Drugs 15 (Suppl. 1): 87-93 (1978) © ADIS Press 1978
Session III: Helminthiasis: Treatment with Oxantel-pyrantel, contd. Chairman: Dr B.D. Alora (Manila)
A Review of Trichuriasis, its Incidence, Pathogenicity and Treatment Pedro P. Chanco, Jr. and Julieta Y. Vidad Faculty of Medicine and Surgery. University of Santo Tomas. Philippines
Summary
The incidence and pathogenicity qf trichuriasis is reviewed. Reference is made to earlier. largely unsucces~ful. treatments. and to mebendazole. Oxantel, the most recent drug shown to be effective against Trichuris is discussed, as is oxantel-pyrantel which promises to be effective against mixed helminthic infections.
J. Incidence The incidence of Trichuris trichiura is very variable, it being more common in the tropical developing countries where sanitation and nutrition are poor. The moist humid climate of these countries, coupled with the use of night soil in agriculture, increase the chances of contracting intestinal parasitism. Keller et al. (I 938) in their study of the incidence and distribution of intestinal parasites in North Carolina found only 0.5 % of 37,346 specimens from
white persons to be positive for Trichuris and the average intensity was a very low, 1,400 eggs/ml of stool. Among the Negroes, he found an incidence of 3 % of 6,301 specimens in the same area, but Negroes in the coastal part of the state had a higher incidence, varying from 10.7% to 24.8% with an average intensity of 1,500 eggs/ ml of faeces. Anders (I 953) found 132 of 13,331 school children in Berlin to be infected with Trichuris, of which 17.5 % showed distinct symptoms and 30 % only slight symptoms, In all the areas studied, the overall inci-
88
A Review of Trichuriasis
dence of Trichuris was only 3 %. This was correlated not with the age but with the poor sanitation of the areas and use of night soil during the immediate postwar period. Neghme and Silver (I 964) found an incidence of trichuriasis of 25 % in the general population and 40 % among school children from 1948 to 1954, but only 19 % and 20 % respectively from 1957 to 1962. He attributed this decrease to the better sanitation, diagnostic facilities and paved streets. Jjumba-Jukasa and Gunders (I 97 J) observed that the incidence of ascariasis and trichuriasis in the Jewish population, after the establishment of the State of Israel in 1948, began to decline by 1950 from the 40 % for ascariasis to less than 1 %, and for trichuriasis from 17 % to 1 %, because of the elimination of Arab grown vegetables from the Jewish markets. Kan and Cheah (I 97 J) found that Trichuris trichiura was the most common helminthic infection encountered in Singapore among adults up to 60 years of age. He also observed more single infections of Trichuris. Chanco and Reyes (I 97 J) using concentration techniques, found an incidence of 76% for Trichuris and only 25 % for Ascaris among 371 medical technology students who were positive for intestinal parasites. Medical technology students have an average age of 19 to 21 and belong to a higher economic echelon of the population and are apparently more health conscious. Araullo-Cruz et al. (1968) in a survey of intestinal helminthiasis among pre-school children, school children and adults of Bay, Laguna in the Philippines obtained an incidence of 85 % for trichuriasis and 82.7% for ascariasis. Pesigan et al. (I968)from 1948 to 1951, out of 123,291 specimens from the general population, obtained an incidence of trichuriasis of 52 %. Other workers in the Philippines have reported incidence rates varying from 52 to 93 %. With one exception only Chanco used concentration techniques (acid-ether concentration technique); the other surveys usually employed only direct faecal smears. They may have reported higher incidences had they used a concentration technique. The incidence of ascariasis reported in these surveys declined with age but that of trichuriasis in-
creased, although those in the lower age groups had more severe infections. This is probably explained by the fact that Ascaris generally leaves the body after 1 or 2 years, of its own accord, whereas an infection with Trichuris builds up with age as more and more raw salads enter the diet of the growing individual. Ascariasis is generally associated with the dirty habits of young children who take soil into their system in one way or another.
2. Pathogenicity
Apparently, Trichuris trichiura has been with man for a long time. Pizzi and Schenone (I955) reported finding the ova of this nematode parasite of man, in great numbers, in the faeces of an Inca child frozen in a mountain, 17,658 feet above sea level, near Santiago. The body was exceptionally well preserved and its antiquity calculated to be 450 years or more. However, the pathogenicity of Trichuris trichiura has not always been universally accepted. Kouri and Valdez Diaz (I953) recorded their views on the pathogenicity of the human whipworm. They claim that two strongly opposed opinions prevail: one group, particularly those workers from areas where infection is mild, makes light of the infection, regarding it as little more than a harmless commensal; the other group, and this includes most workers in the developing countries, believes that it can be markedly pathogenic, causing inflammation, ulceration and in some cases resulting in death. Kouri and his colleague described a condition which they term 'massive infantile trichuriasis' which resists all treatment and ends fatally. Inflammation of the descending colon and the sigmoid occurs, with haemorrhages and mucopurulent stools and often with rectal prolapse. Symptoms may be produced when Trichuris is the only parasite present, but naturally they are aggravated when there is Entamoeba histolytica or Balantidium coli infection also. Guiliani (I 956) reported the presence of Oxyuris in 11.3 % and Trichuris in 2 % of 150 appendices removed and found that the worms were more com-
A Review of Trichuriasis
89
mon (I 7 cases) in chronic appendicitis than in acute with a high or medium worm load ( > I O,OOU oval g), and subacute (2 cases only). Desportes (I 938) re-ex- 40 were retarded by one year or more. Of I 3 I with amined material preserved from autopsies, performed low worm loads, 40 were retarded and of I I 9 who by Brumpt in 1909, on persons dying of various were negative, 28 were retarded. In children with complaints in the old Hospital de la Pitie. The worm loads of more than 5,000 ova/g, 58.3 % were material consisted of caecum and appendix. For retarded and of the 108 children retarded by one year Trichuris, of the 369 caeca examined 50.7% were in- or more, 71 came from poor families. Soriano et al. (1969) from the Philippines reported fected, the maximum number of worms in one organ being 82. Balland, cited by Desportes, examined 389 I 0 cases of rectal prolapse in children with caeca and appendices for a thesis published in I 91 0 trichuriasis. Chanco et al. (I 973) reported 131 cases and reported 54.7% infected with Trichuris. of trichuriasis in which the highest incidence was in Ballesteros Bernudez and Burgos Courlaender the age groups up to I 0 years, although in the 16 to (I 956) reported a chronic diarrhoeal syndrome 20 age group there were almost as many cases. Chancaused by whipworms. The basis for their diagnosis co et al. (I 974) also reported 23 patients, all less than was the presence of adult parasites attached to the 8 years, suffering from prolapse of the rectum secmucosa in rectal prolapsus, which they considered ondary to trichuriasis. pathognomonic. Rectosigmoidoscopy was used to Layrisse et al. (1968) investigated the blood loss confirm the diagnosis, the degree of infection and to due to infection with Trichuris trichiura. He reported reveal other lesions unconnected with the presence of 9 children harbouring whipworms, and no other whipworms. Wong and Tan (I 96 I) from the parasites of significance, to be losing 0.8 to 8.6ml of Pediatric Unit of the General Hospital in Singapore, blood/ day with a mean of 4.1 ml. The blood loss was reported that whipworm infections were by no means roughly proportional to the number of worms always mild and symptomless. With heavy infec- recovered, which in this study ranged from 86 to tions, chronic dysentery and blood loss, anaemia, ab- 3,009. The egg count had no correlation with the dominal pain and tenesmus, ulceration of the rectal blood loss. In the author's opinion, infections with colonic mucosa and prolapse of the rectum may oc- 800 worms may produce blood loss that could cause cur. Similar cases have been reported from Ceylon clinical anaemia, particularly if the child is poorly and by Winship (I 959) from South Africa. Most of nourished and in great need of iron. the patients were children 2 to 5 years of age and had In contrast Hartz (I 954), who made a had symptoms for 6 months to 2 years. 50 % had histopathological study of the colon in Trichuris inhaemoglobin levels below 8.8 % and 35 % below fection in children, believed that the only lesion that 6.0 % and 70 % of the children had rectal prolapse on could be attributed to the infection was mechanical admission. On sigmoidoscopy 90 % were seen to compression of the cells of the colonic mucosa. He have bleeding ulcers. suggested that some of the symptoms found in De Carneri et al. (I 968) investigated the part play- Trichuris infections are caused by irritation of the ed by Trichuris infections in delayed mental and nerves of the colonic mucosa. He further claimed that physical development of children in Northern Italy. in view of the fact that trichuriasis is seldom found Of the 359 children examined, 233 had Trichuris in- without associated infections with other parasites, fection and only I 9 had ascariasis. All patients with Shigella and malnutrition, these factors must be exAscaris also had Trichuris. 47.6 % of the Trichuris in- cluded before accepting Trichuris as the cause of fected children were found to be normal mentally and symptoms like anaemia. Atlas and Gajardo (I 956) in physically. The rest had some disturbance in growth their study of cases of massive trichuriasis in children which in 14 % was considered to be pathological. in Chile, concluded that the factors that probably exWith regard to scholastic progress, of 88 children plain the severe course of infection are the nutritional
A Review of Trichuriasis
deficiency, avitaminosis and very poor sanitary conditions in which the patient lives rather than the whipworm only. The cases they studied were autopsied and found to have histological alterations suggesting pellagra. However, Swartzwelder (t 940) made a detailed analysis of 81 cases of uncomplicated Trichuris infection and from the following results suggesting that whipworms per se can cause symptoms and illness. Most of the patients were from 6 to 15 years old and white patients outnumbered coloured in the ratio of 5: I; there were twice as many females as males. The most frequent symptoms were abdominal or epigastric pain, vomiting, constipation, fever, distention and flatulence, headache, backache, loss of weight and anorexia. The duration of symptoms was 3 months in 44 cases. Most of these 81 cases were clinically diagnosed as parasitism, with chronic appendicitis the next most common diagnosis. Physical examination frequently revealed abdominal tenderness without rigidity. Only 7 cases had a temperature above I 0 1of. The average eosinophil count was 4.2 % and the maximum 24 % . Miranda (t 957) studied the bone marrow in children with ancylostomiasis and trichuriasis. Unfortunately, only 3 of his cases had trichuriasis alone. All the others had both ancylostomiasis and trichuriasis, or ancylostomiasis alone. The bone marrow findings were the same in those with ancylostomiasis alone, with trichuriasis alone, or with both nematode infections.
90
complete eradication of Trichuris in our patients treated for colonic amoebiasis who had concomitant Trichuris infection. Basnuevo (Basnuevo et al., 1952) was an ardent user of hexylresorcinol 1:300, as a retention enema; he published several papers and reported 100 % cure rates. Da Costa et al. (1952) reported that the use of hexylresorcinol crystoids for the removal of Trichuris gave very poor results. Perez-Santiago et al. (t 952) used cyanine dye for the treatment of hookworm and Trichuris and concluded that it was neither as effective an anthelminthic as tetrachlorethylene nor as well tolerated there being toxic side-effects. MacCarthy (t 954) used 0.5g enteric-coated capsules of papain and claimed I 00 % success in the I 0 children treated, without side-effects. Jung (1955) modified the hexylresorcinol retention enema of Basnuevo but cured only I of 22 subjects. It is a disappointing and dangerous drug. Benarroch and Villegas (t 957) found a combination of tetrachlorethylene and chenopodium to be better than hexylresorcinol in removing hookworm, Ascaris and Trichuris but this did not result in the complete eradication of Trichuris. Da Costa (t 956) tried a combination of hexylresorcinol and mepacrine for the treatment of hookworm, ascariasis and trichuriasis but the results were inconclusive. Hoekenga (I956) tried 13 different drugs, or combinations of drugs, and found that a mixture of tetrachlorethylene and oil of chenopodium was best although it did not give a complete cure. Hucker and Schofield (I 957) tried four piperazine compounds - phosphate, acetate, adipate and citrate, in doses equivalent to 500mg of the hexahydrate, tid 3. Treatment for 7 days; they found no significant decrease in egg count. Until the introduction of mebendazole the treatDithiazanine was found by Frye et al. (I 958) to be ment of trichuriasis was always a problem. effective against Trichurisin doses of 200mg given as Maplestone and Mukerji (t 940) prescribed the enteric-coated tablets tid for 5 days. We found (ChanCalcutta Hospital stock mixture of iron for removing co, 1959) diathiazanine iodide in a dose of 100mg tid Trichuris. After 2 weeks treatment with this mixture, after meals for 5 to 7 days gave an 83 % cure rate 18 of I 9 patients were still infected. Good results with fewer side-effects than the 200mg dose. Paine et were claimed with 2 grains of enteric-coated emetine at. (I 960) used 200mg tid for 5 days and claimed an given for 6 days. Enteric-coated tablets of efficacy of 93 % although Basnuevo et al. (I 960) dehydroemetine caused some diminution but not using the same dose, obtained only 62 % success in
91
A Review of Trichuriasis
the treatment for trichuriasis. Riera (J 96 I) used the drug in children at a dose of 100mg/5kg and obtained 50 % cure, including cure of those with rectal prolapse but there were many side-effects such as nausea, vomiting and urticaria. Fernando (1961) also used dithiazanine for the treatment of trichuriasis in children but cleared only II of 24. Correa (J 96 I) treated trichuriasis with either 100 or 200mg tid for 7 days. At the higher dose 9 of II became negative, but in the 100mg dose group all 7 were cured and those on the lower dosage had fewer, milder sideeffects. Vakil and Menta (I 962) used diathiazanine at a dose of 200mg tid for 5 days; 15 of 20 Trichuris cases were freed of parasites and those who were not had a marked decrease in egg counts. Trichlorophenol-piperazine salt was used by Burnett and Wagner (1962) for the treatment of worms, including Trichuris. The drug removed Ascaris and a few of the hookworm but had no action on Trichuris. Huan and Brown (I964) used stilbazium iodide, but of 23 children with Trichuris treated with 8.8mg/kg bid only 9 were cleared, although the rest had a marked reduction in egg count. Campos et al. (J 968) used stilbazium iodide with better success; their most effective dose was 20mg/kg, with which they cured 15 of 20 patients with trichuriasis. Salunkhe et al. (1964) tried thiabendazole, 1.25g to 2.5g in the morning after breakfast in a chocolate-flavoured suspension, as one dose, but found it disappointingly ineffective. With mebendazole, we were able to completely eradicate trichuriasis in 129 (98 %) of 131 cases of all ages. The 2 cases who were not completely cured had egg counts reduced from > 100 oval coverslip to about 20 oval coverslip, indicating a great reduction in worm burden. Most cures were achieved by the time of the first post-treatment examination. There were no side-effects important enough to preclude continuation of treatment and no patient complained of side-effects. Although mebendazole seems to be very effective in the treatment of trichuriasis, it is not the ideal drug for multiple parasitic infections, particularly in the presence of Ascaris which may become erratic or ectopic. We have seen many cases, particularly in
children, of errant Ascaris with the use of mebendazole in the treatment of Trichuris with accompanying ascariasis. Oxantel, the most recent treatment for trichuriasis, is likely to supersede the variety of earlier drugs described. When first used we chose a dose of 10mg/kg, given on a single occasion. The results were poor. By increasing the dose to 20mg/kg we imprOVed our cure rate but still did not attain that we have described using mebendazole (Chanco et al., 1973). Giving oxantel at 20mg/kg, twice, on 2 consecutive days, we improved our cure rate to almost 100 %, but lost the advantage of the single dose regimen. In a study in which 25 patients with trichuriasis were given a single dose of oxantel-pyrantel at a dose of 20mg/kg, 19 patients (76 %) were cured and the egg counts in the remaining 6 diminished from 50 to I I coverslip. Work is now going on in a rural setting, in which people are living in a confined area in the Mountain Province of the Philippines; hookworm is also present. Weare giving oxantel-pyrantel suspension at a dose of 15mg/kg, after breakfast and after supper, in one day, in cases of multiple parasitic infection. These continuing trials with oxantel-pyrantel, using different dosages, in patients without prior treatment for Ascaris, should establish the relative merit of this drug in eliminating Trichuris from those with multiple infection - Ascaris, Trichuris and hookworm.
References Anders. W.: On the incidence of worms (Ascaris and Trichuris) in Berlin schoolchildren. Offentliche Gesundheitsdienst 14: 360-363 (J 952) abstracted in Tropical Diseases Bulletin 50: 432 (J 953). Atias. A. and Gajardo. R.: Massive trichuriasis in children. Boletin chileno de parasitologia 10: 78-79 (1955) abstracted in Tropical Diseases Bulletin 53: 1161-1162 (J 956). Araullo-Cruz. T. and Reyes. W.L.: Intestinal helminths of man in Bay. Laguna. Journal of Manila Medical Society 6: 241-250 (1968). Ballesteros Bermudez. J. and Burgos Courlaender. c.: Whipworms as a cause of chronic diarrhoea in children. Treatment with hexylresorcinol enemas. Jornadas Nacionales de
A Review of Trichuriasis
Puericultura y Pediatria 2: 739-757 (1955) abstracted in Tropical Diseases Bulletin 53: 1161 (1956). Basnuevo. J.G .. Cowley. 0 .. Blanco Rabasa. E .. Achkar. R. and Maduro. F.: One hundred cases of trichocephaliasis cured with enemas of hexy'lresorcinol (Santokin). Revista Kuba de medicina tropical y parasitologia 9/10: 105-108 (1951) abstracted in Tropical Diseases Bulletin 49: 638-639 (1952). Basnuevo. J.G .. Jordan Rodriguez. J .. Borges. F .. Borbola. Liane. Casanova. R .. Alvarez Flores. R. and Vazquez Perez. E.: Treatment of trichuriasis with dithiazanine. Revista Kuba de medicina tropical y parasitologia 1/6: 15-18 (1959) abstracted in Tropical Diseases Bulletin 57: 835-836 (1960). Benarroch. E.\. and Villegas. J.: Comparative efficacy of hexylresorcinol and a mixture of tetrachlorethylene and oil of chenopodium in the treatment of intestinal helminthic infections. Revista de sanidad y asistencia social. 3/4: 197-208 (1954) abstracted in Tropical Diseases Bulletin 53: 1030 (1957). Burnett. H.S. and Wagner. E.D.: Trichlorophenol-piperazine salt in the treatment of Ascaris. hookworm. Trichuris and Strongyloides. Antibiotics and Chemotherapy II: 698-704 (1961) abstracted in Tropical Diseases Bulletin 59: 993 (1962). Campos. R .. Amato Neto. V .. Vasconcellos. AT. de M. and Wanderley. R.A. de S.: Treatment of ascariasis and trichuriasis by stilbazium iodide. Hospital (Rio de Janerio) 71 : 703-709 (1967) abstracted in Tropical Diseases Bulletin 64: 161 (1968). Chanco. P.P.: Observations in the use of dithiazanine iodide (Tel mid) in the treatment of common nematode intestinal parasites of man in the Philippines. Santo Tomas Journal Of Medicine 14: 183-187 (1959). Chanco. P.P. and Reyes. P.R.: Incidence of intestinal parasitism among 609 medical technology students with the use of concentration technics. Santo Tomas Journal of Medicine 26: 347-362 (1971). Chanco. P.P. and Atienza. M.R.: Trichuriasis: incidence. hazards and treatment with mebendazole (R 17635): preliminary report. Journal of the Philippine Society of Microbiology and Infectious Diseases 2: 27-37 (1973). Chanco. P.P .. Goquiolay-Arellano. R. and Atienza. M.R.: The use of mebendazole (Antiox) for the treatment of trichuriasis with rectal prolapse. Philippine Journal of Pediatrics 2: 43-53 (1974). Correa. M.O.A.: A study on the therapeutic action of dithiazanine in human SII'IJIIgyloides and Trichuris infections. Revista do Instituto Adolfo Lutz 18: 123-131 (1958) abstracted in Tropical Diseases Bulletin 58: 715-716 (1961). Da Costa. O.R .. Manceau. J.N .• Maroja. R. and de Andrade. G.c.: On the effect of hexylresorcinol in ankylostomiasis. ascariasis and trichuriasis. Revista do Servico especial de saude publica 4: 465-474 (1951) abstracted in Tropical Diseases.Bulietin 49: 706 (1952).
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Da Costa. O.R.: The action of hexylresorcinol and mepacrine separately and together on hookworm. Ascaris, Trichuris and Enteroi>iu.' infections. Revista do Servico especial de saude publica 8: 257-269 (1955) abstracted in Tropical Diseases Bulletin 53: 1364 (1956). De Carneri. I.. Garofano. M .. and Grassi. L.: Investigation of the part played by Trichuris infections in delayed mental and physical development of children in northern Italy. Rivista di parassitologia 28: 103-122 (1967) abstracted in Tropical Diseases Bulletin 64: 163 (1968). Desportes. c.: A complement to researches on the incidence of Tric/llIri., and Enteroi>ius in Paris. Abstracted in Tropical Diseases Bulletin 35: 678 (1938). Fernando. P.V.D.: Therapy of trichuriasis and ancylostomiasis with dithiazanine. Journal of Tropical Pediatrics. 6: 80-83 (1960) abstracted in Tropical Diseases Bulletin 58: 492-493 (1961). Frye. W.W .. Swartzwelder. C .. Lampert. R .. Abadie. S.H. and Carson. C.B. Jr.: An effective trichuricide suitable for oral administration. American Journal of Tropical Medicine and Hygiene 6: 890-893 (1957) abstracted in Tropical Diseases Bulletin 55: 436-437 (1958). Giuliani. V.: Presence of helminths in appendices removed surgically. Nuori annali d'igiene e microbiologia 6: 454-456 (1955) abstracted in Tropical Diseases Bulletin 53: 642-643 (1956). Hartz. P.H.: Histopathology of the colon in massive trichocephaliasis of children. Documenta de medicina geographica et tropica 5: 303-313 (1953) abstracted in Tropical Diseases Bulletin 51: 712-713 (1954). Hartz. P .H.: Histopathology of the colon in mass Tric/llIri.' infection in children. Archivos Venezolanos de puericultura y pediatria 16: 209-220 (1953) abstracted in Tropical Diseases Bulletin 51: 504-505 (1954). Hoekenga. M.T.: Experiments in the therapy of human trichuriasis and hookworm disease. American Journal of Tropical Medicine and Hygiene 5: 529-533 (1956) abstracted in Tropical Diseases Bulletin 53: 1454 (1956). Huang. Wen-Hsien and Brown. H.W.: Clinical trials ofstilbazium iodide (Monopar) in the treatment of Trichuris and Ascaris infections. American Journal of Tropical Medicine and Hygiene 13: 54-56 (1964) abstracted in Tropical Disea~es Bulletin 61: 681-682 (1964). Hucker. A.G. and Schofield. F.D.: Whipworm infections. Trial of four piperazine compounds. British Medical Journal 1159-1160 (1956) abstracted in Tropical Diseases Bulletin 54: 189 (1957). Jjumba-Mukasa. O.R. and Gunders. A.E.: Prevalence of intestinal helminthic infections in Jerusalem. Harefuah 79: 306-309 (1970) abstracted in Tropical Diseases Bulletin 68: 77 (1971). Jung. R.C.: Use of hexylresorcinol tablet in the enema treatment of whipworm infection. American Journal of Tropical Medicine
A Review of Trichuriasis
and Hygiene 3: 918-921 (1954) abstracted in Tropical Diseases Bulletin 52: 286-287 (1955). Kan. S.P. and Cheah. J.S.: Prevalence and intensity of helminthic infections in adults among the ethnic groups in Singapore. Singapore Medical Journal II: 283-286 (1970) abstracted in Tropical Diseases Bulletin 68: 621 (1971). Keller. A.E .• Leathers. W.S. and Knox. J.e.: The incidence and distribution of Ascaris iUlllbricoides. TricilOceplwius trichiura, Helllellaiepis lIalla, Ellterobius !'I!rlllieularis and Helllel/olepis dilllil/lIIa in 70 countries in North Carolina. American Journal of Hygiene 27: 258-274 (1938). Kouri. P. and Valdes Diaz. R.: Present views on the pathogenicity of Tricilllri.~ triehiura. Revista Kuba de medicina tropical y parasitologia 8: 37-41 (1952) abstracted in Tropical Diseases Bulletin 50: 54 (1953). Layrisse. M.• Aparcedo. L.. Martinez-Torres. e. and Roche. M.: Blood loss due to infection with Trichuris trichiura. American Journal of Tropical Medicine and Hygiene 16: 613-619 (1967) abstracted in Tropical Diseases Bulletin 65: 80 I (1968). MacCarthy. Ethna: Infestation with TricilOceplwiu.~ dispar. Ten cases in an Irish Orthopaedic Hospital. Lancet: 436 (1954) abstracted in Tropical Diseases Bulletin 51: 623 (1954). Maplestone. P.A. and Mukerji. A.K.: The treatment of Trichuris infection with iron. Indian Medical Gazette 74: 607-609 (1939) abstracted in Tropical Diseases Bulletin 37: 660-661 (1940). Miranda. M.: Study of the bone-marrow in children with ankylostomiasis and trichuriasis. Revista de biologia tropical 4: 69-77 (1956) abstracted in Tropical Diseases Bulletin 54: 185-186 (1957). Neghme. A. and Silva. R.: Present state of Ascaris iUlllbricoides and Tric//Ilris trichiura infections in Santiago. Chile. I. Epidemiological Surveys. Boletin Chileno de parasitologia I 8: 54-57 (1963) abstracted in Tropical Diseases Bulletin 61: 930-931 (1964). Paine. D.H.D. et al.: Treatment of trichuriasis with dithiazanine in a hospital for mental defectives. British Medical Journal 12: 770-774 (1960). Perez-Santiago. E .. Oliver-Gonzalez. J. and Thillet. e.J.: The effect of a cyanine dye on infections with hookworm and Trichuris in man. American Journal of Tropical Medicine and Hygiene 2: 307-310 (1953).
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Pesigan. T.P. and Yogore. M.G.: Distribution and prevalence of infection caused by soil-transmitted helminths in the Philippines. The Journal of the Philippine Medical Association. 41: 687-702 (1965). Pizzi. T. and Schenone. H.: Finding of Trichuris triciliura eggs in the intestinal content of an archeologic body of an Inca. Boletin chileno de parasitologia 9: 73-75 (1954) abstracted in Tropical Diseases Bulletin 52: 474 (1955). Riera Zubillaga. A.: Treatment of enterocolitis due to Tricilllris with dithiazanine iodide. Archivos Venezolanos Puericultura y Pediatria 23: 145-150 (1960) abstracted in Tropical Diseases Bulletin 58: 492-493 (1960. Salunkhe. D.S .. Gaitonde. B.B. and Vakil. B.1.: Clinical evaluation of a new anthelmintic thiabendazole [2-(4'-thiazolyllbenzimidazole]. American Journal of Tropical Medicine and Hygiene 13: 412-416 (1964) abstracted in Tropical Diseases Bulletin 61: 1163 (1964). Soriano. L.R .. del Mundo. F. and Naguit-Sim. L.: Rectal prolapse in children with Tric/llIri.s. Journal of the Philippine Medical Association 42: 843-848 (1966) abstracted in Tropical Diseases Bulletin 65: 481 (1969). Swartzwelder. J. Clyde.: Clinical Trichocephalus trichuris infection. An analysis of eighty-one cases. American Journal of Tropical Medicine 19: 473-481 (1939) abstracted in Tropical Diseases Bulletin 37: 660-661 (1940). Vakil. B.1. and Mehta. B.1.: Effect of dithiazanine in ascariasis. trichuriasis. enterobiasis and ankylostomiasis. Journal of the Indian Medical Association 37: 219-222 (1960 abstracted in Tropical Diseases Bulletin 59: 176-177 (1962). Winship. N.: South African Medical Journal 33: 354 (1959). Wong Hock Boon and Tan Kwang Hoh: Severe whipworm infestation in children. Singapore Medical Journal 2: 34-37 (1960 abstracted in Tropical Diseases Bulletin 58: 1278-1279 (1960. Yogore. M.G. and Cabrera. B.D.: A report of intestinal parasitism in the armed forces of the Philippines in W.1. Darby. Nutrition Survey of the Armed Forces of the Philippines pI 16-126 (1957).
Author's address: Prof. P.P. Chanco Jr, 1631 1. Zamara Street, Mini/a. Philippines.
Session III: Helminthiasis: Treatment with Oxantel-pyrantel, contd. Chairman: Dr B.D. Alora (Manila)
A Review of Trichuriasis, its Incidence, Pathogenicity and Treatment Pedro P. Chanco, Jr. and Julieta Y. Vidad Faculty of Medicine and Surgery. University of Santo Tomas. Philippines
Summary
The incidence and pathogenicity qf trichuriasis is reviewed. Reference is made to earlier. largely unsucces~ful. treatments. and to mebendazole. Oxantel, the most recent drug shown to be effective against Trichuris is discussed, as is oxantel-pyrantel which promises to be effective against mixed helminthic infections.
J. Incidence The incidence of Trichuris trichiura is very variable, it being more common in the tropical developing countries where sanitation and nutrition are poor. The moist humid climate of these countries, coupled with the use of night soil in agriculture, increase the chances of contracting intestinal parasitism. Keller et al. (I 938) in their study of the incidence and distribution of intestinal parasites in North Carolina found only 0.5 % of 37,346 specimens from
white persons to be positive for Trichuris and the average intensity was a very low, 1,400 eggs/ml of stool. Among the Negroes, he found an incidence of 3 % of 6,301 specimens in the same area, but Negroes in the coastal part of the state had a higher incidence, varying from 10.7% to 24.8% with an average intensity of 1,500 eggs/ ml of faeces. Anders (I 953) found 132 of 13,331 school children in Berlin to be infected with Trichuris, of which 17.5 % showed distinct symptoms and 30 % only slight symptoms, In all the areas studied, the overall inci-
88
A Review of Trichuriasis
dence of Trichuris was only 3 %. This was correlated not with the age but with the poor sanitation of the areas and use of night soil during the immediate postwar period. Neghme and Silver (I 964) found an incidence of trichuriasis of 25 % in the general population and 40 % among school children from 1948 to 1954, but only 19 % and 20 % respectively from 1957 to 1962. He attributed this decrease to the better sanitation, diagnostic facilities and paved streets. Jjumba-Jukasa and Gunders (I 97 J) observed that the incidence of ascariasis and trichuriasis in the Jewish population, after the establishment of the State of Israel in 1948, began to decline by 1950 from the 40 % for ascariasis to less than 1 %, and for trichuriasis from 17 % to 1 %, because of the elimination of Arab grown vegetables from the Jewish markets. Kan and Cheah (I 97 J) found that Trichuris trichiura was the most common helminthic infection encountered in Singapore among adults up to 60 years of age. He also observed more single infections of Trichuris. Chanco and Reyes (I 97 J) using concentration techniques, found an incidence of 76% for Trichuris and only 25 % for Ascaris among 371 medical technology students who were positive for intestinal parasites. Medical technology students have an average age of 19 to 21 and belong to a higher economic echelon of the population and are apparently more health conscious. Araullo-Cruz et al. (1968) in a survey of intestinal helminthiasis among pre-school children, school children and adults of Bay, Laguna in the Philippines obtained an incidence of 85 % for trichuriasis and 82.7% for ascariasis. Pesigan et al. (I968)from 1948 to 1951, out of 123,291 specimens from the general population, obtained an incidence of trichuriasis of 52 %. Other workers in the Philippines have reported incidence rates varying from 52 to 93 %. With one exception only Chanco used concentration techniques (acid-ether concentration technique); the other surveys usually employed only direct faecal smears. They may have reported higher incidences had they used a concentration technique. The incidence of ascariasis reported in these surveys declined with age but that of trichuriasis in-
creased, although those in the lower age groups had more severe infections. This is probably explained by the fact that Ascaris generally leaves the body after 1 or 2 years, of its own accord, whereas an infection with Trichuris builds up with age as more and more raw salads enter the diet of the growing individual. Ascariasis is generally associated with the dirty habits of young children who take soil into their system in one way or another.
2. Pathogenicity
Apparently, Trichuris trichiura has been with man for a long time. Pizzi and Schenone (I955) reported finding the ova of this nematode parasite of man, in great numbers, in the faeces of an Inca child frozen in a mountain, 17,658 feet above sea level, near Santiago. The body was exceptionally well preserved and its antiquity calculated to be 450 years or more. However, the pathogenicity of Trichuris trichiura has not always been universally accepted. Kouri and Valdez Diaz (I953) recorded their views on the pathogenicity of the human whipworm. They claim that two strongly opposed opinions prevail: one group, particularly those workers from areas where infection is mild, makes light of the infection, regarding it as little more than a harmless commensal; the other group, and this includes most workers in the developing countries, believes that it can be markedly pathogenic, causing inflammation, ulceration and in some cases resulting in death. Kouri and his colleague described a condition which they term 'massive infantile trichuriasis' which resists all treatment and ends fatally. Inflammation of the descending colon and the sigmoid occurs, with haemorrhages and mucopurulent stools and often with rectal prolapse. Symptoms may be produced when Trichuris is the only parasite present, but naturally they are aggravated when there is Entamoeba histolytica or Balantidium coli infection also. Guiliani (I 956) reported the presence of Oxyuris in 11.3 % and Trichuris in 2 % of 150 appendices removed and found that the worms were more com-
A Review of Trichuriasis
89
mon (I 7 cases) in chronic appendicitis than in acute with a high or medium worm load ( > I O,OOU oval g), and subacute (2 cases only). Desportes (I 938) re-ex- 40 were retarded by one year or more. Of I 3 I with amined material preserved from autopsies, performed low worm loads, 40 were retarded and of I I 9 who by Brumpt in 1909, on persons dying of various were negative, 28 were retarded. In children with complaints in the old Hospital de la Pitie. The worm loads of more than 5,000 ova/g, 58.3 % were material consisted of caecum and appendix. For retarded and of the 108 children retarded by one year Trichuris, of the 369 caeca examined 50.7% were in- or more, 71 came from poor families. Soriano et al. (1969) from the Philippines reported fected, the maximum number of worms in one organ being 82. Balland, cited by Desportes, examined 389 I 0 cases of rectal prolapse in children with caeca and appendices for a thesis published in I 91 0 trichuriasis. Chanco et al. (I 973) reported 131 cases and reported 54.7% infected with Trichuris. of trichuriasis in which the highest incidence was in Ballesteros Bernudez and Burgos Courlaender the age groups up to I 0 years, although in the 16 to (I 956) reported a chronic diarrhoeal syndrome 20 age group there were almost as many cases. Chancaused by whipworms. The basis for their diagnosis co et al. (I 974) also reported 23 patients, all less than was the presence of adult parasites attached to the 8 years, suffering from prolapse of the rectum secmucosa in rectal prolapsus, which they considered ondary to trichuriasis. pathognomonic. Rectosigmoidoscopy was used to Layrisse et al. (1968) investigated the blood loss confirm the diagnosis, the degree of infection and to due to infection with Trichuris trichiura. He reported reveal other lesions unconnected with the presence of 9 children harbouring whipworms, and no other whipworms. Wong and Tan (I 96 I) from the parasites of significance, to be losing 0.8 to 8.6ml of Pediatric Unit of the General Hospital in Singapore, blood/ day with a mean of 4.1 ml. The blood loss was reported that whipworm infections were by no means roughly proportional to the number of worms always mild and symptomless. With heavy infec- recovered, which in this study ranged from 86 to tions, chronic dysentery and blood loss, anaemia, ab- 3,009. The egg count had no correlation with the dominal pain and tenesmus, ulceration of the rectal blood loss. In the author's opinion, infections with colonic mucosa and prolapse of the rectum may oc- 800 worms may produce blood loss that could cause cur. Similar cases have been reported from Ceylon clinical anaemia, particularly if the child is poorly and by Winship (I 959) from South Africa. Most of nourished and in great need of iron. the patients were children 2 to 5 years of age and had In contrast Hartz (I 954), who made a had symptoms for 6 months to 2 years. 50 % had histopathological study of the colon in Trichuris inhaemoglobin levels below 8.8 % and 35 % below fection in children, believed that the only lesion that 6.0 % and 70 % of the children had rectal prolapse on could be attributed to the infection was mechanical admission. On sigmoidoscopy 90 % were seen to compression of the cells of the colonic mucosa. He have bleeding ulcers. suggested that some of the symptoms found in De Carneri et al. (I 968) investigated the part play- Trichuris infections are caused by irritation of the ed by Trichuris infections in delayed mental and nerves of the colonic mucosa. He further claimed that physical development of children in Northern Italy. in view of the fact that trichuriasis is seldom found Of the 359 children examined, 233 had Trichuris in- without associated infections with other parasites, fection and only I 9 had ascariasis. All patients with Shigella and malnutrition, these factors must be exAscaris also had Trichuris. 47.6 % of the Trichuris in- cluded before accepting Trichuris as the cause of fected children were found to be normal mentally and symptoms like anaemia. Atlas and Gajardo (I 956) in physically. The rest had some disturbance in growth their study of cases of massive trichuriasis in children which in 14 % was considered to be pathological. in Chile, concluded that the factors that probably exWith regard to scholastic progress, of 88 children plain the severe course of infection are the nutritional
A Review of Trichuriasis
deficiency, avitaminosis and very poor sanitary conditions in which the patient lives rather than the whipworm only. The cases they studied were autopsied and found to have histological alterations suggesting pellagra. However, Swartzwelder (t 940) made a detailed analysis of 81 cases of uncomplicated Trichuris infection and from the following results suggesting that whipworms per se can cause symptoms and illness. Most of the patients were from 6 to 15 years old and white patients outnumbered coloured in the ratio of 5: I; there were twice as many females as males. The most frequent symptoms were abdominal or epigastric pain, vomiting, constipation, fever, distention and flatulence, headache, backache, loss of weight and anorexia. The duration of symptoms was 3 months in 44 cases. Most of these 81 cases were clinically diagnosed as parasitism, with chronic appendicitis the next most common diagnosis. Physical examination frequently revealed abdominal tenderness without rigidity. Only 7 cases had a temperature above I 0 1of. The average eosinophil count was 4.2 % and the maximum 24 % . Miranda (t 957) studied the bone marrow in children with ancylostomiasis and trichuriasis. Unfortunately, only 3 of his cases had trichuriasis alone. All the others had both ancylostomiasis and trichuriasis, or ancylostomiasis alone. The bone marrow findings were the same in those with ancylostomiasis alone, with trichuriasis alone, or with both nematode infections.
90
complete eradication of Trichuris in our patients treated for colonic amoebiasis who had concomitant Trichuris infection. Basnuevo (Basnuevo et al., 1952) was an ardent user of hexylresorcinol 1:300, as a retention enema; he published several papers and reported 100 % cure rates. Da Costa et al. (1952) reported that the use of hexylresorcinol crystoids for the removal of Trichuris gave very poor results. Perez-Santiago et al. (t 952) used cyanine dye for the treatment of hookworm and Trichuris and concluded that it was neither as effective an anthelminthic as tetrachlorethylene nor as well tolerated there being toxic side-effects. MacCarthy (t 954) used 0.5g enteric-coated capsules of papain and claimed I 00 % success in the I 0 children treated, without side-effects. Jung (1955) modified the hexylresorcinol retention enema of Basnuevo but cured only I of 22 subjects. It is a disappointing and dangerous drug. Benarroch and Villegas (t 957) found a combination of tetrachlorethylene and chenopodium to be better than hexylresorcinol in removing hookworm, Ascaris and Trichuris but this did not result in the complete eradication of Trichuris. Da Costa (t 956) tried a combination of hexylresorcinol and mepacrine for the treatment of hookworm, ascariasis and trichuriasis but the results were inconclusive. Hoekenga (I956) tried 13 different drugs, or combinations of drugs, and found that a mixture of tetrachlorethylene and oil of chenopodium was best although it did not give a complete cure. Hucker and Schofield (I 957) tried four piperazine compounds - phosphate, acetate, adipate and citrate, in doses equivalent to 500mg of the hexahydrate, tid 3. Treatment for 7 days; they found no significant decrease in egg count. Until the introduction of mebendazole the treatDithiazanine was found by Frye et al. (I 958) to be ment of trichuriasis was always a problem. effective against Trichurisin doses of 200mg given as Maplestone and Mukerji (t 940) prescribed the enteric-coated tablets tid for 5 days. We found (ChanCalcutta Hospital stock mixture of iron for removing co, 1959) diathiazanine iodide in a dose of 100mg tid Trichuris. After 2 weeks treatment with this mixture, after meals for 5 to 7 days gave an 83 % cure rate 18 of I 9 patients were still infected. Good results with fewer side-effects than the 200mg dose. Paine et were claimed with 2 grains of enteric-coated emetine at. (I 960) used 200mg tid for 5 days and claimed an given for 6 days. Enteric-coated tablets of efficacy of 93 % although Basnuevo et al. (I 960) dehydroemetine caused some diminution but not using the same dose, obtained only 62 % success in
91
A Review of Trichuriasis
the treatment for trichuriasis. Riera (J 96 I) used the drug in children at a dose of 100mg/5kg and obtained 50 % cure, including cure of those with rectal prolapse but there were many side-effects such as nausea, vomiting and urticaria. Fernando (1961) also used dithiazanine for the treatment of trichuriasis in children but cleared only II of 24. Correa (J 96 I) treated trichuriasis with either 100 or 200mg tid for 7 days. At the higher dose 9 of II became negative, but in the 100mg dose group all 7 were cured and those on the lower dosage had fewer, milder sideeffects. Vakil and Menta (I 962) used diathiazanine at a dose of 200mg tid for 5 days; 15 of 20 Trichuris cases were freed of parasites and those who were not had a marked decrease in egg counts. Trichlorophenol-piperazine salt was used by Burnett and Wagner (1962) for the treatment of worms, including Trichuris. The drug removed Ascaris and a few of the hookworm but had no action on Trichuris. Huan and Brown (I964) used stilbazium iodide, but of 23 children with Trichuris treated with 8.8mg/kg bid only 9 were cleared, although the rest had a marked reduction in egg count. Campos et al. (J 968) used stilbazium iodide with better success; their most effective dose was 20mg/kg, with which they cured 15 of 20 patients with trichuriasis. Salunkhe et al. (1964) tried thiabendazole, 1.25g to 2.5g in the morning after breakfast in a chocolate-flavoured suspension, as one dose, but found it disappointingly ineffective. With mebendazole, we were able to completely eradicate trichuriasis in 129 (98 %) of 131 cases of all ages. The 2 cases who were not completely cured had egg counts reduced from > 100 oval coverslip to about 20 oval coverslip, indicating a great reduction in worm burden. Most cures were achieved by the time of the first post-treatment examination. There were no side-effects important enough to preclude continuation of treatment and no patient complained of side-effects. Although mebendazole seems to be very effective in the treatment of trichuriasis, it is not the ideal drug for multiple parasitic infections, particularly in the presence of Ascaris which may become erratic or ectopic. We have seen many cases, particularly in
children, of errant Ascaris with the use of mebendazole in the treatment of Trichuris with accompanying ascariasis. Oxantel, the most recent treatment for trichuriasis, is likely to supersede the variety of earlier drugs described. When first used we chose a dose of 10mg/kg, given on a single occasion. The results were poor. By increasing the dose to 20mg/kg we imprOVed our cure rate but still did not attain that we have described using mebendazole (Chanco et al., 1973). Giving oxantel at 20mg/kg, twice, on 2 consecutive days, we improved our cure rate to almost 100 %, but lost the advantage of the single dose regimen. In a study in which 25 patients with trichuriasis were given a single dose of oxantel-pyrantel at a dose of 20mg/kg, 19 patients (76 %) were cured and the egg counts in the remaining 6 diminished from 50 to I I coverslip. Work is now going on in a rural setting, in which people are living in a confined area in the Mountain Province of the Philippines; hookworm is also present. Weare giving oxantel-pyrantel suspension at a dose of 15mg/kg, after breakfast and after supper, in one day, in cases of multiple parasitic infection. These continuing trials with oxantel-pyrantel, using different dosages, in patients without prior treatment for Ascaris, should establish the relative merit of this drug in eliminating Trichuris from those with multiple infection - Ascaris, Trichuris and hookworm.
References Anders. W.: On the incidence of worms (Ascaris and Trichuris) in Berlin schoolchildren. Offentliche Gesundheitsdienst 14: 360-363 (J 952) abstracted in Tropical Diseases Bulletin 50: 432 (J 953). Atias. A. and Gajardo. R.: Massive trichuriasis in children. Boletin chileno de parasitologia 10: 78-79 (1955) abstracted in Tropical Diseases Bulletin 53: 1161-1162 (J 956). Araullo-Cruz. T. and Reyes. W.L.: Intestinal helminths of man in Bay. Laguna. Journal of Manila Medical Society 6: 241-250 (1968). Ballesteros Bermudez. J. and Burgos Courlaender. c.: Whipworms as a cause of chronic diarrhoea in children. Treatment with hexylresorcinol enemas. Jornadas Nacionales de
A Review of Trichuriasis
Puericultura y Pediatria 2: 739-757 (1955) abstracted in Tropical Diseases Bulletin 53: 1161 (1956). Basnuevo. J.G .. Cowley. 0 .. Blanco Rabasa. E .. Achkar. R. and Maduro. F.: One hundred cases of trichocephaliasis cured with enemas of hexy'lresorcinol (Santokin). Revista Kuba de medicina tropical y parasitologia 9/10: 105-108 (1951) abstracted in Tropical Diseases Bulletin 49: 638-639 (1952). Basnuevo. J.G .. Jordan Rodriguez. J .. Borges. F .. Borbola. Liane. Casanova. R .. Alvarez Flores. R. and Vazquez Perez. E.: Treatment of trichuriasis with dithiazanine. Revista Kuba de medicina tropical y parasitologia 1/6: 15-18 (1959) abstracted in Tropical Diseases Bulletin 57: 835-836 (1960). Benarroch. E.\. and Villegas. J.: Comparative efficacy of hexylresorcinol and a mixture of tetrachlorethylene and oil of chenopodium in the treatment of intestinal helminthic infections. Revista de sanidad y asistencia social. 3/4: 197-208 (1954) abstracted in Tropical Diseases Bulletin 53: 1030 (1957). Burnett. H.S. and Wagner. E.D.: Trichlorophenol-piperazine salt in the treatment of Ascaris. hookworm. Trichuris and Strongyloides. Antibiotics and Chemotherapy II: 698-704 (1961) abstracted in Tropical Diseases Bulletin 59: 993 (1962). Campos. R .. Amato Neto. V .. Vasconcellos. AT. de M. and Wanderley. R.A. de S.: Treatment of ascariasis and trichuriasis by stilbazium iodide. Hospital (Rio de Janerio) 71 : 703-709 (1967) abstracted in Tropical Diseases Bulletin 64: 161 (1968). Chanco. P.P.: Observations in the use of dithiazanine iodide (Tel mid) in the treatment of common nematode intestinal parasites of man in the Philippines. Santo Tomas Journal Of Medicine 14: 183-187 (1959). Chanco. P.P. and Reyes. P.R.: Incidence of intestinal parasitism among 609 medical technology students with the use of concentration technics. Santo Tomas Journal of Medicine 26: 347-362 (1971). Chanco. P.P. and Atienza. M.R.: Trichuriasis: incidence. hazards and treatment with mebendazole (R 17635): preliminary report. Journal of the Philippine Society of Microbiology and Infectious Diseases 2: 27-37 (1973). Chanco. P.P .. Goquiolay-Arellano. R. and Atienza. M.R.: The use of mebendazole (Antiox) for the treatment of trichuriasis with rectal prolapse. Philippine Journal of Pediatrics 2: 43-53 (1974). Correa. M.O.A.: A study on the therapeutic action of dithiazanine in human SII'IJIIgyloides and Trichuris infections. Revista do Instituto Adolfo Lutz 18: 123-131 (1958) abstracted in Tropical Diseases Bulletin 58: 715-716 (1961). Da Costa. O.R .. Manceau. J.N .• Maroja. R. and de Andrade. G.c.: On the effect of hexylresorcinol in ankylostomiasis. ascariasis and trichuriasis. Revista do Servico especial de saude publica 4: 465-474 (1951) abstracted in Tropical Diseases.Bulietin 49: 706 (1952).
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Da Costa. O.R.: The action of hexylresorcinol and mepacrine separately and together on hookworm. Ascaris, Trichuris and Enteroi>iu.' infections. Revista do Servico especial de saude publica 8: 257-269 (1955) abstracted in Tropical Diseases Bulletin 53: 1364 (1956). De Carneri. I.. Garofano. M .. and Grassi. L.: Investigation of the part played by Trichuris infections in delayed mental and physical development of children in northern Italy. Rivista di parassitologia 28: 103-122 (1967) abstracted in Tropical Diseases Bulletin 64: 163 (1968). Desportes. c.: A complement to researches on the incidence of Tric/llIri., and Enteroi>ius in Paris. Abstracted in Tropical Diseases Bulletin 35: 678 (1938). Fernando. P.V.D.: Therapy of trichuriasis and ancylostomiasis with dithiazanine. Journal of Tropical Pediatrics. 6: 80-83 (1960) abstracted in Tropical Diseases Bulletin 58: 492-493 (1961). Frye. W.W .. Swartzwelder. C .. Lampert. R .. Abadie. S.H. and Carson. C.B. Jr.: An effective trichuricide suitable for oral administration. American Journal of Tropical Medicine and Hygiene 6: 890-893 (1957) abstracted in Tropical Diseases Bulletin 55: 436-437 (1958). Giuliani. V.: Presence of helminths in appendices removed surgically. Nuori annali d'igiene e microbiologia 6: 454-456 (1955) abstracted in Tropical Diseases Bulletin 53: 642-643 (1956). Hartz. P.H.: Histopathology of the colon in massive trichocephaliasis of children. Documenta de medicina geographica et tropica 5: 303-313 (1953) abstracted in Tropical Diseases Bulletin 51: 712-713 (1954). Hartz. P .H.: Histopathology of the colon in mass Tric/llIri.' infection in children. Archivos Venezolanos de puericultura y pediatria 16: 209-220 (1953) abstracted in Tropical Diseases Bulletin 51: 504-505 (1954). Hoekenga. M.T.: Experiments in the therapy of human trichuriasis and hookworm disease. American Journal of Tropical Medicine and Hygiene 5: 529-533 (1956) abstracted in Tropical Diseases Bulletin 53: 1454 (1956). Huang. Wen-Hsien and Brown. H.W.: Clinical trials ofstilbazium iodide (Monopar) in the treatment of Trichuris and Ascaris infections. American Journal of Tropical Medicine and Hygiene 13: 54-56 (1964) abstracted in Tropical Disea~es Bulletin 61: 681-682 (1964). Hucker. A.G. and Schofield. F.D.: Whipworm infections. Trial of four piperazine compounds. British Medical Journal 1159-1160 (1956) abstracted in Tropical Diseases Bulletin 54: 189 (1957). Jjumba-Mukasa. O.R. and Gunders. A.E.: Prevalence of intestinal helminthic infections in Jerusalem. Harefuah 79: 306-309 (1970) abstracted in Tropical Diseases Bulletin 68: 77 (1971). Jung. R.C.: Use of hexylresorcinol tablet in the enema treatment of whipworm infection. American Journal of Tropical Medicine
A Review of Trichuriasis
and Hygiene 3: 918-921 (1954) abstracted in Tropical Diseases Bulletin 52: 286-287 (1955). Kan. S.P. and Cheah. J.S.: Prevalence and intensity of helminthic infections in adults among the ethnic groups in Singapore. Singapore Medical Journal II: 283-286 (1970) abstracted in Tropical Diseases Bulletin 68: 621 (1971). Keller. A.E .• Leathers. W.S. and Knox. J.e.: The incidence and distribution of Ascaris iUlllbricoides. TricilOceplwius trichiura, Helllellaiepis lIalla, Ellterobius !'I!rlllieularis and Helllel/olepis dilllil/lIIa in 70 countries in North Carolina. American Journal of Hygiene 27: 258-274 (1938). Kouri. P. and Valdes Diaz. R.: Present views on the pathogenicity of Tricilllri.~ triehiura. Revista Kuba de medicina tropical y parasitologia 8: 37-41 (1952) abstracted in Tropical Diseases Bulletin 50: 54 (1953). Layrisse. M.• Aparcedo. L.. Martinez-Torres. e. and Roche. M.: Blood loss due to infection with Trichuris trichiura. American Journal of Tropical Medicine and Hygiene 16: 613-619 (1967) abstracted in Tropical Diseases Bulletin 65: 80 I (1968). MacCarthy. Ethna: Infestation with TricilOceplwiu.~ dispar. Ten cases in an Irish Orthopaedic Hospital. Lancet: 436 (1954) abstracted in Tropical Diseases Bulletin 51: 623 (1954). Maplestone. P.A. and Mukerji. A.K.: The treatment of Trichuris infection with iron. Indian Medical Gazette 74: 607-609 (1939) abstracted in Tropical Diseases Bulletin 37: 660-661 (1940). Miranda. M.: Study of the bone-marrow in children with ankylostomiasis and trichuriasis. Revista de biologia tropical 4: 69-77 (1956) abstracted in Tropical Diseases Bulletin 54: 185-186 (1957). Neghme. A. and Silva. R.: Present state of Ascaris iUlllbricoides and Tric//Ilris trichiura infections in Santiago. Chile. I. Epidemiological Surveys. Boletin Chileno de parasitologia I 8: 54-57 (1963) abstracted in Tropical Diseases Bulletin 61: 930-931 (1964). Paine. D.H.D. et al.: Treatment of trichuriasis with dithiazanine in a hospital for mental defectives. British Medical Journal 12: 770-774 (1960). Perez-Santiago. E .. Oliver-Gonzalez. J. and Thillet. e.J.: The effect of a cyanine dye on infections with hookworm and Trichuris in man. American Journal of Tropical Medicine and Hygiene 2: 307-310 (1953).
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Pesigan. T.P. and Yogore. M.G.: Distribution and prevalence of infection caused by soil-transmitted helminths in the Philippines. The Journal of the Philippine Medical Association. 41: 687-702 (1965). Pizzi. T. and Schenone. H.: Finding of Trichuris triciliura eggs in the intestinal content of an archeologic body of an Inca. Boletin chileno de parasitologia 9: 73-75 (1954) abstracted in Tropical Diseases Bulletin 52: 474 (1955). Riera Zubillaga. A.: Treatment of enterocolitis due to Tricilllris with dithiazanine iodide. Archivos Venezolanos Puericultura y Pediatria 23: 145-150 (1960) abstracted in Tropical Diseases Bulletin 58: 492-493 (1960. Salunkhe. D.S .. Gaitonde. B.B. and Vakil. B.1.: Clinical evaluation of a new anthelmintic thiabendazole [2-(4'-thiazolyllbenzimidazole]. American Journal of Tropical Medicine and Hygiene 13: 412-416 (1964) abstracted in Tropical Diseases Bulletin 61: 1163 (1964). Soriano. L.R .. del Mundo. F. and Naguit-Sim. L.: Rectal prolapse in children with Tric/llIri.s. Journal of the Philippine Medical Association 42: 843-848 (1966) abstracted in Tropical Diseases Bulletin 65: 481 (1969). Swartzwelder. J. Clyde.: Clinical Trichocephalus trichuris infection. An analysis of eighty-one cases. American Journal of Tropical Medicine 19: 473-481 (1939) abstracted in Tropical Diseases Bulletin 37: 660-661 (1940). Vakil. B.1. and Mehta. B.1.: Effect of dithiazanine in ascariasis. trichuriasis. enterobiasis and ankylostomiasis. Journal of the Indian Medical Association 37: 219-222 (1960 abstracted in Tropical Diseases Bulletin 59: 176-177 (1962). Winship. N.: South African Medical Journal 33: 354 (1959). Wong Hock Boon and Tan Kwang Hoh: Severe whipworm infestation in children. Singapore Medical Journal 2: 34-37 (1960 abstracted in Tropical Diseases Bulletin 58: 1278-1279 (1960. Yogore. M.G. and Cabrera. B.D.: A report of intestinal parasitism in the armed forces of the Philippines in W.1. Darby. Nutrition Survey of the Armed Forces of the Philippines pI 16-126 (1957).
Author's address: Prof. P.P. Chanco Jr, 1631 1. Zamara Street, Mini/a. Philippines.
