Spontaneous Clearance Of Infection Research Articles

Convergent antibody responses are associated with broad neutralization of hepatitis C virus.

Early development of broadly neutralizing antibodies (bNAbs) targeting the hepatitis C virus (HCV) envelope glycoprotein E2 is associated with spontaneous clearance of infection, so induction of bNAbs is a major goal of HCV vaccine development. However, the molecular antibody features important for broad neutralization are not known. To identify B cell repertoire features associated with broad neutralization, we performed RNA sequencing of the B cell receptors (BCRs) of HCV E2-reactive B cells of HCV-infected individuals with either high or low plasma neutralizing breadth. We then produced a monoclonal antibody (mAb) expressed by pairing the most abundant heavy and light chains from public clonotypes identified among clearance, high neutralization subjects. We found distinctive BCR features associated with broad neutralization of HCV, including long heavy chain complementarity determining region 3 (CDRH3) regions, specific VH gene usage, increased frequencies of somatic hypermutation, and particular VH gene mutations. Most intriguing, we identified many E2-reactive public BCR clonotypes (heavy and light chain clones with the same V and J-genes and identical CDR3 sequences) present only in subjects who produced highly neutralizing plasma. The majority of these public clonotypes were shared by two subjects who cleared infection. A mAb expressing the most abundant public heavy and light chains from these clearance, high neutralization subjects had features enriched in high neutralization clonotypes, such as increased somatic hypermutation frequency and usage of IGHV1-69, and was cross-neutralizing. Together, these results demonstrate distinct BCR repertoires associated with high plasma neutralizing capacity. Further characterization of the molecular features and function of these antibodies can inform HCV vaccine development.

Susceptible-infected-susceptible model of disease extinction on heterogeneous directed population networks

Understanding the spread of diseases through complex networks is of great interest where realistic, heterogeneous contact patterns play a crucial role in the spread. Most works have focused on mean-field behavior-quantifying how contact patterns affect the emergence and stability of (meta)stable endemic states in networks. On the other hand, much less is known about longer time scale dynamics, such as disease extinction, whereby inherent process stochasticity and contact heterogeneity interact to produce large fluctuations that result in the spontaneous clearance of infection. Here we show that heterogeneity in both susceptibility and infectiousness (incoming and outgoing degree, respectively) has a nontrivial effect on extinction in directed contact networks, both speeding up and slowing down extinction rates depending on the relative proportion of such edges in a network, and on whether the heterogeneities in the incoming and outgoing degrees are correlated or anticorrelated. In particular, we show that weak anticorrelated heterogeneity can increase the disease stability, whereas strong heterogeneity gives rise to markedly different results for correlated and anticorrelated heterogeneous networks. All analytical results are corroborated through various numerical schemes including network Monte Carlo simulations.

Hepatitis C virus-specific immune responses following direct-acting antivirals administered during recent hepatitis Cvirus infection.

Individuals who spontaneously clear hepatitis C virus (HCV) infection have demonstrated evidence of partial protective immunity, whereas treatment-induced clearance provides little or no protection against reinfection. We aimed to investigate whether treatment of acute HCV infection with direct-acting antivirals (DAA) prevents establishment of, or reverses, T-cell exhaustion, leading to a virus-specific T-cell immune profile more similar to that seen in spontaneous clearance. The magnitude and breadth of HCV-specific T-cell responses before and after DAA or interferon-based therapy in acute or chronic HCV were compared to those of participants with spontaneous clearance of infection, using Enzyme-linked Immunospot (ELISPOT). PBMCs were available for 55 patients comprising 4 groups: spontaneous clearance (n= 17), acute interferon (n= 14), acute DAA (n= 13) and chronic DAA (n= 11). After controlling for sex, the magnitude of post-treatment HCV-specific responses after acute DAA treatment was greater than after chronic DAA or acute IFN treatment and similar to those found in spontaneous clearers. However, spontaneous clearers responded to more HCV peptide pools indicating greater breadth of response. In conclusion, early treatment with DAAs may prevent or reverse some degree of immune exhaustion and result in stronger HCV-specific responses post-treatment. However, individuals with spontaneous clearance had broader HCV-specific responses.

Spontaneous clearance of genital and extragenital Neisseria gonorrhoeae: data from GToG

ObjectivesNeisseria gonorrhoeae (NG) infection can resolve without antibiotic treatment, however the literature describing the frequency of clearance at individual sites, how rapidly it occurs and potential predictive factors is limited....

Long-term follow-up of the incidence of Helicobacter pylori

ObjectivesHelicobacter pylori causes peptic ulcer disease and gastric cancer. Understanding the incidence of H. pylori could help guide research on potential infection prevention strategies. Previous studies indicate infection occurs in young children, but the risk of infection in older children and adolescents is unclear. Our hypothesis was that H. pylori infection is rare in adolescence or adulthood. Our aim was to determine the incidence of H. pylori over a prolonged follow-up in a cohort of 626 noninfected individuals. MethodsParticipants, including index children, mothers, fathers and siblings, from a previous study (1997–2002) were traced, and 883 of 946 participated in this extended follow-up. We used the 13C urea breath test (13C-UBT) to determine the incidence of H. pylori among 626 family members not infected in 2002, including 75 younger siblings who were not born or too young for testing in 2002. ResultsEight (3.8%) of 210 index participants (mean ± standard deviation age 17.92 ± 0.77 years) became infected during 11.07 ± 0.56 years of follow-up (incidence, 3.42 per 1000 person-years; 95% confidence interval (CI), 1.48–6.74). Only one (0.6%) of 165 older siblings became infected (incidence, 0.57 per 1000 person-years; 95% CI, 0.007–3.16) and one of 176 parents became infected (incidence, 0.63 per 1000 person-years; 95% CI, 0.01–3.5). Of 75 younger siblings (age 10.9 ± 2.85 years) who were too young for testing or not yet born in 2002, nine (12%) became infected (incidence, 11.32 per 1000 person-years; 95% CI, 5.27–21.49). The highest incidence of H. pylori infection was in those born after 2005. ConclusionsThe incidence of H. pylori was extremely low in older children and adults in developed countries. Spontaneous clearance of infection was uncommon in our study population.

Interferon λ3 gene (IL28B) is associated with spontaneous or treatment-induced viral clearance in hepatitisC virus-infected multitransfused patients with thalassemia.

Hepatitis C virus (HCV) is the major posttransfusion infection in multitransfused individuals in India with thalassemia major. To our knowledge, this study is the first conducted to correlate and comprehend the effects of the host interleukin (IL)28B gene polymorphism at loci rs12979860 and rs8099917 in spontaneous or interferon (IFN)-induced treatment response in the HCV-seroreactive individuals with thalassemia major. A total of 557 HCV-seroreactive individuals with thalassemia were processed for HCV viral genotyping and host IL28B single-nucleotide polymorphism analysis at loci rs12979860 and rs8099917. Of 557 individuals, 70.92% were found to be HCV RNA positive with Genotype 3 (95.18%) as predominant strain. A favorable CC allele at locus rs2979860 and TT allele at rs8099917 were 75.31 and 77.16%, respectively, which was strongly associated with spontaneous clearance of infection (p < 0.05). Of 85 IFN-treated cases, 56 achieved sustained virologic response (SVR) whereas 27 were relapsed cases. Among these patients who achieved SVR, a favorable CC/TT allele at rs12979860/rs8099917 was found to be predominant with 76.79 and 66.07%, respectively, whereas in the case of relapsed patients, unfavorable CT (55.56%) and TG (59.26%) alleles were found to be predominant. Additionally, low serum ferritin level was significantly associated with SVR. CC at rs12979860 and TT at rs8099917 was strongly associated with spontaneous clearance and SVR in the population with thalassemia. Low age group and low serum ferritin level are important cofactors. This allelic pattern will aid clinicians in making an informed decision about prognosis and therapeutic management.

The Impact of IFN-γ Gene Polymorphisms on Spontaneous Clearance of HCV Infection in Fars Province, Southern of Iran.

Certain polymorphisms in cytokine genes such as IFN-γ may influence the outcome of hepatitis C virus (HCV) infection. Here the frequency of the genotype, allele, and haplotype of IFN-γ gene at some loci is investigated in HCV-infected patients. Totally 255 patients with chronic HCV infection and 44 spontaneously cleared individuals were included. The chronic or clearance states were confirmed using enzyme-linked immunosorbent assay (ELISA) and two different qualitative reverse transcriptase polymerase chain reaction (RT-PCR) techniques. IFN-γ gene polymorphisms were performed by PCR using sequence-specific primers and PCR-RLFP on extracted genomic DNA. The frequency of GG genotype (P = 0.0001, OR: 5.69 and CI: 2.21-14.62) and allele (P = 0.0003, OR: 2.73 and CI: 1.54-4.83) of IFN-γ gene at +2109 locus was significantly higher in cases that spontaneously cleared the infection. Haplotype analysis showed the association of AG haplotype (P = 0.0046, OR = 6.14 and CI = 1.56-25) with spontaneous clearance of the infection. Our finding indicated that individuals with GG genotype at +2109 loci of IFN-γ gene and also AG haplotype (A allele at +874 loci and G allele at +2109 loci) may clear HCV infection more frequently than those with AA and AG genotype at +2109 loci and AA, TA, and TG haplotype.

Helicobacter pylori and Effects on Iron Status in Children: Delineating Causality

<i>Helicobacter pylori</i> and Effects on Iron Status in Children: Delineating Causality

Cellular Immune Responses against Hepatitis C Virus

Cellular immune responses are typically important in recovery from acute infections, and studies of acute hepatitis C confirm that broadly directed CD4+ and CD8+ T cell responses are associated with spontaneous clearance of infection. However, a major unanswered question is what role the cellular immune response plays in progression of liver disease during chronic infection. Classic models of hepatitis C suggest that cellular immune responses promote liver injury, either by causing direct cytolysis of infected cells or by promoting inflammation. However, clinical evidence suggests that persons with cellular immune dysfunction, such as that due to with human immunodeficiency virus (HIV) infection, have more-rapid disease progression. Recent data suggest that cellular immune responses do serve to limit the progression of liver disease, even if they are ineffective at clearance of virus. There is limited information on the effect of HIV coinfection on the cellular immune response to hepatitis C virus, but further study of this issue might shed light on the pathogenesis of liver disease in both immunocompromised and nonimmunocompromised hosts.

13C Urea Breath Testing to Diagnose Helicobacter pylori Infection in Children

The casual relationship between Helicobacter pylori colonization of the gastric mucosa and gastritis has been proven. Endoscopy and subsequent histological examination of antral biopsies have been regarded as the gold standard for diagnosing H pylori gastritis. The C urea breath test is a noninvasive test with a high specificity and sensitivity for H pylori colonization. Increasingly, it is becoming an important tool for use in diagnosing H pylori infection in pediatric populations. This test is particularly well suited for epidemiological studies evaluating reinfection rates, spontaneous clearance of infection and eradication rates after therapy. However, few groups have validated the test in the pediatric age group. The testing protocol has not yet been standardized. Variables include fasting state, dose of urea labelled with 13C, delta cutoff level of 13C carbon dioxide, choice of test meal and timing of collection of expired breath samples. Further studies are urgently needed to evaluate critically the impact of H pylori infection in the children. The 13C urea breath test should prove very useful in such prospective studies.