Critical value of prevalence for vaccination programmes. The case of hepatitis A vaccination in Spain

Programmes using screening and vaccination are efficient in populations with higher levels of antibodies, while in those with lower levels is more efficient to vaccine the whole target population. The prevalence that makes the cost-effectiveness of vaccination programmes equal to that obtained for programmes using screening and vaccination is defined as the critical value of prevalence p*. In this study, a mathematical procedure to obtain the critical value of prevalence is developed. The formula obtained is used to decide the best vaccination strategy against hepatitis A in Spain. If V is the vaccination cost, S the screening cost, PV the predictive value of a positive test result, D the mean disease cost, A the attack rate in susceptible individuals, E the vaccine efficacy and C the vaccination compliance, the critical value of prevalence is equal to: [formula: see text] The critical value of prevalence obtained for vaccination against hepatitis A in Spain with three doses of vaccine Havrix 720 is 22%. This result show that the optimal decision is to implement vaccination programmes without screening for immunity in individuals aged < 15 years and with screening in those aged > 15 years.     

Economic evaluation of various hepatitis B vaccination strategies in children and adolescents

AIM: In this cost-effectiveness study 4 different vaccination strategies against hepatitis B in children and adolescents are evaluated and compared with the situation without immunization. EXAMINATION: Projections are made for the population of the today's adolescents underage 15 and the newborns of the next 30 years. The number of avoided hepatitis B virus (HBV) infections and the cases of disease as well as the costs associated with treatment and vaccination are determined. The course of incidence of the hepatitis B virus is observed for different age groups. RESULTS: Compared to the situation without any vaccination against hepatitis B, a decrease of the remaining infections of at least 18,900 up to 46,600 could be expected during the next 30 years. The treatment costs for the remaining cases of disease could be reduced by 0.4 up to 1.6 billions DM. The remaining expenditures for treatment and vaccination would be limited to 2.3 up to 3.4 billions DM. The net costs of a vaccination are determined as about 14,200 up to 63,000 DM per avoided case of infection. Considering the commonly accepted number of unreported cases of hepatitis B as to be the 5- to 10 fold of the known incidence, all of the 4 compared vaccination strategies will be cost-effective and associated with net savings of about 5,900 up to 36,400 DM per avoided case of hepatitis B virus infection during 30 years. The epidemiological situation will be positive influenced by such a mass vaccination. The minimization of incidence is shown for the different age groups. CONCLUSION: Considering these economical arguments, first the vaccination of all adolescents between age 11 to 15 and second the vaccination of all children/adolescents between age 0 to 15 are the preferable strategies. The immunization of all children/adolescents between age 0 to 15 is the most effective strategy from an epidemiological point of view.     

Cost-effectiveness of hepatitis A vaccination in healthcare workers

OBJECTIVE: To study the cost-effectiveness of vaccination for hepatitis A. SETTING: Hypothetical analysis of students currently enrolled in medical school in the United States. METHOD: A Markov-based model was developed using data from the literature, actual hospital costs, and an annual discount rate of 5%. The incidence rate was based on the lowest annual rate for the US population during the past decade. RESULTS: Over the lifetimes of students currently in medical school, the model estimated that there would be 286 hepatitis A cases with four deaths and 107 lost years of life. With routine vaccination, these numbers would decrease to 17, 0.3, and 6, respectively. The costs per life-year saved and quality adjusted life-year saved were $58,000 and $47,000, respectively. Serologic screening prior to vaccination was less cost-effective than universal vaccination. If the incidence of hepatitis A was underestimated by a factor of 5, the cost per life-year saved would decrease to $5,500. If the incidence of hepatitis was underestimated by a factor of 10, vaccination would result in a net cost savings. CONCLUSION: We conclude that the cost per life-year saved by routine hepatitis A vaccination was similar to many other standard medical modalities. For routine vaccination of medical students to be cost-saving, the incidence rate for hepatitis A must be at least 10 times higher than the rate presently reported for the general population. Serological screening prior to vaccination was not cost-effective.     

Long-term follow-up of hepatitis A vaccination in children

We conducted this follow-up study to evaluate the long-term immunogenicity of an inactivated hepatitis A vaccine in children. Ninety-six children who had seroconversion to antibody to HAV (anti-HAV) after receiving a three-dose schedule of inactivated hepatitis A vaccine were enrolled into this study. Sixty months after the initial vaccination, all vaccinees who received annual follow-up still had protective levels of anti-HAV. The geometric mean titer (GMT) of anti-HAV, peaking at month 7 (4133 mIU/mL), kept declining throughout the follow-up period. The GMTs in months 12, 24, 36, 48 and 60 were 1722, 896, 896, 645 and 403 mIU/mL, respectively. Nine of the vaccinees were hepatitis B virus carriers. Their anti-HAV titers tended to be lower than those of the remaining vaccinees at all time-points, but the difference was not significant (p > 0.05). Natural booster was noted in one vaccinee during the follow-up period. In conclusion, inactivated hepatitis A vaccine is safe and immunogenic in children, the duration of protection against HAV infection is longer than five years.     

Preventive vaccination for viral hepatitis

Viral hepatitis A-E belong to the most important infectious diseases worldwide. Viral hepatitis is highly endemic in most developing countries in Africa, South East Asia, and southern America; however also in industrialized countries as Germany hepatitis A, B and C represent a thread which should not be underestimated. In Germany, there are about 20,000 to 40,000 hepatitis A infections every year, most of them acquired abroad; about 50,000 new hepatitis B infections and about 5,000 to 8,000 infections with hepatitis C virus occur every year. About 500,000 individuals are chronic carriers of hepatitis B virus and roughly the same number is supposed to be chronically infected with hepatitis C virus. As possibilities for therapeutic intervention in chronic hepatitis B and C are still limited, immunoprophylactic measures are of particular importance. Passive and active immunization is available for hepatitis A and B but so far not for hepatitis C. Passive immunization by application of specific immunoglobulins gives protection which is effective within a few hours but is limited according to the amount of immunoglobulin to six to twelve months. Active immunization on the other hand induces a specific immune response starting after a delay of usually days or sometimes weeks but nevertheless lasting for at least several years. The combination of both methods, passive-active immunization, has the advantage of immediate protection due to the immunoglobulin which lasts until the active immunization induces an endogenous antibody production.     

Molecular epidemiology of hepatitis C in Australia

The aim of this study was to determine the distribution of hepatitis C virus (HCV) genotypes in Australian patients with hepatitis C and to identify factors associated with particular genotypes. Serum isolates of HCV-RNA were genotyped using a commercial oligonucleotide hybridization (line probe) assay. Relationships between demographic factors, mode of HCV transmission and HCV genotype were assessed by logistic regression analysis. Among 463 patients with hepatitis C, 425 tested positive for HCV-RNA and a single HCV genotype was identified in 420 cases. The patients' places of birth were Australia or New Zealand (62%), Asia (13%), Europe (12%), Mediterranean (6%), Middle East (6%) and other countries (< 1%). The most common genotypes were type 1 (52%) or type 3 (32%); type 2 (9.3%), type 4 (5.5%) and type 6 (1.7%) were less common. Patients with genotype 1b were older (48 +/- 13 years, P< 0.001) and patients with genotype 3 were younger than the remaining patients (37 +/- 11 years vs 42 +/- 12 years, P< 0.001). Among type 1 isolates, 1b was more common for patients born outside Australia compared with those born in Australia (50% vs 13%, P< 0.001) whereas non-1b subtypes were more common among Australian-born patients. Likewise, 21 of 23 (91%) patients with type 4 were from Egypt and six of seven (86%) with type 6 were from Vietnam. The relative importance of parenteral risk factors for HCV also varied according to geographic origin. Thus, a definite risk factor for HCV acquisition was identified in > 95% of Australian-born patients, but in only 33% of Asian or Mediterranean-born patients. Logistic regression analysis indicated that region of birth and risk factor (intravenous drug use or not) would allow 98% of type 4 cases and 76% of type 1b cases to be identified correctly. In summary, region of birth, patterns of migration over time and risk factors for transmission of HCV interact to determine the distribution of HCV genotypes in a multi-racial community like Australia.     

Changing epidemiology of congenital rubella syndrome in the United States

To describe clinical presentation and epidemiology of US infants with congenital rubella syndrome (CRS) and to identify missed opportunities for maternal vaccination, data from CRS cases reported to the National Congenital Rubella Syndrome Registry (NCRSR) from 1985 through 1996 were analyzed. Missed opportunities for maternal vaccination were defined as missed postpartum, premarital, and occupational opportunities, that is, times when rubella vaccination is recommended but was not given. From 1985 through 1996, 122 CRS cases were reported to the NCRSR. The most frequent CRS-related defect was congenital heart disease. Of the reported infants with CRS, 44% were Hispanic. Of 121 known missed opportunities for rubella vaccination among 94 mothers of infants with indigenous CRS, 98 (81%) were missed postpartum opportunities. CRS continues to occur in the United States. Hispanic infants have an increased risk of CRS. Missed opportunities for postpartum rubella vaccination were identified for 52% of indigenous CRS cases.     

Pertussis vaccination in the United States--new developments and recommendations

The aim was to study how three cues (patient's age and angular position and degree of impaction of the molar) were distributed among removed mandibular third molars associated with pathologic conditions and to compare these results with dentists' treatment decisions in another group of molars consisting of asymptomatic mandibular third molars, as mediated by the same cues. The overall agreement was fairly high between the dentists' treatment decisions and the removal rate among the molars subjected to removal. Thus, molars partially covered by soft tissue in patients aged 19 to 40 years had a high removal rate, and molars totally covered by bone tissue had the lowest removal rate in accordance with the dentists' treatment decisions. There were some exceptions. For example, molars partially covered by soft tissue in horizontal and mesioangular positions were rated higher by the dentists than the removal rates indicated. Distoangular molars in patients aged 26 to 40 years had the highest removal rate but a considerably lower order according to the dentists' decisions. Scientific evidence indicates that molars in mesioangular and horizontal positions present a low risk and molars in distoangular position present the highest risk of developing pathologic conditions, compared with other angular positions.     

Transmission patterns and the epidemiology of hookworm infection

BACKGROUND: This paper presents a suite of models of hookworm transmission dynamics which vary the mixing patterns and rates of contamination and infection between children and adults. In this context mixing refers to the degree of epidemiological communication between children and adults, for example, whether adults are likely to get infected from infective material passed by children. METHODS: Three models are described which represent random mixing, no mixing and restricted mixing respectively. Child, adult and population targeted chemotherapy programmes are examined and compared between these models. Data from a hookworm control programme in Zimbabwe were analysed with respect to their fit to the various models. RESULTS: The analysis suggests that some mixing does occur and that in this study location, the sites where adults deposit faeces are more likely to lead to subsequent contamination than the sites children use. CONCLUSIONS: Mixing patterns may have a profound effect on transmission dynamics and should be considered in relation to design of control programmes.     

The development of rheumatoid arthritis after recombinant hepatitis B vaccination

OBJECTIVE: Hepatitis B vaccination has been associated with reactive arthritis and rarely rheumatoid arthritis (RA). We defined the clinical, serologic, and immunogenetic background of patients developing RA, soon after recombinant hepatitis B vaccination. METHODS: The clinical, serologic, and HLA antigens of a cluster of firefighters who developed arthritis after prophylactic recombinant hepatitis B vaccination (5 subjects), as well as a second group of sporadic cases of arthritis (6 patients) after hepatitis B vaccination are described. RESULTS: Ten of 11 patients fulfilled revised American College of Rheumatology criteria for RA. All cases had persistent arthritis for more than 6 months; at 48 months followup 2 cases no longer had inflammatory arthritis. Nine patients required disease modifying antirheumatic drugs. Five subjects were HLA-DR4 positive. HLA class II genes expressing the RA shared motif were identified in 9/11 patients genotyped for HLA-DRbeta1 and DQbeta1 alleles (0401, 0101, or 0404). All the firefighters shared the HLA-DRbeta1 allele 0301 and the DQbeta1 allele 0201, with which it is in linkage disequilibrium. CONCLUSION: These polymorphic residues in the binding site of the MHC class II molecules of the affected patients appear capable of binding some peptide sequences of the recombinant vaccine peptides they received and may be responsible for hepatitis B vaccine triggering development of RA in these cases. Recombinant hepatitis B vaccine may trigger the development of RA in MHC class II genetically susceptible individuals.     

The prevalence of hepatitis A antibodies among Israeli travellers and the economic feasibility of screening before vaccination

BACKGROUND: Tuberculosis is a recognized complication following renal transplantation. Patients with autosomal dominant polycystic kidney disease are increasingly being offered renal transplantation as an alternative to chronic hemodialysis. These patients are uniquely susceptible to serious upper urinary tract infections that are associated with significant morbidity and mortality. While involvement with gram-negative organisms is well described, mycobacterial infection of native polycystic kidneys after transplantation has not been addressed. METHODS: A case report of a renal transplant recipient who suffered an isolated Mycobacterium tuberculosis infection of a native polycystic kidney and a literature review. RESULTS: Despite appropriate drug therapy, the infection proved refractory, and the patient required nephrectomy. CONCLUSIONS: Mycobacterial tuberculosis, though not common, must be recognized as a potential source of infection of native polycystic kidneys in immunocompromised transplant recipients. Similar to the pattern observed with more common pathogens, these infections may be difficult to eradicate with standard antimicrobial drug regimens.     

Varicella susceptibility and vaccination strategies in young adults

BACKGROUND: Varicella infection causes substantial morbidity in young adults. Most military basic trainees are 18 to 21 years old, yet the Army has no varicella vaccination policy. We therefore determined varicella susceptibility in a population of Army basic trainees, examined variables that might predict antibody status, and developed a vaccination strategies model. METHODS: Fifteen-hundred ninety-five trainees completed a demographic and historical questionnaire. Varicella antibody status was determined on 1201 volunteers. These data plus information from the literature were used to construct a decision tree of vaccination strategies that was applied to the total population of Army basic trainees in 1995 (n = 65,298). RESULTS: Fifty (4.2 percent) of 1201 soldiers were antibody negative. Trainees who lived with no or 1 sibling while growing up were most likely to be seronegative (P < 0.01). The positive predictive value of a history of varicella was 98.5 percent, whereas the negative predictive value of a negative history of varicella was 23 percent. In the vaccination strategies model, serologically testing soldiers with a negative history of varicella and vaccinating those without protective antibodies was the most cost-effective approach. CONCLUSIONS: In young adults a positive varicella history accurately predicts immunity, but verification of a negative history with antibody testing is recommended before vaccination.     

Abdominal hysterectomy practice patterns in the United States

Diets rich in polyunsaturated fatty acids (PUFA) are well known to suppress hepatic lipogenic enzymes compared to fat-free diets or diets rich in saturated fatty acids. However, the mechanism underlying suppression of lipogenic enzymes is not quite clear. The present study was undertaken to investigate whether lipid peroxidation products are involved in suppression of lipogenic enzymes. Therefore, an experiment with growing male rats assigned to six groups over a period of 40 d was carried out. Rats received semisynthetic diets containing 9.5% coconut oil and 0.5% fresh soybean oil (coconut oil diet, peroxide value 5.1 meq O2/kg oil), 10% fresh soybean oil (fresh soybean oil diet, peroxide value 9.5 meq O2/kg oil), or 10% thermally treated soybean oil (oxidized soybean oil diet, peroxide value 74 meq O2/kg oil). To modify the antioxidant state of the rats, we varied the vitamin E supply (11 and 511 mg alpha-tocopherol equivalents per kg of diet) according to a bi-factorial design. Food intake and body weight gain were not influenced by dietary fat and vitamin E supply. Activities of hepatic lipogenic enzymes were markedly influenced by the dietary fat. Feeding either fresh or oxidized soybean oil diets markedly reduced activities of fatty acid synthase, (FAS), acetyl CoA-carboxylase, (AcCX), glucose-6-phosphate dehydrogenase, (G6PDH), 6-phosphogluconate dehydrogenase, and ATP citrate lyase (ACL) relative to feeding the coconut oil diet. Moreover, feeding oxidized soybean oil slightly, but significantly, lowered activities of FAS, AcCX, and ACL compared to feeding fresh soybean oil. Activities of hepatic lipogenic enzymes were reflected by concentrations of triglycerides in liver and plasma. Rats fed the coconut oil diet had markedly higher triglyceride concentrations in liver and plasma than rats consuming fresh or oxidized soybean oil diets, and rats fed oxidized soybean oil had lower concentrations than rats fed fresh soybean oil. The vitamin E supply of the rats markedly influenced concentrations of thiobarbituric acid-reactive substances in liver, but it did not influence activities of hepatic lipogenic enzymes. Because the vitamin E supply had no effect, and ingestion of an oxidized oil had only a minor effect, on activities of hepatic lipogenic enzymes, it is strongly suggested that neither exogenous nor endogenous lipid peroxidation products play a significant role in the suppression of hepatic lipogenic enzymes by diets rich in PUFA. Therefore, we assumed that dietary PUFA themselves are involved in regulation of hepatic lipogenic enzymes. Nevertheless, the study shows that ingestion of oxidized oils, regardless of the vitamin E supply, also affects hepatic lipogenesis, and hence influences triglyceride levels in liver and plasma.     

Immunogenicity of an inactivated hepatitis A vaccine in Dutch United Nations troops

Limited information existed on the immunogenicity of an inactivated hepatitis A vaccine as part of an extensive vaccination schedule. Dutch marines bound for duty in Cambodia received inactivated hepatitis A vaccine (720 ELISA units of antigen, two intra-gluteal doses at a 2-week interval before departure and an intra-deltoid booster vaccination after 8 months) simultaneously with several other vaccines. Hepatitis A antibodies were determined in blood-samples drawn before and after the booster vaccination, using two laboratory tests (modified HAVAB and SBB-ELISA). At 8 months, before the booster vaccination, 52% (modified HAVAB) and 81% (SBB-ELISA) had seroconverted. Risk factors for non-seroconversion were increasing age and a typhoid vaccination. At 11 months 97.6% (modified HAVAB) and 100% (SBB-ELISA) had seroconverted. Non-seroconversion at 8 months was remarkably high. SBB-ELISA was more sensitive in lower titre ranges.