Determination of COVID-19 Late Disorders as Possible Long-COVID and/or Vaccination Consequences.

In this era in which the vast majority of the global population have developed COVID-19 infection and/or got vaccinated against it, identification of the late disorders as the vaccines' side effect or long-COVID manifestation seems essential. This study included the vaccinated individuals of 4 different vaccine regimens including inactivated virus-based, subunit protein, and adenovirus-based vaccines in a follow-up schedule 6-month post the booster shot. All the documented vaccine adverse events were thoroughly assessed considering the cases' medical history by Adverse Events Committee of Pasteur Institute of Iran. Totally 329 individuals who got 3 doses of vaccination were followed 6 months after the booster shots among whom 41 (12.4%) cases with the mean age of 40.9 ± 10.48 years had a type of disorder. Gynecological and osteoarticular involvements were the most common recorded disorders of which 73.1% were possibly linked to vaccination outcomes and the rest were affected by both long-COVID-19 and vaccination. Notably, the average time of symptoms persistence was 155 ± 10.4 days. This study has the advantage of long-term follow-up which presents various forms of late events in each episode of COVID-19 infection and vaccination. About 26.8% of people with persistent complications suffered from both long-COVOD/ vaccination in whom the differentiation between the vaccine side effect and long-COVID manifestation was quite challenging. Long-term follow-up studies in large population seems essential to outline the role of long-COVID and vaccination regarding persistent complications.

Potential Protectivity of a Conjugated COVID-19 Vaccine against Tetanus.

PastoCovac is a subunit protein vaccine against COVID-19 which contains the tetanus toxoid as a carrier conjugated to SARS-CoV-2 RBD. The primary goal of the tetanus application was to elicit a stronger specific response in the individuals. However, conjugate vaccines have the potency to generate anticarrier antibodies in addition to the target antigen. Therefore, the present study aimed to evaluate the PastoCovac vaccine in the humoral immune induction against tetanus. Six groups of individuals, including those who received one, two, or three doses of the PastoCovac vaccine, Td vaccine, and also the controls who received other COVID-19 vaccines (except PastoCovac), were investigated. The anti-tetanus IgG was assessed by an ELISA assay in all vaccinated groups. The antibody persistency against tetanus in the group who received one dose of the PastoCovac vaccine was also assessed on day 60, 90, and 180 after the last injection. The anti-tetanus antibody titer in the three groups of PastoCovac recipients was positive, though additional doses of the vaccine led to a significant antibody rise (p = 0.003). Notably, the comparison of the mean antibody titer between the Td recipients and those who received one/two doses of PastoCovac showed that the mean rise in the antibody titer before and after the injection was not significant. Although the antibody titer on day 180 decreased to a lower level than on day 21, it was still estimated to be highly positive against tetanus. Eventually, none of the PastoCovac recipients presented vaccine side-effects during the follow-up. The current data indicate that the tetanus conjugate vaccine against COVID-19, PastoCovac, could induce immune responses against tetanus, which can persist for at least 6 months. Combination vaccine formulae containing TT and DT as carriers for conjugate vaccines could be considered instead of TT and/or DT boosters in adults if they are indicated.

The impact of ABO blood types on humoral immunity responses and antibody persistency after different COVID-19 vaccine regimens.

This study evaluated the possible effects of blood types on coronavirus disease (COVID-19) vaccine immunogenicity and antibody (Ab) persistency. Five different vaccinated groups against COVID-19 were investigated at Pasteur Institute of Iran from April 2021 to December 2022. Anti-Spike IgG and neutralizing Ab rise were tracked on Day 21 as well as the humoral immune persistency assessment 180 after booster shots. Late adverse events up to 6 months after the booster dose were collected. The results showed that blood type A, led to a significantly higher anti-Spike Ab rise in AstraZeneca primed recipients in comparison with Sinopharm primed ones in heterologous regimens (p: 0.019). Furthermore, blood type O was a great co-effector in homologous AstraZeneca recipients regarding neutralizing Ab rise (0.013). In addition, blood type O led to a better anti-Spike Ab persistency in the Sinopharm homologous group whereas type A had the best effect on neutralizing Ab durability in the same vaccine group. What is more, Rh-positive individuals in AstraZeneca + PastoCovac Plus group had a higher rate of anti-Spike Ab rise (p = 0.001). Neutralizing Ab rise was also induced in AstraZeneca homologous and heterologous regimens of Rh-positive individuals significantly higher than Sinopharm primed cases. The present study showed the potential impact of blood types A/O and Rh-positive on a better humoral immune responses and Ab persistency. It is proposed that blood type A and Rh-positive could increase the Ab rise in AstraZeneca vaccinated individuals. Moreover, blood type O might be a better co-effector of anti-Spike Ab persistency in Sinopharm recipients.

Immunogenicity and safety of heterologous boost immunization with PastoCovac Plus against COVID-19 in ChAdOx1-S or BBIBP-CorV primed individuals.

BACKGROUND: This study aimed at evaluation and comparison of PastoCovac Plus protein-subunit vaccine in parallel with ChAdOx1-S (AstraZeneca) and BBIBP-CorV (Sinopharm) in primarily vaccinated volunteers with two doses of ChAdOx1-S or BBIBP-CorV. MATERIALS AND METHODS: 194 volunteers enrolled the study who were previously primed with 2 doses of ChAdOx1-S or BBIBP-CorV vaccines. They were divided into two heterologous regimens receiving a third dose of PastoCovac Plus, and two parallel homologous groups receiving the third dose of BBIBP-CorV or ChAdOx1-S. Serum samples were obtained just before and 4 weeks after booster dose. Anti-spike IgG and neutralizing antibodies were quantified and the conventional live-virus neutralization titer, (cVNT50) assay was done against Omicron BA.5 variant. Moreover, the adverse events data were recorded after receiving booster doses. RESULTS: ChAdOx1-S/PastoCovac Plus group reached 73.0 units increase in anti-Spike IgG rise compared to the ChAdOx1-S/ ChAdOx1-S (P: 0.016). No significant difference was observed between the two groups regarding neutralizing antibody rise (P: 0.256), indicating equivalency of both booster types. Adjusting for baseline titers, the BBIBP-CorV/PastoCovac Plus group showed 135.2 units increase (P<0.0001) in anti-Spike IgG, and 3.1 (P: 0.008) unit increase in mean rise of neutralizing antibodies compared to the homologous group. Adjustment for COVID-19 history, age, underlying diseases, and baseline antibody titers increased the odds of anti-Spike IgG fourfold rise both in the ChAdOx1-S (OR: 1.9; P: 0.199) and BBIBP CorV (OR: 37.3; P< 0.0001) heterologous groups compared to their corresponding homologous arms. The odds of neutralizing antibody fourfold rise, after adjustment for the same variables, was 2.4 (P: 0.610) for the ChAdOx1-S heterologous group and 5.4 (P: 0.286) for the BBIBP CorV heterologous groups compared to their corresponding homologous groups. All the booster types had the potency to neutralize BA.5 variant with no significant difference. The highest rate of adverse event incidence was recorded for ChAdOx1-S homologous group. CONCLUSIONS: PastoCovac Plus booster application in primed individuals with BBIBP-CorV or ChAdOx1-S successfully increased specific antibodies' levels without any serious adverse events. This vaccine could be administrated in the heterologous regimen to effectively boost humoral immune responses.

A landscape on disorders following different COVID-19 vaccination: a systematic review of Iranian case reports.

There have been massive studies to develop an effective vaccine against SARS-CoV-2 which fortunately led to manage the recent pandemic, COVID-19. According to the quite rapidly developed vaccines in a fast window time, large investigations to assess the probable vaccine-related adverse events are crucially required. COVID-19 vaccines are available of different platforms and the primary clinical trials results presented acceptable safety profile of the approved vaccines. Nevertheless, the long-term assessment of the adverse events or rare conditions need to be investigated. The present systematic review, aimed at classification of probable vaccine-related unsolicited adverse events in Iranian population through the data collection of the published case report studies.The related published case reports were explored via PubMed, Web of Science and Google scholar according to the available published data up to 14th Dec, 2022 using PRISMA guideline. Out of 437 explored studies, the relevant data were fully investigated which totally led to 40 studies, including 64 case reports with a new onset of a problem post-vaccination. The cases were then classified according to the various items, such as the type of adverse event and COVID-19 vaccines.The reported COVID-19 vaccines in the studied cases included BBIBP-CorV, ChAdOx1-S, Sputnik V and COVAXIN. The results showed that the adverse events presented in 8 different categories, including cutaneous involvements in 43.7% (n = 28), neurologic problems (n = 16), blood/vessel involvement (n = 6), cardiovascular involvement (n = 5), ocular disorders (n = 4), liver disorder/failure (n = 2), graft rejection (n = 2) and one metabolic disorder. Notably, almost 60% of the cases had no comorbidities. Moreover, the obtained data revealed nearly half of the incidences occurred after the first dose of injection and the median duration of improvement after the symptom was 10 days (range: 2-120). In addition, 73% of all the cases were either significantly improved or fully recovered. Liver failure following ChAdOx1-S vaccination was the most serious vaccine adverse event which led to death in two individuals with no related medical history.Although the advantages of COVID-19 vaccination is undoubtedly significant, individuals including with a history of serious disease, comorbidities and immunodeficiency conditions should be vaccinated with the utmost caution. This study provides a comprehensive overview and clinical implications of possible vaccine-related adverse events which should be considered in further vaccination strategies. Nevertheless, there might be a bias regarding potential under-reporting and missing data of the case reports included in the present study. Although the reported data are not proven to be the direct vaccination outcomes and could be a possible immune response over stimulation, the people the population with a medium/high risk should be monitored after getting vaccinated against COVID-19 of any platforms. This could be achieved by a carefull attention to the subjects ' medical history and also through consulting with healthcare providers before vaccination.

Evaluation of PastoCovac plus vaccine as a booster dose on vaccinated individuals with inactivated COVID-19 vaccine.

COVID-19 pandemic has been managed through global vaccination programs. However, the antibody waning in various types of vaccines came to notice. Hereby, PastoCovac Plus as a protein subunit vaccine was investigated in immunized health care workers by COVAXIN (BBV152). The booster vaccine was recommended at least three months post the second dose of COVAXIN. Sera collection was done before and after each injection. SARS-CoV-2 PCR test was done monthly to detect any asymptomatic and symptomatic vaccine breakthrough. 47.9 and 24.3% of the participants were seronegative for anti-N and anti-S antibodies three months after the second dose of COVAXIN, respectively. On average, fold-rises of 70, 93, 8 and mean-rises of 23.32, 892.4, 5.59 were recorded regarding neutralizing antibody, quantitative and semi-quantitative anti-Spike antibody, respectively. Anti-Spike and neutralizing antibodies seroconversion was seen 59.3% and 45.7%, respectively. The vaccine breakthrough assessment showed that all the isolated samples belonged to SARS-CoV-2 Delta variant. PastoCovac Plus boosting is strongly recommended in combination with inactivated vaccine platforms against SARS-CoV-2.

A Comparative Study of Immunogenicity, Antibody Persistence, and Safety of Three Different COVID-19 Boosters between Individuals with Comorbidities and the Normal Population.

Data on immunogenicity, immune response persistency, and safety of COVID-19 boosters in patients with comorbidities are limited. Therefore, we aimed to evaluate three different boosters' immunogenicity and safety in individuals with at least one underlying disease (UD) (obesity, hypertension, and diabetes mellitus) with healthy ones (HC) who were primed with two doses of the BBIBP-CorV vaccine and received a booster shot of the same priming vaccine or protein subunit vaccines, PastoCovac Plus or PastoCovac. One hundred and forty subjects including sixty-three ones with a comorbidity and seventy-seven healthy ones were enrolled. The presence of SARS-CoV-2 antibodies was assessed before the booster injection and 28, 60, 90, and 180 days after it. Moreover, the adverse events (AEs) were recorded on days 7 and 21 postbooster shot for evaluating safety outcomes. Significantly increased titers of antispike, antiRBD, and neutralizing antibodies were observed in both UD and HC groups 28 days after the booster dose. Nevertheless, the titer of antispike IgG and anti-RBD IgG was lower in the UD group compared to the HC group. The long-term assessment regarding persistence of humoral immune responses showed that the induced antibodies were detectable up to 180 days postbooster shots though with a declined titer in both groups with no significant differences (p > 0.05). Furthermore, no significant difference in antibody levels was observed between each UD subgroup and the HC group, except for neutralizing antibodies in the hypertension subgroup. PastoCovac Plus and PastoCovac boosters induced a higher fold rise in antibodies in UD individuals than BBIBP-CorV booster recipients. No serious AEs after the booster injection were recorded. The overall incidence of AEs after the booster injection was higher in the UD group than the HC group among whom the highest systemic rate of AEs was seen in the BBIBP-CorV booster recipients. In conclusion, administration of COVID-19 boosters could similarly induce robust and persistent humoral immune responses in individuals with or without UD primarily vaccinated with two doses of the BBIBP-CorV. Protein-based boosters with higher a higher fold rise in antibodies and lower AEs in individuals with comorbidities might be considered a better choice for these individuals.

PastoCovac and PastoCovac Plus as protein subunit COVID-19 vaccines led to great humoral immune responses in BBIP-CorV immunized individuals.

The optimal booster vaccine schedule against COVID-19 is still being explored. The present study aimed at assessment of the immunogenicity and antibody persistency of inactivated-virus based vaccine, BBIP-CorV and protein-subunit based vaccines, PastoCovac/Plus through heterologous and homologous prime-boost vaccination. Totally, 214 individuals who were previously primed with BBIBP-CorV vaccines were divided into three arms on their choice as heterologous regimens BBIBP-CorV/PastoCovac (n = 68), BBIBP-CorV/PastoCovac Plus (n = 72) and homologous BBIBP-CorV (n = 74). PastoCovac booster recipients achieved the highest rate of anti-Spike IgG titer rise with a fourfold rise in 50% of the group. Anti-RBD IgG and neutralizing antibody mean rise and fold rise were almost similar between the PastoCovac and PastoCovac Plus booster receivers. The antibody durability results indicated that the generated antibodies were persistent until day 180 in all three groups. Nevertheless, a higher rate of antibody titer was seen in the heterologous regimen compared to BBIP-CorV group. Furthermore, no serious adverse event was recorded. The protein subunit-based booster led to a stronger humoral immune response in comparison with the BBIP-CorV booster receivers. Both the protein subunit boosters neutralized SARS-CoV-2 significantly more than BBIP-CorV. Notably, PastoCovac protein subunit-based vaccine could be successfully applied as a booster with convenient immunogenicity and safety profile.

Assessment of long-term adverse events regarding different COVID-19 vaccine regimens within an 18-month follow-up study.

Early reports on coronavirus disease 2019 (COVID-19) vaccines presented the short-term adverse events (AEs). This follow-up study investigated a standard regimen based on protein subunit vaccines, PastoCovac and PastoCovac Plus, and the combinational vaccine regimens including AstraZeneca/PastoCovac Plus and Sinopharm/PastoCovac Plus. The participants were followed up to 6 months post the booster shot. All the AEs were collected through in-depth interviews using a valid researcher-made questionnaire and were evaluated regarding the association with the vaccines. Of the 509 individuals, 6.2% of the combinational vaccine participants had late AEs, of whom 3.3% suffered from cutaneous manifestations, followed by 1.1% arthralgia complaints, 1.1% with neurologic disorders, 0.3% ocular problems and 0.3% metabolic complications, with no significant difference between the vaccine regimens. For the standard regimen, 2% of the individuals experienced late AEs as (1%), neurological disorders (0.3%), metabolic problems (0.3%) and involvement of joints (0.3%). Notably, 75% of the AEs were persistent up to the end of the study. A low number of late AEs were captured in 18 months as 12 improbable, 5 unclassifiable, 4 possible and 3 probable associated AEs with the vaccine regimens. The benefits of COVID-19 vaccination far exceed the potential risks and late AEs seem to be uncommon.

Characterization of long COVID-19 manifestations and its associated factors: A prospective cohort study from Iran.

The prevalence and variety complaints of COVID-19 cases in a long term have been investigated in recent studies. The symptoms over the time are various and unpredictable which may persist several weeks after full recovery. The importance of long-COVID-19 manifestations includes its effect on the recovered cases which requires a rational management based on an accurate guideline to handle post-acute COVID-19 state. The aim of this study was to evaluate the incidence of post-acute COVID-19 syndrome and to identify the associated risk factors as well as to compare new and persistent symptoms at different post-acute phases. Totally 254 individuals from Pasteur Institute of Iran (or/and their relatives) were investigated who had a previously confirmed COVID-19 PCR test. The long-term manifestations of the virus were categorized through a time window as acute, ongoing, post-COVID and persistent phases and the individuals were assessed by the face-to-face or the phone call interview according to their complaints. The data were then statistically analyzed to determine the frequency of the symptoms and also the associated factors in which a p value < 0.05 was considered significant. Except a small asymptotic group of five, 249 cases progressed the symptoms to acute phase among which 64.1% reported at least one symptom in post-acute phase. Neurological sequelae were found as the most frequent symptom (91.6%). Furthermore, there was a significant association between the underlying diseases, age and acute phase symptoms to the post-acute phase syndrome susceptibility (p < 0.05). In conclusion, the increasing number of the reports and studies on long COVID-19 which can hugely affect the life quality should be more investigated and explored in terms of the pathophysiology to achieve appropriate treatments in time. The clusters of symptoms, specially a combination of neurological signs, presenting over months after the recovery impose a huge difficulty to the recovered population.

Determination of Human Papillomavirus Type 18 Lineage of E6: A Population Study from Iran.

The epidemiological studies in Iran on HPV18 nucleotide changes are rare. This type of virus is prevalent in the Iranian population. Therefore, in the present study, we aimed to identify the genetic variability in HPV18 in the E6 region to evaluate the prevalence of lineage distribution and sublineages in a sample population in Iran. Overall, 60 HPV18 confirmed cases were investigated between 2019 and 2021. The specimens were collected, and molecular genotyping was done using the Linear Array HPV Genotyping Test. DNA extraction was performed by a viral DNA/RNA kit. The HPV E6 gene was amplified by using type-specific primers designed according to the HPV18 genome prototype sequence. The sequencing of the E6 region was successfully done on 43 samples which were then compared to the reference sequence. The most frequent sublineage of HPV18 in this study was A4 (69.7%), followed by A1 (18.6%) and A3 (11.6%). Neither A2 nor A5 sublineage was not detected in this study. The related nucleotide acid changes according to the main references were as follows: A3: T104C/T232G/T485C/C549A, A4: T104C/T485C/C549A. The predominance of A lineage with the high frequency of A4 sublineage was found in the present research. The importance of sublineages in susceptibility to a progressive form of infection requires to be more investigated among the different population.

Comparing Outcomes of Two Antiviral Therapy Combinations among COVID-19 Patients.

Several therapeutic regimens for COVID-19 have been studied, such as combination antiviral therapies. We aimed to compare outcome of two types of combination therapies atazanavir/ritonavir (ATV/r) or lopinavir/ritonavir (LPV/r) plus hydroxychloroquine among COVID-19 patients. 108 patients with moderate and severe forms of COVID-19 were divided into two groups (each group 54 patients). One group received ATV/r plus hydroxychloroquine, and the other group received hydroxychloroquine plus LPV/r. Then, both groups were evaluated and compared for clinical symptoms, recovery rates, and complications of treatment regimens. Our findings showed a significant increase in bilirubin in ATV/r-receiving group compared to LPV/r receivers. There was also a significant increase in arrhythmias in the LPV/r group compared to the ATV/r group during treatment. Other findings including length of hospital stay, outcome, and treatment complications were not statistically significant. There is no significant difference between protease inhibitor drugs including ATV/r and LPV/r in the treatment of COVID-19 regarding clinical outcomes. However, some side effects such as hyperbilirubinemia and arrhythmia were significantly different by application of atazanavir or lopinavir.

No evidence of occult HBV infection in population born after mass vaccination.

Despite access to efficient hepatitis B virus (HBV) vaccine and universal immunization schedules, HBV infection remains a global health concern. HBV infection has decreased by this program. Nevertheless, breakthrough infections occur due to generation of occult HBV infection (OBI) and surface gene mutants in the immunized population. We aimed to determine the presence of OBI in a population born after initiation of nationwide HBV vaccination in Tehran, Iran. A HBV mass vaccination schedule was launched in Iran in 1993. For this study, we enrolled 1120 cases younger than 24 years. ELISA was applied to evaluate the presence of HBsAg, anti-HBs and anti-HBc. HBV-DNA presence was determined in all HBsAg-negative cases using nested polymerase chain reaction. The prevalence of HBsAg, anti-HBc and anti-HBs was 0.1, 0.54 and 39.9% respectively. Out of 6 anti-HBc-positive individuals, 4 cases also had anti-HBs. One case revealed HBsAg co-existence and the other one showed isolated anti-HBc. HBV-DNA was not detected in HBsAg-negative specimens. A very low prevalence of HBsAg and isolated anti-HBc was observed and no occult HBV infection was detected. It seems that evasion mutants are not a potential threat for HBV universal immunization efficacy in the vaccinated population.

Prevalence of Toxoplasma gondii Antibodies and DNA in Iranian HIV Patients.

BACKGROUND & OBJECTIVE: Toxoplasma gondii infection has public health importance and can lead to serious diseases in immunosuppressed patients, such as HIV cases. Appropriate control of T. gondii infection in HIV patients requires information about the prevalence of T. gondii antibodies and DNA in different population. In this study, we aimed to determine the prevalence of Toxoplasma gondii antibodies and DNA in HIV patients in Tehran, Iran. METHODS: A total of 149 HIV patients from the Iranian Research Center for HIV/AIDS, Tehran, Iran were enrolled in the study. Anti-Toxoplasma IgG and IgM were detected by ELISA and T. gondii DNA was evaluated by PCR and quantita- tive real-time PCR. IgG positive samples were also assessed for their avidity. RESULTS: Anti-Toxoplasma IgG and IgM were positive in 46.3% and 2.7% of cases respectively. 92.7% of our patients showed past infection and 4.3% revealed recently acquired toxoplasmosis based on their IgG avidity test. T. gondii DNA was not detected by PCR but real-time PCR results showed DNA in 4.7% of total patients and 13.1% of the IgG seropositive cases. CONCLUSION: Our findings indicated that latent toxoplasmosis was relatively prevalent in our study population, but new T. gondii infection had low prevalence. Almost half of our patients were IgG negative and at risk of acquiring toxoplasma infection. Low copy numbers of DNA were detected in 4.7% of the cases without any clinical manifestation. Therefore, detection and monitoring of anti-Toxoplasma antibodies and DNA in HIV patients is substantial to estimate the risk of reactivation and new infection.

Naturally occurring NS5A and NS5B resistant associated substitutions in HCV and HCV/HIV patients in iranian population.

BACKGROUND: The introduction of direct acting antivirals (DAAs) for hepatitis C virus (HCV) treatment promises shorter treatment duration, higher cure rates and fewer side effects. Naturally, occurring Resistance Associated Substitutions (RASs) are major challenge to the success of the HCV antiviral therapy. AIM: To determine the naturally occurring NS5A and NS5B RASs in Iranian HCV and HCV/human immunodeficiency virus (HIV) patients. METHODS: A total of 209 DAA-naïve chronic HCV patients including 104 HCV mono-infected and 105 HCV/HIV co-infected cases were enrolled. Amplification and Sanger population sequencing of NS5A and NS5B regions of HCV genome were carried out. The amino acid sequence diversity of the NS5A and NS5B regions were analyzed using geno2pheno HCV. RESULTS: NS5A RASs were detected in 25.5% of HCV and 16.9% of HCV/HIV subjects. In HCV cases, clinically relevant RASs were L28M followed by M28Vand Q30H and Y93H/N. In HCV/HIV subjects, clinically relevant RASs were Y93H/N followed by L28M and P58T and M28V/T and Q30R. NS5B RASs were observed in 11.8% of HCV and 5.9% of HCV/HIV subjects. Clinically relevant substitutions were included V321A/I, C316Y, S282R and L159F. The major S282T mutation was not observed. CONCLUSION: The emergence of RASs is a growing issue in the setting of current treatment with DAAs. Although currently, screening of RASs is recommended before specific DAA regimens, it should be consider in patients with therapeutic failure and in the cases of retreatment.

Significance of serum antibodies against HPV E7, Hsp27, Hsp20 and Hp91 in Iranian HPV-exposed women.

BACKGROUND: Among different types of human papillomavirus (HPV), types 16 and 18 were known to be high-risk agents causing mainly cervical cancer. Up to now, the potential of HPV E7 protein has been proved as a diagnostic marker of cervical cancer. Moreover, the levels of anti-heat shock protein (Hsp) and anti-high mobility group box-1 (HMGB1) antibodies in cancer patients have been useful in tumor diagnosis. The goal of the present study was to determine the efficiency of the potential serologic markers including HPV E7, Hsp20, Hsp27 proteins and Hp91 peptide in Iranian HPV-exposed women, for the first time. METHODS: At first, the recombinant HPV E7, Hsp20 and Hsp27 proteins were expressed in E. coli system, and purified by affinity chromatography under native conditions. Then, antibody responses were detected against the recombinant proteins as well as Hp91 peptide as potential markers in 49 Iranian women who were seropositive for HPV-16 and 18 L1 capsids (i.e., HPV-exposed women) and 49 controls using indirect ELISA. RESULTS: Our data indicated that the seroreactivities of women exposed to HPV16, HPV18 and both of them against the recombinant E7, Hsp20, Hsp27 proteins and Hp91 peptide were significantly higher than those in control group (p < 0.05 for HPV16 or HPV18; p < 0.01 for both of them versus all markers). HPV-exposed women with high antibody responses to HPV-16 and 18 L1 capsids as a commercial biomarker had significant seroreactivity to HPV-16 and 18 E7 and Hsp27 (p < 0.05). The recombinant E7 and Hsp27 proteins showed higher efficiency than Hsp20 and Hp91 for detection of individuals exposed to HPV infections (p < 0.05). CONCLUSION: Generally, the levels of serum E7 and Hsp27 were increased in HPV-16 and 18 L1- seropositive women suggesting their potential value as a diagnostic marker for HPV infections.

5-ALA-induced fluorescence as a marker for diagnostic tissue in stereotactic biopsies of intracranial lymphomas: experience in 41 patients.

OBJECTIVE Stereotactic needle biopsies are usually performed for histopathological confirmation of intracranial lymphomas to guide adequate treatment. During biopsy, intraoperative histopathology is an effective tool to avoid acquisition of nondiagnostic samples. In the last years, 5-aminolevulinic acid (5-ALA)-induced fluorescence has been increasingly used for visualization of diagnostic brain tumor tissue during stereotactic biopsies. Recently, visible fluorescence was reported in the first cases of intracranial lymphomas as well. The aim of this study is thus to investigate the technical and clinical utility of 5-ALA-induced fluorescence in a large series of stereotactic biopsies for intracranial lymphoma. METHODS This prospective study recruited adult patients who underwent frameless stereotactic needle biopsy for a radiologically suspected intracranial lymphoma after oral 5-ALA administration. During biopsy, samples from the tumor region were collected for histopathological analysis, and presence of fluorescence (strong, vague, or no fluorescence) was assessed with a modified neurosurgical microscope. In tumors with available biopsy samples from at least 2 different regions the intratumoral fluorescence homogeneity was additionally investigated. Furthermore, the influence of potential preoperative corticosteroid treatment or immunosuppression on fluorescence was analyzed. Histopathological tumor diagnosis was established and all collected biopsy samples were screened for diagnostic lymphoma tissue. RESULTS The final study cohort included 41 patients with intracranial lymphoma. Stereotactic biopsies with assistance of 5-ALA were technically feasible in all cases. Strong fluorescence was found as maximum level in 30 patients (75%), vague fluorescence in 2 patients (4%), and no visible fluorescence in 9 patients (21%). In 28 cases, samples were obtained from at least 2 different tumor regions; homogenous intratumoral fluorescence was found in 16 of those cases (57%) and inhomogeneous intratumoral fluorescence in 12 (43%). According to histopathological analysis, all samples with strong or vague fluorescence contained diagnostic lymphoma tissue, resulting in a positive predictive value of 100%. Analysis showed no influence of preoperative corticosteroids or immunosuppression on fluorescence. CONCLUSIONS The data obtained in this study demonstrate the technical and clinical utility of 5-ALA-induced fluorescence in stereotactic biopsies of intracranial lymphomas. Thus, 5-ALA can serve as a useful tool to select patients not requiring intraoperative histopathology, and its application should markedly reduce operation time and related costs in the future.

Seroprevalence, molecular epidemiology and quantitation of parvovirus B19 DNA levels in Iranian blood donors.

Human parvovirus B19 (B19) infection is common among blood donors, and healthy blood donors can transmit virus via transfusion. Due to resistance of B19 to viral inactivation methods, there is a potential concern regarding transfusion safety in blood products. We aimed to determine the seroprevalence, molecular epidemiology, and quantitation of B19 DNA levels in blood donors in Tehran, Iran. A total of 500 blood donors from Blood Transfusion Research Center were studied. ELISA was used for detection of B19 IgG and IgM and nested PCR was carried out for detection of B19 DNA. PCR products were subjected to direct sequencing. B19 viral load was determined by real time PCR. B19 IgG, IgM, and DNA were detected in 27.6, 2.6, and 1.2% of donors respectively. Ten samples (2%) were positive for both antibodies while in four cases (0.8%), B19 IgG and DNA detected simultaneously. One case had B19 IgM, IgG, and viremia concurrently. The titers of B19 DNA in four of six donors were more than 106 IU/mL (high level viremia) and all four cases had IgG simultaneously. All B19 isolates categorized in genotype 1A. Our findings indicated that prevalence of B19 DNA in Iranian blood donors was comparable with previous studies throughout the world. High level B19 viremia found in 0.8% of our donors and all viremic donors revealed neutralizing B19 antibody. Therefore implementation of a B19 screening test for each volunteer blood donor does not appear to be necessary but B19 testing for plasma-derived products seems important in Iranian donors.

No Role of Herpes Simplex Virus Type 2 (HSV-2) Infection on HIV Progression in Naïve HIV Patients

Background: Herpes simplex virus type 2 (HSV-2) is a common infection in human immunodeficiency virus (HIV) patients and may accelerate HIV progression by rising HIV viral load and decreasing CD4 count. However, the available data regarding the influence of HSV-2 seropositivity on HIV progression in HIV individuals are inconclusive. Therefore, we aimed to determine HSV-2 seroprevalence in naïve HIV patients and normal controls and also investigate the relation of HIV viral load and CD4 count with HSV-2 seropositivity. Subsequently, we investigated the association of HSV-2 serostatus with changing in CD4 count and HIV viral load in our subjects, after one year follow-up. Methods: In this study, 116 naïve HIV patients and 85 healthy controls from Tehran, Iran were enrolled. HSV-2 IgG antibody was detected by ELISA. CD4 count was determined by flowcytometry, and serum HIV RNA copy numbers were determined using real-time PCR. Results: The prevalence of HSV-2 IgG was 18.1% in naïve HIV patients and 0% in the control group (P=0.000). HSV-2 seroconversion was observed in 2.43% of HIV patients after one year. There was no significant difference regarding HSV-2 serostatus with CD4 count and HIV RNA viral load in our study cohort at baseline and after one year. Conclusion: Our results revealed that the prevalence and incidence of HSV-2 infection are low in our HIV cases, and it is negligible in control group. However, it seems that HIV/HSV2 co-infection has no role on HIV infection acceleration.

Gender and age-specific seroprevalence of human papillomavirus 16 and 18 in general population in Tehran, Iran.

The assessment of the gender and age-specific seroprevalence of human papillomavirus (HPV) is essential for planning of HPV vaccine implementation into the preventive programs. In this study, we aimed to determine the age-specific seroprevalence of HPV-16 and 18 in both males and females in Tehran, Iran. Three hundred and seventy-eight women (10-35 years) and 162 men (10-25 years) from Tehran, Iran, were enrolled. Anti-HPV IgG antibodies against HPV-16 and HPV-18 were detected by ELISA using papillomavirus type 16 and 18 L1-capsids as antigen. HPV-16 antibody was detected in 15.6 and 13.6% of women and men, respectively. Antibody against HPV-18 was found positive in 12.7 and 8% of women and men, respectively. The highest seroprevalence of HPV-16 and 18 were seen in women aged 26-30 years (22.2 and 19.4%, respectively), and the lowest HPV-16 and 18 seropositivity rates were seen in males and females aged 10-15 years (9.3 and 1.9%, respectively). In our cohort of study, in males, both anti-HPV-16 and 18 increased after age 15 years, peaking in men aged 21-25 years. In women, both HPV-16 and 18 seropositivity increased after 15 years, declined at 21-25 years, peaked in women aged 26-30 years and again decreased after 30 years. Our data showed increasing exposure rate to high-risk HPV vaccine types in our studied population over 15 years of age. In order to prevent the HPV-related cancers, implementation of HPV vaccine into the national immunization program in Iran and vaccination of females and males less than 15 years of age are suggested.