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HTLV-I INFECTION IN WESTERN EQUATORIAL AFRICA
1226 African country where HTLV-1 seroprevalence rates seem high (5-10% in adults)8 yet no clinical manifestation related to HTLV-I has been reported. Our study suggests that HTLV-1-related disease is unrecognised rather than absent. The Haut-Ogooue province of eastern Gabon is a mainly rural area at the transition of tropical rain forest to savannah. In a random sample of 885 adults we found 82 (9-3%) with antibodies to HTLV-I (confirmed by western blot [Dupont de Nemours] positivity for antibodies to gag and env gene products).8 This figure masks important variations in seroprevalence between people from the savannah (below 3-5%) and those from the tropical rain forest (above 12%) so we decided to study all adults living in one forest
village. Dot-blot hybridisation for DBV DNA in described in table.
serum
from
patient
Samples AltoA5 are, respectively, from March 12, March 26, May 7, May 15, and May 26,1987. Samples Bl to B5 are from June 26, July 2, and July 6, 1987, and Jan 23 and Dec 28,1988. Samples Cl to C3 are cloned HBV DNA standards of 1000, 100, and 10 pg/ml. was
noted. However,
on no
occasion did this coincide with their
ganciclovir therapy. In all four patients, HBV DNA and viral DNA polymerase fell to undetectable levels during the induction phase of therapy and remained undetectable while the patients were on the maintenance dose (table, figure). However, if a patient stopped taking ganciclovir for more than 6 days, HBV DNA would reappear in his serum (table). HBV DNA levels fell from 100 pg to less than 10 pg within 4 days of the start of treatment (table). This ten-fold reduction represents a drop from 4 x IOS/ml to 4 x 10’/ml of serum? In the patient illustrated in the table, during the period May 26 to June 26, 1987, compliance was poor and ganciclovir therapy was only intermittent. The bloods were drawn before treatment was started and always more than 6 days since the previous ganciclovir therapy. In all four patients, no significant effect on HBsAg titre, HBeAg status, or anti-HBc titre was noted during treatment. Liver function tests were normal before, during, and after ganciclovir. Liver biopsy specimens were not available. Ganciclovir is virustatic for CMV, and retinitis often recurs within a month of the cessation of therapy.3 This pattern was also observed with HBV DNA replication. Serum HBV DNA levels did not change significantly during the time when zidovudine was used alone. This is not surprising because liver cells do not metabolise thymidine efficiently, making it unlikely that high levels of zidovudine (azidothymidine) triphosphate will be attained intracellularly. In contrast purine analogues such as ganciclovir are actively metabolised, and in the duck hepadnavirus model they preferentially inhibit hepatitis virus.’ STEPHEN LOCARNINI Hepatitis Research Unit, Macfarlane Burnet Centre for Medical Research, Fairfield Hospital, Fairfield, Victoria 3078, Australia
KEJIAN GUO RON LUCAS IAN GUST
GJM, Williams R. Natural history and therapy of chronic hepatitis B virus infection. Am J Med 1988; 85 (suppl 2A): 143-46. 2. Gust ID, Burrell CJ, Coulepis AG, Robinson WS, Zuckerman AJ. Taxonomic classification of human hepatitis B virus. Intervirology 1986; 25: 14-29. 3. Pepose JS, Newman C, Bach MC, et al. Pathologic features of cytomegalovirus retinopathy after treatment with the antiviral agent ganciclovir. Ophthalmology 1987; 94: 414-24. 4. Lee B, Luo W, Suzuki S, Robins MJ, Tyrrell DLJ. In vitro and in vivo comparison of the abilities of purine and pyrimidine 2’, 3’-dideoxynucleosides to inhibit duck hepadnavirus. Antimicrob Ag Chemother 1989; 33: 336-39. 1. Alexander
HTLV-I INFECTION IN WESTERN EQUATORIAL AFRICA
SiR,—In Africa the relation between HTLV-I seropositivity and not clear, for only sporadic cases of adult T-cell leukaemia-lymphoma (ATL)1 and tropical spastic paraparesis (TSP)Z-4 have been reported from sub-Saharan Africa, a very large reservoir of HTLV-I infection.s This could suggest that, as in Papua New Guinea,6,7 the serological test is not specific for disease is
HTLV-1 and that there may be cross-reactions with other retroviruses or with non-specific agents. Gabon is an example of an
In this isolated village, in an endemic area for filariasis, we examined and took blood samples from 84 adults. 24 (29%) had antibodies to HTLV-I (by ELISA and western blot); none had antibodies to HIV; and 14 (17%) had antibodies to Treponema pallidum. In 55 microfilaraemia was observed. Clinical examination revealed the first cases of TSP from this region. These were 2 brothers aged 55 and 60. The presentation was very similar, with gradual onset of stiffness and weakness of the legs. Patient 1 had several times consulted different physicians at the province’s main hospital and in Libreville, the capital, but no diagnosis was made. Patient 2 did not seek medical advice and attributed his symptoms to old age. Physical examination disclosed spasticity of the lower legs with hyperreflexia and Babinski’s sign. The older man also had a urinary disturbance. They both had antibodies to HTLV-I. Cerebrospinal fluid was available for case 1 and showed the same HTLV-I western blot pattern as in the serum. Neither had antibodies to T pallidum. In case I we tried to isolate HTL V-I from lymphocytes, and after 2 weeks of culture HTLV-I antigen was detected by immunofluorescence. In the family of these 2 patients 9 of the adults had antibodies to HTLV-1, including the 3 wives of patient 1 and the wife of patient 2. Of their 6 children only the 2 oldest were seropositive (16 and 18 years). Several factors may explain why HTLV-1 disease is unrecognised, including short life expectancy, long latency of HTLV-I infection, the expected low frequency of the disease, non-specificity and gradual onset of symptoms of TSP or the rapidly fatal evolution of ATL, isolated cluster of HTLV-I infection, and ignorance of the diseases by doctors. Thus the absence of reports of TSP or ATL (3 cases of ATL have been diagnosed in Libreville, unpublished) from African countries does not seem to be a strong argument for claiming that positive HTLV-I results are due to cross-reactions. However, a confirmatory test with strict critera for positivity does need to be used if HTLV-1 seroprevalence rates are not to be overestimated. International Centre for Medical Research,
Franceville, Gabon; INSERM U13, Hôpital Claude Bernard, Paris; and Institute of Tropical Medicine, Antwerp, Belgium
E. DELAPORTE*
ICMR, Franceville, and Institute of Tropical Medicine, Antwerp
M. PEETERS
Hôpital Provincial, Franceville
M. SIMONI
Institute of Tropical Medicine,
Antwerp
*Present address: Department Antwerp, Belgium.
of
P. PIOT
Microbiology, Institute of Tropical Medicine, 2000
in Africa. Leukemia Res 1988; 12: 33-43. 2. Gessain A, Francis H, Sonan T, et al. HTLV-I and tropical spastic paraparesis in Africa. Lancet 1986; i: 698. 3. Taelman H, Van Gompel F, Wynants H, et al. HTLV-I associated tropical spastic paraparesis in an African patient residing m Belgium. Ann Soc Belge Méd Trop 1989; 69: 75-76. 4. Kazadi K, Desmyter J, Goubau P, et al. Focus of HTLV-I associated tropical spastic paraparesis in equateur, Zaire. V International Congress on AIDS (Montreal, 1989); abstr B637. 5. Editorial. HTLV-I comes of age. Lancet 1988; i: 217-19. 6. Babona DV, Nurse GT. HTLV-I antibodies in Papua New Guinea Lancet 1988; ii: 1148. 7. Weber JN, Banatvala N, Clayden S, et al. HTLV-I infection in Papua New Guinea. evidence for serologic false positivity. J Infect Dis 1989; 159: 1025-28. 8. Delaporte E, Dupont A, Peeters M, et al. Epidemiology of HTLV-I in Gabon. Int J Cancer 1988; 42: 687-89.
1. Flemming AF. Possible aetiological factors in leukemias
village. Dot-blot hybridisation for DBV DNA in described in table.
serum
from
patient
Samples AltoA5 are, respectively, from March 12, March 26, May 7, May 15, and May 26,1987. Samples Bl to B5 are from June 26, July 2, and July 6, 1987, and Jan 23 and Dec 28,1988. Samples Cl to C3 are cloned HBV DNA standards of 1000, 100, and 10 pg/ml. was
noted. However,
on no
occasion did this coincide with their
ganciclovir therapy. In all four patients, HBV DNA and viral DNA polymerase fell to undetectable levels during the induction phase of therapy and remained undetectable while the patients were on the maintenance dose (table, figure). However, if a patient stopped taking ganciclovir for more than 6 days, HBV DNA would reappear in his serum (table). HBV DNA levels fell from 100 pg to less than 10 pg within 4 days of the start of treatment (table). This ten-fold reduction represents a drop from 4 x IOS/ml to 4 x 10’/ml of serum? In the patient illustrated in the table, during the period May 26 to June 26, 1987, compliance was poor and ganciclovir therapy was only intermittent. The bloods were drawn before treatment was started and always more than 6 days since the previous ganciclovir therapy. In all four patients, no significant effect on HBsAg titre, HBeAg status, or anti-HBc titre was noted during treatment. Liver function tests were normal before, during, and after ganciclovir. Liver biopsy specimens were not available. Ganciclovir is virustatic for CMV, and retinitis often recurs within a month of the cessation of therapy.3 This pattern was also observed with HBV DNA replication. Serum HBV DNA levels did not change significantly during the time when zidovudine was used alone. This is not surprising because liver cells do not metabolise thymidine efficiently, making it unlikely that high levels of zidovudine (azidothymidine) triphosphate will be attained intracellularly. In contrast purine analogues such as ganciclovir are actively metabolised, and in the duck hepadnavirus model they preferentially inhibit hepatitis virus.’ STEPHEN LOCARNINI Hepatitis Research Unit, Macfarlane Burnet Centre for Medical Research, Fairfield Hospital, Fairfield, Victoria 3078, Australia
KEJIAN GUO RON LUCAS IAN GUST
GJM, Williams R. Natural history and therapy of chronic hepatitis B virus infection. Am J Med 1988; 85 (suppl 2A): 143-46. 2. Gust ID, Burrell CJ, Coulepis AG, Robinson WS, Zuckerman AJ. Taxonomic classification of human hepatitis B virus. Intervirology 1986; 25: 14-29. 3. Pepose JS, Newman C, Bach MC, et al. Pathologic features of cytomegalovirus retinopathy after treatment with the antiviral agent ganciclovir. Ophthalmology 1987; 94: 414-24. 4. Lee B, Luo W, Suzuki S, Robins MJ, Tyrrell DLJ. In vitro and in vivo comparison of the abilities of purine and pyrimidine 2’, 3’-dideoxynucleosides to inhibit duck hepadnavirus. Antimicrob Ag Chemother 1989; 33: 336-39. 1. Alexander
HTLV-I INFECTION IN WESTERN EQUATORIAL AFRICA
SiR,—In Africa the relation between HTLV-I seropositivity and not clear, for only sporadic cases of adult T-cell leukaemia-lymphoma (ATL)1 and tropical spastic paraparesis (TSP)Z-4 have been reported from sub-Saharan Africa, a very large reservoir of HTLV-I infection.s This could suggest that, as in Papua New Guinea,6,7 the serological test is not specific for disease is
HTLV-1 and that there may be cross-reactions with other retroviruses or with non-specific agents. Gabon is an example of an
In this isolated village, in an endemic area for filariasis, we examined and took blood samples from 84 adults. 24 (29%) had antibodies to HTLV-I (by ELISA and western blot); none had antibodies to HIV; and 14 (17%) had antibodies to Treponema pallidum. In 55 microfilaraemia was observed. Clinical examination revealed the first cases of TSP from this region. These were 2 brothers aged 55 and 60. The presentation was very similar, with gradual onset of stiffness and weakness of the legs. Patient 1 had several times consulted different physicians at the province’s main hospital and in Libreville, the capital, but no diagnosis was made. Patient 2 did not seek medical advice and attributed his symptoms to old age. Physical examination disclosed spasticity of the lower legs with hyperreflexia and Babinski’s sign. The older man also had a urinary disturbance. They both had antibodies to HTLV-I. Cerebrospinal fluid was available for case 1 and showed the same HTLV-I western blot pattern as in the serum. Neither had antibodies to T pallidum. In case I we tried to isolate HTL V-I from lymphocytes, and after 2 weeks of culture HTLV-I antigen was detected by immunofluorescence. In the family of these 2 patients 9 of the adults had antibodies to HTLV-1, including the 3 wives of patient 1 and the wife of patient 2. Of their 6 children only the 2 oldest were seropositive (16 and 18 years). Several factors may explain why HTLV-1 disease is unrecognised, including short life expectancy, long latency of HTLV-I infection, the expected low frequency of the disease, non-specificity and gradual onset of symptoms of TSP or the rapidly fatal evolution of ATL, isolated cluster of HTLV-I infection, and ignorance of the diseases by doctors. Thus the absence of reports of TSP or ATL (3 cases of ATL have been diagnosed in Libreville, unpublished) from African countries does not seem to be a strong argument for claiming that positive HTLV-I results are due to cross-reactions. However, a confirmatory test with strict critera for positivity does need to be used if HTLV-1 seroprevalence rates are not to be overestimated. International Centre for Medical Research,
Franceville, Gabon; INSERM U13, Hôpital Claude Bernard, Paris; and Institute of Tropical Medicine, Antwerp, Belgium
E. DELAPORTE*
ICMR, Franceville, and Institute of Tropical Medicine, Antwerp
M. PEETERS
Hôpital Provincial, Franceville
M. SIMONI
Institute of Tropical Medicine,
Antwerp
*Present address: Department Antwerp, Belgium.
of
P. PIOT
Microbiology, Institute of Tropical Medicine, 2000
in Africa. Leukemia Res 1988; 12: 33-43. 2. Gessain A, Francis H, Sonan T, et al. HTLV-I and tropical spastic paraparesis in Africa. Lancet 1986; i: 698. 3. Taelman H, Van Gompel F, Wynants H, et al. HTLV-I associated tropical spastic paraparesis in an African patient residing m Belgium. Ann Soc Belge Méd Trop 1989; 69: 75-76. 4. Kazadi K, Desmyter J, Goubau P, et al. Focus of HTLV-I associated tropical spastic paraparesis in equateur, Zaire. V International Congress on AIDS (Montreal, 1989); abstr B637. 5. Editorial. HTLV-I comes of age. Lancet 1988; i: 217-19. 6. Babona DV, Nurse GT. HTLV-I antibodies in Papua New Guinea Lancet 1988; ii: 1148. 7. Weber JN, Banatvala N, Clayden S, et al. HTLV-I infection in Papua New Guinea. evidence for serologic false positivity. J Infect Dis 1989; 159: 1025-28. 8. Delaporte E, Dupont A, Peeters M, et al. Epidemiology of HTLV-I in Gabon. Int J Cancer 1988; 42: 687-89.
1. Flemming AF. Possible aetiological factors in leukemias