Seropositive Adults Research Articles

Nationwide survey of Helicobacter pylori seropositivity and gastric atrophy in Zambia.

Helicobacter pylori (H. pylori) is a common bacterial infection which predominately drives upper gastrointestinal pathology. We carried out a nationwide serological survey in response to the deficiency of robust African data on H. pylori prevalence, age of acquisition, socio-geographic determinants, and impact on gastric physiology. This was a cross-sectional study of archival plasma samples collected during the Zambia Population-based HIV impact Assessment (ZAMPHIA) 2016 survey. ZAMPHIA used a two-stage door-to-door stratified cluster sample approach to collect samples from adults and children from age 0 to 59 years (n = 24,266). We randomly retrieved one fifth of these samples from each of Zambia's 10 provinces and used ELISA to test for H. pylori IgG antibodies, pepsinogen 1 and 2 and gastrin-17. A pepsinogen 1:2 ratio of <3 was used to define gastric atrophy. The analysis of 4050 plasma samples (30% <16 years, 53% females) revealed an overall H. pylori seroprevalence of 79%. By the age of 10 years, more than 75% of the children had H. pylori. Urban residence was associated with increased odds (OR 1.8, 95% CI 1.5-2.2, p < 0.001) and HIV infection was associated with reduced odds (OR 0.7, 95% CI 0.5-0.9, p = 0.02) of H. pylori seropositivity. Gastric atrophy was detected in 6% of H. pylori seropositive adults below 45 years of age and 9% in those between 45 and 59 years. We have confirmed a high prevalence of H. pylori seropositivity in Zambia, predominantly in urban settings. The prevalence of gastric atrophy is broadly consistent with other populations around the globe, but our sample did not include adults over 60 years.

Prevalence of Malnutrition and Associated Factors among HIV Seropositive Adults on Antiretroviral Therapy at the Regional Hospital, Buea, Cameroon

Introduction: Malnutrition refers to deficiencies, excesses, or imbalances in a person’s intake of energy and/or nutrients and HIV which infects CD4 cells causes immune suppression which can further be worsened by poor nutrition. More than 37.7 million people are living with HIV in the world out of which about 36 million are adults. Aims: The study aimed to determine the prevalence of malnutrition and associated factors among human immunodeficiency virus (HIV) seropositive adults on antiretroviral therapy at the HIV care and treatment center of the Buea Regional hospital, Cameroon. Study Design: A Hospital-based Cross sectional study design. Place and duration of study: Buea regional hospital at the HIV care and treatment centre, South West Region of Cameroon between April 2022 to June 2022. Materials and method: We included 139 HIV seropositive individuals (17 men, 177 women age range 26 to 59 years). Nutritional status was assessed using anthropometric and clinical methods. A 24-hour dietary diversity was assessed using a questionnaire. Data was analyzed using SPSS version 25.0. Results: The prevalence of underweight, overweight and obesity among the participants were 1.4 %, 38.8%, and 24.4% respectively. In the bivariate analysis, sex of the participants (χ2 = 4.715, p = 0.030) and attendance to HIV-related counseling sessions (χ2 = 4.512, p = 0.034) were significantly associated with malnutrition. The mean dietary diversity score of the study respondents was 4.97±1.6 with only 37% of the respondents achieving a minimum dietary diversity. In the multivariate logistic regression analysis, the odds of those who received HIV-related counselling being malnourished(overweight) was 3.29 times more than those who did not receive HIV-related counselling (AOR=3.29, p=0.036). Conclusions: There is a high burden of overweight and obesity in the HIV population of the Regional Hospital Buea. The only factor independently associated to malnutrition(overweight) was uptake of nutrition related counselling. Majority of the HIV seropositive patients in the Regional Hospital Buea had a poor dietary diversity. Nutritional counseling should be an important part of persons living with HIV/AIDS (PLWHA) routine follow-up.

Safety and Immunogenicity of a Messenger RNA-Based Cytomegalovirus Vaccine in Healthy Adults: Results From a Phase 1 Randomized Clinical Trial.

This phase 1 trial evaluated the safety, reactogenicity, and immunogenicity of mRNA-1647, a messenger RNA (mRNA)-based cytomegalovirus (CMV) vaccine, in CMV-seronegative and -seropositive adults. Participants were randomly assigned to receive 30, 90, 180, or 300 µg of mRNA-1647 or placebo on a 0-, 2-, and 6-month schedule and followed for 12 months after the last dose. A total of 154 (80 CMV-seronegative and 74 CMV-seropositive) participants were enrolled; 118 participants were randomized to mRNA-1647 and 36 to placebo. Mean (standard deviation) age was 32.5 (8.6) and 35.1 (8.9) years in the placebo and mRNA-1647 groups, respectively, in phase B (63% and 64% female) and 42.5 (6.2) and 33.3 (8.7) years, respectively, in phase C (2% and 16% female). No deaths, related serious adverse events, or adverse events of special interest were reported. Most adverse reactions were grade ≤2 severity. Increased neutralizing antibody, binding antibody, and antigen-specific cell-mediated responses were observed across mRNA-1647 treatment groups, regardless of CMV serostatus. This phase 1, first-in-human trial demonstrated that mRNA-1647 has an acceptable safety profile in adults and elicits humoral and cellular immune responses. Clinical Trials Registration. NCT03382405.

Association between hepatitis A seropositivity and bone mineral density in adolescents and adults: a cross-sectional study using NHANES data.

Osteoporosis, characterized by decreased bone density and increased fracture risk, imposes significant physical, psychosocial, and financial burdens. Early detection and prevention are crucial for managing osteoporosis and reducing the risk of fractures. To investigate the relationship between Hepatitis A seropositivity and bone mineral density (BMD) in adolescents and adults and to explore the potential link between Hepatitis A infection and osteoporosis risk. This cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018 to evaluate the association between hepatitis A seropositivity and BMD in 15,693 participants. Multivariable regression analysis was used to calculate the mean BMD and standard error for adolescents and adults, followed by an independent z-test to determine whether there was a significant difference between the seropositive and seronegative groups. Hepatitis A seropositive adolescents and adults had lower BMD than their seronegative counterparts, with significant differences in lumber spine (mean difference = -0.03 g/cm2, P < 0.01 for both age groups) and pelvis BMDs (mean difference = -0.02 g/cm2, P < 0.01 for the adult age groups), after adjusting for various covariates. This study confirmed that both adolescent and adult individuals seropositive for Hepatitis A antibodies had reduced BMD among both adolescents and adults, especially in the adult group. This finding suggests a possible link between Hepatitis A infection and risk of osteoporosis.

Soluble biomarkers of HIV-1-related systemic immune activation are associated with high plasma levels of growth factors implicated in the pathogenesis of Kaposi sarcoma in adults.

Human Herpesvirus-8 (HHV-8) is the etiologic agent of Kaposi's sarcoma (KS), a multicentric angio-proliferative cancer commonly associated with Human Immunodeficiency Virus (HIV) infection. KS pathogenesis is a multifactorial condition hinged on immune dysfunction yet the mechanisms underlying the risk of developing KS in HHV-8 seropositive adults remains unclear. Here we explored whether soluble markers of HIV-1-related systemic immune activation (SIA) and angiogenesis (VEGF and FGF acidic) are involved in the pathogenesis of KS in adults with HHV8. Blood samples from 99 HIV-1 infected and 60 HIV-1 uninfected adults were collected in Yaoundé, Cameroon. CD3+/CD4+ T cell counts and HIV-1 plasma viral load were determined using the Pima Analyzer and the RT-PCR technique, respectively. Plasma levels of SIA biomarkers (sCD163, sCD25/IL-2Rα, and sCD40/TNFRSF5) and biomarkers of progression to KS (VEGF and FGF acidic) were measured using the Luminex assay. Seropositivity (IgG) for HHV-8 was determined using the ELISA method. Overall, 20.2% (20/99) of HIV-1 infected and 20% (12/60) of HIV-1 uninfected participants were seropositive for HHV8. Levels of sCD163, sCD25/IL-2Rα, sCD40/TNFRSF5, and FGF acidic were higher in the HIV-1 and HHV8 co-infection groups compared to the HIV-1 and HHV8 uninfected groups (all P <0.05). In addition, Higher plasma levels of VEGF correlated with sCD163 (rs = 0.58, P =0.0067) and sCD40/TNFRSF5 (rs = 0.59, P = 0.0064), while FGF acidic levels correlated with sCD40/TNFRSF5 (rs = 0.51, P = 0.022) in co-infected. In HIV-1 mono-infected donors, VEGF and FGF acidic levels correlated with sCD163 (rs =0.25, P = 0.03 and rs = 0.30, P = 0.006 respectively), sCD25/IL-2Rα (rs = 0.5, P <0.0001 and rs = 0.55, P <0.0001 respectively) and sCD40/TNFRSF5 (rs = 0.7, P <0.0001 and rs = 0.59, P <0.0001 respectively) and even in patients that were virally suppressed sCD25/IL-2Rα (rs = 0.39, P = 0.012 and rs = 0.53, P = 0.0004 respectively) and sCD40/TNFRSF5 (rs = 0.81, P <0.0001 and rs = 0.44, P = 0.0045 respectively). Our findings suggest that although the development of KS in PLWH is multifactorial, HIV-associated SIA might be among the key drivers in coinfections with HHV8 and is independent of the patients' viremic status.

Serum neutralizing capacity and T-cell response against the omicron BA.1 variant in seropositive children and their parents one year after SARS-CoV-2 infection.

Durability of immune protection against reinfection with SARS-CoV-2 remains enigmatic, especially in the pediatric population and in the context of immune-evading variants of concern. Obviously, this knowledge is required for measures to contain the spread of infection and in selecting rational preventive measures. Here, we investigated the serum neutralization capacity of 36 seropositive adults and 34 children approximately one year after infection with the ancestral Wuhan strain of SARS-CoV-2 by using a pseudovirus neutralization assay. We found that 88.9% of seropositive adult (32/36) and 94.1% of seropositive children (32/34) convalescents retained the neutralizing activity against the SARS-CoV-2 Wuhan strain (WT). Although, the neutralization effect against Omicron BA.1 (B.1.1.529.1) was significantly lower, 70.6% (24/34) of children and 41.7% (15/36) of adults possessed BA.1 cross-neutralizing antibodies. The spike 1 (S1)-specific T cell recall capacity using an activation-induced marker assay was analyzed in 18 adults and 16 children. All participants had detectable S1-specific CD4 T cells against WT, and 72.2% (13/18) adults and 81,3% (13/16) children had detectable S1 WT-specific CD8 T cells. CD4 cross-reactivity against BA.1 was demonstrated in all investigated adults (18/18), and 66.7% (12/18) adult participants had also detectable specific CD8 BA.1 T cells while we detected BA.1 S1 reactive CD4 and CD8 T cells in 81.3% (13/16) children. Together, our findings demonstrate that infection with the ancestral strain of SARS-CoV-2 in children as well as in adults induces robust serological as well as T cell memory responses that persist over at least 12 months. This suggests persistent immunological memory and partial cross-reactivity against Omicron BA.1.

Persistent CD8 T Cell Marks Caused by the HCMV Infection in Seropositive Adults: Prevalence of HLA-E-Reactive CD8 T Cells

This study investigated the frequency and peptide specificity of long-lasting HCMV-specific CD8 T cells in a cohort of 120 cytomegalovirus seropositive (HCMV+) healthy carriers with the aim of deciphering the relative contribution of unconventional HLA-E- versus conventional HLA-A2-specific CD8 T cells to long-term T cell memory expansion in HCMV immunity. The presence of HCMV-specific CD8 T cells was investigated by flow cytometry using five MHC/peptide tetramer complexes (HLA-A2/pp65, HLA-A2/IE1 and three different HLA-E/UL40). Here, we report that 50% of HCMV+ healthy individuals possess HCMV-specific CD8 T cells, representing ≥0.1% of total blood CD8 T cells years post-infection. Around a third (30.8%) of individuals possess HLA-A2-restricted (A2pp65 or A2IE1) and an equal proportion (27.5%) possess an HLA-E/UL40 CD8 T response. Concomitant HLA-E- and HLA-A2-reactive CD8 T cells were frequently found, and VMAPRTLIL peptide was the major target. The frequency of HLA-E/VMAPRTLIL among total blood CD8 T cells was significantly higher than the frequency of HLA-A2pp65 T cells (mean values: 5.9% versus 2.3%, p = 0.0354). HLA-EUL40 CD8 T cells display lower TCR avidity but similar levels of CD3 and CD8 coreceptors. In conclusion, HLA-E-restricted CD8 T cells against the VMAPRTLIL UL40 peptide constitute a predominant subset among long-lasting anti-HCMV CD8 T cells.

Characterization of Disease Severity and Stability in NMOSD: A Global Clinical Record Review with Patient Interviews.

We sought insights into the classification of and factors associated with relapse severity and disease stability in neuromyelitis optica spectrum disorder (NMOSD) clinical practice worldwide. Neurologists recruited from six countries (the USA, Germany, Italy, Brazil, South Korea, and China) participated in a 30-60minute online survey and submitted two to four clinical records for aquaporin-4-immunoglobulin G (AQP4-IgG)-seropositive adults with NMOSD, which included patient demographics, diagnosis, maintenance treatment history, relapse occurrence, and severity. Separately, patients with NMOSD receiving maintenance therapy were interviewed over the telephone about their treatment journey, as well as perceptions of relapse severity and disease stability, and their potential influence on treatment decisions. Clinical records for 1185 patients with AQP4-IgG-seropositive NMOSD were provided by 389 neurologists (July-August 2020); 33 patients were interviewed (October-November 2020). There was no clear consensus on how relapse severity was defined in clinical practice, with geographical variations in relapse classification also found. Neurologists tended to rely on clinical assessments when determining severity, viewing each relapse in isolation, whereas patients had a more subjective view based on the changes in their daily lives and comparisons with prior relapses. Similarly, there was a disconnect in the definition of disease stability: the complete absence of relapses was more important for patients than for neurologists. A clear consensus on how to assess relapse severity and disease stability is needed to ensure that patients receive appropriate and timely treatment. In the future, clinical measures should be combined with patient-focused assessments.

Understanding Treatment Decisions in Neuromyelitis Optica Spectrum Disorder: A Global Clinical Record Review with Patient Interviews.

We sought insights into neuromyelitis optica spectrum disorder (NMOSD) treatment practices worldwide. Neurologists from the USA, Germany, Italy, Brazil, South Korea, and China completed an online survey, contributing clinical records for aquaporin-4 (AQP4) immunoglobulinG (IgG)-seropositive adults with NMOSD, which included patient demographics, diagnosis, maintenance treatment history, relapse occurrence, and severity. Interviewed patients receiving NMOSD maintenance therapy provided information about their diagnosis, treatment, perceptions about relapse severity or disease stability, and treatment switches. A total of 389 neurologists submitted clinical records for 1185 patients with AQP4-IgG-seropositive NMOSD; 33 patients with NMOSD were interviewed. Approximately 25% (228/910) of patients from the clinical record review (CRR) were initially misdiagnosed; 24% (8/33) of patients interviewed reported formal misdiagnosis. Misdiagnosis was associated with treatment delay and more relapses compared with correct diagnosis (mean 3.3 vs 2.8). Maintenance therapy was not initiated within 2months for 47% (221/472) of patients from the CRR and 24% (8/33) of interviewed patients. Oral corticosteroids/immunosuppressive therapies were typically the first maintenance treatment initiated, except for the USA, where monoclonal antibodies were equally likely to be prescribed. Relapse severity influenced the decision to initiate/change therapy and use monoclonal antibodies. Of interviewed patients, 76% (25/33) did not recall having a choice of treatment and many did not know the rationale for treatment choice. Misdiagnosis of NMOSD appears to be common and is associated with a delay in initiation of maintenance therapy, with decisions influenced by relapse severity. Further real-world studies assessing relapse severity in treatment initiation/switch are required to revise NMOSD treatment recommendations.

SG-APSIC1049: Immunogenicity of Gam-COVID-Vac and Sinopharm BBIBP-CorV vaccines in seropositive and seronegative adults

Objectives: Data comparing the immunogenicity of Sputnik-V and Sinopharm vaccines in seropositive and seronegative groups are lacking. We compared the immunogenicity of Sputnik-V (Gam-COVID-Vac) and Sinopharm (BBIBP-CorV) vaccines in seronegative and seropositive groups. Methods: In total, 60 adults participated the study. The immune response after vaccination was assessed using enzyme immunoassay. IgG levels were measured in all participants at 3 time points: before vaccination, 42 days after the first vaccine dose, and 6 months after the first vaccine dose. The results of the SARS-CoV-2 antibody test were quantified according to the WHO First International Standard and expressed in international units (BAU per mL). Results: The study participants were divided into 2 groups: 30 people (50%) were vaccinated with Sputnik-V (Gam-COVID-Vac) and 30 people (50%) were vaccinated with Sinopharm (BBIBP-CorV). The groups had no difference in sex composition. The highest antibody levels were observed 42 days after vaccination in both the seronegative group (P = .006) and the seropositive group (P &lt; .001). At 6 months after vaccination, the IgG value declined much farther among the seronegative group (P = .003) compared to those who had recovered from COVID-19 before vaccination. However, the “hybrid immunity” generated by the Sputnik-V vaccine had greater strength and duration (P &lt; .001). Conclusions: This study showed that IgG levels in vaccinated individuals who previously recovered from SARS-CoV-2 infection (“hybrid immunity”) were higher than in SARS-CoV-2–naïve individuals. In a comparative part of the study, the Sputnik-V vaccine had greater strength and duration of immune response across the 6-month observation period (P &lt; .001).

Promising efforts to develop an mRNA vaccine against Zika

Zika virus disease is the first and only flaviviral disease that was declared a public health emergency because of devastating birth defects following maternal infection. 1 Wilder-Smith A Osman S Public health emergencies of international concern: a historic overview. J Travel Med. 2020; 27taaa227 Crossref Google Scholar Since its peak in early 2016, the incidence of Zika virus cases has declined due to high population level immunity in affected countries. 2 O'Reilly KM Lowe R Edmunds WJ et al. Projecting the end of the Zika virus epidemic in Latin America: a modelling analysis. BMC Med. 2018; 16: 180 Crossref PubMed Scopus (41) Google Scholar However, Zika virus is still circulating at low levels in some areas and is likely to re-emerge in immunologically naive populations or in sites of previous epidemics once population immunity wanes. 3 Akrami KM de Nogueira BMF do Rosário MS et al. The re-emergence of Zika in Brazil in 2020: a case of Guillain Barré Syndrome during the low season for arboviral infections. J Travel Med. 2020; 27taaa165 Crossref Google Scholar , 4 Hamer DH Chen LH Zika in Angola and India. J Travel Med. 2019; 26taz012 Crossref Scopus (21) Google Scholar Great progress was made to rapidly advance several vaccine candidates into phase 1 and 2 clinical trials, including DNA 5 Wilder-Smith A Vannice K Durbin A et al. Zika vaccines and therapeutics: landscape analysis and challenges ahead. BMC Med. 2018; 16: 84 Crossref PubMed Scopus (60) Google Scholar and inactivated vaccines. 6 Wressnigg NV Hochreiter R Schneider M et al. A randomized, placebo-controlled, blinded phase 1 study investigating a novel inactivated, Vero cell-culture derived Zika virus vaccine. J Travel Med. 2022; taac127 Crossref PubMed Google Scholar The success of mRNA vaccines against COVID-19 in the past 2 years has fuelled research in its potential use against Zika. We welcome the two phase 1 trials using the mRNA vaccine platform for Zika virus by Brandon Essink and colleagues, 7 Essink B Chu L Seger W et al. The safety and immunogenicity of two Zika virus mRNA vaccine candidates in healthy flavivirus baseline seropositive and seronegative adults: the results of two randomised, placebo-controlled, dose-ranging, phase 1 clinical trials. Lancet Infect Dis. 2023; (published online Jan 19.)https://doi.org/10.1016/S1473-3099(22)00764-2 Summary Full Text Full Text PDF Google Scholar published in The Lancet Infectious Diseases. The safety and immunogenicity of two Zika virus mRNA vaccine candidates in healthy flavivirus baseline seropositive and seronegative adults: the results of two randomised, placebo-controlled, dose-ranging, phase 1 clinical trialsThese findings support the continued development of mRNA-1893 against Zika virus, which was well tolerated at all evaluated dose levels and induced strong Zika virus-specific serum nAb responses after two doses, regardless of baseline flavivirus serostatus. Full-Text PDF

The safety and immunogenicity of two Zika virus mRNA vaccine candidates in healthy flavivirus baseline seropositive and seronegative adults: the results of two randomised, placebo-controlled, dose-ranging, phase 1 clinical trials

Developing a safe and immunogenic vaccine against Zika virus remains an unmet medical need. We did two phase 1 studies that evaluated the safety and immunogenicity of two mRNA-based Zika virus vaccines (mRNA-1325 and mRNA-1893) in adults. Two randomised, placebo-controlled, dose-ranging, multicentre, phase 1 trials, one of mRNA-1325 (mRNA-1325 trial) and one of mRNA-1893 (mRNA-1893 trial), were done. For both studies, eligible participants were healthy adults (aged 18-49 years) who were flavivirus seronegative or flavivirus seropositive at baseline. Participants in the mRNA-1325 trial, which was done at three centres in the USA, were randomly assigned centrally (1:4), using a randomisation table, to the placebo group or one of three mRNA-1325 dose groups (10, 25, or 100 μg). All participants received two doses. The mRNA-1325 vaccine encoded the premembrane and envelope E structural proteins (prME) from a Micronesia 2007 Zika virus isolate. Participants in the mRNA-1893 trial, which was done at three centres in the USA and one centre in Puerto Rico, were randomly assigned (1:4) to the placebo group or one of four mRNA-1893 dose groups (10, 30, 100, or 250 μg) using centralised interactive response technology. All participants in the mRNA-1893 trial received dose one on day 1 and then dose two on day 29. The mRNA-1893 vaccine encoded the prME from the RIO-U1 Zika virus isolate. Safety was the primary outcome of each study, which was evaluated in the respective safety populations (mRNA-1325 trial: participants who received at least one dose and provided safety data; mRNA-1893 trial: participants who received at least one dose) and the solicited safety population (mRNA-1893 trial only: received at least 1 dose and contributed solicited adverse reaction data). Endpoints in both trials included solicited adverse reactions within 7 days after vaccination and unsolicited adverse events within 28 days after vaccination. The secondary outcome of both trials was immunogenicity assessed by Zika virus-specific neutralising antibodies (nAbs) in the per-protocol populations in either trial (participants with no major protocol deviations received full dose[s] of assigned dose level within the acceptable time window, had samples drawn within acceptable time window, and had prevaccination and corresponding post-vaccination serum samples for testing). These were descriptive studies, with no formal hypothesis testing in either trial. Both trials are registered with ClinicalTrials.gov, NCT03014089 (mRNA-1325 trial) and NCT04064905 (mRNA-1893 trial). The mRNA-1325 trial was done from Dec 14, 2016, to Aug 16, 2018. 90 participants were enrolled: 53 (59%) participants were women and 37 (41%) were men; 84 (93%) were White; and 74 (82%) were not Hispanic or Latino. All three dose levels of mRNA-1325 (10, 25, and 100 μg) were generally well tolerated, but the vaccine elicited poor Zika virus-specific nAb responses. At 28 days after dose two, geometric mean titres (GMTs) were highest for mRNA-1325 10 μg (10·3 [95% CI 5·9-18·2]). The mRNA-1893 trial was done from July 23, 2019, to March 22, 2021. 120 participants (70 [58%] women and 50 [42%] men) were enrolled, most participants were White (89 [74%]), and not Hispanic or Latino (91 [76%]). In the mRNA-1893 trial, solicited adverse reactions in participants who received a vaccine were mostly grade 1 or 2 and occurred more frequently at higher dose levels and after dose two. No participants withdrew due to an unsolicited treatment-emergent adverse event and most of these events were not treatment related. On day 57, all evaluated mRNA-1893 dose levels induced robust Zika virus-specific nAb responses, independent of flavivirus serostatus, that persisted until month 13. At day 57 in participants who were flavivirus seronegative, plaque reduction neutralisation titre test nAb GMTs were highest for mRNA-1893 100 μg (454·2 [330·0-619·6]); in participants who were flavivirus seropositive, GMTs were highest for mRNA-1893 10 μg (224·1 [43·5-1153·5]) and mRNA-1893 100 μg (190·5 [19·2-1887·2]). These findings support the continued development of mRNA-1893 against Zika virus, which was well tolerated at all evaluated dose levels and induced strong Zika virus-specific serum nAb responses after two doses, regardless of baseline flavivirus serostatus. Biomedical Advanced Research and Development Authority and Moderna.

215b. Real-World Experience of Letermovir Use at an Academic Transplant Center

Abstract Background Letermovir (LMV) is indicated for cytomegalovirus (CMV) prophylaxis in seropositive adults after allogeneic hematopoietic stem cell transplants (alloSCT). LMV is well tolerated compared to its alternatives. Our institution restricts LMV use to high-risk patient groups to maximize the cost/benefit of LMV. Despite these restrictions, LMV was in our institution’s top 50 drug expenditures, prompting a formal evaluation of its use. We describe a real-world experience with LMV at a 576-bed academic transplant center. Methods This was a single center, retrospective, descriptive study of LMV use at a transplant center. Any hospitalized patient who received ≥ 1 dose of LMV between August 2021 and January 2022 was eligible for analysis. Data collection included age, LMV administration data, length of stay, transplant status, Infectious Diseases (ID) consultation, documented rationale for non-criteria uses, and drug cost. The primary outcome was incidence of use not aligning with restriction criteria. The secondary outcome was institutional drug expenditure for non-criteria uses compared to approved uses. Results Over 6 months, 388 doses of LMV were administered to 31 unique patients during 41 admissions. LMV use during 12/41 admissions (31.7%) fell outside the institutional criteria. ID consult occurred in 58.3% (7/12) of cases. 27/31 (87%) were alloSCT patients, including 1 pediatric patient. There was also 1 liver and 1 heart transplant recipient. Reasons for non-criteria use were: primary prophylaxis in the heart transplant patient to avoid ganciclovir toxicity and in 2 alloSCT patients without high risk for CMV, pre-emptive therapy due to CMV reactivation (n=2), and step-down therapy for CMV viremia (n=4). LMV was used for extended periods ( &amp;gt; 100 days from transplant) in 2 cases. Non-criteria use of LMV accounted for $20 414 in drug cost over 6 months, 29% of total expenditure. Conclusion Our data suggest real world use of LMV often differs from the patient types enrolled in the phase 3 trials. Use of LMV as an alternative to available CMV therapies to avoid drug toxicities appears to drive much of this use. In addition, use outside of criteria was frequent and incurred a nontrivial cost. Modification of our criteria, such as requiring an ID consultation for off-label use, should be considered. Disclosures James S. Lewis, PharmD, FIDSA, Cidara: Advisor/Consultant|Merck: Advisor/Consultant|SeLux Diagnostics: Advisor/Consultant.

Association of anti-Ro seropositivity with cardiac rhythm and conduction disturbances.

Anti-Ro/La autoantibodies are especially prevalent in autoimmune diseases but are also relatively frequent in healthy adults. Their arrhythmogenic effect on the immature cardiac conductive system is well established, with substantial evidence demonstrating an increased risk for congenital atrioventricular block in neonates of seropositive mothers. Despite their wide distribution and their arrhythmogenic potential effect, there are no large population studies conducted in seropositive adults. Thus, this is the first large population-based study to examine the association of anti-Ro/La seropositivity with cardiac rhythm and conduction disturbances. This cross-sectional designed study involved the electronic health records of the largest health maintenance organization in Israel. All subjects that were tested positive for anti-Ro/anti-La antibodies between the years 2002 and 2019 were included and were matched by age, gender, and place of residence, with controls. Rates of different cardiac rhythm and conduction disturbances were compared between groups. Sensitivity analyses were performed using propensity score matching. The study population included 17 231 anti-Ro/La seropositive subjects and 84 368 controls. Anti-Ro seropositive patients had higher rates of conduction disturbances (3.0 vs. 1.7%, P < 0.001) and rhythm disturbances (10.5 vs. 7.0%, P < 0.001). Patients who tested positive for anti-La alone did not demonstrate a significant association with arrhythmias. Multivariate logistic regression analysis, controlling for possible confounders, showed an increased risk for cardiac conduction disturbances [odds ratio (OR) 1.44, 95% confidence interval (CI) 1.25-1.66, P < 0.001], as well as for cardiac rhythm disturbances (OR 1.21, 95% CI 1.11-1.31, P < 0.001) among anti-Ro seropositive patients. However, the association with rhythm disturbances was more robust in certain subgroup analyses. Anti-Ro seropositivity is positively associated with adult cardiac conduction disturbances and, to a lesser extent, cardiac rhythm disturbances, regardless of the presence of concurrent autoimmune disease.

Therapeutic Lumbar Punctures in Human Immunodeficiency Virus-Associated Cryptococcal Meningitis: Should Opening Pressure Direct Management?

BackgroundIncreased intracranial pressure (ICP) frequently complicates cryptococcal meningitis. Therapeutic lumbar punctures (LPs) have acute survival benefits in the first week, and we sought to understand the longer-term survival impact of therapeutic LPs.MethodsWe prospectively enrolled human immunodeficiency virus (HIV)–seropositive adults with cryptococcal meningitis from 2013 to 2017 in Uganda. We assessed the association between clinical characteristics, CSF parameters, and 14- and 30-day mortality by baseline ICP. We also assessed 30-day mortality by number of follow-up therapeutic LPs performed within 7 days.ResultsOur analysis included 533 participants. Participants with baseline ICP >350 mm H2O were more likely to have Glasgow Coma Scale (GCS) score <15 (P < .001), seizures (P < .01), and higher quantitative cryptococcal cultures (P < .001), whereas participants with ICP <200 mm H2O were more likely to have baseline sterile CSF cultures (P < .001) and CSF white blood cell count ≥5 cells/µL (P = .02). Thirty-day mortality was higher in participants with baseline ICP >350 mm H2O and ICP <200 mm H2O as compared with baseline ICP 200–350 mm H2O (hazard ratio, 1.55 [95% confidence interval, 1.10–2.19]; P = .02). Among survivors at least 7 days, the 30-day relative mortality was 50% higher among participants who did not receive any additional therapeutic LPs compared to those with ≥1 additional follow-up LP (33% vs 22%; P = .04), irrespective of baseline ICP.ConclusionsManagement of increased ICP remains crucial in improving clinical outcomes in cryptococcal meningitis. Guidelines should consider an approach to therapeutic LPs that is not dictated by baseline ICP.

Letermovir Prophylaxis for Cytomegalovirus Infection in Children After Hematopoietic Cell Transplantation

Cytomegalovirus (CMV) infection is one of the major causes of morbidity following hematopoietic cell transplantation (HCT). Allogeneic HCT (allo-HCT) recipients are at the highest risk of clinically significant CMV reactivation. While letermovir has been approved for prophylactic use in CMV seropositive adults, reports on pediatric data are very limited. The objective of the study was to examine the use of letermovir for prophylaxis from CMV infection in children undergoing allo-HCT in a single center. This retrospective matched-pair analysis study included 39 CMV-seropositive pediatric patients undergoing allo-HCT receiving letermovir as a primary prophylaxis for CMV infection on a compassionate-use basis (LMV group, n=13) or not (control group, n=26). There were no differences in basic characteristics between the analyzed groups. Among patients of the study group, 12 received primary prophylaxis with letermovir from day +1 after HCT. One patient, previously treated with ganciclovir received secondary prophylaxis from day +18. Prophylactic dose of letermovir was adjusted to cyclosporine co-administration, varied in between 120-480 mg, and given orally, once daily. No CMV reactivation was observed during administration of letermovir. Cumulative incidence of CMV reactivation was significantly higher for the control group not receiving prophylaxis. Of the 13 patients of the study group, three died; however, deaths were not attributable to CMV infection. We did not observe any toxicities related to letermovir. Our data support letermovir prophylaxis efficacy and safety in pediatric patients after allo-HCT. Compared with the historical group, prophylactic use of letermovir decreased the number of CMV reactivations in children.

Antibody Titers Against Human Cytomegalovirus gM/gN and gB Among Pregnant Women and Their Infants.

Congenital CMV (cCMV) infection can affect infants born to mothers with preconceptional seroimmunity. To prevent cCMV due to nonprimary maternal infection, vaccines eliciting responses exceeding natural immunity may be required. Anti-gM/gN antibodies have neutralizing capacity in-vitro and in animal models, but anti-gM/gN antibodies have not been characterized among seroimmune pregnant women. Paired maternal and infant cord sera from 92 CMV seropositive mothers and their full-term or preterm infants were tested for anti-gM/gN antibody titers in comparison with anti-gB titers and neutralizing activity. Anti-gM/gN titers were significantly lower than anti-gB titers for all groups and did not correlate with serum neutralizing capacity. Further study is needed to determine if higher anti-gM/gN antibody titers might enhance serum neutralizing capacity among seropositive adults.

Role of ABO Blood Group in SARS-CoV-2 Infection in Households.

An association between certain ABO/Rh blood groups and susceptibility to SARS-CoV-2 infection has been proposed for adults, although this remains controversial. In children and adolescents, the relationship is unclear due to a lack of robust data. Here, we investigated the association of ABO/Rh blood groups and SARS-CoV-2 in a multi-center study comprising 163 households with 281 children and 355 adults and at least one SARS-CoV-2 seropositive individual as determined by three independent assays as a proxy for previous infection. In line with previous findings, we found a higher frequency of blood group A (+ 6%) and a lower frequency of blood group O (−6%) among the SARS-CoV-2 seropositive adults compared to the seronegative ones. This trend was not seen in children. In contrast, SARS-CoV-2 seropositive children had a significantly lower frequency of Rh-positive blood groups. ABO compatibility did not seem to play a role in SARS-CoV-2 transmission within the families. A correction for family clusters was performed and estimated fixed effects of the blood group on the risk of SARS-CoV-2 seropositivity and symptomatic infection were determined. Although we found a different distribution of blood groups in seropositive individuals compared to the reference population, the risk of SARS-CoV-2 seropositivity or symptomatic infection was not increased in children or in adults with blood group A or AB versus O or B. Increasing age was the only parameter positively correlating with the risk of SARS-CoV-2 infection. In conclusion, specific ABO/Rh blood groups and ABO compatibility appear not to predispose for SARS-CoV-2 susceptibility in children.

Chest radiograph patterns and their correlation with CD4 count in adults with Human Immunodeficiency Virus (HIV) in Lagos University Teaching Hospital, Nigeria

The only available treatment for Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) at the moment is antiretroviral therapy (ART). The chest radiograph patterns in adults with HIV could be used as an alternative or surrogate to CD4 count in monitoring the progress of treatment in resource poor settings where these tests and expertise are not available. This study was aimed at evaluating chest the radiograph patterns in HIV sero-positive adults and correlating with the CD4 cells count. This was a cross-sectional study conducted among patients diagnosed of HIV using the National algorithm at the HIV Clinic of the Lagos University Teaching Hospital. A purposive sampling method was employed and three hundred and twenty (320) HIV sero-positive adult participants were recruited. Postero-anterior chest x-ray projection was performed on all the participants and the radiographs were reported by two consultant Radiologists and the CD4 counts was determined. Pulmonary TB was the most frequent finding (22.1%) while bronchitis was the least frequent finding (0.9%). and normal radiograph (52.6%). The CD4 count was less than, 200 cells/mm3 in 38.3% of the participants. There was a strong correlation between chest radiograph patterns and CD4 cells count (r=-0.53; p=0.001). This study revealed that the most predominant radiographic patterns are Pulmonary Tuberculosis. A strong negative correlation was observed between chest radiograph patterns and CD4 count. The Chest radiograph patterns may be recommended as a measure of immunosuppression in adults with HIV in Nigeria.

Binding and neutralizing antibody responses to SARS-CoV-2 in very young children exceed those in adults.

BackgroundSARS-CoV-2 infections are frequently milder in children than adults, suggesting that immune responses may vary with age. However, information is limited regarding SARS-CoV-2 immune responses in young children.MethodsWe compared receptor binding domain–binding antibody (RBDAb) titers and SARS-CoV-2–neutralizing antibody titers, measured by pseudovirus-neutralizing antibody assay in serum specimens obtained from children aged 0–4 years and 5–17 years and in adults aged 18–62 years at the time of enrollment in a prospective longitudinal household study of SARS-CoV-2 infection.ResultsAmong 56 seropositive participants at enrollment, children aged 0–4 years had more than 10-fold higher RBDAb titers than adults (416 vs. 31, P < 0.0001) and the highest RBDAb titers in 11 of 12 households with seropositive children and adults. Children aged 0–4 years had only 2-fold higher neutralizing antibody than adults, resulting in higher binding-to-neutralizing antibody ratios compared with adults (2.36 vs. 0.35 for ID50, P = 0.0004).ConclusionThese findings suggest that young children mount robust antibody responses to SARS-CoV-2 following community infections. Additionally, these results support using neutralizing antibody to measure the immunogenicity of COVID-19 vaccines in children aged 0–4 years.FundingCDC (award 75D30120C08737).