Prevalent Serotypes Research Articles

Serotype distribution, clinical characteristics, and antimicrobial resistance of pediatric invasive pneumococcal disease in Colombia during PCV10 mass vaccination (2017-2022).

Invasive Pneumococcal Disease (IPD) causes significant morbidity and mortality in children under 5 y. Colombia introduced PCV10 vaccination in 2012, and the Neumocolombia network has been monitoring IPD in pediatric patients since 2008. This study is a secondary analysis of a prospective cohort involving pediatric patients with IPD admitted to 17 hospitals in Colombia, from January 1st, 2017, to December 31st, 2022. We present data on serotypes (Spn), clinical characteristics, and resistance patterns. We report 530 patients, 215 (40.5%) were younger than 24 months. Among these, 344 cases (64.7%) presented with pneumonia, 95 (17.9%) with primary bacteremia, 53 (10%) with meningitis, 6 (1.1%) had pneumonia and meningitis, and 32 (6%) had other IPD diagnosis. The median hospital stay was 12 days (RIQ 8-14 days), and 268 (50.6%) were admitted to the ICU, of whom 60 (11.3%) died. Serotyping was performed in 298 (56.1%). The most frequent serotypes were Spn19A (51.3%), Spn6C (7.7%), Spn3 (6.7%), Spn6A (3.6%), and Spn14 (3.6%). Of 495 (93%) isolates with known susceptibility, 46 (9.2%) were meningeal (M) and 449 (90.7%) non-meningeal (NM). Among M isolates, 41.3% showed resistance to penicillin, and 21.7% decreased susceptibility to ceftriaxone. For NM isolates, 28.2% had decreased susceptibility to penicilin, and 24.2% decreased susceptibility to ceftriaxone. Spn19A showed the highest resistant to penicillin at 47% and was linked to multiresistance. The prevalence of PCV10-included serotypes decreased, while serotypes 19A and 6C increased, with Spn19A being associated with multiresistance. These findings had played a crucial role in the decision made by Colombia to modify its immunization schedule by switching to PCV13 in July 2022.

Molecular Characteristics of Virulence Genes in Carbapenem-Resistant and Carbapenem-Sensitive Klebsiella Pneumoniae in Relation to Different Capsule Serotypes in Ningbo, China.

Klebsiella pneumoniae (KP) is a common nosocomial pathogen. Capsules are an important component of KP's virulence, among which the K1, K2, K5, K20, K54, and K57 serotypes are predominant and exhibit varying degrees of virulence. The capsule and virulence genes of 150 carbapenem-resistant Klebsiella pneumoniae (CRKP) and 213 carbapenem-sensitive Klebsiella pneumoniae (CSKP) isolates were examined by polymerase chain reaction (PCR). The isolates were tested for hypermucoviscosity by string tests. Phylogenetic relationships between KP isolates were analyzed using multilocus sequence typing (MLST) and a Galleria mellonella infection model confirmed the differences in virulence. A total of 111 of 363 isolates of KP were detected, the highest detected serotypes were K1, K5, and K2, and CSKP was detected more frequently than CRKP. There was a greater prevalence of K1 and K2 serotypes in CSKP, while in CRKP, K5 serotypes were more prevalent. K1 isolates had the highest detection rates for hypermucoviscosity Klebsiella pneumoniae (hmKP) and hypervirulent Klebsiella pneumoniae (hvKP), and carried the most virulence genes. K54 isolates had the lowest detection rate of hmKP while K5 isolates had the lowest detection rate of hvKP and carried the fewest virulence genes. MLST results for serotypes K1, K20, and K57 showed significant homogeneity, while those for serotypes K2, K5, and K54 showed diversity. The Galleria mellonella infection model showed that the K1 serotype was the most virulent and the K54 serotype was the weakest. CSKP isolates were detected more frequently than CRKP isolates for capsular serotype detection. K1 isolates had the most virulence gene and strongest virulence, K5 isolates carried the fewest virulence genes, and K54 isolates had the weakest virulence. Furthermore, significant homogeneity was observed among K1, K20, and K57 isolates.

Human papillomavirus serotypes and determinants among women with invasive cervical cancer in Katsina state, Northwest-Nigeria: a multicentre study.

Cervical cancer is the leading cause of gynaecological cancer death among women in developing countries and the most preventable of all gynaecological cancers as its infectious aetiological agent, human papillomavirus (HPV), is known. The knowledge of HPV serotype distribution in a sub-region is key to the implementation of an appropriate HPV vaccination programme. To assess the prevalence of HPV-DNA, serotypes and risk-determinants among women with invasive cervical cancer (ICC) in Katsina State, Northwestern Nigeria. This was a cross-sectional, multicenter study involving Federal Teaching Hospital Katsina, General Hospital Katsina and Turai Yar'adua Maternal and Child Hospital Katsina, Nigeria. Sixty-three women with histologically confirmed cervical cancer who fulfilled the criteria were recruited into the study. Tissue blocks with a confirmed diagnosis of ICC were taken to DNA Labs Kaduna for HPV-deoxyribonucleotide acid detection and typing. An interviewer-administered questionnaire developed for the study was used to obtain socio-demographic, reproductive characteristics and the other risk factors for HPV acquisition and persistence. The HPV-positivity rate in ICC was 95.5% while the prevalence of high-risk HPV (Hr-HPV)-DNA in the specimen was 54.6% with 13 HPV-serotypes detected, 9 Hr-HPV types (16,18,31,33,35,45,51,56,82) and 4 low-risk HPV types (6,44,81,89). The most commonly detected HPV serotype among women with a single HPV infection was HPV 81 (40.9%) followed by HPV 16 (28.8%). However, HPV 16 was the most common serotype among those with multiple HPV infections. Prevalence of other detected serotypes were HPV 31 (24.2%), 33 (24.2%), HPV 18 (10.6%), HPV 35 (3.0%), HPV 45 (9.1%), HPV 44 (1.5%), HPV 51 (3.0%), HPV 56 (3.0%), HPV 82 (1.5%), HPV 89 (1.5%) and HPV 6 (1.5%). Forty-four out of 63 women (69.8%) had a single HPV infection, 19 (30.2%) had multiple HPV infections and 15 (24.3%) were co-infected with HPV 16/31/33. There was a statistically significant association between HPV 16 and squamous cell carcinoma (SCC). The study demonstrates a prevalence of HPV-DNA as 95.5% among women with ICC. The most commonly detected HPV serotype was HPV 81 seen in 41% which was an uncommon finding. Furthermore, statistically significant associations between HPV serotypes 16 and 82 with SCC were detected.

What do you get? Transmission of pneumococcal pneumonia.

Streptococcus pneumoniae is a polysaccharide encapsulated bacterium responsible for the majority of cases of community acquired pneumonia. The upper respiratory tract of children becomes colonized with pneumococci early in life, from the first weeks of life up to 18 months. Factors which influence timing of colonization include geographical localization, socio-economic circumstances, and household conditions. Pneumococcal pneumonia to a degree is a seasonal disease, peaking in the winter months. One of the epidemiological determinants is that viral infections (in particular influenza) predispose for pneumococcal pneumonia. The infectious nature of pneumococcal pneumonia was underscored during the COVID-19 pandemic. Due to societal restrictions imposed (face masks, social distancing) the incidence of invasive pneumococcal disease (IPD) dropped, and returned to pre-COVID-19 numbers after lifting of the restrictions. There are 100 different S. pneumoniae serotypes, based on differences in the capsular polysaccharide. Introduction of protein conjugated polysaccharide vaccines (PCV) has reduced the incidence of IPD in children. Because children are the reservoir for other risk groups, in particular the elderly, introduction of PCV has indirectly also reduced the burden of IPD in latter risk group. The first generation of PCV consisted of the seven most prevalent pneumococcal serotypes. After implementation, replacement colonization of the upper respiratory tract with non-vaccine serotypes was observed and also replacement disease. Upcoming 24-valent PCVs will have a much broader coverage, but whether replacement disease now has been eliminated remains to be seen.

Expression and characterization of global consensus nonstructural protein 1 (NS1) of four dengue virus serotypes in Escherichia coli

In the aftermath of the COVID-19 pandemic, a sudden surge in dengue cases was observed globally, compounding public health challenges. Dengue viruses, already a major public health concern, have seen intensified transmission, necessitating improved epidemiological surveillance and targeted interventions. Epidemiological surveys, particularly seroepidemiological surveys, are instrumental in elucidating serotype prevalence and informing vaccination programs. However, the highly variable dengue viruses often hamper the development of universally effective diagnostic tools. To overcome this obstacle in Vietnam, we have designed and developed an effective production system for the global consensus nonstructural protein 1 (NS1) antigens for all four serotypes through an Escherichia coli expression system. These global consensuses NS1 antigens were purified to near homogeneity and their identities were confirmed by mass spectrometry. Exhibiting robust reactivity with dengue-infected patient sera in the Western blot assay, the antigens revealed serotype-specific reactivity profiles, proving their diagnostic potential. Our production method, characterized by a relatively high yield and a straightforward purification protocol, offers a scalable solution for the creation of dengue serotype diagnostic assays in the backdrop of evolving dengue global epidemics.

Emerging pneumococcal serotypes in Iraq: scope for improved vaccine development.

Pneumococcal disease is a global public health concern as it affects the young, aged and the immunocompromised. The development of pneumococcal vaccines and their incorporation in the immunization programs has helped to reduce the global burden of disease. However, serotype replacement and the emergence of non-vaccine serotypes as well as the persistence of a few vaccine serotypes underscores the need for development of new and effective vaccines against such pneumococcal serotypes. In the Middle East, places of religious mass gatherings are a hotspot for disease transmission in addition to the global risk factors. Therefore, the periodic surveillance of pneumococcal serotypes circulating in the region to determine the effectiveness of existing prevention strategies and develop improved vaccines is warranted. Currently, there is a lack of serotype prevalence data for Iraq due to inadequate surveillance in the region. Thus, this review aims to determine the pneumococcal serotypes circulating in Iraq which may help in the development and introduction of improved pneumococcal vaccines in the country.

Reduction of Nontyphoidal Salmonella enterica in Broth and on Raw Chicken Breast by a Broad-spectrum Bacteriophage Cocktail

Globally, nontyphoidal Salmonella (NTS) causes approximately 150 million foodborne illnesses annually; many of which are linked to poultry products. Thus, improving food safety interventions in the poultry sector can reduce foodborne illness associated with prevalent NTS serotypes. Bacteriophages (phages) have shown promise as food-safe alternatives to current antimicrobial practices. However, challenges such as limited host range, bactericidal effectiveness in practical production settings, and the risk of developing host resistance remain as barriers for the widespread use of phages in commercial poultry operations. A broad-spectrum three-phage cocktail was evaluated against S. enterica subsp. enterica serotypes Enteritidis, Typhimurium, and Kentucky. The impact of multiplicity of infection (MOI) on NTS growth was assessed in broth at 22°C for 18 hours (h). Then, phage cocktail efficacy was evaluated on raw chicken breast samples inoculated with the NTS cocktail and stored at 10°C or 22°C for 0, 1, and 5 days or 0, 4, 8, and 16 h, respectively. Most probable number (MPN) calculations were performed for NTS counts on chicken after phage treatment and storage at 10°C to account for samples with NTS counts below the detection limit. In general, a higher MOI corresponded to reduced NTS growth; however, residual nutrition in growth media and initial NTS contamination level affected samples treated with the phage cocktail at identical MOIs. On chicken, phage cocktail treatment significantly reduced NTS counts at 10°C and 22°C. After storage at 10°C for 5 days, NTS counts were reduced by >3.2 log compared to the control. After storage at 22°C for 16 h, NTS counts were reduced by >1.7 log compared to the control. Overall, the phage cocktail was effective at reducing a diverse set of prominent NTS strains in broth and on raw chicken breast, highlighting its potential for commercialization and use alongside other hurdles in poultry production.

Foot and mouth disease (FMD) epidemiology in small ruminants by identifying antibodies for non-structural and structural proteins with a sequential screening approach: A cross-sectional study

Foot and Mouth Disease (FMD) is a transboundary animal disease that causes major economic losses to the livestock industry in developing countries like Pakistan. In this cross-sectional study, a total of n = 315 serum samples were collected from 92 FMD unvaccinated sheep and goats flocks among three districts (Chakwal, Dera Ghazi Khan, and Jhang) of Punjab province, Pakistan. These serum samples were subjected to FMD NSP (3ABC) ELISA test to estimate the seroprevalence of FMD NSP antibodies due to previous infection, and the results showed the overall seroprevalence of NSP antibodies as 31% (95% CI, 26–36) at the animal and 50% (95% CI, 42–59) at flock level. The univariate analysis showed that the introduction of new animals in a flock was found as a potential risk factor OR: 10 (95% CI: 1.4–74) for FMD NSP antibody positivity in small ruminants (sheep and goats). In the final logistic regression model district and the age of animals were found as statistically significant (p = <0.05) risk factors for FMD NSP seropositivity in small ruminants. Among the positive FMD NSP sera, 90 samples were screened for serotype-specific FMD SP antibodies (O, A, Asia-1) by SPCE FMD SP antibodies ELISA tests. The SP antibodies ELISA results showed that 71% (64/90) NSP-seropositive samples were also found positive by at least one SP antibodies ELISA test. The descriptive analysis revealed serotype “O” as the most prevalent serotype with an overall prevalence of 44% (40/90), however, the other serotypes (A and Asia-1) were also identified from all the study districts. The descriptive analysis and ANOVA results showed that the samples with higher mean percentage positive (PP) values for the NSP ELISA test are significantly more positive for FMD SP antibodies ELISA test in a sequential testing approach. In spite of the small sample size, this study provides valuable insight into the epidemiology of FMD in small ruminants.

Genetic diversity and biofilm formation ofinvasive and noninvasive Streptococcus agalactiae isolates: Emergence of hypervirulentCC19 strains in Tehran, Iran.

The prevalence of Streptococcus agalactiae infections in adult populations is increasing. The current study aimed to characterize the genetic features of S. agalactiae strains responsible for different infections. Across-sectional study was performed on 65 S. agalactiae strains (30 invasive and 35 noninvasive) isolated from non-pregnant women. All S. agalactiae isolates were confirmed by atr and dltS PCR assays. Antibiotic susceptibility patterns were determined using the disk diffusion method. Biofilm production was investigated by microtiter plate assay. PCR was done to detect resistance determinants. Isolates were characterized using the multilocus sequence typing (MLST) method. cMLSB, iMLSB, and M phenotypes accounted for 47.7%, 30.8%, and 6.2%, respectively. MDR was detected in 15.4% of noninvasive and 44.6% of invasive isolates. MtP assay indicated that 80% of isolates were biofilm producers. Biofilm formation was common among noninvasive compared with invasive strains (94.3% versus 66.7%). tet (M) (46.2%) and erm (B) (69.2%) were the most prevalent tetracycline and macrolide-resistance genes. The most prevalent serotype was type III (50.8%), followed by Ia (18.4%), II (15.4%), V (12.3%), and IV (3.1%). The frequency of serotype III among biofilm producer strains (81.8%) was found to be significantly higher than that of non-producer isolates (18.2%) (P < 0.05). S. agalactiae was resolved within four clonal complexes, including CC19 (46.2%; in both invasive and noninvasive), followed by CC23 (30.8%; only noninvasive isolates), CC1 (15.4%; only noninvasive isolates) and CC17 (7.6%; only invasive isolates). Themain sequence types (STs) found were ST19 (27.7%), ST17 (7.7%), ST27 (6.2%), and ST28 (4.6%) linked with invasive infections and ST23 (18.4%), ST933 (12.3%), ST644 (9.2%), ST19 (7.7%), ST1 (6.2%) found in noninvasive infections. The high prevalence of CC19 and CC23 clones among S. agalactiae strains reflects the emergence of these lineages as successful clones in Iran.

Bacterial nasopharyngeal colonisation in children in South Africa before and during the COVID-19 pandemic: an observational study

Deployment of non-pharmaceutical interventions such as face masking and physical distancing during the COVID-19 pandemic could have altered the transmission dynamics and carriage of respiratory organisms. We evaluated colonisation with Streptococcus pneumoniae and other upper respiratory tract bacterial colonisers before and during the COVID-19 pandemic. We did two cross-sectional surveys in Soweto, South Africa from July 3 to Dec 13, 2018 (pre-COVID-19 period) and from Aug 4, 2021, to March 31, 2022 (COVID-19 period) in healthy children (aged ≤60 months) who had recorded HIV status and had not received antibiotics in the 21 days before enrolment. At enrolment, we collected nasopharyngeal swab samples from child participants. Following nucleic acid extraction, nanofluidic quantitative PCR was used to screen all samples for 92 S pneumoniae serotypes and 14 other bacteria. The primary objective was to compare the prevalence and density of pneumococcal nasopharyngeal colonisation, overall and stratified by 13-valent pneumococcal conjugate vaccine (PCV13) serotypes and non-vaccine serotypes. Secondary study objectives included a comparison of serotype-specific pneumococcal colonisation and density, as well as colonisation by the 14 other bacteria in the COVID-19 versus pre-COVID-19 period. We used an adjusted multiple logistic and linear regression model to compare the colonisation prevalence and density between study periods. We analysed nasopharyngeal swabs from 1107 children (n=571 in the pre-COVID-19 period; n=536 in the COVID-19 period). We observed no change in overall pneumococcal colonisation between periods (274 [51%] of 536 in the COVID-19 period vs 282 [49%] of 571 in the pre-COVID-19 period; adjusted odds ratio [aOR] 1·03 [95% CI 0·95-1·12]). The prevalence of PCV13 serotypes was lower in the COVID-19 than in the pre-COVID-19 period (72 [13%] vs 106 [19%]; 0·87 [0·78-0·97]), whereas the prevalence of non-typeable S pneumoniae was higher (34 [6%] vs 63 [12%]; 1·30 [1·12-1·50]). The mean log10 density for overall pneumococcal colonisation was lower in the COVID-19 period than in the pre-COVID-19 period (3·96 [95% CI 3·85-4·07] vs 4·72 [4·63-4·80] log10 genome equivalents per mL; p<0·0001). A lower density of non-vaccine serotypes (3·63 [3·51-3·74] vs 4·08 [3·95-4·22] log10 genome equivalents per mL; p<0·0001) and non-typeable S pneumoniae (3·11 [2·94-3·29] vs 4·41 [4·06-4·75] log10 genome equivalents per mL; p<0·00001) was also observed in the COVID-19 period. There was no difference in the density of PCV13 serotypes between the periods. The prevalence of colonisation during the COVID-19 versus pre-COVID-19 period was lower for non-typeable Haemophilus influenzae (280 [49%] vs 165 [31%]; aOR 0·77 [95% CI 0·71-0·84]), Moraxella catarrhalis (328 [57%] vs 242 [45%]; 0·85 [0·79-0·92]), and Neisseria lactamica (51 [9%] vs 13 [2%]; 0·64 [0·52-0·78]), but higher for Acinetobacter baumannii (34 [6%] vs 102 [19%]; 1·55 [1·35-1·77]) and Staphylococcus aureus (29 [5%] vs 52 [10%]; 1·28 [1·10-1·50]). There were variable effects on the colonisation prevalence and density of bacterial organisms during the COVID-19 compared with the pre-COVID-19 period. The lower prevalence of PCV13 serotype together with other respiratory organisms including non-typeable H influenzae and M catarrhalis could have in part contributed to a decrease in all-cause lower respiratory tract infections observed in South Africa during the initial stage of the COVID-19 pandemic. The pathophysiological mechanism for the increase in A baumannii and S aureus colonisation warrants further investigation, as does the clinical relevance of these findings. The Bill & Melinda Gates Foundation.

Circulating trends of hand, foot, and mouth disease in Hubei Province, China: Impact from the COVID-19 pandemic

ObjectivesThis study was performed to investigate the effect of non-pharmaceutical interventions on hand, foot, and mouth disease in Hubei Province China during the coronavirus disease 2019 pandemic. MethodsData and samples were collected from the hand, foot, and mouth disease surveillance laboratory network in Hubei Province between 2018 and 2022. The samples were identified as Enterovirus A71, Coxsackievirus A6or Coxsackievirus A16 via real-time polymerase chain reaction. Representative Coxsackievirus A6 and Coxsackievirus A16 samples were sequenced and subjected to phylogenetic analyses. ResultsA noticeable 3-fold reduction in the number of hand, foot, and mouth disease cases was observed from 2019 to 2020. The age and sex distributions of patients with hand, foot, and mouth disease were approximately the same from 2018 to 2022. The proportion of Coxsackievirus A6 accounted for 86 % in 2020 and 75 % in 2021 for hand, foot, and mouth disease compared with 48 % in 2018, 53 % in 2019, and 29 % in 2022. The proportions of Coxsackievirus A16 in 2020 and 2021 were 2 % and 17 %, respectively, showing a sharp decline in 2018 (37.8 %) and 2019 (35 %). In 2022, Coxsackievirus A16 was the dominant serotype (46 %). Only slight differences were found in the VP1 sequences across the different years. ConclusionsOur study confirmed that a series of non-pharmaceutical interventions during the coronavirus disease 2019 period reduced the transmission of enteroviruses and that long-term restrictions could significantly change the prevalence of enterovirus serotypes causing hand, foot, and mouth disease.

Comparison of Shigella GMMA and glycoconjugate four-component formulations in animals.

Shigellosis is leading bacterial cause of diarrhea with high prevalence in children younger than 5years in low- and middle-income countries, and increasing number of reports of Shigella cases associated to anti-microbial resistance. No vaccines against Shigella are still licensed, but different candidates based on the O-antigen portion of lipopolysaccharides are in clinic. Generalized Modules for Membrane Antigens (GMMA) have been proposed as an alternative delivery system for the O-antigen, and a 4-component vaccine candidate (altSonflex1-2-3), containing GMMA from S. sonnei and S. flexneri 1b, 2a and 3a is being tested in a phase 1/2 clinical trial, with the aim to elicit broad protection against the most prevalent Shigella serotypes. Here, the 4-component GMMA vaccine candidate has been compared to a more traditional glycoconjugate formulation for the ability to induce functional antibodies in mice and rabbits. In mice, in the absence of Alhydrogel, GMMA induce higher IgG antibodies than glycoconjugates and stronger bactericidal titers against all Shigella serotypes. In the presence of Alhydrogel, GMMA induce O-antigen specific IgG levels similar to traditional glycoconjugates, but with a broader range of IgG subclasses, resulting in stronger bactericidal activity. In rabbits, GMMA elicit higher functional antibodies than glycoconjugates against S. sonnei, and similar responses to S. flexneri 1b, 2a and 3a, independently from the presence of Alhydrogel. Different O-antigen based vaccines against Shigella are now in clinical stage and it will be of particular interest to understand how the preclinical findings in the different animal models translate in humans.

Distribution of Extended-Spectrum-β-Lactamase-Producing Diarrheagenic Escherichia coli Clonal Complex 10 Isolates from Patients with Diarrhea in the Republic of Korea.

ESBL-producing E. coli is a public health concern in healthcare settings and the community. Between 2009 and 2018, a total of 187 ESBL-producing pathogenic E. coli isolates were identified, and clonal complex (CC) 10 was the predominant clone (n = 57). This study aimed to characterize the ESBL-producing pathogenic E. coli CC10 strains obtained from patients with diarrhea to improve our understanding of CC10 distribution in the Republic of Korea. A total of 57 CC10 strains were selected for comprehensive molecular characterization, including serotype identification, the analysis of antibiotic resistance genes, the investigation of genetic environments, the determination of plasmid profiles, and the assessment of genetic correlations among CC10 strains. Among the CC10 isolates, the most prevalent serotype was O25:H16 (n = 21, 38.9%), followed by O6:H16 (10, 19.6%). The most dominant ESBL genes were blaCTX-M-15 (n = 31, 55%) and blaCTX-M-14 (n = 15, 27%). Most blaCTXM genes (n = 45, 82.5%) were located on plasmids, and these incompatibility groups were confirmed as IncB/O/K/Z, IncF, IncI1, and IncX1. The mobile elements located upstream and downstream mainly included ISEcp1 (complete or incomplete) and IS903 or orf477. Phylogenetic analysis showed that the CC10 strains were genetically diverse and spread among several distinct lineages. The results of this study show that ESBL-producing pathogenic E. coli CC10 has been consistently isolated, with CTX-M-15-producing E. coli O25:H16 isolates being the major type associated with the distribution of CC10 clones over the past decade. The identification of ESBL-producing pathogenic E. coli CC10 isolates underscores the possible emergence of resistant isolates with epidemic potential within this CC. As a result, continuous monitoring is essential to prevent the further dissemination of resistant ESBL-producing E. coli CC10 strains.

IMMU-29. A CHIMERIC ONCOLYTIC ADENOVIRUS CIRCUMVENTS NEUTRALIZING ANTIBODIES DEVELOPED BY PATIENTS WITH RECURRENT GLIOBLASTOMA TREATED WITH DELTA-24-RGD

Abstract Oncolytic virotherapy holds great potential to treat high-grade gliomas by harnessing virus-mediated oncolysis to stimulate anti-tumor immune responses. However, the efficacy of oncolytic adenoviruses can be hampered by neutralizing antibodies. In this study, we examined sera obtained from a phase 1 clinical trial using oncolytic adenovirus Delta-24-RGD to treat patients with recurrent malignant gliomas. We found that a single intratumoral injection of Delta-24-RGD induced the development of neutralizing antibodies in less than half of the patients but demonstrated remarkable outcomes, with 20% of the patients surviving beyond three years. Conversely, multiple injections of the oncolytic adenovirus induced neutralizing antibodies in 80% of patients (P=0.05) but resulted in no long-term survivors. This inverse correlation led us to further investigate the role of neutralizing antibodies during glioma virotherapy. Examination of Delta-24-RGD-treated murine brain tumors using immunofluorescence displayed colocalization of antibodies and viral proteins. To counteract virus neutralization and maximize oncolysis, we engineered a chimeric virus, Delta-24-RGD-H43m, by replacing the hypervariable regions of the hexon protein from the prevalent serotype 5-based Delta-24-RGD with those from the rare serotype 43. The infectivity, replication, and oncolytic capabilities of Delta-24-RGD-H43m were similar to those of the parental virus. Using clinical trial patient sera, we observed that Delta-24-RGD-H43m displayed significant resilience against the inhibitory effects of neutralizing sera from patients (P=0.01). In murine models with pre-existing immunity to adenovirus, Delta-24-RGD-H43m treatment led to a significantly extended median survival and resulted in a higher percentage of long-term survivors than the parental virus (P=0.005). These results underscore the effectiveness of hexon swapping as a strategy to overcome the dominant immune response against oncolytic viruses, provide valuable insights into the interaction between oncolytic viruses and the host immune system, and lay the foundation to translate to the clinical setting immune-evading virotherapies for glioma patients.

Prevalence of Different Serotypes of Uro-Pathogenic Escherichia Coli(UPEC) causing Recurrent Urinary Tract Infections and the Effect of Cranberry Extract on them

Objective: To determine the prevalence of different serotypes of Uro-Pathogenic Escherichia coli (UPEC) causing recurrent urinary tract infections and to assess the effect of Cranberry extract on them. Material and Methods: It is cross sectional retrospective study conducted in Mayo Hospital Lahore. Atotal of 60 samples of urine were collected from patients admitted in from Urology Department with history of recurrent urinary tract infections. Urine studies were performed including: Urine microscopy, urine culture on CLED medium, biochemical isolation and serotyping of Uro-Pathogenic Escherichia coli. The patients were given Cranberry Extract x 500mg once daily for 3 months, after which a follow-up urine study was performed. Results: A total of 60 urine samples were collected, out of which 15 strains of Uro-Pathogenic Escherichia coli were isolated. 53% of strains tested positive for E.Coli-26 serotype, and 47% tested positive for E.Coli-45 serotype.After taking Cranberry extract for 3 months, 67% of E.coli positive urine samples turned negative. Cranberry extract was 100% effective at eliminating E.Coli-45 serotype infection, but only 38% effective at eliminating E.Coli-26 serotype infection. Conclusion: Findings of this study show promising results of Cranberry extract in mitigating the severity of recurrent urinary tract infections especially those caused by Uro-Pathogenic Escherichia coli-45 serotype.

Prevalence of High-Risk Human Papillomavirus Serotypes and Confrontation with Available Vaccine Antigens: The Case of Cameroon

Prevalence of High-Risk Human Papillomavirus Serotypes and Confrontation with Available Vaccine Antigens: The Case of Cameroon

Exploring Streptococcus pneumoniae capsular typing through MALDI-TOF mass spectrometry and machine-learning algorithms in Argentina: Identifying prevalent NON PCV13 serotypes alongside PCV13 serotypes

IntroductionLaboratory surveillance of Streptococcus pneumoniae serotypes plays a crucial role in effectively implementing vaccines to prevent invasive pneumococcal diseases. The conventional method of serotyping, known as the Quellung reaction, is both time-consuming and expensive. However, the emergence of MALDI-TOF MS technology has revolutionized microbiology laboratories by enabling rapid and cost-effective serotyping based on protein profiles. ObjectivesIn this study, we aimed to investigate the viability of utilizing MALDI-TOF MS technology as an adjunctive and screening method for capsular typing of Streptococcus pneumoniae. Our approach involved developing classification models based on MALDI-TOF MS to discern between Streptococcus pneumoniae strains originating from PCV13 (13-valent pneumococcal conjugate vaccine) and NON PCV13 isolates. MethodsFirstly, we established a comprehensive spectral database comprising isolates of serotypes present in the PCV13 vaccine, along with the top 10 most prevalent NON PCV13 serotypes based on local epidemiological data. This database served as a foundation for developing unsupervised models utilizing MALDI-TOF MS spectra, which enabled us to identify inherent patterns and relationships within the data. Our analysis involved a dataset comprising 215 new isolates collected from nationwide surveillance in Argentina. Our approach involved developing classification models based on MALDI-TOF MS to discern between Streptococcus pneumoniae strains originating from PCV13 (13-valent pneumococcal conjugate vaccine) and NON PCV13 isolates. ResultsAlthough our findings revealed suboptimal performance in serotype classification, they provide valuable insights into the potential of machine learning algorithms in this context. The sensitivity of the models ranged from 0.41 to 0.46, indicating their ability to detect certain serotypes. The observed specificity consistently remained at 0.60, suggesting a moderate level of accuracy in identifying non-vaccine serotypes. These results highlight the need for further refinement and optimization of the algorithms to enhance their discriminative power and predictive accuracy in serotype identification.By addressing the limitations identified in this study, such as exploring alternative feature selection techniques or optimizing algorithm parameters, we can unlock the full potential of machine learning in robust and reliable serotype classification of S. pneumoniae. Our work not only provides a comprehensive evaluation of multiple machine learning models but also emphasizes the importance of considering their strengths and limitations. ConclusionOverall, our study contributes to the growing body of research on utilizing MALDI-TOF MS and machine learning algorithms for serotype identification purposes.

Indirect impact of PCV10 children vaccination on the serotype distribution and antimicrobial resistance of Streptococcus pneumoniae causing invasive disease in adults over 50 in Colombia, 2005–2019: Observational analysis

IntroductionThe introduction of pneumococcal conjugate vaccine (PCV) into childhood vaccination programmes has reduced the prevalence of vaccine serotypes (VTs) that cause invasive pneumococcal disease (IPD) in children. In the elderly population, an impact has also been seen through indirect protection (herd effect). The aim of this study was to estimate the changes in serotype distribution and antimicrobial susceptibility of Streptococcus pneumoniae isolates recovered from adult IPD and to evaluate the indirect effect of immunization with PCV10 based on laboratory records by analyzing the period from 2005 to 2019 for six years before and eight years after the universal PCV10 administration to Colombian children. MethodsA total of 2204 S. pneumoniae isolates from adults (≥50 years) with IPD were analyzed. The analysis examined the percentage changes in proportions (prevalence) and percentage variations in population rates (annual reported rates – ARR) of VTs between the pre-PCV10 (2005–2009) and post-PCV10 (2015–2019) periods. ResultsThe findings were (1) evidence of a significant percentage decrease of pneumococcal VT10 causing IPD in adults (50% pre-PCV10 and 16% post-PCV10); (2) significant increase of serotype 19A (from 1.6% to 14.8%) and less important increase of serotype 3 (from 10.5% to 14.5%) and non-vaccine serotypes (NVT) (from 21.4% to 38.4%) non-significant; and (3) meningitis and non-meningitis multidrug resistant isolates associated with serotype 19A. An improvement in the surveillance system is associated with the immunization of children, as noted by the increased ARRs across the analysis period. ConclusionsOur results show the indirect impact of PCV10 vaccination in children on the VT10 distribution and antimicrobial resistance of S. pneumoniae causing IPD in Colombian adults over 50 when comparing the pre-PCV10 (2005–2009) and post-PCV10 (2015–2019) periods.

Application of Nested PCR and Loop-Mediated Isothermal Amplification (LAMP) to Target 56kDa gene in Scrub Typhus Patients and Phylogenetic Analysis to Identify Orientia tsutsugamushi Strains Circulating In and Around Puducherry

Scrub typhus (ST) is a re-emerging zoonotic disease caused by Orientia tsutsugamushi and is transmitted by chiggers. Serological tests targeting IgM and/or IgG antibodies play a major role in the detection of ST cases. Orientia 56kDa genome is common target for the molecular diagosis of ST to identify the prevalence of specific serotypes of O. tsutsugamushi in and around Puducherry by targeting 56kDa gene with the application of phylogenetic analysis. This prospective laboratory-based study was conducted in a tertiary care teaching hospital, from November 2105 to March 2018. Blood samples were collected from out-patients/in-patients, and those tested positive for ST IgM ELISA (n=140) and an equal number of negative samples were archived and anonymized. Genomic DNA was extracted and analyzed by using Nested PCR and LAMP assay. The positive products were purified and sequenced. Phylogenetic tree was constructed based on the sequences. Among 280 samples, 45 (16.1%) N-PCR and 102 LAMP (36.43%) positivity was observed for 56kDa gene. Forty-one N-PCR positive products were sequenced and accession numbers were obtained (MG601875 to MG601917) for the isolates. Phylogenetic analysis was done by Maximum Likelihood methods and this study has showed that 32.3% are similar to the Karp isolates. Molecular diagnosis of Scrub typhus has become essential in case of doubtful serology and early acute phase of illness. Gene sequencing result indicates that most of them were different from the existing ones, which may belong to the newer strains. The identification of newer strains will be helpful in future for development of scrub typhus vaccine.

Disease Burden of Meningitis Caused by Streptococcus pneumoniae Among Under-Fives in China: A Systematic Review and Meta-analysis.

Streptococcus pneumoniae is the leading cause of meningitis, with a case fatality of up to about 50%. Children younger than 5 years are at greater risk for pneumococcal meningitis compared with other populations. It is of significant importance to provide a comprehensive understanding of the burden of pneumococcal meningitis among under-fives in the low pneumococcal conjugate vaccine (PCV) coverage period in China. A systematic review was conducted. We searched both English (PubMed, Ovid-EMBASE, Biosis, Web of Science, and Cochrane) and Chinese (CNKI, Wanfang, and ViP) databases for studies on bacterial meningitis in China published between January 1980 and July 2022. Ineligible studies were excluded based on study design and data integrity. Heterogeneity was assessed with I2 and estimates of bacterial meningitis morbidity and mortality were pooled using random-effects models. Subgroup analysis was conducted to trace the source of the heterogeneity and summarize average estimates. A total of 13,082 studies were identified in the literature, and 56 studies were finally included for data analysis. The estimated incidence of pneumococcal meningitis was 2.10 cases per 100,000 children younger than 5 years each year (95% CI: 0.59-7.46), with a pooled case fatality rate of 24.59% (95%CI: 19.35-30.28%) in China. It was estimated that 1617.16 (95% CI: 454.35-5744.78) pneumococcal meningitis cases and 548.86 (95% CI: 474.80-627.62) deaths occurred among under-fives in China in 2020. Streptococcus pneumoniae played an important role in the etiology of confirmed bacterial meningitis cases, with a pooled proportion of 22.05% (95% CI: 17.83-26.27%). The most prevalent serotypes were 6B, 14, 19F, 19A, and 23F, which were preventable with a vaccine. Pneumococcal meningitis remains one of the most important health problems among children younger than 5 years in China. Immunization programs should be promoted to avoid preventable cases and deaths.