B control in African countries

1364) emphasises the importance of hepatitis B virus as a major factor determining the risk of virus carriage. This is the basis for the current strategy of infant immunisation to prevent the long-term sequelae of carriage.’ However, we disagree with some of his interpretations of published data. The low rates of HBeAg carriage (and presumably infectiousness) in African women carriers are unexplained, but the apparent decline with age in cross-sectional studies might result from differential survival as well as from loss of the HBeAg carriage state. The efficiency of transmission from African HBeAg carriers


SIR,—Dr Hudson (Dec 1, p young age at infection with 1

their children is also unclear. The few African data available suggest less efficient transmission associated with lower titres of HBV DNA in African HBeAg positive women compared with Asian HBeAg positive women.2,3 This may explain the Senegalese findings that Hudson fmds surprising.4 The association of childhood infection with maternal carriage does not necessarily indicate perinatal transmission, as Hudson suggests. The maternal carriage could merely indicate a high risk environment with many infectious people (in particular, children) in the household. Acute infection of pregnant women as a cause of perinatal infection, even in societies where sexual transmission is the dominant route, is rare and of little public health importance, whereas child-to-child transmission in Africa is very common, peaking at age 2-3 yearsThe mode of transmission is unclearthere is some evidence for both tropical ulcers and arthropods having a role’ but none that unsterile injections are an important risk factor. Indeed a high proportion of injections are given to children in infancy when disease is most prevalent and most vaccines are administered. Yet this is before the peak age of hepatitis B virus transmission. Also, there is little evidence from studies in African countries that unsterile needles are an important source of HIV transmission, although a prospective study of this is in progress. Hudson suggests that the price of a vaccine-prevented liver cancer would be about US$1200. Data from the Gambia that uses life-time risk estimates, rather than only those from middle-aged Taiwanese men, suggest that the cost of preventing one male liver cancer is$150-200 (Hall AJ, Robertson R, Crivelli P, et al, unpublished). It would be unfortunate if speculative research on educational methods of risk factor reduction was given priority over the delivery of a highly effective vaccine. to

Department of Epidemiology and Population Sciences, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK


1. The Gambia Hepatitis Study Group Hepatitis B vaccine in the expanded programme on immunisation the Gambian experience. Lancet 1989, i: 1057-60. 2 Greenfield C, Osidiana V, Krayiannis P, et al. Perinatal transmission of hepatitis B virus in Kenya. its relation to the presence of serum HBV-DNA and anti-HBe in the mother J Med Virol 1986, 19: 135-142 3 Ayoola EA, Ogunbode O, Odelola HA. Congenital transmission of hepatitis B antigen in Nigenans Arch Virol 1981, 67: 97-99. 4 Marinier E, Barrois V, Larouze B, et al Lack of perinatal transmission of hepatitis B virus in Senegal, West Africa J Pediatr 1985; 106: 843-49. 5 Whittle H, Inskip HM, Bradley AK, et al The pattern of childhood hepatitis B infection in two Gambian villages. J Infect Dis 1990, 161: 1112-15 6. Barin F, Perrin J, Chotard J, et al Cross-sectional and longitudinal epidemiology of hepatitis B in Senegal Prog Med Virol 1981; 27: 148-62 7 Vall Mayans M, Hall AJ, Inskip HM, et al. Risk factors for the transmission of hepatitis B virus to Gambian children. Lancet 1990; 336: 1107-09.

SIR,—Dr Hudson argues that behaviour modification, similar to that advocated for control of AID S, be considered as a cost-effective alternative to mass hepatitis B virus (HBV) vaccination in infancy, now thought to be the only effective approach to the control of this infection.’ His conclusion rests on several assumptions. First, Hudson suggests that at US$3 per child, mass immunisation would cost$1135 per life saved. The cost of HBV vaccine is more likely to fall to$0 25-0 50 per dose by the time that HBV vaccine is widely given in the developing world as part of the Expanded Programme on Immunisation (EPI). The reduction in cost will follow from manufacturing economies of sealer dose reduction, and probable incorporation of HBV vaccine into existing diphtheria,

tetanus regimens. It has been shown that the cost-benefit of HBV immunisation is already (with prices in the $09-1 00 range for public sector immunisation) within range of that of other EPI imrnunogens.1 Second, Hudson suggests that education against unsterile injections, which is clearly required for AIDS control, may decrease or eliminate the need for HBV vaccines. His conclusion assumes that this mechanism is an important route of dissemination of HBV infection. In Africa, the bulk of infection takes place in infancy and early childhood, with a frequency, in Liberian villages, of about 30% per year in the first four years of life.3 Almost all carrier-state infections, which account for most cases of cirrhosis and hepatocellular carcinoma, result from horizontal transmission of HBV during this period. It is difficult to see how behaviour modification will have any effect on reducing transmission in this age group. Unsterile needles and syringes probably account for only a small proportion of HBV transmissions, since injections are not commonly given to infants in this age group in rural Africa. Even if this was a major route of transmission, provision of disposable syringes and sterilisation equipment together with training for all who give injections would cost as much as HBV vaccines, and would not protect those infected through horizontal routes. In the same way, even if arthropods are found to be important transmission agents, the cost of maintaining bedbug-free beds throughout Africa would exceed that of mass immunisation. Mass HBV immunisation of newborn babies and infants will be practical and cost-effective in the near future and will provide protection to entire populations irrespective of which mechanisms of spread are important. Demonstration projects must find the best way to incorporate HBV immunisation into EPI at the lowest cost. Such projects are underway in the Gambia, Indonesia, Thailand, China, Kenya, Gabon, and the Cameroons. In addition, Brazil, Egypt, Malaysia, and the Philippines are already embarking upon or will soon begin their own national programmes to incorporate hepatitis B vaccination into EPI. In China, mass immunisation of newborn babies has resulted in a 90% reduction in carrier rate (Zhi-Yi Xu, personal communication). It is unlikely that the behaviour modifications proposed by Hudson could approach the efficacy of such a prevention strategy.

poliomyelitis, and

International Task Force for Hepatitis B Immunization and Laboratory of Virology and Parasitology, Lindsley F Kimball Research Institute of the New York Blood Center, New York, NY 10021, USA International Task Force for Hepatitis B Immunization and Program for Appropriate in Health Care,

Seattle, Washington




1 Maynard JE, Kane MA, Hadler SC. Global control of hepatitis B through vaccination: role of hepatitis B vaccine in the expanded programme on immunization. Rev Infect Dis 1989; 3 (suppl 11) S574-78. 2. Coursaget P, Yvonet B, RelyVeld EH, et al Simultaneous administration of diphthena-tetanus-pertussis-polio and hepatitis B vaccines m a simplified immunization program. Immune response to diphtheria toxoid, tetanus toxoid, pertussis and hepatitis B surface antigen. Infect Immun 1986; 51: 784-87. 3. Prince AM, White T, et al. The epidemiology of hepatitis B infections in Liberian infants. Infect Immun 1980, 32: 675-80.

Horizontal transmission of hepatitis B virus SIR,—The report by Dr Vall Mayans and colleagues from the Gambia (Nov 3, p 1107) suggests an association between hepatitis B virus (HBV) surface antigenaemia in children and the presence of bug infestation in their beds. Their findings reopen the debate as to whether biting insects may be responsible for the horizontal transmission of HBV in the tropics. We have investigated the frequency of HBV serological markers in 100 former prisoners of the Japanese (POWs), who laboured in the Thai-Burma jungles during World War II.1,2 HBV markersHBsAg, anti-HBs, or anti-HBc-were present in 40%. A control group of 100 veterans of the Burma campaign (men who fought at the same time and in the same area, but were not imprisoned) were similarly investigated, and 13% were found to have HBV markers.


Only about 2% of the UK population would be expected to be seropositive.3 Both study groups had higher than normal rates of infection, though those in the POWs were significantly higher than rates in the Burma veterans (p < 0-01). The many potential routes of HBV infection among POWs (tropical ulcers, poorly sterilised surgical equipment, and blood transfusions) did not generally apply to Burma veterans. However, both groups, especially POWs, were exposed to biting insects-notably mosquitoes and bedbugs. Our results provide supportive circumstantial evidence for horizontal transmission of HBV by biting insects in the tropics. If this route of spread is confirmed, then existing strategies of HBV infection control in tropical countries may need to be reconsidered. G. V. GILL D. R. BELL

Liverpool School of Tropical Medicine, Liverpool L3 5QA, UK Virus Reference Laboratory, Central Public Health Laboratory, London NW9

haemorrhage. Hospitalier de Franceville, Gabon, INSERM/U135, Faculté de Médecine de Bicêtre,


94275 Le Kremlin-Bicêtre, France


Centre International de Recherches Médicales, Franceville



Institute of Tropical Medicine, Antwerp, Belgium


GV, Bell DR. Horizontal transmission of hepatitis B in the Thai-Burma jungles—insect borne spread Q J Med 1989, 73: 963. 2. Gill GV, Bell DR, Vandervelde EM Horizontal transmission of hepatitis B virus amongst British 2nd World War soldiers in South-East Asia. Postgrad Med J 1991; 1. Gill

67: 39-41 3 Tedder RS, Cameron CH, Barbara JAJ, Howell D Viral hepatitis markers donors with history of jaundice. Lancet 1980; i 595-96.

evidence of HTLV-1 infection. Kawahara et al did not attempt to detect antigen and it is unclear whether the child was seropositive for HTLV-1 at 11months of age or not. Furthermore, mean serum IgM concentration at 20 days of life is around 50 mg/dl,- their quoted value of 47 mg/dl cannot be due to viral infection. The most likely cause of the subependymal cystic lesions in this child is in-utero




INSERM U13/IMEA, Hôpital Claude Bernard, Paris 1. Kamuro virus.

2. in

Hospitalier de


blood 3.


A, Hayami M, Fujii H, et al Vertical transmission of adult T cell leukaemia Lancet 1983; i: 240

Shigeo H, Kyoko Y, Shigeru K, et al. Mother-to-child transmission of human T-cell leukemia virus type-I Jpn J Cancer Res 1985; 76: 474-80. Shiro N, Yoshiya A, Motohiko I, et al. Search for possible routes of vertical and horizonal transmission of adult T-cell leukemia virus. Jpn J Cancer Res 1984, 75: 1044-45

4. Hino S. Milk-borne transmission of HTLV-I

Transmission of



by saliva

SIR,-Dr Takamatsu and colleagues (Dec 15, p 1515) report detection of hepatitis C virus (HCV) RNA in the saliva of patients with chronic liver disease, and they speculate that saliva may be a source of HCV infection. The possibility of transmission of blood-borne non-A, non-B hepatitis by saliva was reported by us in 1987,1 and we have lately attempted to detect HCV RNA in the saliva of chimpanzees infected with hepatitis C. We analysed the saliva from four chronic HCV carrier chimpanzees. RNA was extracted from 3 ml saliva, reverse transcribed into cDNA, and amplified by "nested" polymerase chain reaction. The external primer pairs were 5’-TACGACTTGGAGCTCATAAC-3’ (sense) and 5’-CCGTAGATCTCGCAATCGAG-3’ (anti-sense), and the inner pairs were 5’-TACGACTTGGAGCTCATAAC-3’ (sense) and 5’-TGACTGGAGTGTGTCTTGCT-3’ (anti-sense). These primers were deduced from the nonstructural region of prototype HCV nucelotide sequences (European patent application 88310922.5). HCV RNA was detected in the saliva of two of the four chimpanzees. HCV RNA was also detected in sera from a recipient chimpanzee inoculated with HCV RNA-positive saliva. Although our data are few, these results strongly suggest that the saliva of patients with HCV infection is infective. Laboratory of Virology, New York Blood Center, New York, NY 10021, USA


K, Kurata T, Shikata T, Sugitani M, Oda T. Experimental transmission of non-A, non-B hepatitis by saliva. J Infect Dis 1987; 155: 1078-79.

1 Abe

Congenital hydrocephalus due to intrauterine HTLV-I infection of

SIR,-Dr Kawahara and colleagues (Dec 8, p 1442) report a case congenital hydrocephalus in which intrauterine infection is

This conclusion may be premature. Vertical transmission is limited to three routes: transplacental, during delivery, and via breast feeding. However, HTLV-1 antigens have been detected in cord blood lymphocytes in only one1 of several studies.2-4 We conducted a case-control study in Gabon in which each of 45 HTLV-1 seropositive pregnant women was matched with 2 HTLV-1 seronegative pregnant women. We found no influence of HTLV-1 infection on either the pregnancy or the infant at birth. Preliminary analysis of cord blood from 20 seropositive women, with the polymerase chain reaction, has revealed no


as a

major route in the endemic cycle

Acta Pediatr 1989; 31: 428-35.

High seroprevalence of HTLV-I Seychelles

in the

SIR,-Human T-lymphotropic virus type I (HTLV-1), which adult T-cell leukaemia and probably tropical spastic is endemic in the Caribbean, Japan, and some areas of Africa. Until recently, little was known about the prevalence of the closely related retrovirus HTLV-11. However, enzyme immunoassays (EIA) with HTLV-1 viral lysate as antigen and making use of the high degree of serological cross-reactivity between the two viruses have shown, when followed by the polymerase chain reaction (PCR) to distinguish HTLV-1 from HTLV-11, high rates of HTLV-11 infection among intravenous drug abusers in the USA1 and Italy.2 A high rate of paraplegia (0-13%) has been observed in the general population of the Seychelles, and a group of 20 TSP patients (17 of whom were HTLV-1 seropositive) was identified.3-5Using an HTLV-1 viral lysate EIA followed by a synthetic peptide EIA specific for HTLV I or II, we have tested a sample of adults on the Seychelles. The study was done on the island ofMahe, where 90% of the total population live. Sera from a sex and age stratified random sample of 1055 adults aged 25-64 were screened by HTLV-1 EIA (Abbott)6 and repeatably reactive specimens were further tested by western blot and radioimmunoprecipitation assay (RIPA). Confirmation of seropositivity required antibodies to both 24 gag and gp46/61 env gene productsConfirmed samples were then typed for HTLV I or II. Sera from individuals infected with HTLV-I or HTLV-11 (as determined by PCR) were used as controls.1 72 (6-82%) of the 501 males and 554 females tested were EIA positive. Of the 70 specimens available for confirmatory testing, 65 (6-16% of the original total) were confirmed; the other 5 were indeterminate. On the assumption that the 2 missing sera would have been confirmed the seroprevalence of HTLV infection was 6-35%. With standardisation for age and sex the prevalence was 4-87%. Of the 70 confirmed and 1 indeterminate sample typed, none was HTLV-11 positive. Women had a signficantly higher rate of HTLV-1 infection than men (p < 0’001) and seroprevalence tended to rise with age (table). HTLV-1 infection was significantly more common among black (n=721) than in white (n=81) or mixed-race (n=227) groups (both p < 0’001) and among unskilled workers than in officej skilled It was more workers (p < O’OOl) or professionals (p

Horizontal transmission of hepatitis B virus.

247 Hepatitis B control in African countries 1364) emphasises the importance of hepatitis B virus as a major factor determining the risk of virus c...
334KB Sizes 0 Downloads 0 Views