How well are we performing the initial assessment of HIV-positive patients? Results from a multicentre cohort in Spain.

OBJECTIVES: The aim of this study was to evaluate adherence to the recommendations of the Spanish guidelines for the initial assessment of patients with HIV infection in the multicentre Cohort of the Spanish HIV/AIDS Network (CoRIS) during the years 2004-2017. METHODS: We calculated the percentage of patients who had each of 11 clinical and analytical recommended examinations performed in their initial evaluation. We evaluated the factors associated with not performing each examination with multivariable logistic regression models. RESULTS: We included 13 612 patients in the study. In the initial assessment, CD4 count and viral load were determined in more than 98.0% of the patients. Serologies for hepatitis A, B and C and syphilis were determined in 55.8%, 66.4%, 89.8% and 81.7% of the patients, respectively. Total cholesterol and creatinine were determined in 78.7% and 78.9% of the patients, respectively. The lowest proportions of examinations were observed for blood pressure, smoking status and latent tuberculosis screening, which were performed in 43.2%, 50.6% and 53.9% of the patients, respectively. Injecting drug users and heterosexual patients (compared to men who have sex with men) and patients with a lower educational level had a higher risk of having an incomplete initial assessment for a substantial number of examinations. Latent tuberculosis screening was less likely in patients with CD4 counts < 200 cells/µL. CONCLUSIONS: The initial assessment of HIV-infected patients is suboptimal for the evaluation of cardiovascular risk, smoking status, screening of syphilis and viral hepatitis, and diagnosis of latent tuberculosis: adherence to the guidelines was low for these examinations.

Billing and payment of commercial and Medicaid health plan adult vaccination claims in Michigan since the Affordable Care Act.

BACKGROUND: Provider concern regarding insurance non-payment for vaccines is a common barrier to provision of adult immunizations. We examined current adult vaccination billing and payment associated with two managed care populations to identify reasons for non-payment of immunization insurance claims. METHODS: We assessed administrative data from 2014 to 2015 from Blue Care Network of Michigan, a nonprofit health maintenance organization, and Blue Cross Complete of Michigan, a Medicaid managed care plan, to determine rates of and reasons for non-payment of adult vaccination claims across patient-care settings, insurance plans, and vaccine types. We compared commercial and Medicaid payment rates to Medicare payment rates and examined patient cost sharing. RESULTS: Pharmacy-submitted claims for adult vaccine doses were almost always paid (commercial 98.5%; Medicaid 100%). As the physician office accounted for the clear majority (79% commercial; 69% Medicaid) of medical (non-pharmacy) vaccination services, we limited further analyses of both commercial and Medicaid medical claims to the physician office setting. In the physician office setting, rates of payment were high with commercial rates of payment (97.9%) greater than Medicaid rates (91.6%). Reasons for non-payment varied, but generally related to the complexity of adult vaccine recommendations (patient diagnosis does not match recommendations) or insurance coverage (complex contracts, multiple insurance payers). Vaccine administration services were also generally paid. Commercial health plan payments were greater for both vaccine dose and vaccine administration than Medicare payments; Medicaid paid a higher amount for the vaccine dose, but less for vaccine administration than Medicare. Patients generally had very low (commercial) or no (Medicaid) cost-sharing for vaccination. CONCLUSIONS: Adult vaccine dose claims were usually paid. Medicaid generally had higher rates of non-payment than commercial insurance.

Age-stratified anti-HAV positivity in Pune, India after two decades: Has voluntary vaccination impacted overall exposure to HAV?

The degree of transmission of hepatitis A virus (HAV) is inversely proportional to the socioeconomic status of a community. Serosurveys conducted at Pune, India during 1982-98 documented significant reduction in HAV exposure of paediatric, higher socioeconomic status (HSS) population. Anti-HAV positivity (ELISA) in age-stratified Pune population representing HSS and lower middle socioeconomic status (LMSS) (n = 1065) and infants till the age of 15 months (n = 690) was determined in 2017. Anti-HAV positivity in the LMSS population decreased significantly in 2017 while an increase was seen in the HSS category. The surprising rise in anti-HAV positivity in the HSS population reflected vaccine- and infection-induced antibodies while only infection-induced antibodies were present in the LMSS category. Lowest antibody prevalence in infants was at 12 months, the recommended age for hepatitis A vaccination. Improved hygiene and selective immunization practices impacted HAV exposure of the LMSS population. The data emphasize the need for hepatitis A vaccination irrespective of socioeconomic status.

Initiation and completion rates of inactivated hepatitis A vaccination among children born between 2005 and 2014 in Zhejiang province, east China.

OBJECTIVES: To evaluate the initiation and completion and timeliness of inactivated hepatitis A vaccine (HAV-I) series, to identify the missed opportunities for HAV-I series, and to examine determinants associated with the completion of HAV-I. METHODS: Children born from 1 January 2005 to 31 December 2014 and registered in Zhejiang provincial immunization information system (ZJIIS), were enrolled in this study. Descriptive statistics were used to describe the initiation and completion, the timeliness and the missed opportunities for HAV-I. Logistic regression analysis was applied to explore the determinants of the completeness of HAV-I. RESULTS: The initiation rate of HAV-I increased from 8.1% for the 2005 birth cohort to 13.2% for the 2014 birth cohort. The completion rate of HAV-I increased from 4.2% for the 2005 birth cohort to 7.8% for the 2014 birth cohort. The timeliness rate of the 1st dose of HAV-I increased from 38.2% for the 2005 birth cohort to 57.9% for the 2014 birth cohort. The timeliness rate the 2nd dose of HAV-I increased from 17.3% for the 2005 birth cohort to 35.3% for the 2014 birth cohort. 78.3% of the children who did not initiated any hepatitis A vaccine, had at least one immunization clinic visit after their 18th month of age. 36.0% of the children who received the 1st dose of HAV-I but did not receive the 2nd dose, had at least one immunization clinic visit after 6 months from the date of receiving the 1st dose of HAV-I. The determinants including year of birth, socio-economic development level of municipals, place of delivery, receipt of MMR/VarV were associated with the completion of HAV-I series. CONCLUSION: Although the initiation and completion of HAV-I series had improved in recent years, these indicators were still lower than those for other vaccines scheduled at the similar age. It is important for providers to identify every opportunity for HAV-I vaccination and to assure that children get protection from this vaccine-preventable disease.

Considerations on the current universal vaccination policy against hepatitis A in Greece after recent outbreaks.

Greece is the only European Union member state that in 2008 included hepatitis A (HAV) vaccine in the routine national childhood immunization program (NCIP). Given that the resources allocated to public health have dramatically decreased since 2008 and that Greece is a low endemicity country for the disease, the benefit from universal vaccination has been questioned. The aim of this paper is to summarize the available epidemiological data of the disease for 1982-2013, and discuss the effects of universal vaccination on disease morbidity. Descriptive analysis, ARIMA modeling and time series intervention analysis were conducted using surveillance data of acute HAV. A decreasing trend of HAV notification rate over the years was identified (p<0.001). However, universal vaccination (~ 80% vaccine coverage of children) had no significant effect on the annual number of reported cases (p = 0.261) and has resulted to a progressive increase of the average age of infection in the general population. The mean age of cases before the inclusion of the vaccine to NCIP (24.1 years, SD = 1.5) was significantly lower than the mean age of cases after 2008 (31.7 years, SD = 2.1) (p<0.001). In the last decade, one third of all reported cases were Roma (a population accounting for 1.5% of the country's total population) and in 2013 three outbreaks with 16, 9 and 25 Roma cases respectively, were recorded, indicating the decreased effectiveness of the current immunization strategy in this group. Data suggest that universal vaccination may need to be re-considered. Probably a more cost effective approach would be to implement a program that will include: a) vaccination of high risk groups, b) universal vaccination of Roma children and improving conditions at Roma camps, c) education of the population and travel advice, and d) enhancement of the control measures to increase safety of shellfish and other foods.

Seroprevalence of hepatitis A virus in a cross-sectional study in Mexico: Implications for hepatitis A vaccination.

Hepatitis A virus (HAV) remains a public health concern worldwide contributing to significant morbidity in developed and developing countries. This cross-sectional database study estimated the overall HAV seroprevalence and the seroprevalence by gender, age, region and socioeconomic status in Mexico. Between January and October 2010, serum samples collected during the National Health and Nutrition survey (ENSANUT 2006) were obtained from subjects aged 1-95 y. Subjects' gender, age, geographical region and socioeconomic status were extracted from the survey and compiled into a subset database by the Mexican National Institute of Public Health. Anti-HAV antibodies were measured using a chemiluminescent immunoassay. A total of 3658 subjects were included in the according-to-protocol cohort. Overall, the HAV seroprevalence was 84.2%. The HAV seroprevalence rates were similar between females (86.1%) and males (82.2%). The percentage of subjects seropositive for anti-HAV antibodies was highest in adults aged ≥ 20 y (96.9%), followed by adolescents aged 10-19 y (80.1%) and lowest in children aged 1-9 y (45.0%) (p < 0.0001). Regionally, the highest HAV seroprevalence rate was observed in the South (88.8%) followed by Central and Northern Mexico and Mexico City (p = 0.02). The HAV seroprevalence was similar between subjects of high socioeconomic (90.1%) status and of low socioeconomic status (86.6%). This study confirms the intermediate HAV endemicity in Mexico. Cost-effectiveness studies are necessary to evaluate the inclusion of an effective hepatitis A vaccine from a population-based perspective in addition to continuous efforts to improve hygiene and sanitation that have a substantial impact on the disease burden.

Prevalence of leptospira in acute hepatitis syndrome and assessment of IL-8 and TNF-alpha level in leptospiral hepatitis.

To study the prevalence of leptospira in acute hepatitis syndrome and to assess interleukin (IL)-8 and tumour necrosis factor (TNF)-alpha levels in the pathogenesis of hepatitis due to leptospiral infection. Two hundred and forty-seven consecutive cases with symptoms of acute hepatitis and 30 healthy controls were enrolled in the study and detailed clinical history was elicited from them. Enzyme-linked immunosorbent assays (ELISAs) for HAV, HBV, HCV and HEV were performed to rule out common viral aetiology of hepatitis. IgM antibodies to leptospira were detected by ELISA. IL-8 and TNF-alpha levels were estimated in leptospira-positive cases and healthy controls by ELISA. Out of 247 cases of acute hepatitis, 46 (18.62%) were observed to be positive for IgM antibodies for leptospira. The mean age of these patients was 31.99 ± 0.28 years (25 males and 21 females; M/F ratio: 1.19:1). The mean ALT, AST and ASP were raised in the majority of patients. IL-8 was found to be elevated (130.81 pg/ml) in a large majority of cases 41/46, 89.1% (P < 0.001). Patients with more severe symptoms were associated with higher levels of IL-8. One mortality was observed due to leptospira. Unpredictably, TNF-alpha level was largely suppressed (45.63 pg/ml) in most of the leptospira-positive patients in comparison with healthy controls. Leptospira-induced hepatitis should be actively looked for in patients negative for A-E viral hepatitis. IL-8 appears to play an important role in the pathogenesis of leptospiral hepatitis. High TNF-alpha should alert clinicians for aggressive in hospital management of patients.

[Assessment of effectiveness and immunogenicity of hepatitis A vaccination in servicemen of Internal Forces of Ministry of Internal Affairs of Russia].

AIM: Comarative assessment of immunological and epidemiological effectiveness of hepatitis A vaccination and duration of immunity after immunization in servicemen. MATERIALS AND METHODS: During 1996-2003, immunogenicity and epidemiologic effectiveness of 3 vaccines against hepatitis A--Havrix 1440 (GlaxoSmithKline, Belgium), Hep-A-in-Vac (Chumakov Institute of Poliomyelitis and Viral Encephalitides, Russia), and Avaxim (Sanofi Pasteur, France)--were evaluated. More than 15,000 servicemen were immunized during that time. In all cases one-dose vaccination without booster was performed. RESULTS: Several cases of acute hepatitis A were registered 12 months and 6-8 months after vaccination in military communities immunized with Havrix 1440 and Hep-A-in-Vac vaccines respectively. Usage of Avaxim vaccine as a single dose in field trials allowed to exclude new cases of acute hepatitis A during time of military service. It was shown that 5 years after single vaccination with Avaxim protective anti-HAV antibody level (20 IU/l) persisted in 90% of Internal Forces servicemen. CONCLUSION: On the basis of performed complex of studies, system of antiepidemic measures was developed, which leads to decrease of hepatitis A incidence. Selective immunization is proposed.

Evidence of vaccine protection among thai medical students and implications for occupational health.

In a cross-sectional study of Thai medical students, we compared the seroprevalence of antibody to measles virus, rubella virus, varicella zoster virus, hepatitis A virus, and hepatitis B virus with self-reports of prior infection or vaccination. Self-report predicted immunity to varicella zoster virus only. These data contribute to risk assessment and occupational health strategies in this resource-limited setting.

Decline in the risk of hepatitis A virus infection in China, a country with booming economy and changing lifestyles.

The objective of the study was to identify the protective factors for the rapid decline in the risk of hepatitis A virus (HAV) infection in China between 1990 and 2006. Results of serological follow-up and data on annual hepatitis A incidence were analysed and correlated with economic growth and HAV vaccine output during the same period. In conclusion, both HAV vaccination and changing lifestyles associated with the booming economy contributed to the rapid risk decline. Changing lifestyles played a major role in the decline especially in the areas with booming economy.

Seroprevalence of hepatitis A virus antibodies among a sample of Egyptian children.

We determined the seroprevalence of hepatitis A virus antibodies (HAV Ab) among 296 Egyptian children aged 2.5-18 years of different social classes to ascertain whether to give HAV vaccine early in life or to leave children to acquire natural immunity. Overall 61.4% were seropositive for HAV Ab. There was a significant increase in the seroprevalence of HAV Ab with higher age and lower social class; in children aged < 6 years, 72.7% of high and 19.0% of low social class were seronegative for HAV Ab. A national vaccination programme for HAV is not a priority. We recommend vaccination against hepatitis A for high social class children at the preschool period without testing for HAV. Vaccination for middle social class children can be done, but only after testing for HAV.

[Is it necessary to investigate anti-hepatitis A virus (HAV) IgM antibodies when the hepatic enzymogram is normal?]. / Es necesario investigar anticuerpos IgM contra el virus de la hepatitis A cuando el enzimograma hepático es normal?

Is it necessary to investigate anti-hepatitis A virus (HAV) IgM antibodies when the hepatic enzymogram is normal? Type A viral Hepatitis (HAV) is the most frequent viral hepatitis around the world, especially in low income countries. In order to confirm this disease, a lot of laboratory tests are annually carried out where HAV is endemic. Our objective was to establish the utility of investigating anti-hepatitis A virus (HAV) IgM antibodies for HAV diagnosis in patients with normal levels of serum aspartate and alanine aminotransferases (AST/ALT). All patients (n = 158) received in the laboratory requesting a hepatic enzymograme and anti-HAV IgM were evaluated in a prospective study between October 2005 and March 2006. Anti-HAV IgM assays were carried out by microparticle enzyme immunoassay (MEIA). The quantification of hepatic enzymes was made in a multianalyzer. The most frequent clinical data were: presumption of hepatitis and jaundice (27.5 and 12.7%). Eighty four of the 158 patients (53%) showed elevated values of ALT and AST, whereas 69 patients in this group (82%) were anti-Hav IgM reactive. The remaining 74 patients (47%) showed normal levels of AST/ALT and none of them were anti-HAV IgM reactive, except 7, who were on control of a confirmed HAV infection. Of the anti-HAV IgM reactive group of patientss, 49% were children under 10 years of age. Laboratory HAV confirmatory tests would have to be made in sequential form, the determination of anti-HAV IgM antibodies being unnecessary when normal values of serum aminotransferases are observed.

The shifting epidemiology of hepatitis A following routine childhood immunization program in Israel.

OBJECTIVES: In 1999 Israel became the first country to introduce immunization against hepatitis A to its national childhood vaccination program. The study objectives were to assess the uptake of hepatitis A vaccine following the new policy and to examine the incidence of hepatitis A and the number of prevented cases. METHODS: Data on incidence of hepatitis A and vaccination rates were obtained from a large health maintenance organization in Israel covering 1.6 million members. We identified all members that were diagnosed by a primary care physician as suffering from hepatitis A, had a positive hepatitis A virus-IgM test result, or were hospitalized due to hepatitis A between 1998 and 2004. RESULTS: The results indicate that 5 years following its inclusion in the national childhood immunization program, vaccination coverage levels with at least one dose of hepatitis A vaccine for children aged under 5 years and 5-14 years were 87% and 51%, respectively. During this period the annual incidence rates declined by 88% from 142.4 to 17.3 per 100,000. The most significant reduction in morbidity was observed among children. CONCLUSIONS: In endemic areas, vaccination of infants and children against hepatitis A may be efficient to greatly reduce the total burden of the disease.

Hepatitis A vaccination in chronic liver disease: is it really required in a tropical country like India?

Vaccination against hepatitis A virus (HAV) has been recommended in patients with chronic liver disease to prevent any decompensation due to superinfection. This may not hold good in high endemic areas for hepatitis A like India. The aim of this study was to find out the seroprevalence of anti-HAV antibodies in patients with chronic liver disease and to justify the need for vaccination against hepatitis A virus in these patients. One hundred and thirty three consecutive patients with cirrhosis of liver attending Gastroenterology department of our Institute between June 2004 and June 2005 were enrolled. Seventy-five healthy persons were taken as controls. The diagnosis of cirrhosis was based on clinical profile, biochemical, radiological (ultrasound abdomen) and endoscopic findings. The etiology of cirrhosis was based on presence of viral markers, history of significant alcohol consumption, autoimmune and metabolic workup. All patients and controls were tested for antiHAV (total) antibodies using commercially available enzyme-linked immunosorbent assay kits. Data from patients and control group were compared by unpaired 't' test and Chi square test. All subjects were in the age group 11 to 75 years. Etiology of chronic liver disease was as follows: HBV- 29.3%, HCV - 14.28%, HBV+HCV dual -1.5%, alcohol- 21.8%, Cryptogenic -23.3%, Wilson"s Disease -1.5% and Budd chiari -1.5%. The prevalence of HAV was 93.2% in patients with cirrhosis of liver and 94.6% in controls. The prevalence was almost similar irrespective of the etiology. In view of high seroprevalence of HAV antibodies among cirrhotic patients in our study and the high cost of the vaccine, the hepatitis A vaccination may not be routinely required in this part of the world.

The economics of routine childhood hepatitis A immunization in the United States: the impact of herd immunity.

OBJECTIVES: Because of the herd-immunity phenomenon, the benefits of immunization against hepatitis A extend beyond those received by those who are vaccinated. This analysis estimates the impact of herd immunity on the cost-effectiveness of routine hepatitis A immunization among US children. PATIENTS AND METHODS: In an economic model, the costs and benefits of hepatitis A immunization were estimated for immunizing all US children at age 1 year over a 10-year period starting in 2005. The future burden of disease from hepatitis A was also estimated with this model, and the fraction that would be prevented by herd immunity was modeled by using a previously published analysis of the relationship between hepatitis A vaccination coverage and declines in hepatitis A incidence. RESULTS: Without accounting for herd-immunity effects, the costs of routine immunization would average 32,000 dollars per quality-adjusted life-year gained for the first 10 cohorts immunized starting with the 2005 birth cohort. Herd-immunity effects would be expected to produce substantial additional benefits, lowering the cost of the immunization program to 1000 dollars per quality-adjusted life-year gained for the first 10 cohorts. Herd-immunity benefits would be greatest for the first few cohorts, more than doubling the benefits of immunization, and would decline over time. In a univariate sensitivity analysis, estimates were most sensitive to vaccination costs but remained below 20,000 dollars per quality-adjusted life-year under all of the assumptions. CONCLUSIONS: Herd-immunity effects more than double the savings from hepatitis A immunization during the first 10 years of the program. After accounting for these effects, immunization is close to cost-neutral on a cost-per-quality-adjusted-life-year basis.

Seroprevalence of hepatitis A among children of different socioeconomic status in Cairo.

To determine seroprevalence of anti-hepatitis A virus (HAV) antibodies and potential risk factors for and age of contracting symptomatic hepatitis A infection among children of different socioeconomic status (SES) in Cairo, we carried out a cross-sectional study on 426 children aged 3-18 years from low SES areas and 142 from high SES areas. Seroprevalence was significantly higher with age. Seropositivity to anti-HAV antibodies was significantly higher among children of low and very low SES, 90%, compared to children of high SES, 50%. Water supply and sewage disposal were the most significant risk factors for HAV seropositivity in children of low SES. Children of high SES were more likely to be vulnerable to infection in adolescence than those of low SES.

[Hepatitis A and E virus antibodies in Chilean children of low socioeconomic status: a one year follow-up study]. / Seguimientos de anticuerpos contra hepatitis A y E en una cohorte de niños de bajo nivel socioeconómico.

BACKGROUND: The seroprevalence of antibodies against hepatitis A virus (HAV) is decreasing in many Latin American countries, along with improvements in sanitary standards. However, there is no information available about low socioeconomic status (LSE) populations. AIM: To assess the evolution of hepatitis A and E virus antibodies in a cohort of LSE Chilean children. MATERIAL AND METHODS: One hundred sixty eight children aged four years, 97 males, coming from public primary care clinics, were studied. Two blood samples were obtained with an interval of one year. Anti-HAV and anti-hepatitis E virus (HEV) antibodies, were detected by ELISA using Abbott kits. RESULTS: Anti-HAV was positive in 19 children (11.3%). After one year of follow-up, only 10 children had sustained reactivity (52.6%). Fourteen children, initially negative, became positive during the follow up (9.4%). Antibody titers to HAV were significantly higher in samples that remained positive, compared with those that lost reactivity. Anti-HEV was found positive in two children (1.2%). One remained positive and the other became negative. CONCLUSIONS: In this cohort of LSE Chilean children, the prevalence to antibodies against HAV and HEV is low. Follow-up detected loss of reactivity to HAV in nearly one half of the children, probably related to lower antibody levels.

Hepatitis A virus: from discovery to vaccines.

Hepatitis A virus (HAV), the causative agent of type A viral hepatitis, is an ancient human virus that was first identified almost 35 years ago. It has several characteristics that make it unique among the Picornaviridae, particularly in terms of its mechanisms of polyprotein processing and virion morphogenesis, and which likely contribute to its pathobiology. Although efficacious vaccines containing formalin-inactivated virus produced in cell culture have been licensed in multiple countries, their use has been limited by cost considerations. Changes in public health sanitation and generally increasing standards of living are leading to a decreasing incidence of acute hepatitis A worldwide, with the result that the prevalence of preexisting immunity among adults is declining in many regions. These changes in the epidemiology of HAV may paradoxically enhance the disease burden, as greater numbers of individuals become infected at older ages when disease is more likely to be clinically evident, thus providing greater incentives for vaccine utilization.