Lower Seroconversion Rates Research Articles

Decline in HIV-1 seroprevalence and low seroconversion rate among injecting drug users at a methadone maintenance program in New York City.

To monitor the trend of HIV-1 seroprevalence, 2,194 newly admitted injecting drug users (IDUs) in a methadone maintenance program in New York City were tested from June 1988 through June 1992. This was a blinded study and unlabeled blood specimens were collected during the required physical examination. There was a significant linear trend (p = .01) toward decline in HIV-1 seropositivity by year of admission as follows: 47.0% in 1988, 43.4% in 1989, 43.2% in 1990, 39.8% in 1991, and 39.1% in 1992. From January 1988 through December 1992, admissions data that included the newly admitted IDUs showed a significant decrease (p < .0002) in self-reported current needle sharing from 11.3% to 5.4%. These two data sources suggest that a continued decline in HIV-1 seroprevalence among new admissions may be related to decreased needle sharing. A volunteer cohort of 235 HIV-1 seronegative IDUs was also enrolled from April 1990 through June 1991 in a study of HIV-1 seroconversion. Follow-up data were available on 177 patients for up to 12 months. For a total observation time of 155 person-years, there were two conversions (1.3 conversions per 100 person-years). A continued decline in HIV-1 seroprevalence among new admissions and a low HIV-1 seroconversion rate among existing patients have contributed to a lower overall HIV-1 prevalence in clinic patients of about 40%. This stands in contrast to 1985-86 estimates of HIV-1 seroprevalence that plateaued at 60%.

Evaluation of a chimpanzee colony for antibodies to hepatitis C virus

The chimpanzee is the only species other than man that is generally susceptible to infection by hepatitis C virus (HCV). Aspects of future studies on vaccines and therapeutics for HCV may continue to depend on the chimpanzee. In an attempt to determine the HCV status of the animals in a chimpanzee colony, the recently developed enzyme immunoassay (EIA) for antibodies to HCV was used. The results of the assay indicated that only 31.3% of the animals that had previously been inoculated with a non-A, non-B hepatitis agent were currently positive in the assay. A retrospective analysis suggested that an additional 20% of the chimpanzees had been positive at some time following infection. Seroconversion to an anti-HCV antibody response using this assay did not appear to correlate with the severity of the initial disease or the development of chronic liver damage. Examination of the EIA-positive samples using the second generation recombinant immunoblot assay (RIBA) containing four HCV antigens suggested that chimpanzees responded differentially to these antigens. Examination of serum samples from 139 uninoculated animals by EIA revealed seven positive samples and ten samples with borderline values. The nature of the reactivities in most of the positive samples could not be resolved, but analysis by RIBA indicated that at least one animal in the breeder colony had been exposed to HCV. Due to the low seroconversion rate and the uncertainties surrounding many of the positive reactions, this assay cannot be used to determine the initial source or extent of spread of HCV infections in the uninoculated animals.

Evidence of marked sexual behavior change associated with low HIV-1 seroconversion in 149 married couples with discordant HIV-1 serostatus

To determine the effect of an HIV-1 counselling program on 149 married Zairian couples with discordant HIV-1 serology, the rates of HIV-1 seroconversion and reported condom utilization have been observed during 382.4 person-years of follow-up (minimum follow-up time per couple of 6 months). Before determination of HIV-1 serostatus and counselling, less than 5% of these couples had ever used a condom. One month after notification of HIV-1 serostatus and counselling, 70.7% of couples reported using condoms during all episodes of sexual intercourse. At 18 months follow-up, 77.4% of the 140 couples still being followed reported continued use of condoms during all episodes of sexual intercourse. At the time of notification of HIV-1 serostatus, 18 couples experienced acute psychological distress. Home-based counselling by trained nurses resolved these difficulties in all but three couples who subsequently divorced. Intensive counselling following notification of HIV-1 serostatus led to low rates of HIV-1 seroconversion (3.1% per 100 person-years of observation) in Zairian married couples with discordant HIV-1 serostatus who voluntarily attended an HIV counselling center.

Immunogenicity and reactogenicity of rhesus rotavirus vaccine given in combination with oral or inactivated poliovirus vaccines and diphtheria-tetanus-pertussis vaccine

Immunogenicity and reactogenicity of the oral rhesus rotavirus vaccine (RRV) were assessed among 72 infants (6 weeks old) in Lahore, Pakistan, from August to December 1985. Special emphasis was placed on the possible interaction or interference caused by giving RRV at the time infants received their first polio immunization. RRV was given to the infants at the same time as diphtheria-tetanus-pertussis (DTP), oral poliovirus vaccine (OPV), or inactivated poliovirus vaccine (IPV). The immune response to RRV was assessed by plaque-reduction neutralization 3 weeks after immunization and serum immunoglobulin (Ig) G and IgA antibody levels to poliovirus type 1 were tested by enzyme-linked immunosorbent assay (ELISA) after polio immunizations. Of the infants in the group given RRV with OPV, 50% had a two- to four-fold rise in neutralization titre against rotavirus, compared with 22% in the group given RRV with DTP and 20% in the group given RRV and IPV ( P < 0·05). Interference by live oral polio vaccination in the response to RRV seems unlikely. We observed no significant difference in rates of seroconversion of IgG antibodies to poliovirus type 1 among infants aged 18 and 21 weeks who received RRV and OPV (81%), RRV with delayed OPV (67%), or RRV and IPV (59%). Administration of RRV was safe and was not associated with adverse reactions in the 6 weeks old infants. The low rate of seroconversion to rotavirus suggests that a more antigen-rich vaccine or multiple doses of the same vaccine might produce a better immune response.

Intradermal vs Intramuscular Hepatitis B Vaccinations-Reply

In Reply.— We applaud the well-designed study by Wistrom et al that demonstrates that low-dose ID inoculation of adults with three 2-μg doses of a recombinant hepatitis B vaccine (Recombivax-HB, Merck Sharp & Dohme) results in lower seroconversion rates and reduced levels of antibody to HBsAg compared with three 10-μg IM injections of the same product. These results are not unexpected. There is a positive correlation between dose and immune response regardless of the type of product used. 1 In our ID study we were able to use the more immunogenic plasma-derived Hepta

Modification of the immune response against hepatitis B virus by the human immunodeficiency virus

Hepatitis B virus and the human immunodeficiency virus are similarly transmitted. Individuals with preexisting HIV infection have a higher chance to become HBsAg carriers than do anti-HIV negative persons. Cytotoxic T cells with specificity for HBcAg, that are under the control of HBcAg-specific helper T cells, are responsible for liver injury. There is good evidence that HIV infection lowers inflammatory activity, is associated with milder liver histology, high levels of viral replication and low seroconversion rates. In addition interferon alpha therapy is less effective in anti-HIV positive subjects. The immune response against HBsAg is helper T-cell dependent and vaccination against hepatitis B is of low effectiveness. In addition, vaccination against hepatitis B may activate the HIV disease and is, therefore, presently not to be recommended.

Endocrine Genes: Analytical Methods, Experimental Approaches, and Selected Systems

<h3>ABSTRACT</h3> <h3>Background</h3> Epidemiologic risk factors for incident SARS-CoV-2 infection as determined via prospective cohort studies greatly augment and complement information from case-based surveillance and cross-sectional seroprevalence surveys. <h3>Methods</h3> We estimated the incidence of SARS-CoV-2 infection and risk factors in a well-characterized, national prospective cohort of 6,738 U.S. adults, enrolled March-August 2020, a subset of whom (n=4,510) underwent repeat serologic testing between May 2020 and January 2021. We examined the crude associations of sociodemographic factors, epidemiologic risk factors, and county-level community transmission with the incidence of seroconversion. In multivariable Poisson models we examined the association of social distancing and a composite score of several epidemiologic risk factors with the rate of seroconversion. <h3>Findings</h3> Among the 4,510 individuals with at least one serologic test, 323 (7.3%, 95% confidence interval [CI] 6.5%-8.1%) seroconverted by January 2021. Among 3,422 participants seronegative in May-September 2020 and tested during November 2020-January 2021, we observed 161 seroconversions over 1,646 person-years of follow-up (incidence rate of 9.8 per 100 person-years [95%CI 8.3-11.5]). In adjusted models, participants who reported always or sometimes social distancing with people they knew (IRR_{always vs. never} 0.43, 95%CI 0.21-1.0; IRR_{sometimes vs. never} 0.47, 95%CI 0.22-1.2) and people they did not know (IRR_{always vs. never} 0.64, 95%CI 0.39-1.1; IRR_{sometimes vs. never} 0.60, 95%CI 0.38-0.97) had lower rates of seroconversion. The rate of seroconversion increased across tertiles of the composite score of epidemiologic risk (IRR_{medium vs. low} 1.5, 95%CI 0.92-2.4; IRR_{high vs. low} 3.0, 95%CI 2.0-4.6). Among the 161 observed seroconversions, 28% reported no symptoms of COVID-like illness (i.e., were asymptomatic), and 27% reported a positive SARS-CoV-2 diagnostic test. Ultimately, only 29% reported isolating and 19% were asked about contacts. <h3>Interpretation</h3> Modifiable epidemiologic risk factors and poor reach of public health strategies drove SARS-CoV-2 transmission across the U.S during May 2020-January 2021. <h3>Funding</h3> U.S. National Institutes of Allergy and Infectious Diseases (NIAID).

Influenza subtype-specific IgA, IgM and IgG responses in patients on hemodialysis after influenza vaccination.

The isotype-specific antibody response to influenza vaccination in 36 patients undergoing chronic intermittent hemodialysis was analyzed by an influenza subtype-specific immunofluorescence test. The immune response was recorded at regular intervals over five months. On the basis of fourfold IgG titer rises as the classical parameter protection from infection was assumed to occur in more than 85% of healthy adults to each of the influenza antigens. In contrast, about 70% of the patients on hemodialysis had responded to influenza A H1N1 and H3N2 vaccines while only 50% of the patients on hemodialysis had responded to influenza B antigen. However, patients showed decreased rates and lower peak responses in IgA, IgM and IgG antibodies to influenza A and B antigens. Probably as a result of the underlying renal disease the different kinetics of antibody responses and the lower influenza specific immunoglobulin levels resulted in lower seroconversion rates in hemodialysis patients compared to those in healthy volunteers.

RANDOMISED TRIAL OF ALTERNATIVE FORMULATIONS OF ORAL POLIOVACCINE IN BRAZIL

In February to July, 1986, an outbreak of type 3 poliomyelitis occurred in north-east Brazil that was linked to type-specific failure of trivalent oral polio vaccine (TOPV). To see if alternative vaccines would improve seroconversion to type 3, 441 children less than 5 years of age who had previously received no or up to four doses of TOPV were randomly assigned to receive one dose of standard TOPV (1000 000, 100 000, and 300 000 median tissue culture infection doses [TCID 50] of types 1, 2, and 3, respectively); a new formulation of TOPV containing twice the dosage of type 3 (600 000 TCID 50); or a monovalent vaccine containing 300 000 TCID 50 of type 3. While rates of seroconversion to types 1 or 2 were equivalent following vaccination with either formulation of TOPV, children who received the new formulation were 2·7 times more likely to seroconvert to type 3. Similar differences for type 3 were observed when monovalent vaccine was compared with standard TOPV, though both groups had received the same dose of type 3 antigen. The low rate of seroconversion to type 3 in the standard TOPV group was associated with a higher rate of reinfection with type 2, which also appeared to interfere to some extent with seroconversion to type 1. These findings extend earlier observations that interference from Sabin type 2 virus may be an important contributory cause of type-specific TOPV failure, and suggest that interference can be overcome with alterations in the formulation.

Biologic and prognostic significance of hepatocyte hepatitis B core antigen expressions in the natural course of chronic hepatitis B virus infection

To elucidate the biologic significance of hepatocyte hepatitis B core antigen (HBcAg) expression and its relation to the natural course of hepatitis B virus (HBV) infection, the patterns of HBcAg were correlated with HBV virus replication state and the disease activity in 598 needle liver biopsies performed on 569 hepatitis B surface antigen (HBsAg) carriers aged 1-81 years. A good correlation of liver HBcAg with serum HBeAg and HBV DNA status was demonstrated. HBcAg was present in the hepatocyte nuclei (nHBcAg) or cytoplasm (cHBcAg), or in both (mixed). Pure nHBcAg was seen mainly in children and young adults; 86% of the patients had non-aggressive disease, but rare cases of chronic active hepatitis (CAH) and HBeAg seroconversion were observed. In contrast, cHBcAg was predominantly associated with CAH (52%) and accompanied by a significantly higher HBeAg seroconversion rate (27%). The HBeAg-negative group, particularly the liver HBcAg-negative subgroup, had a lower frequency of CAH, but an increased incidence of non-aggressive disease as well as cirrhosis and/or hepatocellular carcinoma, indicating that HBeAg seroconversion to anti-HBe does not necessarily mean a favorable prognosis. The results suggest that expression of HBcAg correlates with the liver pathology and the three phases of chronic HBV infection: (1) the early immune tolerance phase is characterized by nHBcAg, mild disease and low HBeAg seroconversion rate; (2) the virus replication/elimination phase by cHBcAg or negative HBcAg, frequent CAH, and high HBeAg seroconversion rate; and (3) the inactive virus replication phase by negative HBcAg and a bipolar disease spectrum.

Is primary cytomegalovirus infection an occupational hazard for obstetric nurses? A serological study.

The results are reported of a 4-year prospective study of the incidence of primary cytomegalovirus (CMV) infection in the nursing staff of a specialist obstetric hospital. The absence of seroconversion found in personnel attending patients with confirmed CMV-infection justifies reassuring staff members in "high-risk" areas of the adequacy of the methods used to combat cross-infection. On the other hand, a low rate of seroconversion (1.2% per annum) in the staff who nurse normal mothers and "rooming-in" babies emphasizes the need for the rigorous observance of hygienic precautions by all personnel in all areas. The results of this Australian investigation are discussed in relation to the northern hemisphere experience of CMV-seroconversion in pediatric nurses.

Hepatitis B vaccine in healthy hospital employees.

A low rate of seroconversion to hepatitis B vaccine is reported. This occurred in healthy hospital employees from two separate institutions. A total of 236 individuals were evaluated in this study and only 53% or 124 persons developed protective levels of antibody to hepatitis B surface antigen following a complete vaccine series. In one hospital, 30% of the vaccine recipients developed antibody but not to a protective level. Employees who received the entire series in the arm or in the arm and buttock (mixed) had a significantly greater number of responders than employees who received the entire series in the buttock (P less than .05). Recipients aged 50 to 59 years had a significantly lower response rate to the vaccine (P less than .05). There was no correlation with the vaccinee's sex or the timing of the second injection. Vaccine was noted to have frozen in one hospital and accounted for some loss of antigenicity. This failure to respond to the vaccine has necessitated the use of booster injections of vaccine and continued antibody monitoring.

A controlled trial of 6 months thrice weekly lymphoblastoid interferon versus no therapy in chronic hepatitis B virus infection: A preliminary analysis of the first 32 patients

A controlled trial of lymphoblastoid interferon versus no therapy in patients positive for HBsAg, HBeAg and DNA polymerase activity with separate randomisation for sexual preference and histology is underway. Thirty two patients have been followed for a minimum period of 6 months of whom 15 have been randomised to receive interferon thrice weekly for 6 months after a 5-day induction phase. Five treated patients developed an hepatitis-like illness during the 3rd month of therapy concurrent with an abrupt and complete loss of DNA polymerase activity from serum. In 3 this was permanent and anti-HBe subsequently developed; 2 of these have also lost HBsAg. In the other 2 patients inhibition of viral replication was transient. In 5 further treated patients DNA polymerase activity was completely inhibited throughout treatment only to return as soon as interferon was withdrawn. In this group serum aminotransferase became normal during treatment. In the remaining 5 treated patients, inhibition of DNA polymerase activity was never complete and serum aminotransferases were unaffected. All the control patients remain seropositive for HBsAg, HBeAg and DNA polymerase activity. The low seroconversion rate in treated patients and the absence of seroconversion in the control group are probably a reflection of the exclusion of patients with marked elevation of serum aminotransferases. The occurrence of an hepatitis-like illness in the 3rd month of therapy in a third of the patients and the loss of HBsAg in 2 of 3 who eventually seroconverted are likely to be a consequence of therapy rather than spontaneous events.(ABSTRACT TRUNCATED AT 250 WORDS)

Hepatitis B vaccine: low postvaccination immunity in hospital personnel given gluteal injections.

Although other investigators have found excellent response rates to the hepatitis B vaccine, we report here an unusually low rate of seroconversion following hepatitis B vaccination in a group of apparently healthy medical center personnel. Only 67% of these individuals developed adequate postvaccination antibodies to HBsAg, in contrast to 85 to 96% in other studies. A significant decrease in seroconversion with increasing age was noted with a 54% seroconversion rate in vaccines over the age of 40; all of whom had received gluteal injections. Employees at another facility had been given deltoid injections from the same vaccine lot and had an overall seroconversion rate of 90%. Subsequently, nonresponders from the first group were revaccinated. Seven of the ten individuals tested developed anti-HBs. We believe the relatively low rate of seroconversion in individuals above the age of 40 may have been related to gluteal injection of the hepatitis B vaccine, and further investigation is warranted.

Live attenuated varicella vaccine: Immunization of healthy children with the OKA strain

Ninety-one healthy children were immunized with one of three preparations of the OKA strain of live attenuated varicella zoster virus in order to gain sufficient information on safety and immunogenicity to justify vaccine studies in immunosuppressed children. The OKA-Biken vaccine was studied in a dose response trial. Two additional clinical trails were conducted with the OKA strain that was further passaged: a frozen aqueous (OKA-RIT-Aq) form and a lyophilized (OKA-RIT-Ly) form were tested. With each of these vaccines clinical reactivity was minimal and virus shedding, viremia, and transmission of the vaccine virus were absent. Excellent seroconversion rates of 100 and 94% were induced with approximately 500 pfu of OKA-Biken and OKA-RIT-Ly vaccine, respectively. A lower seroconversion rate was noted for OKA-RIT-Aq, presumably on the basis of defective individual vials. Diluted OKA-Biken vaccine induced less seroconversion but even the 5 pfu dose produced antibody responses in 81% of the vaccinees. In vitro specific cellular immune responses to varicella virus antigens were demonstrated in each group of vaccinees, including all but two of those vaccines who failed to seroconvert. The data indicate that two preparations of the OKA strain are sufficiently safe and immunogenic in healthy children to support further studies in immunocompromised children.

An assessment of the effectiveness of the measles immunization programme in Lagos, Nigeria.

Sera from 224 children (mean age 10·2 months) were tested for the presence of measles haemagglutinating antibodies prior to measles vaccination. Six to eight weeks later, they were re-tested.The sera conversion rate was 53·5%. The geometric mean titre was 60 in the sero-converters. The sero-converters were significantly younger than the non-sero-converters (P<0·02) and their mean age was 9·79 months; the mean age of non-sero-converters was 10·1 months.The proportion of non-sero-converters was higher in those who were at least 12 months old than in younger children.It therefore appeared that the low sero-conversion rate was due to other factors in addition to persistent maternal antibodies because the results were the opposite of what would be expected if only maternal antibodies were responsible. It is postulated that vaccine inactivation due to poor storage is an important cause of non-sero-conversion and a plea is made for an effective ‘cold chain’ from the time of vaccine manufacture to its use in the ...

Evaluation of a mass measles immunization campaign in Yaoundé, Cameroun

A mass measles immunization campaign carried out in Yaoundé, Cameroun, has been evaluated. Sixty per cent of the children were immune to measles at the time of the campaign. Only 51 % of the susceptible children received vaccine. This was caused by a lack of attendance at the vaccination centres and errors in the selection of children given vaccine. The vaccine administered was relatively ineffective: 40% seroconversion. Difficulties which probably contributed to the low seroconversion rate included sub-optimal vaccine titre, inadequate doses of vaccine, and the relatively long time of vaccine utilization under tropical temperatures. Overall, 83 % of the vaccine given to the vaccinating team was wasted. Future immunization campaigns can be improved through better screening of the children, improved handling of the vaccine, the use of marker vaccines, and improved health education.

Polio Vaccination in Developing Countries

We have recently come across the Letter to the Editor from Dr. Shanti Ghosh,1 commenting on the trivalent oral polio virus vaccine trials reported by Hardy, et al. in Pediatrics.2 Although 96 to 100% of infants demonstrated satisfactory levels of immunity in Hardy's group, using a microneutralization titer technique, Dr. Ghosh describes disappointing results in children in India and Nigeria as indicated by low seroconversion rates, as well as very low enterovirus excretion rate in pre- and postimmunization specimens (7.8%).