- Email: [email protected]
Persistence of antibodies to Trypanosoma brucei gambiense after treatment of human trypanosomiasis in Uganda
250
10 ml plasma from each donor were retested twice by RT-PCR on separate samples. Of the first 127 units tested 92 had a midrange ALT value (45-89 IU/1), for which units are discarded but donors not deferred, and 35 had a high ALT (> 90 IU/1), resulting in permanent deferral of the donors. 64 of these units were screened only by C 100-3 anti-HCV enzyme immunoassay (EIA) (HCV EIA 1-0) and 63 were screened by c22, c200 based EIA (HCV EIA 2-0, Ortho Diagnostics). Only 1 unit (midrange ALT) was repeatedly positive for HCV RNA by RT-PCR on multiple samples. This donation was confirmed anti-HCV negative by both EIA 1-0 and 2-0. Sugitani’s and our results demonstrate that PCR can detect HCV infections in units with raised ALT that are missed by the best antibody-screening tests, and therefore support the value of continued ALT testing in blood banks, to complement routine anti-HCV screening. However, Sugitani’s recommendation for automated PCR as an additional routine screening method in blood banks would need further studies on ALT-normal units to find how many HCV infections are missed by both anti-HCV and ALT
pools,
screening tests.
Department of Laboratory Medicine, University of California, San Francisco, CA 94143, USA
-
TIMOTHY SANKARY JOSEPH ROMEO PAUL ULRICH MICHAEL BUSCH GIRISH H. VYAS
hospital laboratory. To rule out relapse or re-infected CATT-positive subjects were checked for parasite in blood, saliva, or CSF, according to clinical presentation. We found that proportion of CATT-positive individuals in a population of formerly treated trypanosomiasis cases decreased over time (figure). However, about half the subjects who were seen 24-36 months after treatment remained CATT positive. Thus, interpretation of CATT screening might pose problems in areas of active transmission, when a proportion of the population has already been treated for trypanosomiasis. Here, serological screening will not differentiate infected individuals from old cases. When testing is for case-finding, this might increase the number of patients false-positive by CATT and thus decrease specificity. If population testing is done for surveillance, it might lead to an overestimate of the,prevalence rates and hinder inferences from the
the Moyo cases,
observed trends. This investigation received financial support from the UNDP/World Bank/WHO special programme for research and training in tropical diseases.
Epicentre, 8 rue St Sabin, 75011 Paris, France
CHRISTOPHE PAQUET THIERRY ANCELLE
Médecins Sans Frontières, Paris
MARC GASTELLU-ETCHEGORRY JORGE CASTILLA IRENA HARNDT
1.
T, Van Meirvenne NA. Card-agglutination test with stained (CATT) for the serological diagnosis of T.b. gambiense trypanosomiasis. Ann Soc Belg Med Trop 1978; 58: 169-76. Cattand P. Diagnosis of African human trypanosomiasis. WHO Expert Committee on Trypanosomiasis. Geneva’ WHO, 1985 TRY/EC/WP/85.21 Van Nieuwenhove S, Declercq J Mass serodiagnosis and treatment of serological positives as a control strategy in trypanosomiasis gambiensis. Proceeding of a symposium on sleeping sickness screening. Antwerp; Nov, 1983. 47-50
Magnus E,
Vervoort
trypanosomes
1. Ulrich PP, Romeo JM, Lane PK, Kelly I, Daniel LJ, Vyas GN. Detection, semiquantitation, and genetic variation in hepatitis C virus: sequences amplified from the plasma of blood donors with elevated alanine aminotransferase. J Clin Invest 1990; 86: 1609-14.
Persistence of antibodies to Trypanosoma brucei gambiense after treatment of human trypanosomiasis in Uganda SIR,-Most of the control programmes in areas affected by Trypanosoma brucei gambiense use the card agglutination trypanosomiasis test (CATT).1 Affected villages are visited regularly by mobile teams with the objective of testing the entire population?,3 In north-west Uganda, the human African trypanosomiasis prevalence is up to 30% in some parts, and the high rate of transmission prompted repeat screening visits within short periods. Therefore, many already treated individuals are probably screened at each visit. Thus, it is important to document the course of the serological response in treated cases. From January to March, 1992, we surveyed with CATT former trypanosomiasis patients treated at Moyo Hospital, Uganda, during the past 3 years. All had had a positive CATT (wet blood and/or diluted serum) at diagnosis, associated with evidence of the parasite in blood, saliva, or cerebrospinal fluid (CSF). Recruitment was from patients attending scheduled follow-up over 2 years. Since attendance at follow-up decreased over time, we also selected former patients from hospital records and searched for the people still living in Moyo and its surrounds. 457 subjects were recruited (follow-up 3-36 months after initial diagnosis). CATT was done in
2.
3.
African trypanosomiasis: treatment or more
aggressive aggressive research? more
SIR,-Dr Hunter and colleagues (April 18, p 956) present findings suggesting that subcurative chemotherapy is an important cause of post-treatment reactive encephalopathy (PTRE) in mice infected with Trypanosoma brucei brucei and recommend that patients with African trypanosomiasis should receive more aggressive treatment. Their argument is similar to that of Jennings et al,’ who speculated that subcurative chemotherapy results in a rapid disappearance of trypanosomes from the bloodstream, but in their persistence in the central nervous system (CNS). The immune system might "concentrate" on the surviving parasites in the CNS, thereby causing meningoencephalitis. In a report of 598 patients with sleeping sickness due to T brucei gambiense, who were treated with melarsoprol, we provided some arguments against this hypothesise We emphasise that the relevance to human medicine of this new study, done in a small number of mice, is doubtful. Pentamidine and suramin sodium, drugs that cross the blood-brain barrier poorly (and which would thus be thought subcurative and, according to Hunter et al, more likely to induce PTRE) do not cause such an encephalopathy in man, even when used in patients with abnormal cerebróspinal fluid (CSF) fmdings. Diminazene, one of the subcurative drugs used in their experiments, although never licensed for human use for commercial reasons, has been widely used in thousands of patients in Zaire (some of whom certainly had a few trypanosomes in the CNS despite normal CSF white blood cell count) during shortages of pentamidine, and it has never been reported to induce PTRE. Melarsoprol, a highly curative and trypanocidal drug, which is still the standard treatment for patients with CNS involvement, frequently ’induces PTRE, whereas eflornithine, a drug which is trypanostatic and kills trypanosomes slowly, rarely, if ever, induces this condition. We recognise that the mouse model is useful to study potential new trypanocidal drugs or combinations of these drugs, and that the contribution of the Glasgow group in that field has been outstanding. However, this model has some limits. For instance, eflornithine (DFMO) monotherapy was not very effective in murine trypanosomiasis,3yet it has proved curative in more than 90% of patients .4
10 ml plasma from each donor were retested twice by RT-PCR on separate samples. Of the first 127 units tested 92 had a midrange ALT value (45-89 IU/1), for which units are discarded but donors not deferred, and 35 had a high ALT (> 90 IU/1), resulting in permanent deferral of the donors. 64 of these units were screened only by C 100-3 anti-HCV enzyme immunoassay (EIA) (HCV EIA 1-0) and 63 were screened by c22, c200 based EIA (HCV EIA 2-0, Ortho Diagnostics). Only 1 unit (midrange ALT) was repeatedly positive for HCV RNA by RT-PCR on multiple samples. This donation was confirmed anti-HCV negative by both EIA 1-0 and 2-0. Sugitani’s and our results demonstrate that PCR can detect HCV infections in units with raised ALT that are missed by the best antibody-screening tests, and therefore support the value of continued ALT testing in blood banks, to complement routine anti-HCV screening. However, Sugitani’s recommendation for automated PCR as an additional routine screening method in blood banks would need further studies on ALT-normal units to find how many HCV infections are missed by both anti-HCV and ALT
pools,
screening tests.
Department of Laboratory Medicine, University of California, San Francisco, CA 94143, USA
-
TIMOTHY SANKARY JOSEPH ROMEO PAUL ULRICH MICHAEL BUSCH GIRISH H. VYAS
hospital laboratory. To rule out relapse or re-infected CATT-positive subjects were checked for parasite in blood, saliva, or CSF, according to clinical presentation. We found that proportion of CATT-positive individuals in a population of formerly treated trypanosomiasis cases decreased over time (figure). However, about half the subjects who were seen 24-36 months after treatment remained CATT positive. Thus, interpretation of CATT screening might pose problems in areas of active transmission, when a proportion of the population has already been treated for trypanosomiasis. Here, serological screening will not differentiate infected individuals from old cases. When testing is for case-finding, this might increase the number of patients false-positive by CATT and thus decrease specificity. If population testing is done for surveillance, it might lead to an overestimate of the,prevalence rates and hinder inferences from the
the Moyo cases,
observed trends. This investigation received financial support from the UNDP/World Bank/WHO special programme for research and training in tropical diseases.
Epicentre, 8 rue St Sabin, 75011 Paris, France
CHRISTOPHE PAQUET THIERRY ANCELLE
Médecins Sans Frontières, Paris
MARC GASTELLU-ETCHEGORRY JORGE CASTILLA IRENA HARNDT
1.
T, Van Meirvenne NA. Card-agglutination test with stained (CATT) for the serological diagnosis of T.b. gambiense trypanosomiasis. Ann Soc Belg Med Trop 1978; 58: 169-76. Cattand P. Diagnosis of African human trypanosomiasis. WHO Expert Committee on Trypanosomiasis. Geneva’ WHO, 1985 TRY/EC/WP/85.21 Van Nieuwenhove S, Declercq J Mass serodiagnosis and treatment of serological positives as a control strategy in trypanosomiasis gambiensis. Proceeding of a symposium on sleeping sickness screening. Antwerp; Nov, 1983. 47-50
Magnus E,
Vervoort
trypanosomes
1. Ulrich PP, Romeo JM, Lane PK, Kelly I, Daniel LJ, Vyas GN. Detection, semiquantitation, and genetic variation in hepatitis C virus: sequences amplified from the plasma of blood donors with elevated alanine aminotransferase. J Clin Invest 1990; 86: 1609-14.
Persistence of antibodies to Trypanosoma brucei gambiense after treatment of human trypanosomiasis in Uganda SIR,-Most of the control programmes in areas affected by Trypanosoma brucei gambiense use the card agglutination trypanosomiasis test (CATT).1 Affected villages are visited regularly by mobile teams with the objective of testing the entire population?,3 In north-west Uganda, the human African trypanosomiasis prevalence is up to 30% in some parts, and the high rate of transmission prompted repeat screening visits within short periods. Therefore, many already treated individuals are probably screened at each visit. Thus, it is important to document the course of the serological response in treated cases. From January to March, 1992, we surveyed with CATT former trypanosomiasis patients treated at Moyo Hospital, Uganda, during the past 3 years. All had had a positive CATT (wet blood and/or diluted serum) at diagnosis, associated with evidence of the parasite in blood, saliva, or cerebrospinal fluid (CSF). Recruitment was from patients attending scheduled follow-up over 2 years. Since attendance at follow-up decreased over time, we also selected former patients from hospital records and searched for the people still living in Moyo and its surrounds. 457 subjects were recruited (follow-up 3-36 months after initial diagnosis). CATT was done in
2.
3.
African trypanosomiasis: treatment or more
aggressive aggressive research? more
SIR,-Dr Hunter and colleagues (April 18, p 956) present findings suggesting that subcurative chemotherapy is an important cause of post-treatment reactive encephalopathy (PTRE) in mice infected with Trypanosoma brucei brucei and recommend that patients with African trypanosomiasis should receive more aggressive treatment. Their argument is similar to that of Jennings et al,’ who speculated that subcurative chemotherapy results in a rapid disappearance of trypanosomes from the bloodstream, but in their persistence in the central nervous system (CNS). The immune system might "concentrate" on the surviving parasites in the CNS, thereby causing meningoencephalitis. In a report of 598 patients with sleeping sickness due to T brucei gambiense, who were treated with melarsoprol, we provided some arguments against this hypothesise We emphasise that the relevance to human medicine of this new study, done in a small number of mice, is doubtful. Pentamidine and suramin sodium, drugs that cross the blood-brain barrier poorly (and which would thus be thought subcurative and, according to Hunter et al, more likely to induce PTRE) do not cause such an encephalopathy in man, even when used in patients with abnormal cerebróspinal fluid (CSF) fmdings. Diminazene, one of the subcurative drugs used in their experiments, although never licensed for human use for commercial reasons, has been widely used in thousands of patients in Zaire (some of whom certainly had a few trypanosomes in the CNS despite normal CSF white blood cell count) during shortages of pentamidine, and it has never been reported to induce PTRE. Melarsoprol, a highly curative and trypanocidal drug, which is still the standard treatment for patients with CNS involvement, frequently ’induces PTRE, whereas eflornithine, a drug which is trypanostatic and kills trypanosomes slowly, rarely, if ever, induces this condition. We recognise that the mouse model is useful to study potential new trypanocidal drugs or combinations of these drugs, and that the contribution of the Glasgow group in that field has been outstanding. However, this model has some limits. For instance, eflornithine (DFMO) monotherapy was not very effective in murine trypanosomiasis,3yet it has proved curative in more than 90% of patients .4