 12 individuals may have had a further reducing impact on the posttreatment result. In addition, if the same cut-off of epg for heavy infection is used based on 20 % of the population, 9 individuals were found to fall into this category after treatment compared to 36 before treatment. This represented 8 % of the infected individuals. In Iyanfoworogi, the targeted village, a significant reduction in the mean intensity of A. lumbricoides for the entire community examined was found after treatment (Table 2). A separate analysis was undertaken of the target group (2-15 years: n = 105) and the adult age classes (^16 years: n = 94). This revealed a highly significant reduction in intensity in the child age classes (t = 9-93, P < 00001) as expected, but in the adult age classes a significant reduction in intensity was also observed ( pre-treatment versus post-treatment) despite the fact that these individuals deliberately did not receive treatment as part of the study design (t = 3-71, P^ ) (Table 2, Fig. 2B).

5 Treatment tactics for Ascaris control CH i 3 <" c CD 0) g c i Total Age group Age class Total Age group Fig. 2. Mean intensity of Ascaris lumbricoides expressed as eggs per gram of faeces (epg) pre- ( ) and posttreatment {M) in (A) Akeredolu (mass treatment) and (B) Iyanfoworogi (targeted treatment). Data are presented for all ages, greater than 16 years and less than IS years. In Akeredolu, where mass treatment was provided to all willing participants, a similarly highly significant reduction in intensity in all age classes was observed (Table 2, Fig. 2 A). In this village samples were obtained from 92 adults and 132 children. When the relationship between post-treatment intensity values and age was investigated in Akeredolu no significant relationship was found, in contrast to the trend observed prior to treatment (Fig. 3A). This pattern differed in Iyanfoworogi where a significant difference was detected between the 1 to 14-year-old age classes in contrast to the 15 to 50- year-old age classes (Fig. 3B). Intensity did differ significantly between age class (P < ) with values being higher in the adult age classes. With regard to T. trichiura and hookworm, the administration of levamisole under the study regime was not found to have any strong long-term impact on intensity. Only in Iloba, where no drug was administered, a significant reduction in the intensity of T. trichiura was observed (P < 00001) (Table 3). Finally, an analysis was undertaken to compare the impact of treatment in the three experimental Age class Fig. 3. Mean intensity of Ascaris lumbricoides (epg) pre- (H) and post-treatment ( ) for all ages classes in (A) Akeredolu and (B) Iyanfoworogi. villages. A repeated measures analysis of variance on the log(x+l) transformed counts of intensity of A. lumbricoides was undertaken in order to compare the difference (or change) in intensity after treatment in Alakowe, Iyanfoworogi and Akeredolu. This recorded a significant difference in the impact of the three treatments (F ratio = 26-88; D.F. = 2,617; P < ). Individual comparisons also recorded some significant differences between the mass and selective treatments (2 = 7-11; Ps 00001), the mass and targeted treatments (t = 2-65; P ^ 0082) and the selective versus the targeted treatments (t = 4-63; P^ ). DISCUSSION Control strategies can be viewed in terms of shortterm and long-term objectives (WHO, 1987). Longterm objectives, which would constitute a reduction in prevalence and intensity of soil-transmitted helminths, would involve the improvement of sanitary facilities, the provision of safe water supplies, the promotion of personal and food hygiene and the safe disposal of waste. These objectives are likely to take a long time to implement, to be costly and will need to be accompanied by social, economic and educational development (WHO, 1987). In the short

6 . O. Asaolu, C. V. Holland and D. W. T. Crompton 296 term the objectives would be to substantially reduce morbidity and mortality due to the soil-transmitted helminths. Community-based chemotherapy is regarded as the principle way to achieve these shortterm objectives and the best and most cost effective approach to the application of chemotherapy is under review (Davis, 1985). The main issues relate to the extent of population coverage, the frequency of drug administration and the duration of the attack phase (Yokogawa, 1985; Davis, 1985; Seo & Chai, 1979; Seo et al. 1980). The current study focused upon the efficacy of mass, targeted and selective chemotherapeutic strategies as a means of shortterm control of ascariasis in endemic village communities. Under the conditions of the study design and the drug regimes used, no significant effects were observed against hookworm infection and trichuriasis. Based on their experience in Kenya, Stephenson, Latham & Oduori (1980) have strongly supported the concept of mass treatment in preference to other chemotherapeutic approaches. Advantages include elimination of time and cost spent on regular stool examination and the use of relatively unqualified personnel to undertake the programme. The present study illustrated the effectiveness of mass treatment in significantly reducing Ascaris intensity. In contrast, Elkins, Haswell-Elkins & Anderson (1986) have argued that, in spite of the availability of cheap and effective drugs, the frequent use of large quantities of anthelmintics necessary in mass chemotherapy will be prohibitively expensive for most developing countries. The soil-transmitted helminths are more prevalent and the worm burdens are much higher among the child age classes, particularly those aged 2-15 years. In fact, in the order of % of the worms in a given community may be harboured by this age group (Oduntan, 1974; Nwosu, 1983; Elkins et al. 1986). Children are obviously at greater risk in terms of morbidity associated with heavy worm burdens and are likely to act as significant contributors of infective stages into their environment. Children have therefore been suggested as a suitable target group for anthelmintic treatment as an alternative to mass chemotherapy (Nwosu, 1983; Haswell-Elkins, Elkins & Anderson, 1989). Apart from the advantage of using a smaller quantity of the drug there are significant practical advantages in administration. Children can be easily reached through their attendance at school (Stephenson et al. 1980). In the present study targeted treatment of children aged 2-15 years was found to be an effective strategy both in terms of reducing helminth intensity in the community as a whole, as well as the child age classes. It was of particular interest that the adults, who had received no treatment, also showed a significant reduction in Ascaris egg counts. A related observation has been made by Bundy et al. (1990) who undertook age-targeted chemotherapy with albendazole (children aged 2-15 years) on the island of Montserrat. A marked reduction in intensity of T. trichiura was observed not only in the target age classes but also in young adults (16 25 years) of whom less than 4 % had received treatment. Comparisons between the present study in Nigeria and that of Bundy et al. (1990) are difficult to make because the overall prevalence of A. lumbricoides in Montserrat was found to be no more than 1-8%. Nevertheless the auchors concluded that the target treatment in Montserrat had had an effect on A. lumbricoides similar to that observed against T. trichiura. In the targeted village in the present study (Iyanfoworogi) no adults received treatment as part of the study and there was no evidence that a significant number undertook self treatment. The application of treatment at 3-monthly intervals as undertaken in the present study may not be practical under conditions of scarce resources. Despite this, evidence has indicated that even when mass treatment is provided, intervals of 2 4 months are necessary to reduce Ascaris intensity to low levels (Anderson, 1986). An important characteristic of the population biology of the intestinal helminths is their aggregated distribution within a community (see Anderson, 1986). In general, most individuals harbour few or no worms whereas a small number of hosts harbour very heavy worm burdens. There is also increasing evidence that individuals are in fact predisposed to harbour heavy or light helminth infections. The identification and selection of such individuals for chemotherapy is based on the assumption that they are predisposed to heavy infection and could be subjected to repeated anthelmintic treatment without having to repeat assessment of their faecal egg output prior to each round of treatment. By treating such individuals, the intensity of infection, the morbidity associated with heavy infection and contamination of the environment with infective stages in the community as a whole would be considerably reduced. Our findings indicate that under these study conditions the selective approach has little impact on the prevalence and intensity of Ascaris within the community as a whole. One important problem with the selective approach is that no account of new immigrants into the village was taken after the programme started in March This issue does not arise with respect to the mass or targeted approach because every new immigrant child in the targeted village and all new subjects in the mass village automatically qualify for treatment. This means that constant surveillance and stool examination would still be required in the selective treatment approach. Haswell-Elkins et al. (1989) pointed out that the selective strategy may not be more effective than age-targeted treatment if heavily

7 Treatment tactics for Ascaris control 297 infected individuals are not identified at each round of treatment. Recently, Keymer & Pagal (1990) have emphasized that the impact of selective treatment is very much dependent upon the mechanisms responsible for the generation of over-dispersion and predisposition, mechanisms which are still relatively unknown. In addition, and perhaps even more importantly, the selective approach had a negative impact on the attitude of the village inhabitants to treatment. There was considerable resentment when certain individuals were selected while others were excluded. This is in contrast to the targeted approach ; adults were able to understand that their children were at risk and needed treatment. Finally the identification of heavily infected individuals using an indirect measure of intensity, egg counts, is worthy of comment. Haswell-Elkins et al. (1989) found that a single egg count per individual was 65 % effective in identifying the heavily infected group both before and after treatment. In large-scale control programmes, practical and logistical factors are likely to determine the use of egg counts as estimates of helminth intensity in contrast to worm burdens. In conclusion, although mass treatment proved to be the most effective strategy, in reducing Ascaris intensity in the study area, targeted treatment was also found to have a significant impact both in the child and untreated adult age classes. Whatever treatment tactic is adopted in a control programme many local factors will need to be considered and will include epidemiology of the infections, characteristics of the target populations and components of the delivery system used (Davis, 1985). An evaluation of the relative cost of these approaches in terms of man hours, transportation and material input will be the subject of a further paper. The authors wish to thank J. O. Jegede, M. A. Adeyemi and R. C. Stoddart for skilled field and technical assistance. The financial support of ICI Pharmaceuticals, U.K., is gratefully acknowledged. The authors are also grateful to Graham Medley for his helpful comments on the manuscript. REFERENCES ANDERSON, R. M. (1986). The population dynamics and epidemiology of intestinal nematode infections. Transactions of the Royal Society of Tropical Medicine and Hygiene 80, ANDERSON, R. M. (1989). Transmission dynamics of Ascaris lumbricoides and the impact of chemotherapy. In Ascariasis and its Prevention and Control (ed. Crompton, D. W. T., Nesheim, M. C. & Pawlowski, Z. S.), pp. 2S London and Philadelphia: Taylor ANDERSON, R. M. & MEDLEY, G. F. (1985). Community control of helminth infections of man by mass and selective chemotherapy. Parasitology 90, BUNDY, D. A. P., WONG, M. S., LEWIS, L. L. & HORTON, J. (1990). Control of geohelminths by delivery of targeted chemotherapy through schools. Transactions of the Royal Society of Tropical Medicine and Hygiene 84, CROMPTON, D. w. T. (1989). Prevalence of ascariasis. In Ascariasis and its Prevention and Control (ed. Crompton, D. W. T., Nesheim, M. C. & Pawlowski, Z. S.), pp London and Philadelphia: Taylor DAVIS, A. (1985). Ascariasis: drugs and drug policy. In Ascariasis and its Public Health Significance (ed. Crompton, D. W. T., Nesheim, M. C. & Pawlowski, Z. S.), pp London and Philadelphia: Taylor ELKINS, D. B., HASWELL-ELKINS, M. & ANDERSON, R. M. (1986). The epidemiology and control of intestinal helminths in the Pulicat region of Southern India. I. Study design and pre-and post-treatment observations on Ascaris lumbricoides infection. Transactions of the Royal Society of Tropical Medicine and Hygiene 80, HASWELL-ELKINS, M., ELKINS, D. & ANDERSON, R. M. (1989). The influence of individual, social group and household factors on the distribution of Ascaris lumbricoides within a community and implications for control strategies. Parasitology 98, HOLLAND, c. v. & ASAOLU, s. o. (1990). Ascariasis in Nigeria. Parasitology Today 6, KEYMER, A. E. & PAGAL, M. (1990). Predisposition to helminth infection. In Hookworm Disease : Current Status and New Directions, (ed. Schad, G. A. & Warren, K. S.), pp London and Philadelphia: Taylor NWOSU, A. B. c. (1983). The human environment and helminth infections: a biomedical study of four Nigerian villages. In Human Ecology and Infectious Diseases (ed. Croll, N. A. & Cross, J. H.), pp New York: Academic Press Inc. ODUNTAN, s. o. (1974). The health of Nigerian children of school age (6-15 years). II. Parasitic and infective conditions, the special senses, physical abnormalities. Annals of Tropical Medicine and Parasitology 68, OYERINDE, J. P. o. (1978). Human Ancylostoma infections in Nigeria. Annals of Tropical Medicine and Parasitology 72, SEO, B. s. & CHAI, j. Y. (1979). Frequency distribution of Ascaris lumbricoides in rural Koreans with special relevance to the effect of changing endemicity. Korean Journal of Parasitology 17, SEO, B. S., CHO, S. Y., CHAI, J. Y. & MONG, S. T. (1980). Comparative efficacy of various interval mass treatment of Ascaris lumbricoides infection in Korea. Korean Journal of Parasitology 18, STEPHENSON, L. s. (1987). Impact of Helminth Infection on Human Nutrition. London and Philadelphia: Taylor STEPHENSON, L. S., LATHAM, M. C. & ODUORI, M. L. (1980). Costs, prevalence and approaches to control of ascariasis in Kenya. Journal of Tropical Pediatrics 26, TAREN, D. L. & CROMPTON, D. w. T. (1989). Nutritional interactions during parasitism. Clinical Nutrition 8,

8 . O. Asaolu, C, V. Holland and D. W. T. Crompton 298 WALSH, j. A. & WARREN, K. s. (1979). Selective primary care. New England Journal of Medicine 301, WORLD HEALTH ORGANIZATION (1985). Diagnostic techniques for intestinal parasitic infections (IPI) applicable to primary health care (PHC) services. WHO/P.D.P./85.2, Geneva. WORLD HEALTH ORGANIZATION (1987). Prevention and control of intestinal parasitic infections. WHO Technical Report Series No Geneva. WORLD HEALTH ORGANIZATION (1990). The USe of essential drugs. WHO Technical Report Series No Geneva. YOKOGAWA, M. (1985). JOICFP's experience in the control of ascariasis within an integrated programme. In Ascariasis and its Public Health Significance (ed. Crompton, D. W. T., Nesheim, M. C. & Pawlowski, Z. S.), pp London and Philadelphia: Taylor