Model-based estimates of risks of disease transmission and economic costs of seven injection devices in sub-Saharan Africa*
Donatus U. Ekwueme,1 Bruce G. Weniger,2 & Robert T. Chen3
OBJECTIVE: To investigate and compare seven types of injection devices for their risks of iatrogenic transmission of bloodborne pathogens and their economic costs in sub-Saharan Africa.
METHODS: Risk assumptions for each device and cost models were constructed to estimate the number of new hepatitis B virus (HBV) and human immunodeficiency virus (HIV) infections resulting from patient-to-patient, patient-to-health care worker, and patient-to-community transmission. Costs of device purchase and usage were derived from the literature, while costs of direct medical care and lost productivity from HBV and HIV disease were based on data collected in 1999 in Côte d'Ivoire, Ghana, and Uganda. Multivariate sensitivity analyses using Monte Carlo simulation characterized uncertainties in model parameters. Costs were summed from both the societal and health care system payer's perspectives.
FINDINGS: Resterilizable and disposable needles and syringes had the highest overall costs for device purchase, usage, and iatrogenic disease: median US$ 26.77 and US$ 25.29, respectively, per injection from the societal perspective. Disposable-cartridge jet injectors and automatic needle-shielding syringes had the lowest costs, US$ 0.36 and US$ 0.80, respectively. Reusable-nozzle jet injectors and auto-disable needle and syringes were intermediate, at US$ 0.80 and US$ 0.91, respectively, per injection.
CONCLUSION: Despite their nominal purchase and usage costs, conventional needles and syringes carry a hidden but huge burden of iatrogenic disease. Alternative injection devices for the millions of injections administered annually in sub-Saharan Africa would be of value and should be considered by policy-makers in procurement decisions.
Keywords Disease transmission; Iatrogenic disease/epidemiology; Injections/instrumentation/economics; Needles/adverse effects/economics; Syringes/adverse effects/economics; Injections, Jet; Hepatitis B/transmission; HIV infections/transmission; Risk factors; Costs and cost analysis; Models, Theoretical; Africa South of the Sahara (source: MeSH, NLM).
Mots clés Transmission maladie; Affection iatrogénique/épidémiologie; Injections/instrumentation/économie; Aiguille/effets indésirables/économie; Injections flash; Seringue/effets indésirables/économie; Hépatite B/ transmission; HIV, Infection/transmission; Facteur risque; Coût et analyse coût; Modèle théorique; Afrique subsaharienne (source: MeSH, INSERM).
Palabras clave Transmisión de enfermedad; Enfermedad iatrogénica/epidemiología; Inyecciones/instrumentación/economía; Agujas/efectos adversos/economía; Jeringas/efectos adversos/economía; Inyecciones a chorro; Hepatitis B/transmisión; Infecciones por VIH/transmisión; Factores de riesgo; Costos y análisis de costo; Modelos teóricos; África al Sur del Sahara (fuente: DeCS, BIREME).
Introduction
The Expanded Programme on Immunization has been increasingly successful in reducing the incidence of vaccine- preventable diseases in developing countries (1), where, unfortunately, a pattern of unsafe injection practices has been observed (2). Simonsen et al. estimated the prevalence of unsafe injections to range from 20% up to at least 50% in these countries. In 20-80% of health centres in sub-Saharan Africa there are insufficient supplies and equipment to guarantee safe injection (3). Incorrect injection practices include reuse of contaminated needles and syringes without sterilization between patients (4); incorrect disposal of used needles and syringes in the community (5); absence of swabbing with alcohol or acetone of the reusable nozzles of needle-free jet injectors between consecutive patients (6); and other unsafe practices, such as changing needles but not syringes between patients (7).
When not properly sterilized, or if contaminated, needles and syringes can produce local abscesses (8, 9) and can transmit bloodborne infections between patients (10, 11). Needlestick injuries can transmit infectious agents from patients to health care workers (12-15), while incorrect disposal can transmit disease to the community as a consequence of both needlestick injuries and improper reuse (3). Hepatitis B virus (HBV) (16) and human immunodeficiency virus (HIV) (17) are two of the most important bloodborne pathogens in terms of prevalence, morbidity, and mortality, especially in many parts of the developing world (4, 18). Complications associated with HBV infection include chronic active hepatitis, cirrhosis of the liver, primary hepatocellular carcinoma, and premature death (16). HIV infection leads to the acquired immunodeficiency syndrome (AIDS), opportunistic infections, and premature death.
It is estimated that humans in health care settings receive each year between 8 and 12 billion parenteral injections, of which about one billion are for vaccines (19). In addition to routine immunizations for children, emergency campaigns in 1996 alone accounted for the administration of more than 240 million doses of vaccine (20). The plans for global measles control and eradication (21) can be expected to require billions more injections than are currently administered. As the number of vaccine injections increases, it may become increasingly difficult to ensure the safety of every injection, and thus to minimize risk for consequent iatrogenic disease (7).
Since 1997, WHO, the United Nations Children's Fund (UNICEF), and the United Nations Population Fund (UNFPA) have strongly recommended (22-24) the use of "auto-disable" needles and syringes (25) designed to prevent improper reuse. (Originally called "auto-destruct", these syringes were renamed because they still require proper disposal and destruction by incineration or other means.) The three agencies also agreed on a policy of "bundling", which requires donors of vaccine for developing countries also to supply a corresponding number of auto-disable needles and syringes along with "sharps" collection boxes to permit safe disposal.
The full risks and economic costs of conventional needles and syringes and alternative injection delivery technologies have not been adequately compared. We investigated the risks of iatrogenic disease transmission and the economic costs associated with various such devices for the parenteral administration of vaccines and other medications. Sub-Saharan Africa was selected as the setting for the model, because injection practices there are often unsafe, and severe financial barriers exist for the introduction of newer technologies.
Methods
The risk model
Three major categories of transmission of bloodborne infections by injection devices were modelled. First, patient-to-patient transmission can occur when a device is reused without sterilization or when it is incorrectly sterilized and transfers infected blood between patients. Second, transmission from patient-to-health care worker occurs when an accidental needlestick injury transfers infectious patient blood to the worker. Third, patient-to-community transmission may occur from improper disposal of needles and syringes, as when people scavenging waste dumps receive needlestick injuries. Devices "recycled" from dumps may also be reused unsterile, producing iatrogenic abscesses and transmission of pathogens.
A risk model was constructed for each of these routes of transmission, building on previous models (4, 13, 26, 27), in order to estimate the number of new HBV or HIV infections that might result from seven injection technologies. The general model is represented by the following equation:
In order to simplify Eq. 1 and because vaccines are administered mainly to young children, we ignored the decrease in susceptibility to HBV infection that occurs among groups of increasing age, due to immunity from incident HBV infections (as evidenced by the presence of hepatitis B core antibody).
We studied the use of seven devices for the parenteral delivery of vaccine and other medications (see Box 1) (28-31). Disease costs were totalled from the economic perspectives both of the health care system ("payer's" direct medical costs only) and of society (direct medical and lost productivity costs). The societal perspective allows a comprehensive assessment of the overall impact of different injection technologies on the economies of the countries concerned. The perspective of the health care system focuses on the narrower impact for national health care expenditures.
HBV and HIV prevalence
The prevalence of carriers of HBV surface antigen in the population of vaccinees whose blood might contaminate injection equipment was estimated at 10% (the "base case") for countries in sub-Saharan Africa, with a lower estimate of 5% and an upper of 15% used for sensitivity analysis (16, 32, 33) (Table 1). HIV seroprevalence was also estimated at 10% on the basis of reported rates exceeding 5% but less than 15% in 16 countries in the region (17). An HIV seroprevalence range of 2-25% was used for the sensitivity analysis. The 2% rate was estimated on the basis of data from the 19 countries in the region with the lowest reported values, ranging from 0.08% in Mauritius to 4.16% in Gabon (17). The 25% rate was based on data from eight countries with values ranging from 16% in Malawi to 36% in Botswana.
Transmission from patient to patient
For the base case, it was assumed that after every sterile injection with either a resterilizable needle and syringe (N&S) or a disposable N&S, non-sterile reuse would occur 30% of the time (range: 15-50% for the sensitivity analysis) (2, 4, 26) (Table 1). We assumed no risk to patients of blood exposure for the auto-disable N&S, auto-shielding N&S, and disposable- cartridge jet injector devices. For manual-shielding N&S devices, the base case assumed one non-sterile reuse 15% of the time (range: 1-30%) (34). For reusable-nozzle jet injector devices, we assumed a worst-case scenario in which health care workers did not swab the nozzle with alcohol or acetone between patients (6), contrary to the manufacturers' recommendations. On this basis we estimated a 1% probability (range: 0.1-5.0%) that the device would expose the next patient to transferred blood (6, 35-37).
The probability of newly acquiring HBV infection as a result of exposure to reuse of or to needlestick injury from an unsterile injection device containing blood from an infected person was assumed to be 30% (range: 20-40%) (Table 1). For acquisition of HIV infection, 0.3% was used for the base case (range: 0.2-0.5%). These rates for HBV and HIV were based on empirical data from needlestick injury case series and surveillance (2, 38-43). We assumed that needles and jet injector nozzles contaminated with blood or tissue fluid from intramuscular or subcutaneous injections would transmit infection at rates similar to those observed in the above studies of injuries from needles used for drawing blood or other intravascular access.
Transmission from patient to health care worker
On the basis of data from the literature (2) and the observations in Côte d'Ivoire, Ghana, and Uganda (33, 51), we assumed a base-case frequency for needlestick injuries of 5% (range: 1- 8%) for each use of the resterilizable N&S (which requires more handling to disassemble, clean, and sterilize), and 3% (range: 2-5%) for the disposable N&S (Table 1). Table 1 also provides the modelled probabilities for needlestick injuries for other devices (2, 29, 33, 34, 37, 51). The manual-shielding N&S carried some needlestick injury risk because of the possibility that health care workers would intentionally not activate the safety features, in order to reuse the device. The hypothetical auto-shielding N&S and both types of jet injectors were assumed to have no risk of needlestick injury.
Transmission from patient to community
This route for acquiring infection is a consequence of improper disposal of sharps and needlestick injury outside the original health care setting where the device was originally used. In the model, the probabilities assumed for unsafe disposal (Table 1) are multiplied by those for needlestick injuries with various devices. Of course, the auto-shielding N&S and both types of jet injectors present no risk to the community. Because of the absence of data, we ignored possible patient-to-patient transmission from reuse of such disposed sharps salvaged in the community.
Economic costs
Costs of purchasing and using devices
For each injection device studied, data were collected from UNICEF (44) and WHO (45-48), device manufacturers (30, 49, 50), and the literature (5) for purchase prices of the items themselves, as well as the costs of necessary equipment (e.g. sterilizers, spare parts, supplies, and other consumables, including items for proper sharps disposal). In addition, the costs of labour for maintenance of necessary equipment and for actual administration of vaccine were estimated. The value of vaccine wasted in the routine use of some devices (e.g. purging air from reusable-nozzle jet injector) was also considered. All costs, including capital costs for equipment and reusable supplies, were amortized for the expected number of injections over the lives of the equipment or supplies, and converted to cost per injection. In order to account for uncertainties about such purchase and usage costs, in the sensitivity analysis the calculated base-case values were varied by factors of 25% for the lower estimate and 200% for the upper. Table 1 summarizes the overall total of such costs for each device. The individual component costs and details of the calculations, along with reference citations to the sources used (5, 30, 44, 45, 47-50) are provided in Annex Table A (available on the Bulletin web site: http://www.who.int/bulletin).
Direct medical care costs
Medical care costs were based upon data from original sources in Côte d'Ivoire, Ghana, and Uganda collected by the first author from June to December 1999 (33, 51). These direct costs for each new HBV and HIV infection were determined by modelling the reported costs, frequencies, coverage, and duration of outpatient visits, inpatient care, diagnostic tests, and occasional antiviral therapies for HBV (i.e. interferon in Côte d'Ivoire only) and for HIV (i.e. zidovudine, lamivudine, and indinavir). HBV infections were assumed to have been acquired in the first year of life as a result of unsafe vaccination or other injection. It was also assumed that the resulting direct medical costs would all be incurred in the year of the average age of premature death resulting from this disease (Côte d'Ivoire: 43 years, Ghana: 40 years, Uganda: 41 years). These direct medical costs were then discounted at 3% to present net values, using standard methods (52).
HIV infections from unsafe injection were also assumed to have been acquired in the first year of life. Using models and methods described by Over et al. (53) and Mansergh et al. (54), symptomatic AIDS and death were assumed to ensue among infected infants at a rate of 10% per year until, by the age of 10 years, all had become symptomatic and died within a year. The direct medical costs attributable to HIV infection were discounted by 3% (conversion rate of 0.806) to the present value. Foreign currencies were converted to US$ at the year 2000 exchange rates (55). The arithmetic means of the present value totals of direct medical costs for the three countries were used as single sub-Saharan Africa estimates for the model. Additional details and assumptions for the input values and calculations of direct medical costs are described in Annex Table B (available on the Bulletin web site: http:// www.who.int/bulletin).
Indirect costs - lost productivity
Lost productivity was the sole indirect cost considered for iatrogenic HBV and HIV diseases (Table 1) and was modelled using an adaptation of the method of Over et al. for determining lost productivity from perinatal HIV transmission (53) (see footnote o in Annex Table B), available on the Bulletin web site: http://www.who.int/bulletin, for further explanation). Average annual earnings in public or private sectors collected from original sources in Côte d'Ivoire, Ghana, and Uganda (33) were adjusted for unemployment rates, and then applied to the years of life lost. This was calculated as the difference between average life expectancy at birth (51 years in Côte d'Ivoire, 57 in Ghana, 48 in Uganda) and the earlier average age of death due to HBV (Côte d'Ivoire: 43 years, in Ghana: 40 years, Uganda 41 years) or to HIV (6 years in all three countries).
As assumed by Over et al. (53), HIV-infected infants were assumed to have only 15% of average adult income during the "lost" years from 6 to 15 years (e.g. for tasks such as child care, wood gathering, and other domestic chores), and full income (100%) thereafter to the age of 50 years. From the ages of 51 to 65 years, income was adjusted to 85% of the average. For both HBV and HIV, the amounts of future lost income were discounted at 3% per year, standardized to US$ for the year 2000 exchange rates, and averaged among the three countries for the regional base-case amounts shown in Table 1. To avoid counting lost productivity in full years for both the year of premature death and year of death after normal life expectancy, only half of lost income was counted in those first and last years of the discounting model. Further details, input data, and the lost productivity discounting formula are provided in Annex Table B and Annex Box B (available on the Bulletin web site: http://www.who.int/bulletin).
Sensitivity analysis
In order to ascertain the degree of uncertainty inherent in the point estimates for the purchase and usage costs of each injection device and for the direct medical and indirect (lost productivity) costs of HBV and HIV disease, we performed multivariate sensitivity analyses using the Monte Carlo simulation sampling method (56-58).
For various base-case point estimates of input data in Annex Table B, lower and upper estimates were made and modelled in parallel runs. For example, in Uganda, the number of days of hospitalization for HIV disease averaged 14 days (lower and upper estimates 7 days and 31 days, respectively). In Ghana, the average number of follow-up doctors' visits for HIV care varied from two to 10, around a base case of four. In Côte d'Ivoire, the average cost of a laboratory test for hepatitis B surface antigen was US$ 42.14, with US$ 14.05 and US$ 84.27 set as the lower and upper estimates, respectively. Calculated device purchase and usage costs (Annex Table A, available on the Bulletin web site: http://www.who.int/bulletin) were varied by 25% and 200% to produce lower and upper estimates. Parallel runs of the model using such lower and upper cost estimates were used, along with the base-case estimates, to construct triangular probability distributions (59) for the Monte Carlo analyses (the triplicate input costs are provided in the final three sections of Table 1). The triangular probability distribution is often used in the absence of a large data set when the mean value is small and the standard deviation is large (60).
The simulations were conducted using @RISK software (Palisade Corporation, Newfield, NY, USA) (61), an add-in to Excel® spreadsheet software (Microsoft Corporation, Redmond, WA, USA). On each of 1000 simulation runs, a value for each parameter was drawn from its associated distribution and used to calculate risk and cost estimates for each injection device. For each device, the output of the simulation runs produced the mean, standard deviation, 5th, 50th (median), and 95th percentiles.
Results
Cost of device purchase and usage
The device with the highest purchase price and usage cost was the manual-shielding N&S, at US$ 0.54 each (Table 1, with input details provided in Annex Table A (available on the Bulletin web site: http://www.who.int/bulletin). The reusable-nozzle jet injector was the least expensive to buy and use, at US$ 0.04 per injection. The conventional disposable N&S was calculated to cost US$ 0.10 per injection.
Number of disease cases produced
Base-case point estimates for the predicted number of HBV and HIV infections resulting from one million injections with each of the modelled devices are shown in Table 2. The conventional resterilizable N&S caused the greatest number of iatrogenic infections per million injections (n = 9545), followed closely by the disposable N&S (n = 9002). The manual-shielding N&S incurred somewhat less then half this burden (n = 4145). In contrast, both the auto-disable N&S and reusable-nozzle jet injector produced relatively few HBV and HIV infections (n = 276 and n = 273 respectively). Of course, the reusable-cartridge jet injector and the hypothetical auto-shielding N&S produced no infections according to the model.
Costs of disease
The overall economic burdens of HBV and HIV disease resulting from the predicted iatrogenic infections are summarized in Table 3. The overall societal costs attributable to the resterilizable N&S and disposable N&S were US$ 26.71 and US$ 25.18 respectively, as the base case point estimates per injection (HBV and HIV costs combined). Each use of an auto-disable N&S was estimated to produce disease costs of US$ 0.77, which was nearly identical to the point estimates for the reusable-nozzle jet injector (US$ 0.76).
The Monte Carlo sensitivity analyses of these disease costs, also in Table 3, reveal medians that vary only slightly from the point estimates of each injection device for HBV disease, but somewhat more widely for HIV/AIDS. The 5th and 95th percentiles reveal modest ranges. For example, the resterilizable N&S ranged from US$ 11.71 to US$ 40.19 for HBV disease, and from US$ 0.90 to US$ 4.46 for HIV/AIDS.
Overall costs
Combining all costs for a societal perspective - device purchase and usage, medical costs, and lost productivity - it was estimated that the most expensive technology for administering vaccines is the resterilizable N&S, at US$ 26.77 per injection (Fig. 1). The next most expensive is the disposable N&S (US$ 25.29). The lowest costs were for the disposable-cartridge jet injector and auto-shielding N&S, at US$ 0.36 and US$ 0.54, respectively. Intermediate costs were found for the reusable-nozzle jet injector (US$ 0.80) and auto- disable N&S (US$ 0.91).
Looking only from the health care payer's perspective (Fig. 2), the relative overall costs of the various devices change. The manual-shielding N&S takes the lead as the most expensive device at a median cost of US$ 0.81 per injection, followed by identical costs (US$ 0.67) for both the resterilizable N&S and disposable N&S. The disposable-cartridge jet injector moves up to fifth in order of cost (US$ 0.37), no longer being the lowest cost. The lowest cost is now for the reusable-nozzle jet injector (US$ 0.06). The auto-disable N&S becomes next to lowest, at US$ 0.16.
The multivariate sensitivity analyses found median costs to be similar to the base-case results (Table 3, Fig. 1). For example, the HBV disease cost attributable to each injection with the resterilizable N&S was US$ 24.66 in the base case and US$ 23.17 (94%) in the multivariate sensitivity analyses. For HIV disease, the corresponding values were US$ 2.05 and US$ 2.24 (109%) respectively. The 5th and 95th percentiles revealed modest ranges. For example, for the disposable N&S, the HBV disease cost ranged from US$ 11.45 to US$ 38.02 (around a base case of US$ 23.25, median US$ 22.09).
Discussion
Our modelling reveals that unsafe parenteral injection in sub- Saharan Africa causes a substantial health and economic burden from iatrogenic disease. Most of this cost is hidden because new infections are usually unrecognized, or cannot be linked to a causative injection, and because most of the disease sequelae are greatly delayed. We found that the most commonly used injection devices, resterilizable and disposable needles and syringes, actually cost around US$ 0.67 per injection in direct medical costs, and a staggering US$ 25 to US$ 27 in overall costs when lost productivity from premature death was included. These costs are high relative to estimated annual expenditures of US$ 33 per capita for all public and private health purposes by countries in sub-Saharan Africa (62).
Our input assumptions and findings are consistent with those of previous work on the incorrect use of injection devices (2, 4, 7, 26, 63). Another mathematical model assumed that a needle would be reused between one and four times (4). We assumed a probability of 0.3 (range: 0.15-0.5). An average of 33% of health centres in Chad, Côte d'Ivoire, Uganda, and Swaziland reused syringes or needles without sterilization (3). A macrolevel analysis by Kane et al. for the entire population of sub-Saharan Africa calculated the annual number of new HBV and HIV infections attributable to unsafe injection to be 780 052 and 51 208 respectively (26).
Our modelling exercise is limited by the numerous assumptions and input cost estimates that must be made, as there is a paucity of published, scientifically gathered sources for such data. Nevertheless, the risk and cost estimates used here are relatively conservative. They excluded the economic consequences of disease and premature death arising from other bloodborne pathogens that can be contracted by unsafe injection, e.g. hepatitis C, Trypanosoma sp., Plasmodium sp., and agents of haemorrhagic fever. We also ignored treatment costs for opportunistic infections associated with HIV/AIDS, such as tuberculosis, as well as burial costs, which can be substantial in developing countries (64, 65). Also excluded were the indirect costs for the time of others in caring for a patient. Thus, the Bulletin results are probably underestimates of the true costs of unsafe injection.
This problem is not peculiar to sub-Saharan Africa or other developing countries. A survey in Eastern Europe in 1992-93 revealed about half of health centres were administering unsafe injections (1). HBV and HIV spread widely in Romanian orphanages due to needle and syringe reuse (66-69), as did HBV in the Republic of Moldova (70). Fortunately, the problem is becoming increasingly recognized (19). In 1994, more than 50 African countries endorsed the Yamoussoukro Declaration on the safety of injections and its goal of 95% safe practice (1). As a result, the auto-disable N&S that cannot be reused is now the normative standard of care for developing country immunization programmes (22-24). We estimated US$ 0.14 per injection to buy and use them, plus an additional US$ 0.77 per injection for the medical costs of consequential needlestick injuries, which they do not prevent (Fig. 1).
Reusable-nozzle jet injectors are a needle-free vaccination technology formerly used in Africa for mass immunization campaigns, such as control of meningococcal (71) and yellow fever (72) outbreaks. We calculated they cost only US$ 0.06 per injection from the health care payer's perspective. Such devices have delivered billions of injections in mass immunization campaigns and epidemic control activities since their introduction in the 1950s (73). However, their high initial capital cost and complex maintenance requirements make them unsuitable for routine immunization clinics. We therefore modelled them only for mass campaigns with an assumed usage of 1000 doses on each day of use (Annex Table A, available on the Bulletin web site: http:www.who.int/bulletin). The Program for Appropriate Technology in Health (PATH) estimated that low-volume use of such devices would result in a much higher direct cost of US$ 0.20 per injection (50).
In the mid-1980s, concern about the possibility of bloodborne disease transmission between consecutive vaccinees from reusable-nozzle jet injectors (Annex Box A, available on the Bulletin web site: http:www.who.int/bulletin) arose following an outbreak of hepatitis B in California, USA, caused by a Med-E-Jet® device (35, 74, 75). A 1990s study in Brazil identified contamination in 1-6% of ejectates collected immediately after the vaccination of patients (6). The Public Health Laboratory Service of the United Kingdom of Great Britain and Northern Ireland, with assistance from WHO, pioneered an animal model to identify and quantify blood at levels theoretically sufficient to transmit HBV in succeeding injections. The Public Health Laboratory Service found contamination of ejectates and/or transmission of HBV in the succeeding injection occurred with all devices tested (36). These and other unpublished studies formed the basis for the Bulletin modelled base case assumption that these devices would transmit blood 1% of the time.
In 1997, liability risk led to manufacturer withdrawal of the Ped-O-Jet® from the market, followed by its recall by the United States military (76, 77). In 1998, WHO recommended that such injectors should not be used until testing det monstrated their safety (78). The United States Centers for Disease Control and Prevention recommended that public health authorities weigh the potential risk against the benefit in certain situations where the rapid vaccination of large numbers of people is required and the use of needles and syringes is not practical (79, 80). As a result, the world lacks a high-speed device of unquestioned safety for intramuscular or subcutaneous vaccination for use in influenza pandemics, measles eradication, response to biological terrorism, or other necessary mass immunization campaigns. This vulnerability will probably disappear when high-speed jet injectors with disposable cartridges are developed.
Low-workload jet injectors with disposable cartridges now exist (73, Annex Box A, available on the Bulletin web site: http:www.who.int/bulletin), but they are not affordable for use in the developing world because of the current expense of their cartridges - US$ 0.25-0.50 per injection. We modelled these at the lower cost. Also impeding their acceptance are their proprietary, non-interchangeable cartridges. Universal standards for a common cartridge might enhance market demand for such technology and reduce their costs through mass production. Another obstacle is the need for end users to fill the empty cartridges manually in the clinic. Vaccine manufacturer prefilling would be highly convenient and save users the expense of purchasing empty cartridges. One such prefilled cartridge was successfully pilot tested in both industrialized and developing countries (81-84), but its further development was halted for unspecified reasons.
Needlestick injuries have been a focus of concern in both developing (29) and industrialized countries (12-14, 85, 86). In the USA, occupational safety regulations now require safer injection devices, such as the needle-shielding syringes and needle-free injectors we modelled (87-89). But needle- shielding syringes remain too expensive (modelled at US$ 0.54) for developing countries. Future needle-free vaccine technologies, such as mucosal (90) or transcutaneous (91, 92) immunization, would avoid the dangers of injection. However, they will probably take many years to be registered in developed countries and their costs may put them out of reach of developing countries for decades.
The hidden disease and economic cost of unsafe injections are enormous. Health ministries in sub-Saharan Africa, and the international agencies and initiatives that promote immunization and therapeutic injections should recognize this burden. To rephrase Hippocrates' Epidemics, in selecting injection technology, one should "do less harm". 
Acknowledgements
This research was supported in part by Dr Ekwueme's appointment to the Research Participation Program at CDC, administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the United States Department of Energy and CDC, and by a consultation on behalf of the World Health Organization. He gratefully acknowledges the invaluable contributions and assistance in the collection of original data from: Côte d'Ivoire (Kakau Aka, Mami Pieorno Aby-Sy, Timothy Herrick, Alassane Mahassadi, Ouattara Siguifota, Kone Souleymane, Mamadou Moustapha Sy and others from Baptist Hospital Ferke and Sakassou General Hospitals, the University Hospital Centers of Treichville and Yopougon, and WHO-Côte d'Ivoire); Ghana (Ernestina Agyepong, F. Avokey, Martin P. Mandara, Anthony Nsaiah-Asare, Paapa Obimpeh, Andrew Seidu Korkor, and others at the Ghanaian Ministry of Health, UNICEF-Ghana, and WHO-Ghana); and Uganda (John Barenzi, Robert Basaza, Patrick Isoke, P.K. Kataaha, Tonny Mubiru, Grace Murindwa, Francis Omaswa, Rachel N. Seruyange, Susan Seruyange, Sam Zaramba, and others from the Ugandan Ministry of Health, UNICEF-Uganda, Ugandan Blood Bank Transfusion Service, and Mulago, Rubaga, and Mildmay hospitals).
The authors thank Halima Dao, Frank Ferguson, Robert Harrington, Janine Jagger, Robert E. Jones, Mikko Lainejoki, Gordon Larsen, John Livengood, John Lloyd, Larry Petersen, Rohit Patel, John Stengel, and Michel Zaffran for data, assistance, and advice. We also acknowledge Hazel Dean, Martin Meltzer, Mark Miller, and Mary McCauley for their comments and suggestions on early drafts.
Conflicts of interest: none declared.
Résumé
Estimations tirées de la modélisation du risque de transmission de maladies et du coût économique liés à sept dispositifs d'injection en Afrique subsaharienne
OBJECTIF: Etudier et comparer sept types de dispositifs d'injection du point de vue du coût économique et du risque de transmission iatrogénique de germes à diffusion hématogène en Afrique subsaharienne.
MÉTHODES: Des hypothèses de risque et des modèles de coûts ont été établis pour chaque dispositif de manière à estimer le nombre de nouvelles infections par le virus de l'hépatite B (HBV) et le virus de l'immunodéficience humaine (VIH) à la suite d'une transmission d'un patient à l'autre, d'un patient à un agent de soins de santé et d'un patient à la communauté. Les coûts d'achat et d'utilisation des dispositifs ont été tirés des données publiées, tandis que les coûts des soins médicaux directs et de la perte de productivité associée à la maladie dans le cas des infections à HBV et à VIH ont été tirés de données recueillies en 1999 en Côte d'Ivoire, au Ghana et en Ouganda. Des analyses multivariées de sensibilité au moyen du modèle de Monte Carlo ont permis de caractériser l'intervalle d'incertitude des paramètres du modèle. Les coûts ont été additionnés du double point de vue de la société et du système de soins de santé.
RÉSULTATS: Les aiguilles et seringues restérilisables et jetables avaient le coût global le plus élevé en ce qui concerne l'achat, l'utilisation et les maladies iatrogéniques, avec un coût sociétal médian par injection de US $26,77 pour le matériel restérilisable et US $25,29 pour le matériel jetable. Les injecteurs sans aiguille à cartouche jetable et les seringues à dispositif automatique de protection de l'aiguille avaient le coût le plus faible, soit respectivement US $0,36 et US $0,80. Les injecteurs sans aiguille à buse réutilisable et les aiguilles et seringues autobloquantes avaient un coût intermédiaire, soit respectivement US $0,80 et US $0,91 par injection.
CONCLUSION: Malgré leur coût nominal d'achat et d'utilisation, les aiguilles et seringues conventionnelles comportent un risque non visible mais important de maladie iatrogénique. D'autres dispositifs d'injection utilisables pour les millions d'injections pratiquées chaque année en Afrique subsaharienne seraient intéressants et devraient être examinés par les responsables de l'élaboration des politiques lors des décisions d'achat.
Resumen
Estimaciones basadas en modelos de los riesgos de transmisión de enfermedades y el costo económico de siete dispositivos de inyección en el África subsahariana
OBJETIVO: Investigar y comparar siete tipos de dispositivos de inyección en cuanto a su riesgo de infección iatrogénica por patógenos de transmisión hematógena y su costo económico en el África subsahariana.
MÉTODOS: Se elaboraron hipótesis de riesgos para cada dispositivo y modelos de costos para estimar el número de nuevas infecciones por los virus de la hepatitis B (VHB) y de la inmunodeficiencia humana (VIH) debidas a la transmisión entre pacientes, de paciente a agente de salud, y de paciente a la comunidad. Los costos asociados a la compra y el uso de los dispositivos se calcularon a partir de información hallada en la literatura, mientras que los costos de la atención médica directa y de la productividad perdida como consecuencia de las infecciones por el VHB y el VIH se basaron en datos reunidos en 1999 en Côte d'Ivoire, Ghana y Uganda. Los intervalos de incertidumbre de los parámetros del modelo se determinaron mediante análisis de sensibilidad multifactoriales basados en el método de Monte Carlo. Se sumaron los costos obtenidos desde la perspectiva tanto de la sociedad como de los contribuyentes al sistema de atención de salud.
RESULTADOS: Las agujas y las jeringas reesterilizables y desechables se asociaron a los costos globales más altos en lo que atañe a la compra, el uso y las enfermedades iatrogénicas: medianas de US$ 26,77 y US$ 25,29, respectivamente, por inyección desde el punto de vista de la sociedad. Los costos más bajos correspondieron a los inyectores sin aguja con cartucho desechable y las jeringas con protección automática de la aguja: US$ 0,36 y US$ 0,80, respectivamente. Los inyectores de presión con boquilla reutilizables y las agujas y jeringas no reutilizables obtuvieron resultados intermedios, con US$ 0,80 y US$ 0,91, respectivamente, por inyección.
CONCLUSIÓN: A pesar de su costo nominal de adquisición y uso, las agujas y las jeringas convencionales comportan una carga oculta pero enorme de enfermedades iatrogénicas. El uso de dispositivos de inyección alternativos en los millones de inyecciones que se administran anualmente en el África subsahariana sería una medida inestimable, que debería ser tenida en cuenta por los formuladores de políticas en las decisiones de compra.
References
1. State of the world's vaccines and immunization 1996. Geneva: World Health Organization; 1996. p. 1-161. WHO document WHO/GPV/96.04.
2. Simonsen L, Kane A, Lloyd J, Zaffran M, Kane M. Unsafe injections in the developing world and transmission of bloodborne pathogens: a review. Bulletin of the World Health Organization 1999;77:789-800.
3. Dicko M, Oni AQ, Ganivet S, Kone S, Pierre L, Jacquet B. Safety of immunization injections in Africa: not simply a problem of logistics. Bulletin of the World Health Organization 2000;78:163-9.
4. Aylward B, Kane M, McNair-Scott R, Hu DJ. Model-based estimates of the risk of human immunodeficiency virus and hepatitis B virus transmission through unsafe injections. International Journal of Epidemiology 1995;24:446-52.
5. Aylward B, Lloyd J, Zaffran M, McNair-Scott R, Evans P. Reducing the risk of unsafe injections in immunization programmes: financial and operational implications of various injection technologies. Bulletin of the World Health Organization 1995;73:531-40.
6. Brito GS, Chen RT, Stefano IC, Campos AM, Oselka G. The risk of transmission of HIV and other blood-born diseases via jet injectors during immunization mass campaigns in Brazil. 10th International Conference on AIDS; 1994 Aug 7-12; Yokohama, Japan. AIDSLINE 10:301. Available from: URL: http://www.aegis.org/pubs/aidsline/1994/dec/m94c3258.html (accessed on 22 March 2002).
7. Changing needles but not the syringe: an unsafe practice. Weekly Epidemiological Record 1987;62:345-52.
8. Greaves WL, Hinman AR, Facklam RR, Allman KC, Barrett CL, Stetler HC. Streptococcal abscesses following diphtheria-tetanus toxoid-pertussis vaccination. Pediatric Infectious Diseases 1982;1:388-90.
9. Soeters R, Aus C. Hazards of injectable therapy. Tropical Doctor 1989;19: 124-6.
10. Mann JM, Francis H, Davachi F, Baudoux P, Quinn TC, Nzilambi, et al. Risk factors for human immunodeficiency virus seropositivity among children 1-24 months old in Kinshasa, Zaire. Lancet 1986;2:654-7.
11. Lepage P, Van de Perre P. Nosocomial transmission of HIV in Africa: What tribute is paid to contaminated blood transfusions and medical injections? Infection Control and Hospital Epidemiology 1988;9:200-3.
12. Jagger J, Hunt EH, Brand-Elnaggar J, Pearson RD. Rates of needlestick injury caused by various devices in a university hospital. New England Journal of Medicine 1988;319:284-8.
13. Jagger J, Hunt EH, Pearson RD. Estimated cost of needlestick injuries for six major needled devices. Infection Control and Hospital Epidemiology 1990;11:584-8.
14. Armstrong SE. The cost of needlestick injuries: The impact of safer medical devices. Nursing Economics 1991;9:426-30.
15. Sagoe-Moses C, Pearson RD, Perry J, Jagger J. Risks to health care workers in developing countries. New England Journal of Medicine 2001;345:538-41.
16. Kane M, Clements J, Hu D. Hepatitis B. In: Jamison DT, Mosley HW, Measham AR, Robadilla JL, editors. Disease control priorities in developing countries. New York: Oxford University Press; 1993. p. 321-30.
17. Report on the global HIV/AIDS epidemic. Geneva: Joint United Nations Programme on HIV/AIDS (UNAIDS); 2000. pp. 1-137. UNAIDS document UNAIDS/00.13E. Available from: URL: http://www.unaids.org/epidemic_update/report/Epi_report.pdf (accessed on 23 March 2002).
18. Hu DJ, Kane MA, Heymann DL. Transmission of HIV, hepatitis B virus, and other bloodborne pathogens in health care settings: a review of risk factors and guidelines for prevention. Bulletin of the World Health Organization 1991;69:623-30.
19. Safe injection - vital to health. Geneva: World Health Organization; 1999. Available from: URL: http://www.who.int/vaccines-access/injection_safety/Injections_Safety/vital_to_Health/ (accessed on 23 March 2002).
20. Zaffran M, Lloyd J, Clements J, Stilwell B. A drive to safer injections. Geneva: World Health Organization; 1997. WHO document WHO/GPV/SAGE.97/ WP.05.
21. Progress towards global measles control and elimination, 1990-1996. Morbidity and Mortality Weekly Report 1997;46:893-7.
22. World Health Organization, United Nations Children's Fund. WHO-UNICEF policy statement for mass immunization campaigns. Geneva: World Health Organization; 1997. p. 1-4. WHO document WHO/EPI/LHIS/97.04 Rev.1.
23. World Health Organization, United Nations Children's Fund, United Nations Population Fund. Safety of injections: WHO-UNICEF-UNFPA joint statement on the use of auto-disable syringes in immunization services. Geneva: World Health Organization; 1999. p. 1-4. WHO document WHO/V&B/99.25. Available from: URL: http://www.who.int/vaccines-documents/ DocsPDF99/www9948.pdf (accessed on 23 March 2002).
24. GPV declares war on unsafe injections. Vaccine and Immunization News 1997;5:1-5. Geneva: World Health Organization. WHO document GPV/ VIN/97.03. Available from: URL: http://www.who.int/vaccines-documents/DoxNews/pdf-news/e_vin05.pdf (accessed on 23 March 2002).
25. Lloyd JS, Milstien JB. Auto-disable syringes for immunization: issues in technology transfer. Bulletin of the World Health Organization 1999;77:1001-7.
26. Kane A, Lloyd J, Zaffran M, Simonsen L, Kane M. Transmission of hepatitis B, hepatitis C and human immunodeficiency viruses through unsafe injections in the developing world: model-based regional estimates. Bulletin of the World Health Organization 1999;77:801-7.
27. Owens DK, Nease RF. Occupational exposure to human immunodeficiency virus and hepatitis B virus: A comparative analysis of risk. American Journal of Medicine 1992;92:503-12.
28. Nelson CM, Sutanto A, Suradana IG. Use of SoloShot autodestruct syringes compared with disposable syringes, in a national immunization campaign in Indonesia. Bulletin of the World Health Organization 1999;77:29-33.
29. Steinglass R, Boyd D, Grabowsky M, Laghari AG, Khan MA, Qavi A, et al. Safety, effectiveness and ease of use of a non-reusable syringe in a developing country immunization programme. Bulletin of the World Health Organization 1995;73:57-63.
30. Device achieves breakthrough in battle against spread of AIDS, other blood-borne diseases [press release]. Little Elm (TX): Retractable Technologies Inc.; 1997.
31. Younger B, Hunt EH, Robinson C, McLemore C. Impact of a shielded safety syringe on needlestick injuries among health-care workers. Infection Control and Hospital Epidemiology 1992;13:349-53.
32. Coursaget P, Kane MA. Overview of clinical studies in developing countries. In: Ellis RW, editor. Hepatitis B vaccines in clinical practice. New York: Marcel Dekker; 1993. p. 209-28.
33. Ekwueme DU. Comparative cost analysis of injection delivery technologies in sub-Saharan Africa, 28 December 1999. p. 1-128. Consultant's report submitted to the World Health Organization, 1999.
34. Charney W. Retractable safety syringe activation study. Journal of Health Care Safety, Compliance and Infection Control 1998;2:413-5.
35. Canter J, Mackey K, Good LS, Roberto RR, Chin J, Bond WW, et al. An outbreak of hepatitis B associated with jet injections in a weight reduction clinic. Archives of Internal Medicine 1990;150:1923- 7.
36. Hoffman PN, Abuknesha RA, Andrews NJ, Samuel D, Lloyd JS. A model to assess the infection potential of jet injectors used in mass immunisation. Vaccine 2001;19:4020-7.
37. Grabowsky M, Hadler SC, Chen RT, Bond WW, De Brito G. Risk of transmission of hepatitis B virus or human immunodeficiency virus from jet injectors and from needles and syringes. Atlanta (GA): Centers for Disease Control and Prevention, 1994. Unpublished document.
38. Grady GF, Lee VA, Prince AM, Gitnick GL, Fawaz KA, Vyas GN, et al. Hepatitis B immune globulin for accidental exposures among medical personnel: final report of a multicenter controlled trial. Journal of Infectious Diseases 1978;138:625-38.
39. Seeff LB, Wright EC, Zimmerman HJ. Type B hepatitis after needlestick exposure: prevention with hepatitis B immune globulin. Annals of Internal Medicine 1978;88:285-93.
40. Recommendations for preventing transmission of human immunodeficiency virus and hepatitis B virus to patients during exposure-prone invasive procedures. Morbidity and Mortality Weekly Report Recommendations and Reports 1991;40(RR-8):1-9.
41. Bell DM, Shapiro CN, Culver DH, Martone WJ, Curran JW, Hughes JM. Risk of hepatitis B and human immunodeficiency virus transmission to a patient from an infected surgeon due to percutaneous injury during an invasive procedure: estimates based on a model. Infectious Agents and Disease 1992;1:263-9.
42. Culver J. Preventing transmission of blood-borne pathogens: a compelling argument for effective device-selection strategies. American Journal of Infection Control 1997;25:430-3.
43. Henderson DK, Fahey BJ, Willy M, Schmitt JM, Carey K, Koziol DE, et al. Risk for occupational transmission of human immunodeficiency virus type 1 (HIV-1) associated with clinical exposures. Annals of Internal Medicine 1990;113:740-6.
44. Supply catalogue. Copenhagen: United Nations Children's Fund; 1997.
45. World Health Organization, United Nations Children's Fund. EPI product information sheets: 1997 edition. Geneva: World Health Organization. WHO document WHO/EPI/LHIS/97.01.
46. World Health Organization, United Nations Children's Fund. EPI Product information sheets: 1998 supplement. Geneva: World Health Organization. WHO document WHO/EPI/LHIS/98.03.
47. EPI syringe and sterilizer study. Geneva: World Health Organization; 1985. p. 1-28. WHO document EPI/CCIS/85.6.
48. Choice of syringes for the EPI. Weekly Epidemiological Record 1986;61:41-3.
49. Keystone Dental Group. Ped-O-Jet January 1997 price list. Cherry Hill (NJ): Ped-O-Jet International, Keystone Industries; 1997. p. 1-4.
50. Cost analysis of various vaccine delivery systems. In: HealthTech Product Development Plan -MEDiVAX. low-workload jet injector. Seattle (WA): Program for Appropriate Technology in Health; 1996. Unpublished document.
51. Department of Vaccines and Biologicals. Assessing the whole cost of injection technologies: case studies in Africa. In: Technet consultation, Harare, 6- 10 December 1999. Geneva: World Health Organization, 2000. WHO document WHO/ATT/TECHNET.99/Session 3/WP.3. Available from: URL: http://www.who.int/vaccines-documents/DocsPDF00/www536.pdf (accessed on 23 March 2002).
52. Drummond MF, O'Brien BJ, Stoddart GL, Torrance GW. Methods for the economic evaluation of health care programmes. 2nd ed. Oxford: Oxford University Press; 1997.
53. Over M, Bertozzi S, Chin J. Guidelines for rapid estimation of the direct and indirect costs of HIV infection in a developing country. Health Policy 1989;11:169-86.
54. Mansergh G, Haddix AC, Steketee RW, et al. Cost-effectiveness of short-course zidovudine to prevent perinatal HIV type 1 infection in a sub-Saharan African developing country setting. JAMA 1996;276:139-45.
55. The world factbook 2001. Virginia: McLean (VA): Central Intelligence Agency; 2001. Available from: URL: http://www.cia.gov/cia/publications/factbook/ (accessed on 30 May 2002).
56. Critchfield GC, Willard KE. Probabilistic analysis of decision trees using Monte Carlo simulation. Medical Decision Making 1986;6:85-92.
57. Dobilet P. Begg CB, Weinstein MC, Braun P, McNeil BJ. Probabilistic sensitivity analysis using Monte Carlo simulation: a practical approach. Medical Decision Making 1985;5:157-77.
58. Dittus RS, Roberts SD, Wilson JR. Quantifying uncertainty in medical decisions. Journal of the American College of Cardiology 1989;14(3 Suppl A):23A-28A.
59. Evans M, Hastings N, Peacock B. Statistical distributions. 2nd ed. New York: John Wiley and Sons; 1993.
60. Oakshott L. Business modeling and simulation. Washington (DC): Pitman Publishing; 1997.
61. Palisade Corporation. Guide to using @RISK: risk analysis and simulation add-in for Microsoft Excel or Lotus 1-2-3, Windows version. Newfield (NY): Palisade Corporation; 2000.
62. World Bank. Health expenditure, services and use. In: World development indicators 2000. Washington (DC): World Bank; 2000. p. 92.
63. Patient exposures to HIV during nuclear medicine procedures. Morbidity and Mortality Weekly Report 1992;41:575-8.
64. Davachi F, Baudoux P, Ndoko K, N'Galy B, Mann J. The economic impact on families of children with AIDS in Kinshasa, Zaire. In: Fleming A, Carballo M, FitzSimons DW, Bailey MR, Mann J, editors. The global impact of AIDS. New York: Alan R. Liss; 1988. p. 167-9.
65. Foster S. The economic impact of AIDS in Zambia. Washington (DC): World Bank; 1993. Unpublished paper prepared for the Human Resources and Poverty Division.
66. Hersh BS, Popovici F, Apetrei RC, Zolotusca L, Beldescu N, Calomfirescu, A, et al. Acquired immunodeficiency syndrome in Romania. Lancet 1991; 338:645-9.
67. Hersh BS, Popovici F, Jezek Z, Satten GA, Apetrei RC, Beldescu N, et al. Risk factors for HIV infection among abandoned Romanian children. AIDS 1993;7:1617-24.
68. Feilden R. Final report: Choosing a sustainable policy for giving safe injections in Romania. New York: United Nations Children's Fund; 1993. Unpublished document.
69. Holding R, Carlsen W. Deadly needles: fast track to global disaster. San Francisco Chronicle 1998 Oct 27. p. A-1 et seq. Available from: URL: http:// sfgate.com/cgi-bin/article.cgi?file=/chronicle/archive/1998/10/27/ MN52NEE.DTL (accessed on 24 March 2002).
70. Hutin YJF, Harpaz R, Drobeniuc J, Melnic A, Ray C, Favorov M, et al. Injections given in healthcare settings as a major source of acute hepatitis B in Moldova. International Journal of Epidemiology 1999;28:782-6.
71. Spiegel A, Moren A, Varaine F, Baudon D, Rey M. Aspects épidémiologiques et contrôle des épidémies de méningite à méningocoque en Afrique [Epidemiologic aspects and control of meningococcal meningitis epidemics in Africa]. Cahiers Santé 1994;4:231-6. In French.
72. Artus JC. Vaccination de masse par le vaccin souche Rockefeller 17D au Sénégal. Utilisation des "Ped-O-Jet" [Mass vaccination with the Rockefeller 17D strain in Senegal. Use of the "Ped-O-Jet"]. Médecine Tropicale 1966;26:527-36. In French.
73. Reis EC, Jacobson RM, Tarbell S, Weniger BG. Taking the sting out of shots: control of vaccination-associated pain and adverse reactions. Pediatric Annals 1998;27:375-86.
74. Hepatitis B associated with jet gun injection - California. Morbidity and Mortality Weekly Report 1986;35:373-6.
75. Transmission of hepatitis B associated with jet gun injection. Weekly Epidemiological Record 1986;61:309-11.
76. United States Department of Defense. Automatic jet hypodermic injection units/withdrawal (DPSC 970147). Fort Detrick (MD): United States Army Medical Material Agency; 1997. Medical material quality control document MMQC- 97-1169. Available from: URL: http://review.detrick.army.mil/ usamma/mmqc_messages/Q971169.txt (accessed on 27 March 2002).
77. Centers for Disease Control and Prevention (CDC). Needle-free injection technology: policies (WHO, CDC, and DoD). Atlanta (GA): National Immunization Program, CDC. Available from: URL: http://www.cdc.gov/nip/dev/jetinject.htm#policies (accessed on 4 March 2002).
78. Safety of injections in immunization programmes: WHO recommended policy. Geneva: World Health Organization; 1998. p. 1-11. WHO document WHO/ EPI/LHIS/96.05 Rev.1. Available from: URL: http:// www.who.int/gpv-documents/DocsPDF/www9665.pdf (accessed on 27 March 2002).
79. Centres for Disease Control and Prevention. Jet injectors. In: General recommendations on immunization. Recommendations of the Advisory Committee on Immunization Practices (ACIP). Morbidity and Mortality Weekly Report, Recommendations and Reports 1994;43(RR-1):1-38.
80. Centres for Disease Control and Prevention. Jet injectors. In: General recommendations on immunization. Recommendations of the Advisory Committee on Immunization Practices (ACIP) and the American Academy of Family Physicians (AAFP). Morbidity and Mortality Weekly Report, Recommendations and Reports 2002;51(No. RR-2):1-38.
81. Galy M, Genet A, Saliou P. Un progrès dans le domaine de l'injection sans aiguille: le système Imule® [Progress in the field of needle-free injection: the Imule® system]. STP Pharma Pratiques 1992;4:261-6. In French.
82. Fisch A, Cadilhac P, Vidor E, Prazuck T, Dublanchet A, Lafaix C. Immunogenicity and safety of a new inactivated hepatitis A vaccine: a clinical trial with comparison of administration route. Vaccine 1996;14:1132-6.
83. Parent du Châtelet I, Lang J, Schlumberger M, Vidor E, Soula G, Genet A, et al. Clinical immunogenicity and tolerance studies of liquid vaccines delivered by jet-injector and a new single-use cartridge (Imule®): comparison with standard syringe injection. Vaccine 1997;15:449-58.
84. Schlumberger M, Parent du Châtelet I, Lafarge H, Genêt A, Gaye AB, Monnereau A, et al, Coût de l'injection d'anatoxine tétanique par injecteur sans aiguille (Imule®) lors d'une vaccination collective au Sénégal : comparaison avec l'injection par seringues et aiguilles restérilisables [Cost of tetanus toxoid injection by needle-free injector (ImuleÔ) in a mass vaccination in Senegal: comparison with resterilizable syringes and needles]. Cahiers Santé 1999;9: 319-26. In French.
85. Laufer FN, Chiarello LA. Application of cost-effectiveness methodology to the consideration of needlestick-prevention technology. American Journal of Infection Control 1994;22:75-82.
86. Holding R, Carlsen W. Epidemic ravages caregivers. Thousands die from diseases contracted through needlesticks. San Francisco Chronicle 1998 April 13. p. A-1 et seq. Available from: URL: http://www.sfgate.com/cgi-bin/article.cgi?file=/chronicle/archive/1998/04/13/MN64658.DTL (accessed on 24 March 2002).
87. International Health Care Worker Safety Center. State legislation on needle safety, updated 01/24/02. Charlottesville (VA): University of Virginia Health System; 2002. Available from: URL: http://www.med.virginia.edu/medcntr/ centers/epinet/statelist.html (accessed on 24 March 2002).
88. Voelker R. Needlestick bill passes [Quick uptakes]. JAMA 2000;284:2585.
89. Occupational Safety and Health Administration. Occupational exposure to bloodborne pathogens; needlestick and other sharps injuries; final rule. Washington (DC): Federal Register; 2001. 29 CFR Part 1910. 66:5318- 25. Available from: URL: http://www.osha-slc.gov/FedReg_osha_pdf/FED20010118A.pdf (accessed on 27 March 2002).
90. Levine MM, Dougan G. Optimism over vaccines administered via mucosal surfaces. Lancet 1998;351:1375-6.
91. Tang D-C, Shi Z, Curiel DT. Vaccination onto bare skin. Nature 1997;388: 729- 30.
92. Guerena-Burgueno F, Hall ER, Taylor DN, Cassels FJ, Scott DA, Wolf MK, et al. Safety and immunogenicity of a prototype enterotoxigenic Escherichia coli vaccine administered transcutaneously. Infection and Immunity. 2002; 70:1874-80.
* The mention of trade names is for identification purposes only and does not imply endorsement by the authors, the United States Centers for Disease Control and Prevention, or the United States Department of Health and Human Services.
1 Prevention Effectiveness Fellow, National Immunization Program (NIP), Centers for Disease Control and Prevention (CDC), Atlanta, GA, USA. Currently, Senior Health Economist, Epidemiology and Health Services Research Branch, Division of Cancer Prevention and Control, National Center for Chronic Disease Prevention and Health Promotion, CDC. Correspondence should be sent to this author at Mailstop K-55, CDC, 4770 Buford Highway, Atlanta, GA 30341, USA (email: dce3@cdc.gov).
2 Assistant Chief for Vaccine Development, Vaccine Safety and Development Branch, NIP, CDC, Atlanta, GA, USA.
3 Chief, Vaccine Safety and Development Branch, NIP, CDC, Atlanta, GA, USA.
Ref. No. 99-0135