Invasive Vibrio cholerae 01 E1 Tor Inaba in a 3-day-old neonate: Case report

A 3-day-old girl with invasive V. cholerae infection is described. Her mother had cholera in the perinatal period. Because of retracted nipples, she expressed milk and fed her infant by bottle. The infant died on the 2nd day of admission. © 2007 The Liverpool School of Tropical Medicine

Recombinant production of a novel fusion protein: Listeriolysin o fragment fused to s1 subunit of pertussis toxin

Background: Some resources have suggested that genetically inactivated PTs bear a more protective effect than chemically inactivated products. This study aimed to produce new version of PT, by cloning an inactive PTS1 in a fusion form with N-terminal half of the LLO pore-forming toxin. Methods: Deposited pdb structure file of the PT was used to model an extra disulfide bond. Codon-optimized ORF of the PTS1 was used to make recombinant constructs of PTS1 and LLO-PTS1 in the pPSG-IBA35 vector. The recombinant PTS1 and LLO-PTS1 proteins were expressed in BL21 DE3 and SHuffle T7 strains of E. coli and purified by affinity chromatography. Cytotoxic effects of the recombinant proteins were examined in the MCF-7 cell line. Results: The purity of the products proved to be more than 85, and the efficiency of the disulfide bond formation in SHuffle T7 strain was higher than BL21 DE3 strain. No cytotoxicity of the recombinant proteins was observed in MCF-7 cells. Soluble recombinant PTS1 and LLO-PTS1 proteins were produced in SHuffle T7 strain of E. coli with high efficiency of disulfide bonds formation. Conclusion: The LLO-PTS1 with corrected disulfide bonds was successfully expressed in E. coli SHuffle T7 strain. Due to the safety for human cells, this chimeric molecule can be an option to prevent pertussis disease if its immunostimulatory effects would be confirmed in the future. © 2021, Pasteur Institute of Iran. All rights reserved

Estimation of the wastage rate of MMR and pentavalent vaccines in open and closed vials in three western provinces of Iran

Background: Vaccine wastage is one of quality indicators of immunization program and high vaccine wastage will increase overall costs and impede efforts towards a more efficient and sustainable program. We aimed at estimating of the wastage rates of Measles-Mumps-Rubella (MMR) and pentavalent (diphtheria-tetanus-pertussis-hepatitis B -Haemophilus influenza type b) vaccines in different vaccine vial sizes. Study design: Multicentre descriptive study using existing data. Methods: This study was in three provinces (Hamadan, Kermanshah and Kordestan) of Iran including 131,135 populations with 2,548 under-1years children. Twenty-seven health facilities were selected randomly from nine districts in three provinces of western part of Iran. Six-months data including vaccination and vaccine stock records collected from April to September 2017. Finally, number of opened vials and number of target population vaccinated were collected and data were analysed to estimate the wastage rates in both unopened and opened vials of both antigens. Results: The wastage rate for combined MMR 2-dose and 5-dose opened vials for three provinces was 29%(Hamadan 18%, Kermanshah 14% and Kordestan 52%). The wastage rate for combined pentavalent single-dose and 10-dose vials for three provinces was 17% (in Kordestan33%, 11% Kermanshah 11% and Hamedan 3%). The total average of pentavalent single-dose and 10-dose vials wastage rate was 5% and varied 13% for urban and 3% for rural areas. The average of discarded unopened vials wastage rate in all facilities for MMR was 3.9% (3.2% for MMR 2-dose vial and 10.2% for MMR 5-dose vial). This rate was 1.7% for pentavalent total (1.9% for single dose vial and 0.4% for 10 dose vial). Conclusion: The vaccine wastage rates in Iran are in line with other countries and lower than the suggested rate based on WHO policies for multi-dose vials. The wastage rates were different for in provinces, districts and health facilities. The MMR total wastage rate in rural is higher than those in urban areas. However, the pentavalent total wastage rate was higher in urban area

Cost-effectiveness analysis of the introduction of rotavirus vaccine in Iran

Background: Although the mortality from diarrheal diseases has been decreasing dramatically in Iran, it still represents an important proportion of disease burden in children <5 years old. Rotavirus vaccines are among the most effective strategies against diarrheal diseases in specific epidemiological conditions. This study aimed to evaluate the cost-effectiveness of the introduction of rotavirus vaccine (3 doses of pentavalent RotaTeq® (RV5)) in Iran, from the viewpoints of Iran's health system and society. Methods: The TRIVAC decision support model was used to calculate total incremental costs, life years (LYs) gained, and disability-adjusted life years (DALYs) averted due to the vaccination program. Necessary input data were collected from the most valid accessible sources as well as a systematic review and meta-analysis on epidemiological studies. We used WHO guidelines to estimate vaccination cost. An annual discount rate of 3 was considered for both health gain and costs. A deterministic sensitivity analysis was performed for testing the robustness of the models results. Results: Our results indicated that total DALYs potentially lost due to rotavirus diarrhea within 10 years would be 138,161, of which 76,591 could be prevented by rotavirus vaccine. The total vaccination cost for 10 cohorts was estimated to be US 499.91 million. Also, US 470.61 million would be saved because of preventing outpatient visits and inpatient admissions (cost-saving from the society perspective). We estimated a cost per DALY averted of US 2868 for RV5 vaccination, which corresponds to a highly cost-effective strategy from the government perspective. In the sensitivity analysis, all scenarios tested were still cost-saving or highly cost-effective from the society perspective, except in the least favorable scenario and low vaccine efficacy and disease incidence scenario. Conclusion: Based on the findings, introduction of rotavirus vaccine is a highly cost-effective strategy from the government perspective. Introducing the vaccine to the national immunization program is an efficient use of available funds to reduce child mortality and morbidity in Iran. © 2014 Elsevier Ltd

Toward an Alum Free Mono-Component Monovalent Pertussis Vaccine: A Cytokine Response Assay

BACKGROUND: Current evidence indicates the resurgence of whooping cough despite high coverage of whole-cell (wP) and acellular (aP) pertussis vaccines. OBJECTIVE: To investigate the cytokine response to a genetically inactivated protein containing the S1 subunit of pertussis toxin (PTS1) with and without the Listeriolysin O (LLO-PTS1), in comparison with current wP and aP vaccines in the mice model. METHODS: Thirty-six female NMRI mice aged 8 to 12 weeks (25 ± 5 g) were divided into six groups, including control (n=6) and five treated groups (n=6/each). Treated groups received intraperitoneal injection of recombinant PTS1, recombinant fusion LLO-PTS1, aP, wP, and sham (phosphate-buffered saline), whereas the control group did not receive anything. After 60 days, the serum levels of IFN-γ, IL-4, and IL-17 cytokines were evaluated by ELISA method. RESULTS: Our findings showed LLO-PTS1 significantly increased IL-17 and IL-4 cytokines compared with wP and aP vaccines. IFN-γ failed to increase substantially in the LLO-PTS1 group compared to others, but it was non-inferior to standard vaccines. CONCLUSION: Our alum free mono-component monovalent recombinant fusion protein (LLO-PTS1) could bear the capacity to stimulate the release of IFN-γ similar to wP and aP vaccines in the mouse model. Besides, it showed better results in stimulating the release of IL-17 and IL-4 response. This study can be regarded as a platform for further probes in booster pertussis vaccine development

Cost-Effectiveness Analysis of the Introduction of HPV Vaccination of 9-Year-Old-Girls in Iran

Objectives: To estimate the cost effectiveness of introducing the quadrivalent human papillomavirus (HPV) vaccine into the national immunization program of Iran. Methods: The CERVIVAC cost-effectiveness model was used to calculate incremental cost per averted disability-adjusted life-year by vaccination compared with no vaccination from both governmental and societal perspectives. Calculations were based on epidemiologic parameters from the Iran National Cancer Registry and other national data sources as well as from literature review. We estimated all direct and indirect costs of cervical cancer treatment and vaccination program. All future costs and benefits were discounted at 3 per year and deterministic sensitivity analysis was used. Results: During a 10-year period, HPV vaccination was estimated to avert 182 cervical cancer cases and 20 deaths at a total vaccination cost of US 23,459,897; total health service cost prevented because of HPV vaccination was estimated to be US 378,646 and US 691,741 from the governmental and societal perspective, respectively. Incremental cost per disability-adjusted life-year averted within 10 years was estimated to be US 15,205 and US 14,999 from the governmental and societal perspective, respectively, and both are higher than 3 times the gross domestic product per capita of Iran (US 14,289). Sensitivity analysis showed variation in vaccine price, and the number of doses has the greatest volatility on the incremental cost-effectiveness ratio. Using a two-dose vaccination program could be cost-effective from the societal perspective (incremental cost-effectiveness ratio = US 11,849). Conclusions: Introducing a three-dose HPV vaccination program is currently not cost-effective in Iran. Because vaccine supplies cost is the most important parameter in this evaluation, considering a two-dose schedule or reducing vaccine prices has an impact on final conclusions. © 201

Cost-Effectiveness Analysis of the Introduction of HPV Vaccination of 9-Year-Old-Girls in Iran

Objectives: To estimate the cost effectiveness of introducing the quadrivalent human papillomavirus (HPV) vaccine into the national immunization program of Iran. Methods: The CERVIVAC cost-effectiveness model was used to calculate incremental cost per averted disability-adjusted life-year by vaccination compared with no vaccination from both governmental and societal perspectives. Calculations were based on epidemiologic parameters from the Iran National Cancer Registry and other national data sources as well as from literature review. We estimated all direct and indirect costs of cervical cancer treatment and vaccination program. All future costs and benefits were discounted at 3 per year and deterministic sensitivity analysis was used. Results: During a 10-year period, HPV vaccination was estimated to avert 182 cervical cancer cases and 20 deaths at a total vaccination cost of US 23,459,897; total health service cost prevented because of HPV vaccination was estimated to be US 378,646 and US 691,741 from the governmental and societal perspective, respectively. Incremental cost per disability-adjusted life-year averted within 10 years was estimated to be US 15,205 and US 14,999 from the governmental and societal perspective, respectively, and both are higher than 3 times the gross domestic product per capita of Iran (US 14,289). Sensitivity analysis showed variation in vaccine price, and the number of doses has the greatest volatility on the incremental cost-effectiveness ratio. Using a two-dose vaccination program could be cost-effective from the societal perspective (incremental cost-effectiveness ratio = US 11,849). Conclusions: Introducing a three-dose HPV vaccination program is currently not cost-effective in Iran. Because vaccine supplies cost is the most important parameter in this evaluation, considering a two-dose schedule or reducing vaccine prices has an impact on final conclusions. © 201

Molecular characterization of non-polio enteroviruses isolated from children with acute flaccid paralysis in IRAN, 2015�2018

In addition to polioviruses, non-polio enteroviruses (NPEVs) are frequently isolated from patients with acute flaccid paralysis (AFP) worldwide. In polio-free countries, there have been expectations that with disappearing wild poliovirus from the community, the rate of AFP would decrease, but the increasing number of AFP cases proved this notion to be wrong. There are speculations that NPEVs might be the cause of increasing AFP rate. The aim of this study was to investigate frequency, genetic diversity, circulation patterns of NPEVs isolated from AFP cases in Iran from 2015 to 2018. Fifty-three NPEVs were isolated from stool specimens of AFP cases during four years of AFP surveillance. Nested PCR and VP1 sequencing revealed 20 NPEV types in which Echovirus 3 (13.2), Echovirus 6 (13.2), Echovirus 7 (7.5), Echovirus 13 (7.5) and Echovirus 21 (7.5) were the most frequent. Coxsackie B viruses were isolated for the first time in AFP cases in Iran. The phylogenetic analysis of Echovirus 3 and Echovirus 6 revealed that Iranian echovirus strains belonged to the same cluster, indicating these viruses have been circulating in Iran for a long time. Compared to global Echovirus 3 and Echovirus 6 references, Echovirus 3 and Echovirus 6 strains detected in this study were closely related to Indian and Malaysia strains, respectively. The results of this study demonstrated a wide variety of NPEV types in Iranian patients, some of which had not been reported in previous studies. Moreover, this study highlights the need for NPEV surveillance in AFP cases. © 2020, Springer Science+Business Media, LLC, part of Springer Nature

The commotion project: Computational methods for moving and deforming objects in extreme waves

Ship Hydromechanics and Structure