Guest Editorials Drugs 9: 241-246 (1975)
Treatment of Typhoid Fever and Typhoid Carriers in Southeast Asia ... Viewpoint from South Vietnam N. N. Linh and K. Arnold University of Saigon Medical School, Saigon
The summary of the article on page 316 of this issue is important because it emphasises the fact that this disease is still common in Southeast Asia. It is endemic and epidemic in Vietnam with large numbers of cases occurring each year. Human carriers are the only source or reservoir of typhoid fever, and water is the main vehicle of transmission. It follows, therefore, that an attack on the disease can be made in three ways: (a) curative drugs for the individual patient; (b) bactericidal drugs (or other means such as surgery, i.e. cholecystectomy) for the carrier; and, (c) most important of all, treatment of the water supply. A fourth approach is also in use and involves an attempt to induce immunity to the disease by means of a vaccine. There have been several recent reports of in vivo and in vitro resistance of salmonella typhi to chloramphenicol [1-7]. This was first describhd in Mexico [1] but has now been documented in Vietnam [2-5] and Thailand [6-7]. This year in Vietnam we have found the incidence of in vitro chloramphenicol resistance to be greater than 80%. Consequently, it would be unwise to start treatment with chloramphenicol in a typhoid fever patient !n Vietnam. The drugs we recommend at present are co-trimoxazole (2 to 3 tablets 2 times daily for 15 days) if the patient is able to take oral medication, or ampicillin 2 to 4g intravenously if the patient is in coma, followed by the same dose orally when the patient is able to take drugs by mouth, for a total of 15 days. The disadvantage of IV ampicillin is that it is extremely expensive. A parenteral form of cotrimoxazole has only recently become available. It has been used successfully in the Philippines [8] and in Vietnam [9]. The parenteral dose we suggest is 2 ampoules twice daily (each ampoule contains 80mg trimethoprim and 400mg
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sulphamethoxazole). A new drug, amoxycillin, which is similar to ampicillin but is better absorbed from the gastro-intestinal tract and gives a higher blood level, is now under study for the treatment of typhoid fever. If after initiation of treatment, the antibiogram shows that the S. typhi is sensitive to chloramphenicol we recommend that this drug be used and the co-trimoxazole or ampicillin be discontinued. We agree with Dr Rowland that corticosteroids have little place in the treatment of typhoid fever, because they probably have no effect on the underlying disease process. The effect on the temperature is undesirable (unless there is hyperpyrexia), since this parameter is an important indicator of the patient's response to antibacterial treatment and is a clinical guide to in vivo resistance. Typhoid carriers have responded to prolonged courses of ampicillin but there are other factors to consider in discussing the management of the carrier state in Southeast Asia. In developing countries where typhoid fever is common, the emphasis should be on the purification of the water supply. It is a small accomplishment to treat only a few carriers since recontamination and re-infection will be only slightly reduced due to the large numbers of people involved. An even more discouraging aspect is the problem of identifying the carrier. In Vietnam, it is extremely difficult to obtain follow-up on patients in order to examine stool specimens to detect the carrier state. Even if follow-up is possible, the facilities for culture of the stool and then identification of the organism, are not widely available. It would appear therefore that emphasis on managing the typhoid carrier is a luxury that only a developed nation can afford. Priority in developing countries of Southeast Asia should be on improving diagnostic facilities and treating the water supply. An observation of importance concerning the carrier state is that in one study where co-trimoxazole was used for the treatment of typhoid fever and follow-up was carried out, there were no carriers detected [10]. Preliminary results of therapy with co-trimoxazole in chronic typhoid carriers suggest that it is at least as effective as ampicillin [11] . Immunisation is extensively used as a protective measure against typhoid fever by the military. But its value and effectiveness is not universally acclaimed in civilian populations where the disease is endemic and epidemic, since, if the resources are available for a large scale on-going mass immunisation programme, then these efforts are better directed to improving the water supply. r
2 3
References Vazquez, v.; Calderon, E. and Rodtriguez, R.S.: Chloramphenicol-resistant strains of Salmonella typhosa. New Engl. J. Med. 286: 1220 (1972). Truong, V.S.; Quynh, P.D. and Hung, NK.: Acta Medica Vietnam 18: 17 (1973). Chi. H.K.; Rue. T.M. and Phat. V.M.: Acta Medica Vietnam 18: 85 (1973).
4
Butler, T.; Linh. NN.; Arnold. K. and Pollack. M.: Chloramphenicol-resistant typhoid fever in Vietnam associated with R-factor. Lancet 2: 983 (1973). Linh. NN: Typhoid fever treated with chloramphenicol and co-trimoxazole. Lancet I: 1222 (1974).
Typhoid Fever and Typhoid Carriers in Southeast Asia 6 7 8
Anderson. E.S.: Salmonella surveillance. Group H resistance factors in Southern Asia. WHO Weekly Epidemiology Reports 49: 245 (I974). Lampe. R.M.; Mansuwan. P. and Duangmani. C: Chloramphenicol·resistant typhoid. Lancet 1: 623 (1974). Siasoco. R.E. and Hipolito. E.F.: A comparison of the efficacy of trimethoprim·sulfamethoxazole (Bactrim) and chloramphenicol in the treatment of typhoid fever. Philipp. J. Inter. Med.ll: 39 (1973).
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Linh. N.N.: Typhoid fever treated with chlor· amphenicol and co·trirnoxazole. Lancet 1: 1222 (1974). Lasse"e, R.: Personal Communication. Pichler. H.; Knothe. H.; Spitzy. K.H. and Vielkind. G.: Treatment of chronic carriers of Salmo· nella typhi and Salmonella paratyphi B with trimethoprim·sulfamethoxazole. Journal of Infectious Diseases IZ8 (Suppl): 743 (1973).
Authors' address: Dr Nguyen Ngoc Linh and Dr Keith Arnold, University of Saigon Medical School, Saigon (South Vietnam) .
. . . Viewpoint from Thailand U. Lexomboon and P. Mansuwan Children's Hospital, Bangkok
Typhoid fever is still one of the most common public health problems in many developing countries, particularly in Southeast Asia. The high morbidity due to typhoid of up to 130 cases per 100,000 has been reported in certain areas. In Thailand alone, approximately 2,000 cases of typhoid fever are recorded annually. Typhoid bacillus is a parasite found only in man. Multiplication of the organism is insignificant outside the human body. The occurrence of typhoid fever, then, is dependent upon the connection between faecal material of the infected person and the mouth of the susceptible individual. Infected individuals and healthy carriers are, therefore, responsible for endemic typhoid fever. Detection and supervision of infected cases and healthy carriers are the only means to control the disease. In spite of the fact that numerous antibacterial agents have been used effectively in the treatment of typhoid fever, the general management of the patients is still of great importance. Good nursing care and adequate fluid and
Treatment of Typhoid Fever and Typhoid Carriers in Southeast Asia ... Viewpoint from South Vietnam N. N. Linh and K. Arnold University of Saigon Medical School, Saigon
The summary of the article on page 316 of this issue is important because it emphasises the fact that this disease is still common in Southeast Asia. It is endemic and epidemic in Vietnam with large numbers of cases occurring each year. Human carriers are the only source or reservoir of typhoid fever, and water is the main vehicle of transmission. It follows, therefore, that an attack on the disease can be made in three ways: (a) curative drugs for the individual patient; (b) bactericidal drugs (or other means such as surgery, i.e. cholecystectomy) for the carrier; and, (c) most important of all, treatment of the water supply. A fourth approach is also in use and involves an attempt to induce immunity to the disease by means of a vaccine. There have been several recent reports of in vivo and in vitro resistance of salmonella typhi to chloramphenicol [1-7]. This was first describhd in Mexico [1] but has now been documented in Vietnam [2-5] and Thailand [6-7]. This year in Vietnam we have found the incidence of in vitro chloramphenicol resistance to be greater than 80%. Consequently, it would be unwise to start treatment with chloramphenicol in a typhoid fever patient !n Vietnam. The drugs we recommend at present are co-trimoxazole (2 to 3 tablets 2 times daily for 15 days) if the patient is able to take oral medication, or ampicillin 2 to 4g intravenously if the patient is in coma, followed by the same dose orally when the patient is able to take drugs by mouth, for a total of 15 days. The disadvantage of IV ampicillin is that it is extremely expensive. A parenteral form of cotrimoxazole has only recently become available. It has been used successfully in the Philippines [8] and in Vietnam [9]. The parenteral dose we suggest is 2 ampoules twice daily (each ampoule contains 80mg trimethoprim and 400mg
Typhoid Fever and Typhoid Carriers in Southeast Asia
242
sulphamethoxazole). A new drug, amoxycillin, which is similar to ampicillin but is better absorbed from the gastro-intestinal tract and gives a higher blood level, is now under study for the treatment of typhoid fever. If after initiation of treatment, the antibiogram shows that the S. typhi is sensitive to chloramphenicol we recommend that this drug be used and the co-trimoxazole or ampicillin be discontinued. We agree with Dr Rowland that corticosteroids have little place in the treatment of typhoid fever, because they probably have no effect on the underlying disease process. The effect on the temperature is undesirable (unless there is hyperpyrexia), since this parameter is an important indicator of the patient's response to antibacterial treatment and is a clinical guide to in vivo resistance. Typhoid carriers have responded to prolonged courses of ampicillin but there are other factors to consider in discussing the management of the carrier state in Southeast Asia. In developing countries where typhoid fever is common, the emphasis should be on the purification of the water supply. It is a small accomplishment to treat only a few carriers since recontamination and re-infection will be only slightly reduced due to the large numbers of people involved. An even more discouraging aspect is the problem of identifying the carrier. In Vietnam, it is extremely difficult to obtain follow-up on patients in order to examine stool specimens to detect the carrier state. Even if follow-up is possible, the facilities for culture of the stool and then identification of the organism, are not widely available. It would appear therefore that emphasis on managing the typhoid carrier is a luxury that only a developed nation can afford. Priority in developing countries of Southeast Asia should be on improving diagnostic facilities and treating the water supply. An observation of importance concerning the carrier state is that in one study where co-trimoxazole was used for the treatment of typhoid fever and follow-up was carried out, there were no carriers detected [10]. Preliminary results of therapy with co-trimoxazole in chronic typhoid carriers suggest that it is at least as effective as ampicillin [11] . Immunisation is extensively used as a protective measure against typhoid fever by the military. But its value and effectiveness is not universally acclaimed in civilian populations where the disease is endemic and epidemic, since, if the resources are available for a large scale on-going mass immunisation programme, then these efforts are better directed to improving the water supply. r
2 3
References Vazquez, v.; Calderon, E. and Rodtriguez, R.S.: Chloramphenicol-resistant strains of Salmonella typhosa. New Engl. J. Med. 286: 1220 (1972). Truong, V.S.; Quynh, P.D. and Hung, NK.: Acta Medica Vietnam 18: 17 (1973). Chi. H.K.; Rue. T.M. and Phat. V.M.: Acta Medica Vietnam 18: 85 (1973).
4
Butler, T.; Linh. NN.; Arnold. K. and Pollack. M.: Chloramphenicol-resistant typhoid fever in Vietnam associated with R-factor. Lancet 2: 983 (1973). Linh. NN: Typhoid fever treated with chloramphenicol and co-trimoxazole. Lancet I: 1222 (1974).
Typhoid Fever and Typhoid Carriers in Southeast Asia 6 7 8
Anderson. E.S.: Salmonella surveillance. Group H resistance factors in Southern Asia. WHO Weekly Epidemiology Reports 49: 245 (I974). Lampe. R.M.; Mansuwan. P. and Duangmani. C: Chloramphenicol·resistant typhoid. Lancet 1: 623 (1974). Siasoco. R.E. and Hipolito. E.F.: A comparison of the efficacy of trimethoprim·sulfamethoxazole (Bactrim) and chloramphenicol in the treatment of typhoid fever. Philipp. J. Inter. Med.ll: 39 (1973).
9 10 II
243
Linh. N.N.: Typhoid fever treated with chlor· amphenicol and co·trirnoxazole. Lancet 1: 1222 (1974). Lasse"e, R.: Personal Communication. Pichler. H.; Knothe. H.; Spitzy. K.H. and Vielkind. G.: Treatment of chronic carriers of Salmo· nella typhi and Salmonella paratyphi B with trimethoprim·sulfamethoxazole. Journal of Infectious Diseases IZ8 (Suppl): 743 (1973).
Authors' address: Dr Nguyen Ngoc Linh and Dr Keith Arnold, University of Saigon Medical School, Saigon (South Vietnam) .
. . . Viewpoint from Thailand U. Lexomboon and P. Mansuwan Children's Hospital, Bangkok
Typhoid fever is still one of the most common public health problems in many developing countries, particularly in Southeast Asia. The high morbidity due to typhoid of up to 130 cases per 100,000 has been reported in certain areas. In Thailand alone, approximately 2,000 cases of typhoid fever are recorded annually. Typhoid bacillus is a parasite found only in man. Multiplication of the organism is insignificant outside the human body. The occurrence of typhoid fever, then, is dependent upon the connection between faecal material of the infected person and the mouth of the susceptible individual. Infected individuals and healthy carriers are, therefore, responsible for endemic typhoid fever. Detection and supervision of infected cases and healthy carriers are the only means to control the disease. In spite of the fact that numerous antibacterial agents have been used effectively in the treatment of typhoid fever, the general management of the patients is still of great importance. Good nursing care and adequate fluid and
