study on the taxonomy, diagnosis, epidemiology
Krepel, H.P.Citation
Krepel, H. P. (1994, June 28). Oesophagostomum bifurcum infection in man. A study on the taxonomy, diagnosis, epidemiology. Retrieved from https://hdl.handle.net/1887/13885
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TREATMENT OF MIXED OESOPHAGOSTOMUM AND HOOKWORM INFECTION: EFFECT OF ALBENDAZOLE, PYRANTEL PAMOATE,
LEVAMISOLE AND THIABENDAZOLE
H.P. Krepel, T. Haring, S. Baeta and A.M. Polderman
Published in the Transactions of the Royal Society of
Abstract
Oesophagostomum bijurcum has recently been recognised as a common parasite of man in
northern Togo and in Ghana. In a preliminary trial several anthelmintics were evaluated in the treatment of mixed Oesophagostomum and hookworm infections. Diagnosis was based on coproculture, since the eggs of Oesophagostomum and hookworm cannot be distinguished on morphological grounds. Of the anthelmintics tested, albendazole was most effective against both parasites. Pyrantel pamoate, 2 x 10 mg/kg, was effective against
Oesophagostomum but not against hookworm. The cure rates for both parasites were
Introduction
Oesophagostomum spp. are nematodes classified in the same superfamily as hookworm
(Strongyloidea), and are common parasites in animals. Infections in humans were considered to be accidental and the parasite was thought not to be able to complete its life cycle [1,2,3]. In northern Togo and north-east Ghana, however, clinical manifestations of human oesophagostomiasis are quite common and 'helminthoma' is frequently observed [4]. In a recent survey, it has been shown that man can be considered a normal host of
Oesophagostomum in these regions. Third-stage Oesophagostomum larvae were cultured from
25% of the population studied, and adult Oesophagostomum worms were isolated after anthelmintic treatment. These were identified as Oesophagostomum bifiircum, a common parasite of monkeys [1,2].
There is virtually no experience with anthelmintic treatment of human Oesophagostomum infections. Earlier reports of human oesophagostomiasis were mainly clinical and infections were recognized only during surgery or at autopsy. Other methods of diagnosis were not available. Anthelmintic treatment was, therefore, not considered.
Many anthelmintic drugs might be effective against O. bifurcum, such as those used for chemotherapy of human hookworm infection and thiabendazole which has been used in the treatment of Oesophagostomum infection in monkeys [7]. Some data on the efficacy of various anthelmintics in treating hookworm infection are shown in Table 1.
Since Oesophagostomum eggs are similar to those of hookworm, diagnosis is based on distinguishing the third-stage larvae of both parasites, which are obtained after culture of infected faeces. This paper reports the effect of a number of anthelmintics on mixed
Oesophagostomum and hookworm infections, evaluated using this method. In addition, the
most promising anthelmintic, albendazole, was evaluated in more detail using egg counts as well as faecal cultures, and during follow-up at 1 week and 1 month.
Materials and methods
Preliminary trials
Table 1. Reported cure rates of hookworm infection obtained with several anthelmintics. Anthelmintic Albendazole Levamisole Pyrantel pamoate Thiabendazole Mebendazole Dosage 400 mg 2.5-10 mg/kg S 2 x 2.5-10 mg/kg 10 mg/kg ^ 2 x 10 mg/kg 50 mg/kg 2 x 100 mg, 3 d > 2 x 100 mg, 3 d Cure rate (%) 83-100 0-93 23-69 30-96 37-92 27-79 45-95 70-80 References 8,9,10 11 11 12 13,14,15 12,16 14,17 9
hundred and thirteen double infections with Oesophagosiomum and hookworm were identified. The very great majority of hookworm larvae cultured were N.americanus. On very rare occasions a few larvae of A.duodenale were also found. Eighteen additional cases of single Oesophagosiomum infections were not included for statistical reasons. The 313 subjects (210 females and 103 males) were asked to participate, after the treatment trial had been thoroughly explained to them. Name, age, sex and village of the participants were recorded. Pre-treatment stool samples were taken on the day of treatment; post-treatment samples were obtained one to 3 weeks later.
Stool samples were collected in plastic vials and were taken to the laboratory to be processed on the same day. Stool cultures were performed using the classical petri-dish method [6]. Because of the wide variation in the number of larvae obtained from a single culture, 3 cultures of each stool sample were made to reduce the variability (unpublished observations). The total number of Oesophagosiomum and hookworm larvae found in these cultures was counted and classified and scored as follows: -, no larvae found; +, 1-9 larvae found;
+ + , 10-99 larvae found; and + + + , > 100 larvae found.
Table 2. Treatment schedules, numbers of participants, and cure rates for Oesophagostomum and hookworm infection. Drug Albendazole Pyrantel pamoate Levamisole(*) Thiabendazole Dosage 400 mg 800 mg 10 mg/kg 2 x 10 mg/kg 50/150 mg 100/300 mg 2 x 25 mg/kg Males 24 8 28 16 6 15 6 Females 43 16 67 12 45 12 15 Total 67 24 95 28 51 27 21 Cure rate(%) Oesophagostomum 87% 83% 59% 82% 37% 41% 57% i Hookworm 61% 67% 32% 18% 6% 30% 5%
(*) Dosages shown are for children and adults.
Further evaluation of albendazole
With the most promising drug, albendazole, a second trial was carried out. Twenty-eight persons (19 males, 9 females; mean age 16.5 years, range 7-50) were treated with 400 mg albendazole. Stool samples were collected before, and one week after and one month after, treatment. With each stool sample, 2 egg counts were made by Kato-Katz method using 25 mg of faeces. Stool cultures were processed and classified as in the preliminary trials.
Results
Preliminary trials
For Oesophagostomum, the most effective single dose treatment was albendazole, 400 mg (Table 2). Cure rates were high, and post-treatment larval scores (post-LS) were low, irrespective of the corresponding pre-treatment larval scores (pre-LS) (Table 3).
Table 3. Pre- and post-treatment larval scores (*) of infections with Oesophagostomum and hookworm. Treatment Albendazole 400mg Albendazole 800 mg Pyrantel pamoate 10 mg/kg Pyrantel pamoate 2 x 10 mg/kg Levamisole 50/150 mg (**) Levamisole 100/300 mg (**) Thiabendazole 2 x 25 mg Score + + + + + + Total + + + + + + Total + + + + + + Total + + + + + + Total + + + + + + Total + + + + + + Total + + + + + + Total Oesophagost Pre-treatment 29 25 13 67 12 11 1 24 37 36 22 95 4 13 11 28 5 16 30 51 13 13 l 27 7 5 9 21 -27 21 10 11 8 1 25 24 7 3 11 9 3 5 ll 6 5 ' 3 4 5 mum Post-treatment + 2 3 2 1 3 " 7 9 8 1 2 1 2 7 3 5 7 3 -4 + + + + + . 1 1 . -" -" 5 3 6 1 -1 . 4 15 1 2 1 1 1 1 Pre-treatment 19 30 18 67 7 12 5 24 31 31 33 95 4 11 13 28 4 13 34 51 5 10 12 27 1 3 17 21 Hookworm -10 20 11 5 8 3 18 9 3 2 3 2 1 2 4 2 . -1 Post-treatment + 7 5 3 2 3 1 11 9 3 -2 2 1 2 1 1 4 3 . 1 2 + + 2 4 2 . 1 1 2 10 6 2 3 5 1 8 12 2 1 7 1 1 9 + + + . 1 2 -3 21 -3 6 -2 21 -1 . 1 5
Table 4. Egg count and larval scores (*) of hookworm and Oesophagostomum before,
one week and one month after, treatment with albendazole 400 mg. Pre-treatment (/»=28) L3 larvae of Oesophagost + + + + + + L3 larvae of hookworm + + + + + + Egg counts 1-300 301-1000 >1000 -omum 6 19 3 3 10 15 0 10 12 6 1 week (n: + 5 18 2 3 6 6 1-300 7 11 3 =25) + + 1 5 301-1000 2 2 -2 2 0 1 month (n = + 6 15 2 2 5 X 1-300 7 2 3 =23) + + 1 12 13 301-1000 21 7 1
(*) Larval scores indicated by - (negative), +, + +, or + + + (see text).
When the dosages were doubled, a significant increase of the cure rates was observed in persons treated with pyrantel pamoate, 2 x 10 mg/kg. The cure rates in participants treated with a double dose of albendazole or levamisole were virtually the same as with single dose regimens.
For hookworm, treatment was less effective in all treatment groups. Of the single dose treatments, the highest cure rate (61%) and the lowest post-LS were achieved in persons treated with albendazole, 400 mg. The effect of treatment with pyrantel pamoate, 10 mg/kg, was small (cure rate 32%) and there was almost no effect with levamisole, 50/150 mg, and thiabendazole. In the latter 2 groups, higher post-LS were seen especially in persons with higher pre-LS.
Treatment with pyrantel pamoate, 2 x 10 mg/kg, gave even lower cure rates than the single dosage (18% vs 32%).
Further evaluation of albendazole
Egg counts and larval scores for Oesophagostomum and hookworm before and after treatment are given in Table 4. Most participants had pre-treatment egg counts of less than 1000 eggs/g. Pre-LS of hookworm were slighlty higher than those for Oesophagostomum.
Oesophagostomum larvae were detected in none of the post-treatment cultures.
For hookworm, 60% (15/25) and 65% (15/23) of the patients were negative on culture 1 and 4 weeks after treatment, respectively. One week after treatment, only 4 stool samples contianed eggs. Four weeks after treatment, 11 stools contained eggs; of these, cultures remained negative in three cases, and a species diagnosis could not be made.
Discussion
When O. bifurcum was recognized as a common parasite of man, treatment of the infected subjects became one of the many aspects to be investigated. The present study showed that albendazole was more effective than pyrantel pamoate, levamisole or thiabendazole in the treatment of mixed Oesophagostomum and hookworm infection.
For Oesophagostomum infection, the effect of albendazole was approached only by pyrantel pamoate, 2 x 10 mg/kg. Pyrantel pamoate, 10 mg/kg, gave poorer results, as did thiabendazole. The low cure rate of the latter, as well the occurrence of side effects reported by others [12,16], excluded this drug from further evaluation. The cure rates achieved with levamisole were low.
For hookworm also, albendazole was more effective than the other drugs tried. The low cure rate achieved with thiabendazole confirmed earlier reports [12,16]. The poor results obtained with pyrantel pamoate and levamisole can be accounted for by the presence of Necator
americanus as the predominant hookworm in the region, as it is reported to respond less well
to treatment with these drugs [11,14,15].
Although albendazole was the most effective drug for the treatment of Oesophagostomum infection in the preliminary trial, the cure rates for hookworm were poor in comparison to those of earlier reports (Table 1). In part, this could be explained by the use of a more sensitive method of evaluation (faecal culture). In the second experiment, however, the effect of treatment was assessed with both egg counts and larval counts one week as well as 4 weeks after treatment. Again, cure rates were high for Oesophagostomum (100%) but not for hookworm. Assessed one week and one month after treatment respectively, the cure rates for hookworm were 60% and 65% when based on cultures and 84% and 52% when based on egg counts. Rapid re-infection was unlikely because the treatment trial was conducted in the middel of the dry season, when little transmission occurs.
Acknowledgements
The research in Togo was supported and assisted by the Minister of Health and the Minister of Education. The advice Mr. K.D. Amouzou, administrative director of Dapaong Hospital, and the assistance of Ms Lamboni Assibi, were of great value. The contributions of B. de Jonge and A. de Joode were much appreciated. We thank Dr. J. Horton, Smith Kline and French Laboratories, who provided us with albendazole, and Dr O. Vanparijs, Janssen Pharmaceuticals, who supplied levamisole.
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