Serologic Evidence Of Prior Infection Research Articles

Model-based estimates of age-structured SARS-CoV-2 epidemiology in households

BackgroundUnderstanding how infectious disease transmission varies from person to person, including associations with age and contact behavior, can help design effective control strategies. Within households, transmission may be highly variable because of differing transmission risks by age, household size, and individual contagiousness. Our aim was to disentangle those factors by fitting mathematical models to SARS-CoV-2 household survey and serologic data.MethodsWe surveyed members of 3,381 Utah households from January-April 2021 and performed SARS-CoV-2 antibody testing on all available members. We paired these data with a probabilistic model of household importation and transmission composed of a novel combination of transmission variability and age- and size-structured heterogeneity. We calculated maximum likelihood estimates of mean and variability of household transmission probability between household members in different age groups and different household sizes, simultaneously with importation probability and probabilities of false negative and false positive test results.Results12.8% of individual participants, residing in 17.4% of the participating households, showed serologic evidence of prior infection or reported a prior positive test on the survey. Serologically positive individuals in younger age groups were less likely than older adults to have tested positive during their infection according to our survey results. Our model results suggested that adolescents and young adults (ages 13–24) acquired SARS-CoV-2 infection outside the household at a rate substantially higher than younger children and older adults. Our estimate of the household secondary attack rate (HSAR) among adults aged 45 and older exceeded HSARs to and/or from younger age groups at a given household size. We found lower HSAR in households with more members, independent of age differences. The age-specific HSAR patterns we found could not be explained by age-dependent biological susceptibility and transmissibility alone, suggesting that age groups contacted each other at different rates within households.ConclusionsWe disentangled several factors contributing to age-specific infection risk, including non-household exposure, within-household exposure to specific age groups, and household size. Within-household contact rate differences played a significant role in driving household transmission epidemiology. These findings provide nuanced insights for understanding community outbreak patterns and mechanisms of differential infection risk.

Delirium Associated with COVID-19 in Critically ill Children: An Observational Cohort Study.

Delirium is an under-recognized problem in critically ill children. Although delirium is common in adults hospitalized with COVID-19, the relationship between pediatric COVID-19 and delirium has not been described. To address this gap, we characterized delirium in critically ill children with different manifestations of COVID-19 and investigated associations among demographic, disease, and treatment factors. We hypothesized that multisystem inflammatory syndrome in children (MIS-C) would be associated with a higher incidence of delirium given its underlying pathophysiology of hyperinflammation. Retrospective, single-center cohort study. Quaternary-care pediatric intensive care unit (PICU). Children less than 18 years of age hospitalized in the PICU between March 2020 and March 2023 with either active SARS-CoV-2 infection or serological evidence of prior infection. The cohort included 149 PICU hospitalizations among children with evidence of COVID-19. Patients were categorized by reason for PICU admission: 75 (50%) for COVID-19 respiratory disease, 36 (24%) MIS-C, and 38 (26%) any other primary reason with positive COVID-19 testing. Delirium was diagnosed in 43 (29%) patients. Delirium incidence was highest in patients requiring invasive mechanical ventilation (IMV) (56% vs 7.5% in patients who did not require IMV, p < .001). Patients who were exposed to opioids, dexmedetomidine, paralytics or benzodiazepines more frequently experienced delirium compared to those unexposed (p < .001, p < .001, p < .001 and p = .001, respectively). After multivariable adjustment, delirium was associated with IMV (HR 3 [95% CI 1.5-5.7]), female sex (HR 2.4 [1.2-4.7]), and developmental disability (HR 3.4 [95% CI 1-11.1]). There was no association between delirium and reason for PICU hospitalization. Delirium was common among children hospitalized with COVID-19. The overall incidence was much less than has been reported in adults with COVID-19. Delirium reduction efforts should focus on children with developmental disability and minimizing ongoing risks during IMV.

Establishment of human post-vaccination SARS-CoV-2 standard reference sera

There is a critical need to understand the effectiveness of serum elicited by different SARS-CoV-2 vaccines against SARS-CoV-2 variants. We describe the generation of reference reagents comprised of post-vaccination sera from recipients of different primary vaccines with or without different vaccine booster regimens in order to allow standardized characterization of SARS-CoV-2 neutralization in vitro. We prepared and pooled serum obtained from donors who received a either primary vaccine series alone, or a vaccination strategy that included primary and boosted immunization using available SARS-CoV-2 mRNA vaccines (BNT162b2, Pfizer and mRNA-1273, Moderna), replication-incompetent adenovirus type 26 vaccine (Ad26.COV2·S, Johnson and Johnson), or recombinant baculovirus-expressed spike protein in a nanoparticle vaccine plus Matrix-M adjuvant (NVX-CoV2373, Novavax). No subjects had a history of clinical SARS-CoV-2 infection, and sera were screened with confirmation that there were no nucleocapsid antibodies detected to suggest natural infection. Twice frozen sera were aliquoted, and serum antibodies were characterized for SARS-CoV-2 spike protein binding (estimated WHO antibody binding units/ml), spike protein competition for ACE-2 binding, and SARS-CoV-2 spike protein pseudotyped lentivirus transduction. These reagents are available for distribution to the research community (BEI Resources), and should allow the direct comparison of antibody neutralization results between different laboratories. Further, these sera are an important tool to evaluate the functional neutralization activity of vaccine-induced antibodies against emerging SARS-CoV-2 variants of concern. ImportanceThe explosion of COVID-19 demonstrated how novel coronaviruses can rapidly spread and evolve following introduction into human hosts. The extent of vaccine- and infection-induced protection against infection and disease severity is reduced over time due to the fall in concentration, and due to emerging variants that have altered antibody binding regions on the viral envelope spike protein. Here, we pooled sera obtained from individuals who were immunized with different SARS-CoV-2 vaccines and who did not have clinical or serologic evidence of prior infection. The sera pools were characterized for direct spike protein binding, blockade of virus-receptor binding, and neutralization of spike protein pseudotyped lentiviruses. These sera pools were aliquoted and are available to allow inter-laboratory comparison of results and to provide a tool to determine the effectiveness of prior vaccines in recognizing and neutralizing emerging variants of concern.

Seroprevalence of SARS-CoV-2 in self-reported COVID-19-free children

IntroductionCOVID-19 poses risks and leads to complications for vulnerable populations, including children. Unreported cases of COVID-19 among children hinder our understanding of the true disease burden. In this study, we aimed to investigate the proportion of children who report no prior infection to SARS-CoV-2 but who nevertheless exhibit serological evidence of prior infection. MethodsBetween November 2022 and February 2023, we recruited children and adolescents under 19 years of age who lacked a prior history of SARS-CoV-2 infection. Participants underwent SARS-CoV-2 antibody testing to assess the presence of IgG antibodies specific to nucleocapsid (N) and spike (S) proteins. Demographic and contact information were also collected. ResultsAmong 260 COVID-19-free children, the overall anti-N antibody positivity rate, which varied across age groups (4%–25%), was 9.2% (24/260). Contact with individuals who were positive for COVID-19, particularly the children's mothers, significantly increased the likelihood of antibody positivity. The median age of the 34 children who remained unvaccinated against COVID-19 was lower than that of the children who were vaccinated (6.5 vs. 9 years; p < 0.001). Until January 2024, the overall infection rate was 41.9% (99/236) among children who were negative for anti-N antibodies, irrespective of vaccination status or the presence of chronic disease. ConclusionWe discovered previously undisclosed cases of SARS-CoV-2 infection among children. The risk of seropositivity increases substantially with household contact. Regarding children who report no prior exposure to COVID-19, clinicians must remain vigilant, as SARS-CoV-2 remains a concern.

Wuchereria bancrofti infection is associated with progression to clinical visceral leishmaniasis in VL- endemic areas in Muzaffarpur, Bihar, India.

Co-endemicity of neglected tropical diseases (NTDs) necessitates that these diseases should be considered concomitantly to understand the relationship between pathology and to support disease management and control programs. The aims of the study were to assess the prevalence of filarial infection in asymptomatic Leishmania donovani infected individuals and the correlation of Wuchereria bancrofti infection with progression to clinical visceral leishmaniasis (VL) in Bihar, India. Within the Muzaffarpur-TMRC Health and Demographic Surveillance System (HDSS) area, a cohort of Leishmania seropositive (n = 476) or seronegative individuals (n = 1130) were sampled annually for three years for filarial infection and followed for progression to clinical VL. To corroborate the results from the cohort study, we also used a retrospective case-control study of 36 VL cases and 71 controls selected from a subset of the HDSS population to investigate the relationship between progression to clinical VL and the prevalence of filarial infection at baseline. Our findings suggest a higher probability of progression to clinical VL in individuals with a history of filarial infection: in both the cohort and case-control studies, progression to clinical VL was higher among filaria infected individuals (RR = 2.57, p = 0.056, and OR = 2.52, p = 0.046 respectively). This study describes that progression to clinical VL disease is associated with serological evidence of prior infection with W. bancrofti. The integration of disease programs for Leishmania and lymphatic filariasis extend beyond the relationship of sequential or co-infection with disease burden. To ensure elimination targets can be reached and sustained, we suggest areas of co-endemicity would benefit from overlapping vector control activities, health system networks and surveillance infrastructure.

HPV16 and HPV18 seropositivity and DNA detection among men who have sex with men: a cross-sectional study conducted in a sexual health clinic in London

ObjectivesMen who have sex with men (MSM) have an increased risk of human papillomavirus (HPV) infection and related diseases compared with men who have sex exclusively with women. From April...

Does serological evidence of prior infection with SARS-CoV-2 indicate immunity

Does serological evidence of prior infection with SARS-CoV-2 indicate immunity

An Outbreak of Human Parvovirus B19 Hidden by Dengue Fever.

Seasonal outbreaks of dengue often result in hundreds of dengue-suspected cases where a clinical diagnosis cannot be confirmed. Usually, during large outbreaks of dengue and other pathogens that can cause acute febrile illnesses, the search for secondary pathogens with similar disease outcomes is rare. Using total RNA sequencing and targeted diagnostic assays, we discovered an outbreak of parvovirus B19 in dengue-suspected patients that occurred from November 2013 to February 2014. Of the 182 cases investigated, 63% were viremic for the B19 virus. Moreover, we found that >43% of infected patients had no serological evidence of prior infection. Parvovirus B19 is a typical childhood infection, yet we observed that 82% of the infected patients were adults. Additionally, we perceived that infected adults had significantly higher presentations of myalgia than in children. We also obtained viral protein (VP) 1/VP2 gene nucleotide sequences from 43 patients. Our results support the utility of next-generation sequencing for symptomatic patients with unknown etiologies during seasonal outbreaks of dengue and other arborviruses. Our findings could improve the vigilance of hospitals and laboratories by raising awareness of co-circulating pathogens such as parvovirus B19 that may be hidden in plain sight.

Viral and parasitic pathogen burden and the association with stroke in a population-based cohort.

Background Higher cumulative burden of viral and bacterial pathogens may increase the risk of stroke, but the contribution of parasitic infections in relation to cumulative pathogen burden and risk of stroke has rarely been examined. Aim To estimate the association of multiple persistent viral and parasitic infections with stroke in a representative sample of adults in the United States. Methods Serological evidence of prior infection was categorized as positive for 0-1, 2, 3, or 4-5 infections based on immunoglobulin G seropositivity to cytomegalovirus, hepatitis A virus, hepatitis B virus, Toxoplasma gondii, and Toxocara spp. in 13,904 respondents from the National Health and Nutrition Examination Survey III. Regression analysis was used to estimate the cross-sectional association between serological evidence of prior infection and history of stroke adjusting for demographic risk factors, and potential mediators of stroke. Results Age-adjusted models that included serological evidence of prior infection to cytomegalovirus, hepatitis A virus, hepatitis B virus, Toxoplasma gondii, and Toxocara spp. showed that adults in the highest serological evidence of prior infection category (4-5 infections) had a higher prevalence of stroke (5.50%, 95% confidence interval 2.44-10.46%) than those in the lowest serological evidence of prior infection categories (1.49%, 95% confidence interval 1.01-2.11%), and a trend test suggested a graded association between serological evidence of prior infection and stroke ( p = 0.02). In multivariable logistic regression models, the positive association of serological evidence of prior infection with stroke prevalence remained significant after adjustment for other significant risk factors (odds ratio = 1.4, p = 0.01) but was only significant among those aged 20-59 (odds ratio = 2.0, p = 0.005) and not among those aged 60-69 ( p = 0.78) or 70 and older ( p = 0.43). Conclusion We found support for a connection between serological evidence of prior infection to cytomegalovirus, hepatitis A virus, hepatitis B virus, Toxoplasma gondii, and Toxocara spp. and stroke among those aged 20-59. There may be a need to consider common parasitic infections in addition to viral and bacterial pathogens when calculating serological evidence of prior infection in relation to cerebrovascular disease.

Re-detection vs. new acquisition of high-risk human papillomavirus in mid-adult women.

To understand high-risk (hr) human papillomavirus (HPV) epidemiology in mid-adulthood, we assessed whether associations between incident detection of hrHPV DNA and recent sexual behavior differed according to whether or not there was serologic evidence of prior infection. From 2011 to 2012, we enrolled 409 women aged 30-50 years into a 6-month longitudinal study. We collected health and sexual behavior histories, enrollment sera for HPV antibody testing, and monthly self-collected vaginal swabs for HPV DNA genotyping. Generalized estimating equations logistic regression identified risk factors for type-specific incident hrHPV DNA, stratified by type-specific hrHPV serostatus at enrollment. Population attributable risks of hrHPV due to prior and recent exposure were estimated. When type-specific hrHPV serology was negative, recent sexual risk behavior was positively associated with incident hrHPV DNA (odds ratio in women reporting ≥3 recent sexual risk behaviors [e.g., new or multiple partners] vs. no recent sexual activity = 9.8, 95% CI: 2.4-40.6). No associations with recent sexual behavior were observed with positive type-specific hrHPV serology. Thirty percent of incident hrHPV DNA detection was attributable to prior infection (with positive serology) and 40% was attributable to recent sexual risk behavior (with negative serology). The proportion of incident hrHPV DNA detection attributable to recent sexual risk behavior decreased with increasing age. Among women with serologic evidence of prior infection, re-detection of the same hrHPV type is likely due to reactivation or intermittent detection of persistent infection. Without serologic evidence of prior infection, new detection is likely due to new acquisition or to intermittent detection of persisting infection.

Donors deferred for self‐reported Chagas disease history: does it reduce risk?

Current Food and Drug Administration guidance specifies that all blood donors must be asked about a history of Chagas disease. We identified all American Red Cross donors deferred for Chagas disease history from January 2000 to August 2011. Attempts were made to contact all deferred donors and invite them back for anti-Trypanosoma cruzi testing. After January 2007, all accepted donors (no Chagas history) were anti-T. cruzi tested. Over the 12-year period (approx. 88 million donor presentations), 34 donors had a Chagas deferral. When contacted, seven reported risk (e.g., travel or residence in an endemic area, vector exposure) and six were anti-T. cruzi tested with one radioimmunoprecipitation assay (RIPA) positive. Six others had answered the question incorrectly. The remaining 21 could not be contacted but from the donor record it could be determined that 13 were Hispanic ethnicity or Spanish speaking and/or provided specific details of Chagas risk or disease. In 12 years, only 28 potentially infected donors were identified using the Chagas question. Limited testing data suggest that few of these would have had serologic evidence of prior infection. In contrast, nearly 5 years of anti-T. cruzi screening identified 488 RIPA-positive donors, none of whom answered "yes" to the Chagas question. According to estimates in this study, the value of retaining the questionnaire in addition to testing translates to preventing the collection of 0.4 infected donors per billion. Thus, the Chagas history question has no meaningful value.

Temporal Dynamics of the Transcriptional Response to Dengue Virus Infection in Nicaraguan Children

Dengue is the most prevalent mosquito-borne human illness worldwide. The ability to predict disease severity during the earliest days of the illness is a long-sought, but unachieved goal.We examined human genome-wide transcript abundance patterns in daily peripheral blood mononuclear cell (PBMC) samples from 41 children hospitalized with dengue virus (DENV) infection in Nicaragua, as well as 8 healthy control subjects. Nine patients had primary dengue fever (DF1), 11 had dengue fever with serologic evidence of prior DENV infection, i.e., secondary dengue fever (DF2), 12 had dengue hemorrhagic fever (DHF), and 9 had dengue shock syndrome (DSS). We identified 2,092 genes for which transcript abundance differed significantly between patients on days 3–6 of fever and healthy subjects (FDR<1%). Prior DENV infection explained the greatest amount of variation in gene expression among patients. The number of differentially expressed genes was greatest on fever day 3 in patients with DF1, while the number in patients with DF2 or DHF/DSS was greatest on day 5. Genes associated with the mitotic cell cycle and B cell differentiation were expressed at higher levels, and genes associated with signal transduction and cell adhesion were expressed at lower levels, in patients versus healthy controls. On fever day 3, a set of interferon-stimulated gene transcripts was less abundant in patients who subsequently developed DSS than in other patient groups (p<0.05, ranksum). Patients who later developed DSS also had higher levels of transcripts on day 3 associated with mitochondrial function (p<0.01, ranksum). These day 3 transcript abundance findings were not evident on subsequent fever days.In conclusion, we identified differences in the timing and magnitude of human gene transcript abundance changes in DENV patients that were associated with serologic evidence of prior infection and with disease severity. Some of these differential features may predict the outcome of DENV infection.

Seropositive Human Subjects Produce Interferon Gamma after Stimulation with Recombinant Cryptosporidium hominis gp15

Cryptosporidiosis is an important cause of diarrhea worldwide. In normal hosts, infection is self-limited and associated with seroconversion and partial immunity to reinfection. Immunity is associated with interferon gamma (IFNgamma) production. Cryptosporidium surface proteins gp15 and gp40 are among the immunodominant proteins in terms of antibody responses. We asked the question of whether these antigens also stimulate production of IFNgamma in patients who have serologic evidence of prior infection. Whole blood from seropositive donors was stimulated with recombinant gp15 and gp 40 from Cryptosporidium hominis and Cryptosporidium parvum or His-tag controls. C. hominis gp15 stimulated increased production of IFNgamma. By contrast, there was no significant increase after stimulation with C. parvum gp15 or either gp40 preparation. IFNgamma production in response to C. hominis gp15 was noted in both CD4(+) and CD8(+) cells. This highlights the potential for C. hominis gp15 as a vaccine candidate for human cryptosporidiosis.

Primary cutaneous B-cell lymphoma

Primary cutaneous B-cell lymphomas include extranodal marginal zone B-cell lymphoma, follicular lymphoma, large B-cell lymphoma, and, rarely, mantle cell lymphoma. Our purpose in conducting this review was to determine the clinical and behavioral characteristics of primary cutaneous B-cell lymphomas, their relationship to infectious triggers, and therapeutic response. We conducted a retrospective chart review of 23 adult patients presenting to the dermatology clinic at M. D. Anderson Cancer Center with primary cutaneous B-cell lymphoma between January 1999 and May 2003. Primary cutaneous B-cell lymphomas generally present on the head and neck, with the trunk and extremities afflicted to a lesser extent. Patients were found to have serologic evidence of prior infection with Borrelia burgdorferi (n = 10), Helicobacter pylori (n = 5), and Epstein-Barr virus (n = 6). Overall, treatment of primary cutaneous B-cell lymphoma should involve multiple modalities; however, specific treatment aimed at concurrent or suspected infection, particularly B burgdorferi, is a helpful adjunct and may achieve complete remission in a small subset of patients.

How Clean Must Our Drinking Water Be: The Importance of Protective Immunity

Cryptosporidium parvum is an important cause of epidemic diarrhea. Few studies have assessed whether serological evidence of prior infection in adults is related to a reduced occurrence of enteric illness. Serum samples and enteric illness event data were obtained in 2000 and 2001 from 326 people served by 1 of 2 unfiltered surface sources or 1 groundwater source. In 2001, filtration was initiated at 1 of the surface sources. Poisson regression related illness episodes with serological responses to the 15/17- and 27-kDa Cryptosporidium antigen groups. Subjects with moderately strong responses to the 15/17-kDa antigen had <65% of the risk of all 1-3-day episodes of diarrheal or gastrointestinal illness and <40% of the risk of all >/=4-day episodes, compared with subjects without a moderately strong response. Water source, change in water treatment, and very weak responses were unrelated to illness events. Endemic Cryptosporidium infections are a common cause of diarrheal and gastrointestinal illness in persons without a moderately strong response to the 15/17-kDa antigen group. Users of surface-derived drinking water are more likely to have strong serological responses to this antigen group and may be at a lower risk of endemic gastrointestinal illness caused by Cryptosporidium infection.

Human herpesvirus 8 genome is not found in whole bone marrow core biopsy specimens of patients with plasma cell dyscrasias.

Recently, molecular evidence of the gamma herpesvirus, human herpesvirus 8 (HHV-8), was found in the nonmalignant bone marrow stromal cells of patients with multiple myeloma using a polymerase chain reaction (PCR)-based assay. Other investigators have been unable to confirm either the presence of HHV-8 using molecular techniques or serologic evidence of prior infection with HHV-8. In order to maximize the likelihood of detection of small quantities of the virus and minimize the risk of potential nucleic acid contamination, we used entire bone marrow biopsy core specimens for DNA extraction and amplification. These specimens included both malignant plasma cells and bone marrow stromal cells and were subjected to minimal manipulation prior to DNA extraction and PCR. We tested eight patients with various plasma cell dyscrasias and compared them to negative controls with non-Hodgkin's lymphoma using standard PCR assays utilizing the KS330(233)primers and probe for HHV-8. This assay is reproducibly positive in Kaposi's sarcoma tissue. We found no evidence of HHV-8 DNA in either the lymphoma controls or the samples from patients with the plasma cell dyscrasias using these methods. We conclude that HHV-8 is unlikely to play a major role in the pathogenesis of the plasma cell dyscrasias in the majority of patients with these diseases. This report adds to the body of evidence that HHV-8 is not associated with plasma cell dyscrasias like multiple myeloma.

Application of low-avidity immunoglobulin G studies to diagnosis of Epstein-Barr virus infectious mononucleosis

Single serum samples from 121 patients suffering from clinical infectious mononucleosis were tested by an indirect immunofluorescence assay for avidity of Epstein-Barr virus (EBV) capsid antigen immunoglobulin G (IgG), involving a wash step with phosphate-buffered saline-8 M urea. Ninety-four samples showed serological markers of recent EBV infection (presence of viral-capsid antigen-specific IgM [87 cases] and/or presence of IgG in the absence of EBV nuclear antigen antibodies [85 cases]). The remaining 27 cases had serological evidence of prior infection (presence of viral-capsid IgG and EBV nuclear antibodies and absence of IgM). In the avidity assay, 89 samples from patients with recent infection showed low-avidity IgG and 25 samples from patients with prior infection had high-avidity IgG. The avidity assay showed a sensitivity that was at least equal to those of classical serological procedures for diagnosing EBV infectious mononucleosis. Further studies are necessary, however, to establish the specificity of the assay and the duration of low-avidity antibodies.

Herpes simplex virus infection as a risk factor for human immunodeficiency virus infection in heterosexuals.

To determine if infection with herpes simplex virus (HSV) type 2 is associated with human immunodeficiency virus (HIV) type 1 infection among patients attending sexually transmitted diseases clinics, a case-control study was done on coded sera from 179 HIV-1-infected patients and 367 age-, race-, and gender-matched HIV-1-seronegative patients. Although only 13 (2.3%) of 546 patients had a history of genital herpes treatment, 72% and 56.6%, respectively, had serologic evidence of prior infection with HSV-1 and -2. HSV-1 antibody prevalence was similar among both patient groups; however, HSV-2 antibodies were more common among those infected with HIV-1. Among heterosexual men, 62.7% of those infected with HIV-1 had HSV-2 antibodies compared with 46.7% of those not infected (P less than .01). The HSV-2 seroprevalence among women with or without HIV infection was 78.1% and 57.7%, respectively (P less than .02). A history of intravenous drug use and a reactive serologic test for syphilis were each independently associated with HIV-1 infection in heterosexuals. These data suggest that the two most common causes of genital ulcerative disease in the United States, genital herpes and syphilis, may contribute to increased risk for HIV-1 infection among heterosexuals.

Characterization of human cytotoxic lymphocytes directed against cells infected with typhus group rickettsiae: evidence for lymphokine activation of effectors.

An in vitro culture and assay system was used to determine whether cytotoxic lymphocytes are generated in humans after rickettsial infection. Peripheral blood mononuclear cells (PBMC) were obtained from six individuals with serologic evidence of prior infection with typhus group rickettsiae and from six nonimmune individuals. After PBMC from immune individuals were stimulated in vitro for 7 days with rickettsial antigen, they were capable of lysing typhus group rickettsia-infected, autologous phytohemagglutinin (PHA)-induced blasts, but not uninfected PHA-blasts. No cytotoxic effector cells were generated when either PBMC from immune individuals were placed in culture for 7 days without antigenic stimulation, or when PBMC from nonimmune individuals were stimulated in vitro with antigen for 7 days. Freshly isolated PBMC from immune donors were also unable to lyse typhus group rickettsia-infected autologous PHA-blasts or an autologous rickettsia-infected lymphoblastoid cell line (LCL). Neither supernatants from antigen-stimulated cultures of PBMC from immune donors nor recombinant human interferon-gamma were capable of significantly lysing typhus group rickettsia-infected PHA blasts by this assay. Populations of cytotoxic effector cells depleted of OKT3, OKT4, or OKT8-positive cells by treatment with the respective monoclonal antibodies and complement were assayed for their cytotoxic capacity. The results suggest that the cytotoxic effector cell population is predominantly OKT3 and OKT8-positive, but OKT4-negative. Positive selection with the use of a fluorescence-activated cell sorter also suggested that most of the cytotoxic effector cells are OKT8-positive. PBMC from immune donors after in vitro stimulation with rickettsial antigen were capable of significantly lysing infected autologous LCL or infected HLA-mismatched LCL as compared with the respective uninfected controls. In addition, PBMC from either immune donors or nonimmune donors after stimulation in vitro for 7 days with media containing purified lymphokines were capable of significantly lysing autologous infected LCL as compared with the uninfected autologous control. We conclude that lysis of cells infected with typhus group rickettsiae is mediated by a lymphokine-activated killer.

Chlamydia trachomatis: its role in tubal infertility.

We compared the prevalence of antibody to Chlamydia trachomatis among 88 women undergoing an evaluation for infertility and 49 women attending an antenatal clinic. Demographic data regarding sexual behavior were also collected. Eighteen women had tubal infertility and 70 had infertility due to a variety of other reasons. In comparison with women who had other causes for infertility, women with tubal infertility began coitus sooner (17.7 +/- 2.2 years vs. 19.5 +/- 3.4 years, P less than .05) and had more lifetime sex partners (4.5 vs. 1.33, P less than .001). Women with tubal infertility had a higher prevalence of antibody to C. trachomatis (13 of 18) than did women with nontubal causes for infertility (6 of 70, P less than .0001) or pregnant women (11 of 49, P = .0003). This high prevalence of antibody to C. trachomatis among women with tubal infertility was independent of sexual experience. By immunoblot analysis, an antigen of approximately 57,000 Da was immunodominant in 11 of 13 seropositive subjects with tubal infertility vs. 2 of 6 seropositive subjects with nontubal infertility (P = .046) and 1 of 11 seropositive pregnant women (P = .0003). Thus, women with tubal infertility frequently have serological evidence of prior infection with C. trachomatis and have a distinctive antigen-specific humoral immune response. These results further support the etiologic role of infection with C. trachomatis in tubal infertility.