An investment case for maternal and neonatal tetanus elimination.

INTRODUCTION: Globally, 13 countries have yet to eliminate maternal and neonatal tetanus. While efforts have improved access to tetanus toxoid containing vaccines (TTCVs) and increased clean delivery practices, reaching elimination targets (<1 case of neonatal tetanus per 1000 live births per district per year) may require significant resources to reach the remaining high risk and hard-to-reach districts. METHODS: We estimated the cost to achieve maternal and neonatal tetanus elimination (MNTE) in three years in the remaining 13 countries: Afghanistan, Angola, Central African Republic, Democratic Republic of the Congo, Guinea, Mali, Nigeria, Pakistan, Papua New Guinea, Somalia, South Sudan, Sudan, and Yemen. Costs were estimated for: (1) vaccination campaigns using standard TTCVs and TT-Uniject™ targeting women of reproductive age in high risk areas, (2) additional vaccinations delivered to pregnant women at antenatal care (ANC) clinics, (3) clean delivery and umbilical cord care promotion, (4) neonatal tetanus surveillance strengthening, and (5) validation activities. We forecasted the averted mortality to assess the cost-effectiveness of achieving MNTE. RESULTS: It will cost an estimated US$197.7 million to realize MNTE over three years. These costs include $161.4 million for vaccination campaigns, $6.1 million for routine vaccination during ANC, $23.3 million for promotion of clean delivery practices, $4 million for surveillance, and $3 million for validation of MNTE. Achieving MNTE will avert approximately 70,000 neonatal deaths over ten years of vaccine protection, resulting in approximately 4.4 million life years gained. It will cost $2,900 per death averted and $45 per life year gained. CONCLUSION: Maternal and neonatal tetanus can be eliminated with significant financial investment, high prioritization, and strong political will. While substantial costs must be incurred to reach hard-to-reach populations, MNTE should be accomplished as a matter of health equity, and will significantly contribute to reaching the United Nations' Sustainable Development Goals.

Is patient insurance type related to physician recommendation, administration and referral for adult vaccination? A survey of US physicians.

This study evaluated physician practices and perceived barriers for influenza, tetanus, diphtheria, pertussis (Tdap), and zoster vaccination of adults in the United States (US), with emphasis on patients with Medicare versus commercial insurance. A cross-sectional internet-based survey of board-certified general/family practitioners and internists (N = 1,000) recruited from a national US physician panel was conducted in May 2017. For influenza, rates of physician recommendation (84% of Medicare patients, 82% of commercially-insured patients), administration (80% Medicare, 78% commercial), and referral (11% Medicare, 11% commercial) were similar regardless of insurance type. Tdap recommendation was higher for commercial compared to Medicare patients (59% vs. 54%, p < 0.001); while zoster recommendation was higher for Medicare patients than commercial (59% vs. 55%, p < 0.001). For Tdap and zoster, higher administration rates were reported in commercial patients (64% Tdap, 36% zoster) than Medicare (56% Tdap, 32% zoster), and referral rates were higher for Medicare patients (19% Tdap, 49% zoster) than commercial (14% Tdap, 42% zoster). Over 40% of physicians would be much more likely to administer Tdap and zoster vaccines if they were covered under Medicare Part B, with more physicians indicating financial barriers as "major" or "moderate" for Medicare than commercial patients. These differences may be related to financial barriers associated with adult vaccinations that are covered under Medicare Part D and involve patient out-of-pocket costs. Efforts to reduce financial barriers associated with adult vaccinations covered under Medicare Part D and to improve patient and physician knowledge could positively impact physician recommendation, administration, and referral for adult vaccination in the US.

The economic value of increasing geospatial access to tetanus toxoid immunization in Mozambique.

BACKGROUND: With tetanus being a leading cause of maternal and neonatal morbidity and mortality in low and middle income countries, ensuring that pregnant women have geographic access to tetanus toxoid (TT) immunization can be important. However, immunization locations in many systems may not be placed to optimize access across the population. Issues of access must be addressed for vaccines such as TT to reach their full potential. METHODS: To assess how TT immunization locations meet population demand in Mozambique, our team developed and utilized SIGMA (Strategic Integrated Geo-temporal Mapping Application) to quantify how many pregnant women are reachable by existing TT immunization locations, how many cannot access these locations, and the potential costs and disease burden of not covering geographically harder-to-reach populations. Sensitivity analyses covered a range of catchment area sizes to include realistic travel distances and to determine the area some locations would need to cover in order for the existing system to reach at least 99% of the target population. RESULTS: For 99% of the population to reach health centers, people would be required to travel up to 35km. Limiting this distance to 15km would result in 5450 (3033-7108) annual cases of neonatal tetanus that could be prevented by TT, 144,240 (79,878-192,866) DALYs, and $110,691,979 ($56,180,326-$159,516,629) in treatment costs and productivity losses. A catchment area radius of 5km would lead to 17,841 (9929-23,271) annual cases of neonatal tetanus that could be prevented by TT, resulting in 472,234 (261,517-631,432) DALYs and $362,399,320 ($183,931,229-$522,248,480) in treatment costs and productivity losses. CONCLUSION: TT immunization locations are not geographically accessible by a significant proportion of pregnant women, resulting in substantial healthcare and productivity costs that could potentially be averted by adding or reconfiguring TT immunization locations. The resulting cost savings of covering these harder to reach populations could help pay for establishing additional immunization locations.

Assessment of tetanus immunity status by tetanus quick stick and anamnesis: a prospective double blind study.

BACKGROUND: In patients with wounds admitted to Emergency Departments (ED) acquiring tetanus vaccination history by interview is very unreliable. Protected patients may receive unnecessary prophylaxis and unprotected nothing. Aim of the study was to evaluate tetanus immunity status comparing the traditional anamnestic method with the Tetanus Quick Stick (TQS), a rapid immunochromatographic test. METHODS: A double-blind prospective study was carried out in the ED of the 1,000 bed teaching hospital Umberto I in Rome. Adult patients (≥18) with wounds attending at the ED were randomly included. Tetanus immunity status was evaluated by healthcare workers (HCWs) comparing the TQS test with the anamnesis. TQS test was performed by a trained HCW and afterwards the anamnesis about tetanus immunity status was collected by another HCW unaware of the TQS result. Also cost analysis was carried out. RESULTS: Overall 400 patients (242 males and 158 females) were included, mean age was 46.7 ± 20.2 years (median 44 range 18 - 109), 304 (76.0%) were italians and 96 foreigners (24.0%). Overall, 209 (52.2%) resulted TQS +, and protective immunity level was associated to lower mean age (40.1 ± 16.8 vs 53.8 ± 21,1; p<0,01). Using the anamnestic method 336 (84.0%) patients resulted "unprotected", 52 (13.0%) "partially unprotected" and 12 (3.0%) "completely protected". TQS test results showed that 154 (45.8%) out of 336 "unprotected" and 45 (86.5%) out of 52 "partially unprotected" actually had a protective antibody level. Finally two (16.7%) out of 12 "completely protected" group presented a non protective antibody level. Following only the anamnestic method 201 (50.0%) patients would have received some inappropriate treatment. Adopting TQS test in all patients would also be cost-effective saving € 1.95/patient. As tetanus immunity is inversely related to age, for <51 years old patients unnecessary treatment would have been avoided in 57.1% of patients, with a mean reduction per patient of € 7.50/patient with the TQS vs. € 12.69/patient without. CONCLUSIONS: The study showed that tetanus protective immunity prevalence among adult patients attending our ED is about 50% and is mainly influenced by class age. TQS use allowed to reduce drastically inappropriate tetanus vaccine and immunoglobulins booster treatment. Also TQS use reduced costs.

Effectiveness and cost of quick diagnostic tests to determine tetanus immunity in patients with a wound in French emergency departments.

BACKGROUND: Tétanos Quick Stick® (TQS) is a test for tetanus immunity screening for wounded patients in emergency departments (EDs), but represents additional costs compared with a medical interview on vaccination history. The study objective was to assess the effectiveness and cost of the TQS in French EDs. METHODS: We performed a model-based analysis that simulates screening of tetanus immunity and risk of tetanus based on prophylaxis administration. Strategies compared were: i) diagnosis of tetanus immunity by "TQS"; ii) "Medical Interview" (current practice). The study population was 1,658,000 French adults seeking ED care for a wound in 2012. Model parameters were estimated based on French national surveillance data, and published literature. Outcome measures were number of tetanus cases, life years gained and costs (2012 €) from a societal perspective. RESULTS: Use of TQS had negligible impact on health outcomes (0.02 tetanus cases/year in France vs. 0.41 for "Medical Interview"), but resulted in a decrease in annual costs of €2,203,000 (-42%). Base case and sub-group analysis showed that with the same effectiveness, the average cost per patient was: €13 with "Medical Interview" vs. €11.7 with TQS for the overall cohort; €28.9 with "Medical Interview" vs. €21 with "TQS" for tetanus-prone wounds; €15 with "Medical Interview" vs. €14.1 with "TQS" for patients aged ≥65 years; and €6.2 with "Medical Interview" vs. €7.8 with "TQS" for non-tetanus-prone wounds. CONCLUSIONS: Use of TQS is as effective and less costly than "Medical Interview" when applied in ED to wounded patients with tetanus-prone wounds or aged ≥65 years. However, it is more expensive in patients with non-tetanus-prone wounds.

Effectiveness and cost of immunization recall at school-based health centers.

BACKGROUND AND OBJECTIVE: Effectiveness of recall for immunizations has not been examined in the setting of school-based health centers (SBHCs). We assessed (1) immunization rates achieved with recall among sixth-grade girls (demonstration study); (2) effectiveness of recall among sixth-grade boys (randomized controlled trial [RCT]); and (3) cost of conducting recall in SBHCs. METHODS: During October 2008 through March 2009, in 4 Denver public SBHCs, we conducted (1) a demonstration study among 265 girls needing ≥ 1 recommended adolescent vaccine and (2) an RCT among 264 boys needing vaccines, with half randomized to recall and half receiving usual care. Immunization rates for recommended adolescent vaccines were assessed 6 months after recall. First dose costs were assessed by direct observation and examining invoices. RESULTS: At the end of the demonstration study, 77% of girls had received ≥ 1 vaccine and 45% had received all needed adolescent vaccines. Rates of receipt among those needing each of the vaccines were 68% (160/236) for tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine, 57% (142/248) for quadrivalent meningococcal conjugate vaccine, and 59% (149/253) for the first human papillomavirus vaccine. At the end of the RCT, 66% of recalled boys had received ≥ 1 vaccine and 59% had received all study vaccines, compared with 45% and 36%, respectively, of the control group (P < .001). Cost of conducting recall ranged from $1.12 to $6.87 per recalled child immunized. CONCLUSIONS: SBHC-based recall was effective in improving immunization rates for all adolescent vaccines, with effects sizes exceeding those achieved with younger children in practice settings.

[Epidemiological and economic impact of tetanus vaccination in Colombian adults]. / Impacto epidemiológico y económico de la vacunación contra el tétanos en adultos de Colombia.

OBJECTIVE: Assess the potential epidemiological and economic impact of vaccinating the over-15 Colombian population against tetanus with a booster dose every 10 years. METHODS: A cost-effectiveness analysis of tetanus vaccination with a booster dose every 10 years was conducted in Colombia and compared with the current strategy (2, 4, 6, 18, and 60 months). Estimates of the burden of disease were based on three official data sources. A Markov model from the perspective of the third party payer was developed. The time horizon was the lifetime of a person. Deterministic and probabilistic sensitivity analyses were conducted. RESULTS: In Colombia, 30 to 48 cases of tetanus resulting in 9.6 to 10.1 deaths are reported each year. Although booster vaccination for the entire population was cost-effective (the cost per disability-adjusted life year [DALY] avoided was US$ 11,314 in the entire population), gender-based differentiation of the results showed that it would not be cost-effective in women (cost per DALY avoided was US$ 4,903 in men and US$ 22,332 in women). CONCLUSIONS: This is the first study that evaluates the cost-effectiveness of a tetanus vaccine booster dose every 10 years in a developing country. Use of this measure would be cost-effective in Colombia, especially for men. As a result of the gender-based differences in the results, any decision about its use in women of childbearing age should take current vaccination into account.

Impacto epidemiológico y económico de la vacunación contra el tétanos en adultos de Colombia / Epidemiological and economic impact of tetanus vaccination in Colombian adults

OBJETIVO: Evaluar el potencial impacto epidemiológico y económico de la vacunación antitetánica en la población colombiana mayor de 15 años de edad, con dosis de refuerzo cada 10 años. MÉTODOS: Se realizó un análisis de costo-efectividad de la vacunación con refuerzo cada 10 años contra el tétanos en Colombia, comparándola con la actual estrategia (2, 4, 6, 18 y 60 meses). La carga de enfermedad se estimó con base en tres fuentes oficiales de datos. Se realizó un modelo de Markov desde la perspectiva del tercer pagador. El horizonte temporal fue el tiempo de vida de una persona. Se realizaron análisis de sensibilidad determinístico y probabilístico. RESULTADOS: En Colombia se notifican anualmente entre 30 y 48 casos de tétanos que ocasionan entre 9,6 y 10,1 muertes. Si bien la vacunación con refuerzo resultó costo-efectiva para toda la población (el costo por año de vida ajustado por discapacidad [AVAD] evitado fue de US$ 11 314 en toda la población), al discriminar los resultados por género no sería costoefectiva en las mujeres (el costo por AVAD evitado en hombres fue de US$ 4 903, y en mujeres de US$ 22 332). CONCLUSIONES: Este es el primer estudio que evalúa la costo- efectividad de una dosis de refuerzo cada 10 años de la vacuna contra el tétanos en un país en desarrollo. La aplicación de esta medida sería costo-efectiva en Colombia, especialmente para los hombres. Las diferencias en los resultados por género obliga a que cualquier decisión de implementación deba tener en cuenta la vacunación actual en mujeres en edad fértil.

OBJECTIVE: Assess the potential epidemiological and economic impact of vaccinating the over-15 Colombian population against tetanus with a booster dose every 10 years. METHODS: A cost-effectiveness analysis of tetanus vaccination with a booster dose every 10 years was conducted in Colombia and compared with the current strategy (2, 4, 6, 18, and 60 months). Estimates of the burden of disease were based on three official data sources. A Markov model from the perspective of the third party payer was developed. The time horizon was the lifetime of a person. Deterministic and probabilistic sensitivity analyses were conducted. RESULTS: In Colombia, 30 to 48 cases of tetanus resulting in 9.6 to 10.1 deaths are reported each year. Although booster vaccination for the entire population was cost-effective (the cost per disability-adjusted life year [DALY] avoided was US$ 11,314 in the entire population), gender-based differentiation of the results showed that it would not be cost-effective in women (cost per DALY avoided was US$ 4,903 in men and US$ 22,332 in women). CONCLUSIONS: This is the first study that evaluates the cost-effectiveness of a tetanus vaccine booster dose every 10 years in a developing country. Use of this measure would be cost-effective in Colombia, especially for men. As a result of the gender-based differences in the results, any decision about its use in women of childbearing age should take current vaccination into account.

Financing immunization of adults in the United States.

Immunization is one of the most effective and cost-effective prevention measures available. As a result of universal vaccination of children, polio has been eliminated in the United States and much of the world, measles and rubella are no longer endemic diseases in the United States, and most of the other vaccine-preventable diseases of childhood are at or near record lows. A recent review of clinical preventive services by Partnership for Prevention gave childhood immunization a perfect score of 10, based on clinically preventable burden and cost-effectiveness.

Immunogenicity and safety of four different doses of Haemophilus influenzae type b-tetanus toxoid conjugated vaccine, combined with diphtheria-tetanus-pertussis vaccine (DTP-Hib), in Indonesian infants.

Widespread use of Haemophilus influenzae type b (Hib) conjugated vaccine in industrialized countries has resulted in a dramatic decline in the incidence of invasive Hib diseases, but the vaccine's cost has prevented its inclusion in basic immunization programs in developing countries. To overcome this problem, combination with diphtheria-tetanus-pertussis (DTP) vaccine or reduction in the dose of Hib vaccine has been proposed. To evaluate the immunogenicity and adverse reactions from lower doses of Hib-polyribosylphosphate (PRP) conjugated with tetanus toxoid (PRP-T), a double-blind study was conducted in Jakarta, Indonesia, and its suburbs. A total of 1048 infants 6 weeks to 6 months of age received three doses of DTP vaccine combined with the usual 10 microg dose or with a reduced dose of 5, 2.5 or 1.25 microg of PRP-T at two-monthly intervals. Antibodies were measured prior to the first dose and 4-6 weeks following the third dose. Adverse reactions were similar among all four groups. The only significant difference was a higher rate of irritability (p<0.02) and of temperature elevation >38 degrees C (p<0.009) after doses 1 and 2 in the lowest dose group (1.25 microg PRP-T) compared to the other groups. All participants tested had a 4-fold increase in antibodies against all DTP antigens. In addition, after a fourth booster dose of Hib, 99.6% of infants produced >or=0.15 microg/ml of antibody to Hib-PRP, and 96.4% showed levels >or=1.0 microg/ml after primary immunization, level that correlate with short- and long-term immunity, respectively. Antibody titers to the PRP antigen showed no significant differences among dosage groups with the exception of the 5.0 microg group, which had a significantly higher GMC than the 1.25 microg group (p<0.012). This study demonstrates that primary vaccination with half, one-fourth, or one-eighth of the usual dose of PRP-T, combined with DTP vaccine, produces protective immune responses, and has side effects that are comparable to DTP vaccination alone. In these lower dosages, PRP-T conjugate vaccine can lower vaccine costs to a level that is affordable for infant immunization programs in developing countries.

Replacement of the in vivo neutralisation test for efficacy demonstration of tetanus vaccines ad us. vet.

The bacterium Clostridium (C.) tetani is an ubiquitous pathogen. This anaerobic, gram-positive bacterium can form spores and can be found in the whole environment. It enters the body via injuries of the skin and wounds where it releases the neurotoxin "tetanospasmin" (= tetanus toxin). The animals most susceptible to tetanus infection are horses and sheep. Only active immunisation by tetanus vaccine provides effective protection against tetanus intoxication. The marketing authorisation requirements stipulate that efficacy of tetanus vaccines ad us. vet. must be demonstrated in all target animal species via determination of neutralising tetanus serum antitoxin concentrations. The standard method used for this purpose is still the toxin neutralisation test (TNT), as it quantifies the tetanus toxin-neutralising effect of tetanus serum antibodies in vivo. In this test, tetanus toxin is added to dilutions of serum from vaccinated horse and sheep. The serum dilutions are then administered to mice or guinea pigs, which are observed for toxic symptoms. Against the background of animal protection, the goal of one project of the Paul-Ehrlich-Institut (Bundesministerium fuer Bildung und Forschung (Federal Ministry for Education and Research), 0312636) was to establish an alternative to the toxin neutralisation test, enabling the testing of efficacy of tetanus vaccines with serological in vitro methods. For this purpose, a so-called double antigen ELISA (DAE) was established which enables the testing of sera of different species in one assay. In addition, the sera were tested in an indirect ELISA for horses and sheep separately. Altogether, ten groups of horses and eight groups of sheep were immunised with ten animals per group each. The tetanus vaccines comprised almost all products authorised for the German market at the start of the project. 564 horse sera and 257 sheep sera were tested using the two ELISA methods. Some sera were also tested in vivo. The kinetics of antibody responses were recorded. The in vitro DAE method seems to be suitable to replace the mouse neutralisation test used for the detection of tetanus antitoxin in sera of target animal species. The comparison of some sera in the ELISA and the TNT showed good equivalence of results. Nevertheless, before an ELISA titre in horse and sheep sera indicating unambiguous protection against tetanus can be fixed, further comparative assays of low titre sera in the TNT and the DAE will have to be performed.

[Function of tetanus immunoglobulin in case of injury: administration often unnecessary]. / Doelmatigheid van tetanusimmunoglobuline bij een verwonding: toediening vaak onnodig.

OBJECTIVE: To calculate the number of tetanus immunoglobulin (TIG) injections given in order to prevent one patient developing tetanus (number needed to treat (NNT)) and the accompanying costs. DESIGN: Functional study. METHOD: The risk of developing tetanus was calculated from the results of a national study on tetanus immunity in the general population of the Netherlands (1995-1996; n = 7715) and from official notifications of tetanus in the period 1984-1996 (n = 30 persons born before 1945). According to current vaccination policy TIG is advised for unvaccinated persons and those with an unclear vaccination status as well as those vaccinated more than 15 years ago. RESULTS: The tetanus risk after injury was estimated at 0.5-2 per million for unvaccinated individuals. Immunity was lowest (< 50%) in men born before 1936 and women born before 1950. The NNT for these groups was a minimum of 530.000. With a mortality of 10% and costs of 20 Euro per TIG injection, the cost of each life saved was found to be a minimum of 105 million Euro. The NNT and cost per life saved were astronomical for those persons born after 1955. CONCLUSION: The current TIG policy is inefficient. Thanks to the success of the National Immunisation Programme it is now justified to limit the administration of TIG to those who are at the highest risk i.e. those who are known to be unvaccinated, women born before 1950 and men born before 1936.

Incremental cost-effectiveness of supplementary immunization activities to prevent neonatal tetanus in Pakistan.

OBJECTIVE: This study aimed to estimate the incremental cost-effectiveness of supplementary immunization activities to prevent neonatal tetanus in the Loralai district of Pakistan. The supplemental immunization activities were carried out in two phases during 2001-03. METHODS: A state-transition model was used to estimate the effect of routine vaccination with tetanus toxoid as well as vaccination with tetanus toxoid during supplementary immunization activities. The model follows each woman in the target population from birth until the end of her childbearing years, using age-specific fertility data and vaccination history to determine the number of births at risk for neonatal tetanus. Recently published data on the incidence of neonatal tetanus from Loralai were used to determine the number of cases occurring with and without supplementary immunization activities. Data on the costs of the activities were collected from the UNICEF office in Balochistan and from the Provincial Health Department. FINDINGS: Using base-case assumptions we estimated that the supplementary immunization activities would prevent 280 cases of neonatal tetanus and 224 deaths from neonatal tetanus between 2001 and 2034. Implementation of the supplementary activities was relatively inexpensive. The cost per tetanus toxoid dose delivered was 0.40 U.S. dollars. In the base-case analysis the cost per death averted was 117.00 U.S. dollars (95% confidence interval (CI) = 78-205 U.S. dollars) and the cost per disability-adjusted life year (DALY) averted was 3.61 U.S. dollars (95% Cl = 2.43-6.39 U.S. dollars). CONCLUSION: Compared with similar analyses of other interventions, the cost per DALY averted is a favourable cost-effectiveness ratio. However, if routine diphtheria-tetanus-pertussis vaccination coverage in the Loralai district had been higher (at a coverage rate of about 80%) the cost-effectiveness of the intervention would have been even more favourable, at 2.65 U.S. dollars per DALY averted.

Standard and alternative regimens of Haemophilus influenzae type b conjugate vaccine (polyribosylribitol phosphate-tetanus toxoid conjugate vaccine) elicit comparable antibody avidities in infants.

BACKGROUND: Haemophilus influenzae type b conjugate vaccines are relatively expensive in the developing world. Previous study of the type b conjugate vaccine polyribosylribitol phosphate-tetanus toxoid conjugate vaccine showed that two dose and fractional three dose schedules elicit protective antibody concentrations equivalent to three full doses. METHODS: Antibody avidity was measured in 73 of these vaccinees with a modified enzyme-linked immunosorbent assay using NH(4) SCN as the chaotrope. Avidity index (AI) is the molarity causing a 50% reduction in OD(405). RESULTS: The postprimary series AI was similar for all dosing regimens. Preboost AI was highest in those receiving three half-doses, although there was no statistical difference among groups. Rises in avidity from age 8 to 12 months were also similar among regimens. Our data support the equivalence of anti-polyribosylribitol phosphate IgG avidity in infants primed with these alternative regimens. CONCLUSIONS: Given the known correlation of avidity with assays of bacterial killing and memory priming, these potentially more economical alternative schedules should be studied in the developing world.

Economic evaluation of use of diphtheria, tetanus, and acellular pertussis vaccine or diphtheria, tetanus, and whole-cell pertussis vaccine in the United States, 1997.

OBJECTIVE: To compare the economic costs and benefits associated with using either diphtheria and tetanus toxoids and acellular pertussis vaccine (DTaP) or diphtheria and tetanus toxoids and whole-cell pertussis vaccine (DTwP) in the United States in 1997. DESIGN: Standard cost-benefit analysis, from both the societal and health care system perspectives, was performed for each combination vaccine as well as for the pertussis components singly. SETTING: A simulated cohort of 4.1 million children from birth to age 15 years. MAIN OUTCOME MEASURES: Net costs (savings) and benefit-cost ratios (BCRs) RESULTS: Without a vaccination program, diphtheria, tetanus, and pertussis disease caused more than 3 million cases and more than 28,000 deaths, at a cost of $23.6 billion. From the societal perspective, net savings because of the use of DTaP and DTwP were $22.510 million and $22.623 million, respectively. The net savings from the acellular pertussis component and the whole-cell pertussis component only were $4.362 million and $4.474 million, respectively. Benefit-cost ratios for DTaP from a societal and health care system perspective were 27:1 and 9:1, respectively. Sensitivity analyses of key variables did not result in appreciable changes in results. CONCLUSIONS: Compared with no program, vaccination with DTaP or DTwP resulted in substantial savings, regardless of the perspective taken and for all sensitivity analyses conducted. Compared with DTwP, use of DTaP generated a small cost increase that might be offset by the value of other factors, such as increased confidence in pertussis vaccination resulting from reduced adverse events. Arch Pediatr Adolesc Med. 2000;154:797-803

[Cost of tetanus toxoid injection using a jet-injector (Imule) in collective immunization in Senegal: comparison with injection using a syringe and resterilizable needle]. / Coût de l'injection d'anatoxine tétanique par injecteur sans aiguille(Imule) lors dúne vaccination collective au Sénégal: comparaison avec l'injection par seringues et aiguilles restérilisables.

Needle-less jet injectors were developed by the US army after World War II. Their principal use, however, has been in the administration of lyophilized vaccines from multidose vials to at-risk populations in developing countries. In 1983, a hepatitis B epidemic occurred among customers of a beauty clinic in California (USA) following the use of jet-injectors, demonstrating a clear risk of cross-contamination associated with this technique. As a result, the WHO and Unicef stopped recommending jet-injectors for collective immunizations in developing countries. To eliminate the risk of contamination, Pasteur Mérieux Sérums et Vaccins (now Aventis Pasteur) developed, in 1990, jet-injectors for use with single-use vaccine cartridges. These injectors were tested for tetanus toxoid, DTP, influenza, hepatitis A and typhoid Vi vaccination. The immunogenic reaction was as strong and the injection as well tolerated as for injections using a standard needle and syringe. The additional cost of the Imule technique was evaluated in a district-wide (127,000 inhabitants) tetanus toxoid immunization program at Velingara, Senegal in 1993. The total cost was estimated to be 1.51 FF (76 F CSA, 0.32 US dollars) for one dose of tetanus vaccine given by needle and syringe and 2.41 FF (121 F CSA, 0.56 US dollars) for one dose given by Imule. Thus, the additional cost of injection by ImuleTM was 0.90 FF (45 F CSA, 0.21 US dollars). The cost of cross infection in sub-Saharan Africa has been estimated to be 2.37 FF (118 F CSA, 0.55 US dollars) per injection if injection practices are not supervised. Therefore, the Imule technique may be considered to be cost-effective. However, the technique is still not completely reliable, as shown by the total breakdown of four jet injectors during this vaccination session. Lyophilized vaccines have also not been tested in the field. Vaccinators prefer Imule, training is easy and immunization can be carried out on a day-to-day basis with no vaccine wastage. Imule is not yet in mass production, which would reduce costs. In the face of the ever-increasing risk of cross-contamination during vaccination sessions in sub-Saharan Africa, the Imule technique deserves considerable attention.

The introduction of routine Haemophilus influenzae type b conjugate vaccine in Chile: a framework for evaluating new vaccines in newly industrializing countries.

OBJECTIVE: To determine the burden of Haemophilus influenzae type b (Hib) disease, the safety and immunogenicity of Hib conjugate vaccine, the practicality of combining Hib conjugate and diphtheria-tetanus-pertussis vaccines and the effectiveness of routine vaccination. STUDY DESIGNS: A series of studies were carried out involving infants and children in Santiago, Chile. The study designs included retrospective surveillance, cost-benefit analysis, randomized placebo-controlled trials of safety and immunogenicity and a Phase IV postlicensure evaluation of vaccine effectiveness. RESULTS: The studies included in this stepwise process showed that Hib invasive disease was a significant public health problem with a substantial economic burden; that combining Hib conjugate and diphtheria-tetanus-pertussis vaccines was practical, safe and elicited a strong immunologic response; and that the combined formulation afforded a high level of protection against invasive Hib disease (90% effectiveness). CONCLUSIONS: In July, 1996, Chile became only the third newly industrializing country to introduce routine Hib conjugate vaccination. New vaccines, such as Hib conjugates, will be more expensive than existing ones. The stepwise process used in Chile may serve as an example for the evaluation of new vaccines in nonindustrialized countries.