A mathematical model of hepatitis B virus transmission and its application for vaccination strategy in china.

BACKGROUND: Before universal infant immunization against hepatitis B virus (HBV) in 1986 China was a region endemic for HBV infection. The prevalence of HBV infection in the population was about 60% and the proportion of chronic HBV carriers around 10%. These HBV carriers could progress to chronic hepatitis B, cirrhosis, and primary hepatocellular carcinoma. Since 1976, large-scale sero-surveys of HBV infection have been carried out and a lot of data have been collected. METHOD: This paper describes a mathematical model developed to predict the dynamics of HBV transmission and to evaluate the long-term effectiveness of the vaccination programme. We used a compartment model expressed by a set of partial differential equations based on the characteristics of HBV infection. RESULTS: All parameters, expressed in the model as a non-linear function of age and time since vaccination, were estimated using sero-survey data. The model fits well with both pre-vaccination and post-vaccination sero-surveys. The observed and estimated age-specific prevalence rates of HBV infection and HBV carriage agree with each other. According to our model, if all newborns are vaccinated according to schedule, the rate of HBV carriage will decline sharply over time to 0.2% in 70 years. By then, the ratio of acute hepatitis B will be less than 0.5% and the ratio of chronic hepatitis B will be around 5%. CONCLUSIONS: The results suggest that HBV infection in China can be controlled in just one generation, and eventually eliminated. Our model shows that vaccination coverage is the most important indicator for the elimination of HBV transmission. The higher the vaccination coverage, the better the long-term effectiveness of immunization. Thus, the key to controlling and eliminating HBV transmission in China is to find ways to immunize all infants throughout the country, especially in poor, rural areas.

Injections given in healthcare settings as a major source of acute hepatitis B in Moldova.

BACKGROUND: Reported rates of acute hepatitis B are high in many former Soviet Union republics and modes of transmission are not well defined. METHODS: Two case-control studies were undertaken in Moldova to identify risk factors for acute hepatitis B in people aged 2-15 years (children) and > or =15 years (adults). Serologically confirmed acute hepatitis B cases occurring between 1 January 1994 and 30 August 30 1995, were matched on age, sex, and district of residence to three potential controls who were tested for hepatitis B markers to exclude the immune. Stratified odds ratios (SOR) were calculated using bivariate and multivariate methods. RESULTS: In multivariate analysis, compared with the 175 controls, the 70 adult cases (mean age 25 years, 66% male) were more likely to report receiving injections in the 6 months before illness during a dental visit (SOR = 21; 95% CI: 3.7-120), a hospital visit (SOR = 35; 95% CI: 7.2-170), or a visit to the polyclinic (SOR = 13; 95% CI: 2.4-74). Among children, receiving injections during a hospital visit (SOR = 5.2; 95% CI: 1.2-23) was the only exposure reported significantly more often by the 19 cases (mean age 8 years, 68% male) compared with the 81 controls. CONCLUSION: These results, along with reported unsafe injection practices in Moldova, suggest that injections are a major source of hepatitis B virus transmission and highlight the importance of proper infection-control procedures in preventing transmission of blood-borne infections.

PIP: Two case-control studies were conducted between January 1994 and August 1995 to determine the relative importance of injections and other exposures as a source of acute hepatitis B in Moldova among adults (aged 15 years) and children (aged 2-15 years). Results showed that injections in various health care settings were associated with acute hepatitis B and showed a higher proportion among adults compared with children. Contact with an HBsAg-positive person was also associated with illnesses; however, there was no statistically significant association between acute hepatitis B and other exposures. The risk of HBV transmission following percutaneous exposure is high (at least 30%). Calculation of the population attributable to risk suggests that injections associated with acute hepatitis B cases occurred in adults (52%) and children (21%). Adverse effects of injections may not be apparent in causing chronic infections. Transmission of blood-borne pathogens through unsafe injection practices is a problem increasingly identified worldwide.

Low risk of sexual transmission of hepatitis C virus in Somalia.

The prevalence in Somalia of antibody to hepatitis C virus (anti-HCV) was determined in a survey of 236 female prostitutes, 80 sexually transmitted disease (STD) clinic patients, 79 male soldiers, and 43 tuberculosis patients. Of 98 (22%) serum samples repeatedly anti-HCV reactive by first and second generation enzyme-linked immunosorbent assay kits, only 8 (1.8%) were anti-HCV positive by immunoblot assay (RIBA-2). Anti-HCV seropositivity by immunoblot assay was not associated with any risk group or with positive syphilis serology (found in 18% of subjects) or antibody to human immunodeficiency virus 1 (in 1.4% of subjects). These data indicate that sexual transmission of hepatitis C virus is not common in Somalia among sexually active populations, including female prostitutes and other groups at high risk of STDs and the acquired immune deficiency syndrome.

PIP: In Somalia in 1990, health workers collected blood samples from 486 people at high risk of sexually transmitted diseases (STDs) and HIV-1 infection, who lived in Mogadishu, Merca, and Chismayu, so the Ministry of Health could determine the prevalence of the antibody to hepatitis C virus (anti-HCV). The population consisted of 236 female prostitutes, 80 STD clinic patients, 79 male soldiers, and 43 tuberculosis patients. 1st and 2nd generation enzyme-linked immunosorbent assays (ELISAs) detected 98 (22%) anti-HCV positive serum samples which were repeatedly positive. Yet, the immunoblot assay (RIBA-2) detected only 8 (1.8%) anti-HCV positive serum samples, suggesting considerable false positive anti-HCV ELISA results. 18% (79) of all subjects tested positive for syphilis, with all but 6 being prostitutes. 30.9% of the prostitutes had syphilis. Prostitutes made up almost all HIV-1 infected subjects (5 of 6), which comprised 1.4% of all study subjects. When the researchers analyzed just the 8 RIBA-2 confirmed anti-HCV positive samples, HCV infection was not associated with age, sex, risk group, positive syphilis serology, or HIV-1 infection. None of the subjects with HCV infection tested positive for HIV-1. Just 3 of the 8 HCV-infected patients tested positive for syphilis. Subjects positive for anti-HCV were older than other study subjects (32 years vs. 28 years). These results show that HCV has a low likelihood of being transmitted sexually among Somalis, even in those populations at high risk of STDs. They also indicate that HIV-1 infection was rather rare in 1990 in Somalia, perhaps due to low trade activity between Somalia and the rest of Africa.

The role of sexual transmission in the epidemiology of hepatitis C virus in black South Africans.

The role of sexual transmission of hepatitis C virus in Black South Africans was evaluated by a seroprevalence study of sentinel populations at varying risk for sexually transmitted diseases (STD). Prevalence of anti-hepatitis C virus antibodies was found to be 1.8% in an STD clinic sample of 272, 0.7% in a family planning sample of 148, 3.3% in a sample of 246 'blue collar' workers (81% of rural origin), and 0.9 in a sample of 117 new blood donors. All samples were from Black adults. The differences between them were not significant (P = 0.2348). In contrast, the prevalence of anti-human immunodeficiency virus antibodies in the STD sample (5.5%) was statistically significantly different (P = 0.00095) from the family planning clinic sample (1.4%) and the blue collar sample (0.8%) as well as from the reported prevalence for black blood donors in the Johannesburg area (0.7%). No evidence supporting a role for sexual transmission of hepatitis C virus was found, while the prevalence of infection appeared to be higher in rural populations and in males. These features are similar to hepatitis B in this population.

Efficacy of thermoplastic elastomer and latex condoms as viral barriers.

The barrier efficacy of a thermoplastic elastomer (TPE) and three brands of latex condoms was compared in a passive-leak test and in a dynamic model of simulated intercourse. Fifteen replicates of each of the condoms were challenged with bacteriophage T7 (100 nm) and the polio virus Type 1 (PV-1, 27 nm). In the passive test, no condom leaked either virus. In the dynamic model, no TPE condoms leaked either virus and no latex condoms leaked T7. Two samples of one commercially available latex condom leaked T7 but not PV-1. These data support that intact latex condoms are effective in vivo viral barriers and extend the finding to TPE condoms as well. Given its substantial equivalence to latex as a viral barrier, TPE condoms are an alternative choice for individuals with latex allergies. The TPE material is also more resistant to common environmental conditions that affect latex adversely and should therefore be a superior choice if condoms must be stored for extended periods in suboptimal conditions.

PIP: A microbiologist at Loma Linda University in California used T7 (100 nm), a virulent bacteriophage of Escherichia coli, and the poliovirus type 1 (PC-1) (27 nm) to compare the efficacy of the viral barrier of latex and new thermoplastic elastomer (TPE) condoms. The scientist used a passive test and a simulated intercourse model to compare the 2 condom types. The simulation consisted of a condom-covered disposable centrifuge tube with 4 ml of virus which was inserted into an outer condom with 2 ml of virus-free medium. This apparatus was withdrawn and inserted 30 times within 30 seconds into a commercially produced latex vagina. The tests with T7 used 15 condoms of each brand. The tests with PV-1 used 14 condoms of each brand. The only TPE condom brand was Tactylon. Latex condom brands were Shiek, Trojan-Enz, and Lifestyles. No virus passed through the barrier during the passive test. T7 leaked through 2 latex condoms (13.3%) of the same brand (Trojan-Enz) during the simulated intercourse test. On the other hand, PV-1 did not leak through any of the condoms. Tactylon effectively prevented the passage of both T7 and PV-1. These findings confirmed that latex condoms tend to block passage of both small and large viruses. They indicated that TPE condoms also block passage of small and large viruses. Thus, the effective maximum pore size in all of the TPE condoms and in all but 2 of the latex condoms was too small to let HIV (80-120 nm) and hepatitis B virus (about 42 nm) filter through. Clinical trials have indicated the breakage rate of TPE condoms is not significantly different from that of latex condoms. Advantages of the TPE condom are its ability to resist environmental effects, e.g., ultraviolet light and heat, which deteriorate the latex condom and it does not have antioxidants and accelerators the latex condom has which cause allergic reactions, e.g., dermatitis.

Effectiveness of mandatory transmissible diseases screening in Indian blood donors.

This study was undertaken to determine the prevalence of transfusion transmitted diseases (TTDs) among local blood donors, the safety offered by the four mandatory tests (for HIV, HBsAg, syphilis and malaria) and to assess alanine aminotransferase (ALT) as a surrogate test. A total of 313 blood donors were tested for HBsAg, hepatitis B core (HBc) antibody, hepatitis C (HCV) antibody, HIV antibody, and IgM antibody to cytomegalovirus (CMV-IgM). The serum alanine aminotransferase levels were also done on each unit of blood. The prevalence of various markers was 7(2.2%) for HBsAg, 57 (18.2%) for anti HBc (total), 1 (0.3%) for anti HCV, 16 (5.1%) for anti CMV. None of the donors were positive for HIV, VDRL or malaria. ALT level was raised in 16.5 per cent of donors and showed no correlation with hepatitis markers. ALT was not found to be useful as a surrogate marker for routine screening of donors. Sensitive tests like ELISA and immunofluoresence for malaria antigen should be applied for screening for malaria. VDRL test may be used to detect high risk donors rather than detection of syphilis when stored blood is used. HBsAg and HIV tests should be routinely done on every unit of blood and anti HCV tests should be done regularly, if possible.

Seroprevalence and mother-to-infant transmission of hepatitis C in asymptomatic Egyptian women.

OBJECTIVES: In this study, we sought to determine (1) the prevalence of hepatitis C virus (HCV) RNA, or its antibodies, in a healthy parturient Egyptian population and (2) the risk of mother-to-infant transmission in this population. METHOD: The serum of 499 pregnant Egyptian women was tested for anti-HCV with ELISA-3 and for HCV RNA by polymerase chain reaction (PCR). Neonatal cord blood and infant blood were similarly tested for anti-HCV and HCV RNA. RESULTS: Recombinant immunoblot assay (RIBA) detected anti-HCV in 65/499 (13%) women; of these, 20/65 (31%) were PCR-positive. The total number of babies born was 499. Of the original group, 97 mothers and infants (HCV-negative) were lost to follow up and were excluded. Sixty-five anti-HCV-positive infants were born vaginally to the 65 anti-HCV-positive mothers, of which twenty (31%) corresponding mothers and babies were also positive for HCV RNA. Of these twenty babies, three died of hepatocellular disease by six months of age; sixteen developed chronic liver disease; the remaining nine remained asymptomatic but were serologically and PCR-positive. The mother-to-infant transmission rate was significantly increased (5%; P < 0.0001). Of the seropositive children, 45/65 (69%; P < 0.0001) seroreverted by eighteen months of age. CONCLUSION: There is a high prevalence of anti-HCV in healthy pregnant Egyptian women and vertical transmission is a major risk for chronic HCV carriers.

PIP: Hepatitis C virus (HCV) seropositivity among Egyptian women has been estimated at 13-22%. This study investigated the magnitude of risk of vertical HCV transmission in 499 consecutive, apparently healthy Egyptian women attending antenatal clinics at United Arab Emirates university teaching hospitals in 1994-96. 65 maternal serum samples (13%) were positive for HCV by confirmatory recombinant immunoblot assay and the infants of all these women were anti-HCV positive. HCV RNA was detected by polymerase chain reaction in 20 (31%) of these maternal-infant pairs. Of the 20 infants who were HCV RNA-positive at birth, 4 died of hepatocellular disease before 18 months of age and the remaining 16 developed chronic liver disease. 45 (69%) of the 65 infants seropositive at birth seroconverted over the course of the 18-month follow-up period (mean age of seroconversion, 15 months). These findings indicate that high levels of HCV viremia, like enhanced levels of HIV viremia, facilitate maternal-infant virus transmission. The presence of HCV RNA in the cord blood of the 3 infants who died in the first 3 months of life suggests transplacental pathogenesis in a small proportion of cases. Acquisition at delivery remains the predominant mode of HCV transmission, however, and can be reduced by appropriate screening and counseling of pregnant seropositive chronic carriers of disease.

Frequency of hepatitis B, C and D and human immunodeficiency virus infections in multi-transfused thalassemics.

Of forty multi-transfused thalassemia patients (26 males, 14 females; mean age 8.1 +/- 5.3 years, range 1-35) with no clinical or biochemical evidence of liver disease, HBsAg, anti-hepatitis C virus and anti-human immunodeficiency virus antibodies were present in 18 (45%), 7 (17.5%) and 1 (2.5%) cases respectively. Three of the 18 (16.7%) HBsAg positive patients were anti-delta antibody positive. Our results indicate that more than 50% of multi-transfused thalassemia patients show serological evidence of one or more of hepatitis B, C and D and human immunodeficiency virus infection.

PIP: Transfusion of whole blood or blood components is the mainstay of treatment in patients with beta-thalassemia and hemophilia. Owing to the scarcity of reports regarding the frequency of transfusion-transmitted hepatitis virus infections in thalassemia patients, the frequency of such infections was studied in India in 40 multi-transfused thalassemia patients (26 males, 14 females; mean age 8.1 +or- 5.3 years, range 1-35) with no clinical or biochemical evidence of liver disease. The enzyme-linked immunosorbent assay (ELISA) technique (Abbott) was used for all tests. The patients had received an average of 80 units (range 10-250) of blood. A majority of these units had been screened for hepatitis B surface antigen (HBsAg) using RPHA. HBsAg antibodies were present in 18 (45%), antihepatitis C virus (HCV) in 7 (17.5%), and antihuman immunodeficiency virus in 1 (2.5%) case, respectively. Of 18 HBsAg positive patients, antidelta and anti-HCV antibodies were present in 3 and 4 patients, respectively; 1 patient had both the antibodies. 4 of 40 (10%) patients had evidence of both hepatitis B virus (HBV) and HCV infection. In a US study, the frequencies of HBsAg and anti-HBs positively among thalassemics were 4.5% and 43.5%, respectively. In contrast, 90% of hemophiliacs show serological evidence of HBV infection. Routine screening of blood donors by CEP or RPHA technique was started in the hospital blood bank 7 years ago. The sensitivity of these techniques is much lower than that of RIA and ELISA and a majority of the patients has received initial blood transfusions before HBsAg screening was started. The study indicated that more than 50% of multi-transfused thalassemia patients showed serological evidence of one or more HBV, HCV, HDV, and HIV infection. Thus, screening of blood units for HBV, HCV, and HIV infections to be used for thalassemic patients and vaccination of thalassemic patients against hepatitis B is imperative.

Hepatitis B and breastfeeding.

PIP: Globally, there are over 350 million carriers of hepatitis B virus (HBV). In areas where persistent HBV infection is endemic, transmission is generally either perinatal or horizontal (through close contact between children). Given the finding of small amounts of hepatitis B surface antigen in breast milk, breast feeding has been suggested as an additional mechanism of HBV transmission. The research literature includes no documentation that breast feeding confers any additional risk to infants of HBV carriers, however. Active immunization with hepatitis B vaccine can prevent development of the persistent carrier state in 70-90% of infants of carrier mothers. Administration of hepatitis B immune globulin within 24 hours of birth together with the first dose of vaccine increases this rate to 85-90%. The World Health Organization has recommended that all infants receive hepatitis B vaccine as a part of routine childhood immunization. Where feasible, the first dose should be administered within 48 hours of birth. Even in settings where HBV is highly endemic and immunization is not available, exclusive breast feeding for 4-6 months remains the recommended method of infant nutrition.^ieng

[The general conclusions of the II Congress of Nursing Assistants. Nursing assistants demand more information on AIDS and hepatitis]. / Conclusiones generales al II Congreso de Auxiliares de Enfermería. Los auxiliares de enfermería demandan más información sobre SIDA y hepatitis.

PIP: More than 300 nursing assistants took part in the 2nd National Congress of Nursing Assistants that featured the topics of drug addiction,hepatitis, and AIDS. The conclusions affirmed the lack of precise information about the risk that health personnel are exposed to during contact with hepatitis or AIDS patients. This hinders the establishment of maximum preventive safety. The fear of AIDS extends to the families of these workers who contemplate abandoning their profession. Until 1989 there had been 1 known case of a health worker becoming infected with AIDS from contact with a patient, but it could not be confirmed if this was the only case because of lack of studies. On the other hand, the reticence of these workers also has to be penetrated for appropriate analysis. The infected patients receive maximum care in view of the fact there is no vaccine or effective treatment available for AIDS. However, the suspicion of a patient being infected with HIV has to be conveyed immediately to assistant nurses who are in contact with the patient. The confidentiality of the infection has to be preserved, by all professionals have to know that this is a high risk case, and it has to appear in the clinical history chart. Substances used by drug addicts have to classified accurately with their consequences and the preventive measures that society has to establish for checking the spread of drug addiction.^ieng

Doctors at risk of hepatitis B and HIV infection from patients in Nigeria.

The aim of this study was to assess the degree of residents' concern about acquiring hepatitis B virus (HBV) and human immunodeficiency virus (HIV) infection from their patients at the University College Hospital, Ibadan, Nigeria. We surveyed 149 resident doctors. The response was 89%. Nine per cent of the resident doctors reported percutaneous exposures to needles contaminated with blood of patients infected with HBV or HIV. Eighty per cent of the residents experienced moderate to major concern about contracting these viral infections from their patients. The majority of the doctors (54-64%) indicated that they should be allowed to decide for themselves whether to treat the infected patients. A substantial proportion of them (46-49%) believed that refusing to take care of the patient was not unethical. About 86-96% of the doctors believed that the hospital as well as the Residency Training Programme administrators were not concerned about the risk of acquiring the viruses from their patients. In general, the results demonstrate a major degree of concern about acquiring HBV and HIV infections among resident doctors. Moreover, there is a need for the hospital and Residency Training Programme administrators to formally address these concerns so as to motivate well and reassure these doctors. No such study exists that exclusively address this important and topical subject in doctors in tropical Africa.

PIP: In Ibadan, Nigeria, 149 resident physicians completed a questionnaire revolving around their degree of exposure to hepatitis B virus (HBV) or HIV-infected patients, their concern about acquiring these infections, and the effect of this concern on their caring for patients and on the health policies of the University College Hospital. 9% had been stuck by a needle contaminated with the blood of an HBV- or HIV-infected patient. The 12 residents reporting a needle stick had 21 needle-stick exposures altogether. 54% of the residents used universal precautions while performing procedures no more than 50% of the time. 61-67% estimated their risk of acquiring these infections as no greater than 1/10,000, which compares to the estimate found in the literature. Yet 80% had moderate to high concern about acquiring HBV or HIV infection from their patients. 32-34% of residents reported that their concerns about acquiring these infections would not adversely affect patient care. 60-77% of residents would continue to care for patients with HBV or HIV infection if given a choice. 54-64% believed that they should be allowed to decide themselves whether to provide care to infected patients. About 50% did not consider it unethical to refuse to care for infected patients. 86-96% thought that the hospital and the residency training program administrators did not worry about the risk of acquiring HBV or HIV infection from their patients. These findings show that resident physicians are greatly concerned about acquiring HBV and HIV infections. They also indicate a need for the hospital and training program administrators to formally handle these concerns in order to motivate and reassure the residents.

[Some considerations about hepatitus C virus]. / Algunas consideraciones sobre el virus de la hepatitis C.

PIP: Hepatitis C refers to the portion of non-A, non-B hepatitis that is parenterally transmitted. No formal classification of the virus has yet been achieved, but it is known to be heterogeneous, a trait with implications for both antiviral therapy and vaccine development. Hepatitis C virus has a nearly uniform distribution around the world. The highest infection rates are found in patients with non-A, non-B hepatitis associated with transfusion, hemophiliacs receiving coagulation factors, intravenous drug users, and renal dialysis patients. Screening for hepatitis C, even using third generation ELISA tests, has not completely eliminated risk of transmission during blood transfusions. Nonpercutaneous routes of transmission have been poorly defined. There is evidence that hepatitis C virus is sexually transmitted, but less efficiently than hepatitis B or HIV. Hepatitis C infections have been found in newborns and in children receiving transfusions, undergoing renal dialysis, or hospitalized. The high percentage of hepatitis C in persons with no history of parenteral exposure has stimulated search for nonparenteral forms of transmission, especially vertical transmission. The resulting data have been contradictory. Results of recent studies using polymerase chain reaction appear to indicate that perinatal transmission occurs, but an elevated viral load of hepatitis C is required to produce infection. The majority of hepatitis C cases are asymptomatic. Normal serum aminotransferase levels may mask persistent infection and progression to cirrhosis. More serious consequences of chronic infection may include persistent acute or chronic hepatitis, with cirrhosis developing in 20-30% of cases, and hepatocellular carcinoma. The most effective treatment of chronic infection, alpha interferon, is associated with a relapse rate of 80-90%. Prevention is thus the most effective intervention to combat hepatitis C.^ieng

The relationship between therapeutic injections and high prevalence of hepatitis C infection in Hafizabad, Pakistan.

To determine the prevalence and routes of transmission of hepatitis C virus (HCV) infection in Hafizabad, Pakistan, we collected sera in 1993 from a geographically based random sample of residents, and in 1994 identified 15 HCV-infected individuals (cases) and 67 age and sex matched uninfected individuals (controls). Initially we approached 504 households, and collected serum from a randomly selected household member in 309 (64%). Twenty persons (6.5%) had anti-HCV antibody; 31% percent had hepatitis B core antibodies, and 4.3% had hepatitis B surface antigen. In the case-control study, persons who received more therapeutic injections (categorized as averaging 1, 2-4, 5-9 or > 10 injections per year in the previous 10 years) were more likely to be infected with HCV (odds ratio 0, 1.5, 2.5 and 6.9 respectively, P = 0.008) compared to persons averaging 0 injections per year. Efforts to limit therapeutic injections to only those that are medically indicated and that use sterile equipment are essential in order to prevent transmission of HCV.

PIP: To determine the prevalence of hepatitis C virus (HCV) infection in Hafizabad, Pakistan, sera were collected in 1993 from a geographically representative random sample of 309 adults and children. 20 serum samples (6.5%) had anti-HCV antibodies, 89 (31%) had hepatitis B core antibodies, and 12 (4.3%) had hepatitis B surface antigens. The prevalence of HCV increased markedly with age; no cases were detected among children under 10 years old. A follow-up study of 15 of these HCV cases and 67 age- and sex-matched healthy controls was conducted in 1994. Compared to noninfected controls, HCV cases were significantly more likely to have received 5 or more injections in the previous 10 years (odds ratio, 5.4; 95% confidence interval, 1.2-28.0). Only 5 HCV cases had received blood transfusions, and none reported intravenous drug use. Inspection of 3 private health clinics in Hafizabad exposed disposable syringes and needles--used primarily for vitamin B complex, chloroquine, and penicillin--soaking in a bowl of tepid water. Extrapolation of this study's findings suggests 800 new cases of HCV and 109 HCV-related deaths in Hafizabad each year. HCV infection could be reduced substantially by efforts to limit injections to those that are medically essential and to ensure the use of sterile equipment.

Unsafe injections and the transmission of hepatitis B and C in a periurban community in Pakistan.

Following reports of frequent deaths associated with jaundice and chronic liver disease among adults in a periurban community of Karachi, Pakistan, an investigation was conducted to evaluate the relationship between injections and viral hepatitis infections, to identify the reasons why patients received frequent injections, and to observe the injection practices employed in clinics. Two hundred and three adult patients were interviewed as they left each of the 18 area clinics. Practitioners were interviewed and three consecutive injections were observed at each clinic. Eighty-one per cent of patients received an injection on the day of the interview. Of the 135 patients who provided a serum sample, 59 (44%) had antibodies against hepatitis C virus and 26 (19%) had antibodies against hepatitis B virus. Patients who received more injections were more likely to be infected with hepatitis C. If oral and injected medications were equally effective, 44% of patients preferred injected medication. None of the practitioners knew that hepatitis C could be transmitted by injections. Non-sterile syringes and needles that had been used earlier in the day on other patients were used for 94% of the observed injections. Interventions to limit injections to those which are safe and clinically indicated are needed to prevent injection-associated infections in Pakistan and other low-income countries.

Unsafe injections in the developing world and transmission of bloodborne pathogens: a review.

Unsafe injections are suspected to occur routinely in developing countries. We carried out a literature review to quantify the prevalence of unsafe injections and to assess the disease burden of bloodborne infections attributable to this practice. Quantitative information on injection use and unsafe injections (defined as the reuse of syringe or needle between patients without sterilization) was obtained by reviewing the published literature and unpublished WHO reports. The transmissibility of hepatitis B and C viruses and human immunodeficiency virus (HIV) was estimated using data from studies of needle-stick injuries. Finally, all epidemiological studies that linked unsafe injections and bloodborne infections were evaluated to assess the attributable burden of bloodborne infections. It was estimated that each person in the developing world receives 1.5 injections per year on average. However, institutionalized children, and children and adults who are ill or hospitalized, including those infected with HIV, are often exposed to 10-100 times as many injections. An average of 95% of all injections are therapeutic, the majority of which were judged to be unnecessary. At least 50% of injections were unsafe in 14 of 19 countries (representing five developing world regions) for which data were available. Eighteen studies reported a convincing link between unsafe injections and the transmission of hepatitis B and C, HIV, Ebola and Lassa virus infections and malaria. Five studies attributed 20-80% of all new hepatitis B infections to unsafe injections, while three implicated unsafe injections as a major mode of transmission of hepatitis C. In conclusion, unsafe injections occur routinely in most developing world regions, implying a significant potential for the transmission of any bloodborne pathogen. Unsafe injections currently account for a significant proportion of all new hepatitis B and C infections. This situation needs to be addressed immediately, as a political and policy issue, with responsibilities clearly defined at the global, country and community levels.

PIP: Unsafe injections and the consequent transmission of bloodborne pathogens are suspected to occur routinely in the developing world. This paper presents a review of the literature to determine the prevalence of unsafe injection practices and assess the disease burden of bloodborne infections. Quantitative data on injection usage and unsafe injection practices, such as the reuse of unsterilized syringe or needles between patients, is obtained by reviewing published articles and unpublished reports of the WHO. In addition, the transmissibility of hepatitis B and C viruses and HIV was determined using information from studies of needle-stick injuries. All epidemiological researches that associate injections with bloodborne diseases were examined to assess the attributable burden of bloodborne infections. It was estimated that each person in developing countries receives an average of 1.5 injections per annum. However, institutionalized children, children and adults who are sick or confined in hospitals, often receive 10-100 times as many injections. Of these injections, 95% are therapeutic, a majority of which are unnecessary. At least 50% of injections in 14 of 19 countries were unsafe. Furthermore, 18 studies present convincing evidence on the association of unsafe injection practices and the transmission of bloodborne viruses such as hepatitis B and C, Ebola, Lassa virus infections and malaria. Such practices account for a significant number of hepatitis B and C infections.

Transmission of hepatitis B, hepatitis C and human immunodeficiency viruses through unsafe injections in the developing world: model-based regional estimates.

Thousands of millions of injections are delivered every year in developing countries, many of them unsafe, and the transmission of certain bloodborne pathogens via this route is thought to be a major public health problem. In this article we report global and regional estimates of the number of hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections that may occur from unsafe injections in the developing world. The estimates were determined using quantitative data on unsafe injection practices, transmission efficiency and disease burden of HBV, HCV and HIV and the prevalence of injection use obtained from a review of the literature. A simple mass-action model was used consisting of a generalized linear equation with variables accounting for the prevalence of a pathogen in a population, susceptibility of a population, transmission efficiency of the pathogen, proportion of injections that are unsafe, and the number of injections received. The model was applied to world census data to generate conservative estimates of incidence of transmission of bloodborne pathogens that may be attributable to unsafe injections. The model suggests that approximately 8-16 million HBV, 2.3-4.7 million HCV and 80,000-160,000 HIV infections may result every year from unsafe injections. The estimated range for HBV infections is in accordance with several epidemiological studies that attributed at least 20% of all new HBV infections to unsafe injections in developing countries. Our results suggest that unsafe injections may lead to a high number of infections with bloodborne pathogens. A major initiative is therefore needed to improve injection safety and decrease injection overuse in many countries.

PIP: This paper reports global and regional estimates of the prevalence of hepatitis B virus (HBV), hepatitis C virus (HBV), and HIV infections that may occur as a result of unsafe injection practices in the developing countries. The estimates were determined using quantitative information on unsafe injection practices, transmission efficiency of pathogen, and disease burden of hepatitis B and C viruses, as well as HIV and the prevalence of injection usage as observed in the literature reviews. A simple mass-action model was utilized in the study and was applied to world census data to generate the conservative estimates of interest. The model showed that about 8-16 million HBV, 2.3-4.7 million HCV, and 80,000-160,000 HIV infections may result from unsafe injections each year. It was also noted that the estimated range of HBV infection is consistent with a number of epidemiological studies that attribute at least 20% of all new cases of HBV infection to unsafe injections in the developing world. Given that unsafe injections may contribute to a high number of infections with bloodborne pathogens, a major effort is necessitated to improve injection safety and reduce injection overuse in many countries.

Intrafamilial transmission of hepatitis C virus (HCV): a major mode of spread in the Saudi Arabia population.

Age-specific prevalence of antibody to hepatitis C virus (anti-HCV) was studied in 831 Saudis (441 males, 390 females; 1-53 years old) from Al Baha region, south-west Saudi Arabia. There was a gradual exposure to HCV early in life with a gradual increase with age, reaching a peak of 5.3% in the 30-40 years age group. The overall prevalence was 3.6% and 3.1% in males and females, respectively, with no statistical difference. Comparison of positivity in family members of seven anti-HCV-positive index cases (15/44) with those of five anti-HCV-negative index cases (2/44) showed a statistically significant association (chi 2 10.5 with Yates' correction). This points to intrafamilial transmission of HCV as a route of spread among the Saudi population.

PIP: Over 90% of transfusion-related hepatitis is caused by non-A, non-B (NANB) hepatitis which has been diagnosed serologically by means of the recently cloned NANB agent designated hepatitis C virus (HCV) using a recombinant based assay. The age-specific prevalence of anti-HCV was studied in healthy Saudis, since silent carriers of NANB hepatitis occur among healthy blood donors as evidenced by a 10% rate of post transfusion hepatitis. In a prospective hospital-based study 381 children aged 1-14 treated for other ailments, 253 blood donors aged 15-53, and 192 pregnant women aged 15-38 were included who had no percutaneous exposure to blood. Also, 44 household members of 7 persons found anti-HCV positive were compared with 44 enzyme-linked immunosorbent assay (ELISA). Age-specific exposure to HCV peaked at 5.3% in the 20-40 age group after early childhood exposure. The prevalence of anti-HCV was 3.6% in males and 3/1% in females. A father and mother were found anti-HCV positive among household members of 7 anti-HCV positive cases. A 4-year old boy and a 7-year old boy in 2 families were found anti-HCV positive among household members of 5 anti-HCV-negative persons. Anti-HCV positivity in family members of HCV+index cases (15/44) was statistically significant compared with HCV index cases (2/44). Routine screening of donated blood is urged because of the high endemicity of HCV in Saudis, and the modes of transmission of HCV also requires further research.

Risk factors for horizontal transmission of hepatitis B virus in a rural district in Ghana.

Most hepatitis B virus (HBV) infections in sub-Saharan African infants and children are acquired through horizontal transmission, but the exact mechanisms of spread have not been documented. The authors conducted a study in rural Ghana which determined seroprevalence in a probability sample of 1,385 individuals of all ages, and evaluated risk factors for horizontal transmission of HBV in a subsample of 547 children aged 1-16 years who were not hepatitis B surface antigen (HBsAg) carriers. Most residents in this district live in compounds which typically contain 2-4 households each. Overall prevalence of HBV seropositives (any HBV marker) was 74.7% (95% confidence interval (CI) 72.5%-76.9%). Prevalence of HBsAg was 20.9% (95% CI 18.8%-23.1%). The data suggest a continuous nonuniform acquisition of HBV infection with advancing age predominantly through horizontal transmission in childhood, with the household, rather than the domestic compound, being the primary place for transmission. The behaviors most strongly associated with prevalence of HBV were sharing of bath towels (OR = 3.1, 95% CI 2.1-4.5), sharing of chewing gum or partially eaten candies (OR = 3.4, 95% CI 2.3-5.0), sharing of dental cleaning materials (OR = 2.5, 95% CI 1.3-4.6), and biting of fingernails in conjunction with scratching the backs of carriers (OR = 2.5, 95% CI 1.6-4.3).

PIP: Most hepatitis B virus (HBV) infections in sub-Saharan African infants and children are acquired through horizontal transmission. Findings are reported from a study conducted in rural Ghana to measure seroprevalence in a probability sample of 1385 people of all ages, and evaluate risk factors for the horizontal transmission of HBV in a subsample of 547 children aged 1-16 years who were not hepatitis B surface antigen (HBsAg) carriers. Most residents in the sample area live in compounds which typically contain 2-4 households each. The overall prevalence of HBV seropositives was 74.7% and the prevalence of HBsAg was 20.9%. These data suggest a continuous nonuniform acquisition of HBV infection with advancing age mainly through horizontal transmission in childhood, with the household, rather than the domestic compound, being the main place for transmission. The sharing of bath towels, sharing of chewing gum or partially eaten candies, sharing of dental cleaning materials, and biting of fingernails together with scratching the backs of carriers are the behaviors found to be most strongly associated with HBV prevalence.

Sexual transmission of hepatitis B in Mwanza, Tanzania.

BACKGROUND: Hepatitis B virus (HBV) is endemic and poses a grave public health problem in Africa where it is mainly transmitted from mother to baby or during childhood. Sexual transmission has also been suggested to play a role in East Africa, but this has never been properly demonstrated. Additional preventive strategies may be proposed if sexual transmission of HBV occurred in this region where HIV and other STDs are highly prevalent. GOALS: To determine the prevalence of markers for hepatitis B virus (HBV)and other sexually transmitted diseases (STD) in routine blood samples taken from three populations in Mwanza, Tanzania, and to use the data collected to look at the association between hepatitis B and other STDs, including human immunodeficiency virus (HIV). STUDY DESIGN: Routine blood samples were collected from 1,025 patients attending a clinic for STDs, 253 voluntary blood donors from secondary schools, and 952 blood donors who gave blood in a hospital specifically for a relative who needed a blood transfusion. All samples were tested for HIV by double enzyme-linked immunosorbent assay (ELISA), and for syphilis using the Treponema pallidum hemagglutination (TPHA) and rapid plasma reagin (RPR) tests. Two markers for HBV were examined by the double ELISA method, the presence of the anti-hepatitis B core antigen (anti-HBc) and the hepatitis B surface antigen (HBsAg). RESULTS: There were high prevalences of HBV, syphilis, and HIV in relative donors and STD patients. Although HBV markers were more prevalent in men of increasing ages, syphilis and HIV markers were more prevalent in young women. Evidence of past infection with HBV (presence of anti-HBc) was associated with serologic markers of recent treponemal infection (both TPHA and RPR positive) in both sexes (men odds ratio [OR] = 1.91, P < 0.011; women OR = 2.34, P < 0.02) and with HIV in men (OR = 1.93, P < 0.003). Current infection with HBV (presence of HBsAg) was associated with recent syphilis in men (OR = 2.13, P < 0.006). In STD patients, current infection with HBV was associated with Trichomonas vaginalis in women (OR = 3.57, P < 0.002) and recent syphilis in men (OR = 3.46, P < 0.001). There was no further association between HBV markers and any other STD pathogen or any particular STD syndrome, nor was there any association between current HBV infection and HIV in both sexes. The population attributable fraction for sexual acquisition of hepatitis B is estimated at 7.2% in men and 3.0% in women, based on the association between hepatitis B and syphilis. CONCLUSIONS: These findings suggest that sexual acquisition of hepatitis B occurs at low levels in Mwanza, and that HBV can be prevented through enhancement of the current HIV/STD control activities, in addition to improved vaccination strategies.

PIP: To investigate the role of sexual transmission of hepatitis B virus (HBV) in East Africa, a cross-sectional serosurvey was conducted in 3 populations with potentially divergent exposure to sexually acquired pathogens. Included were 253 voluntary blood donors (predominantly secondary school students), 952 relative blood donors, and 1025 patients with sexually transmitted diseases (STDs) from Mwanza, Tanzania. The overall prevalence of hepatitis B surface antigen (HBsAg)--a measure of current infection--was 9.9% in voluntary donors, 11.2% in relative donors, and 8.1% in STD patients, with a 2.2:1 carrier ratio of men to women. The prevalences of human immunodeficiency virus (HIV), anti-hepatitis B core antigen (anti-HBc), and past or recent syphilis were significantly lower among voluntary donors than in the other 2 groups. Evidence of past infection with HBV (anti-HBc) was associated with recent syphilis in both men and women (odds ratios (ORs), 1.91 and 2.34, respectively) and with HIV in men (OR, 1.93). Current infection with HBV (HBsAg) was associated with recent syphilis in men (OR, 2.13). In STD patients, current HBV was associated with Trichomonas vaginalis in women (OR, 3.57) and recent syphilis in men (OR, 3.46). There was no significant association between HBV and gonorrhea. Based on the association between syphilis and HBV, the population attributable fraction for sexual acquisition of HBV is estimated at 7.2% in men and 3.0% in women. Overall, these findings suggest that the sexual acquisition of HBV occurs at low levels in Mwanza. Improved vaccination strategies, early detection and treatment of syphilis, and programs aimed at reducing HIV transmission should enhance the control of HBV.

The cost of unsafe injections.

Unsafe injection practices are associated with substantial morbidity and mortality, particularly from hepatitis B and C and human immunodeficiency virus (HIV) infections. These inadvertently transmitted bloodborne diseases become manifest some considerable time after infection and hence may not be appropriately accounted for. Annually more than 1.3 million deaths and US$ 535 million are estimated to be due to current unsafe injection practices. With the global increase in the number of injections for vaccination and medical services, safer injecting technologies such as auto-disable syringes must be budgeted for. Investment in health education and safer disposal will also reduce infections associated with unsafe injecting practices. Safer injecting practices are more expensive than current less safe practices, but the additional cost is more than offset by the reduction in disease that would result.

PIP: Unsafe injection practices, defined as the use of unsterilized injection equipment in patients, are linked with substantial morbidity and mortality in certain bloodborne diseases including hepatitis B and C infections, as well as infection with HIV. It is estimated that over 1.3 million lives are lost annually as a result of unsafe injection practices and more than US$535 million is spent each year to treat emerging bloodborne diseases. With the significant increases in the number of injections for immunization and medical services globally, safer injecting technologies such as the use of auto-disable syringes and oral aerosol or oral formulations must be considered. Likewise, investment in health education and promoting safe, convenient, and effective disposal of injection equipment will also decrease infections associated with unsafe injection practices. Finally, although safer injecting technologies are more costly than the existing less safe practices, the additional cost is more than offset by the resultant decrease in bloodborne diseases.