Molecular identification and characterization of measles virus genotypes circulating in Afghanistan, 2008-2018.

The measles virus (MV) remains a leading cause of morbidity and mortality in children under 5 years of age. Molecular identification of circulating wild-type MV) strains is a vital component of the measles elimination program. We received 159 oral swab samples from Afghanistan during 2008-2018. Viral RNA was extracted, followed by one-step RT-PCR and positive amplicons were subject to sequencing for genotype identification. Out of 159 total samples, 52% (83/159) were detected positive by RT-PCR. Genotype D4 was identified from 2.4% (2/83), genotype H1, 4.8% (4/83), and genotype B3, 92.7% (77/83) cases, respectively.

Immunogenicity of Different Routine Poliovirus Vaccination Schedules: A Randomized, Controlled Trial in Karachi, Pakistan.

Background: We assessed immunity against polioviruses induced with a new Pakistani poliovirus immunization schedule and compared it to alternative poliovirus immunization schedules. Methods: Newborns were randomized to undergo vaccination based on 1 of 5 vaccination schedules, with doses administered at birth and at 6, 10, and 14 weeks of age. Arm A received inactivated poliovirus vaccine (IPV) at all time points. Arm B received bivalent oral poliovirus vaccine (bOPV) at all time points. Arms C and D received bOPV at the first 3 time points and bOPV plus IPV at the final time point (the current schedule). Arm E received trivalent OPV (tOPV) at all time points. At 22 weeks of age, all children received 1 challenge dose of tOPV, and children in arm D received 1 additional IPV dose. Sera were analyzed for the presence of poliovirus neutralizing antibodies at birth and 14 and 22 weeks of age. Results: Seroconversion for poliovirus type 1 (PV1) at 22 weeks of age was observed in 80% of individuals in arm A, 97% in arm B, 94% in arm C, 96% in arm D, and 94% in arm E; for PV2, seroconversion frequencies were 84%, 19%, 53%, 49%, and 93%, respectively; and for PV3, seroconversion frequencies were 93%, 94%, 98%, 94%, and 85%, respectively. Conclusions: The current immunization schedule in Pakistan induced high seroconversion rates for PV1 and PV3; however, it induced PV2 seroconversion in only half of study subjects. There is a growing cohort of young children in Pakistan who are unprotected against PV2; and this creates an increasing risk of a large-scale outbreak of poliomyelitis caused by circulating vaccine-derived PV2.

Rotavirus surveillance in Pakistan during 2015-2016 reveals high prevalence of G12P[6].

The G12 rotavirus genotype has emerged globally since their first detection in 1987 from the Philippines; however it remains a rare cause of gastroenteritis in Pakistan. Rotavirus surveillance conducted during 2015-2016, assessed 3446 children <5 years hospitalized for gastroenteritis and found 802 (23.2%) positive on ELISA. Genotyping of a subset of positive samples (n = 319) revealed G12P[6] (11.28%) as the third most common G/P combination following G3P[8] (28.5%) and G1P[8] (12.5%); G2P[4] (10.65%) and G3P[6] (8.15%) were other frequently detected strains. Phylogenetic analysis of G12 strains from Pakistan revealed high genetic similarity to G12 strains from Italy, Thailand, Korea, and Great Britain as well as local strains within G12 lineage III. In conclusion, G12P[6] was a major contributor of RVA gastroenteritis in Pakistani children. Robust surveillance after the introduction of rotavirus vaccines will help determine the evolution of G12 and other circulating genotypes in the country.

Predictive network analysis identifies JMJD6 and other potential key drivers in Alzheimer's disease.

Despite decades of genetic studies on late-onset Alzheimer's disease, the underlying molecular mechanisms remain unclear. To better comprehend its complex etiology, we use an integrative approach to build robust predictive (causal) network models using two large human multi-omics datasets. We delineate bulk-tissue gene expression into single cell-type gene expression and integrate clinical and pathologic traits, single nucleotide variation, and deconvoluted gene expression for the construction of cell type-specific predictive network models. Here, we focus on neuron-specific network models and prioritize 19 predicted key drivers modulating Alzheimer's pathology, which we then validate by knockdown in human induced pluripotent stem cell-derived neurons. We find that neuronal knockdown of 10 of the 19 targets significantly modulates levels of amyloid-beta and/or phosphorylated tau peptides, most notably JMJD6. We also confirm our network structure by RNA sequencing in the neurons following knockdown of each of the 10 targets, which additionally predicts that they are upstream regulators of REST and VGF. Our work thus identifies robust neuronal key drivers of the Alzheimer's-associated network state which may represent therapeutic targets with relevance to both amyloid and tau pathology in Alzheimer's disease.

Mucosal Type of Chronic Suppurative Otitis Media and the Long-Term Impact on Hearing Loss.

Introduction Worldwide the chronic suppurative otitis media (CSOM) is one of the most common infectious diseases in childhood and is a common cause of impaired hearing. The disease remains a challenging entity for the healthcare system of resource-limited nations despite the advances in modern medicine. The nature of hearing loss in CSOM is mainly conductive, the sensorineural hearing loss (SNHL) is also reported in such patients. The purpose of the study was to identify SNHL in patients with the mucosal type of CSOM and to find the impact of long-term discharging ears on bone conduction (BC) thresholds. Methods Patients with a diagnosis of the mucosal type of CSOM were identified from the record of ENT, Head and Neck Surgery clinic between January 2019 and January 2020. The patients were divided into three groups based on the duration of the disease: groups I, II, and III for 1-5 years, 5-10 years, and 10-15 years, respectively. Pure tone audiogram was reviewed, and data of BC was recorded for 500, 1000, and 2000 Hz. The descriptive frequency was calculated for SNHL in each group and group I was compared with other groups using a chi-square test. The mean BC threshold of group I was compared with other groups using a t-test. SPSS version 26 (IBM Corp., Armonk, New York) was used for statistical analysis. Results A total of 154 patients were included in the study. There were 73 males and 81 females. The mean age was 26 years. The minimum age was 12 years and the maximum age was 58 years. Active ear discharge was the presenting complaint in 84 patients. The right ear was involved in 88 patients, and the left ear was involved in 66 patients. SNHL was present in 30 out of 154 patients, i.e., 19.5%. The number of patients in each of the groups I, II, and III was 95, 28, and 31, respectively. The group I was compared with group II using the chi-square test, the p-value was found not significant, i.e., >0.05. The group I was then compared with group III using the same statistical test, and the p-value was found significant, i.e., <0.05. The mean BC threshold for an average of three speech frequencies for each of the three groups was 16.9, 18.7, and 22.9, respectively. The mean BC threshold of group I was compared with that of group II using a t-test, and the p-value was found not significant, i.e., >0.05. The mean BC threshold of group I was then compared with that of group III using a t-test, and the p-value was found significant, i.e., <0.05. Conclusions The findings of our study reproduce the presence of SNHL in a sizable proportion of the patients with a mucosal type of CSOM. Furthermore, the elevation of the BC threshold also appears statistically significant on analysis in association with the protracted duration of CSOM, highlighting the adverse impact of delaying the surgical repair. However, the clinical importance remains unclear because the maximum losses in the BC threshold seen in the patients are not severe enough to necessarily make them hard of hearing. Nevertheless, these statistically significant results influence clinical thought process and measures for an early remedy, including surgery, and need to be considered in time to prevent progressively worsening hearing loss in such cases.

Possible Enzymatic Downregulation of the Natriuretic Peptide System in Patients with Reduced Systolic Function and Heart Failure: A Pilot Study.

BACKGROUND: In patients with reduced systolic function, the natriuretic peptide system affects heart failure (HF) progression, but the expression of key activating (corin) and degrading enzymes (neprilysin) is not well understood. METHODS AND RESULTS: This pilot study (n=48) compared plasma levels of corin, neprilysin, ANP, BNP, and cGMP in control patients with normal ejection fractions (mean EF 63 ± 3%) versus patients with systolic dysfunction, with (EF 24 ± 8%) and without (EF 27 ± 7%) decompensated HF (dHF), as defined by Framingham and BNP criteria. Mean ages, use of beta blockers, and ACE-inhibitors-angiotensin receptor blockers were similar between the groups. Corin levels were depressed in systolic dysfunction patients (797 ± 346 pg/ml) versus controls (1188 ± 549, p<0.02), but levels were not affected by dHF (p=0.77). In contrast, levels of neprilysin (p<0.01), cGMP (p<0.001), and ANP (p<0.001) were higher in systolic dysfunction patients than controls and were the highest in patients with dHF. CONCLUSIONS: Levels of neprilysin, ANP, BNP, and cGMP increased in patients with reduced systolic function and were the highest in dHF patients. Conversely, corin levels were low in patients with reduced EF with or without dHF. This pattern suggests possible enzymatic downregulation of natriuretic peptide activity in patients with reduced EF, which may have diagnostic and prognostic implications.

Identification of measles virus genotype B3 associated with outbreaks in Islamabad, Pakistan, 2013-2015.

BACKGROUND: Measles virus infection remains a significant cause of childhood mortality and morbidity despite continued global efforts and the availability of a safe and effective vaccine. Molecular analysis of indigenous measles viruses could provide critical information on outbreak linkages and transmission pathways that can aid the implementation of appropriate control programs in Pakistan. METHODS: Blood samples and throat swabs were collected from subjects suspected with measles in Islamabad, Pakistan from 2013 to 2015. Serum samples were tested for the presence of measles immunoglobulin M (IgM) antibodies using enzyme-linked immunosorbent assay (ELISA) while throat swabs were used for the isolation (Vero/SLAM cell line) and subsequent characterization and phylogenetic analysis of measles strains. RESULTS: Of 373 blood samples, 66% tested positive for measles IgM. Male subjects were more often infected (58%) than female (42%) with the highest frequency of positive cases (63%) in the 0-5-years age group. Among the positive cases, only 13% had received one or two doses of the measles vaccine, while 87% were unvaccinated. Of 80 throat swabs, 29 (36%) showed a measles virus-specific cytopathic effect (CPE) and were characterized as genotype B3 through partial sequencing of the nucleoprotein (N) gene. Phylogenetic analysis revealed the Pakistani B3 strains to be closely related to strains from neighboring countries (Iran and Afghanistan) as well as with B3 viruses from the USA, Germany, and the UK. CONCLUSIONS: The study results showed that despite the availability of an effective vaccine, the burden of measles infections is very high in Pakistan due to poor routine immunization coverage even in major cities, including the capital city of Islamabad. It is imperative that national health authorities take urgent strategic steps to improve routine immunization and implement adequate molecular identification methods to tackle future measles outbreaks.

Evaluation of vaccine derived poliovirus type 2 outbreak response options: A randomized controlled trial, Karachi, Pakistan.

BACKGROUND: Outbreaks of circulating vaccine derived polioviruses type 2 (cVDPV2) remain a risk to poliovirus eradication in an era without live poliovirus vaccine containing type 2 in routine immunization. We evaluated existing outbreak response strategies recommended by the World Health Organization (WHO) for control of cVDPV2 outbreaks. METHODS: Seronegative children for poliovirus type 2 (PV2) at 22 weeks of life were assigned to one of four study groups and received respectively (1) one dose of trivalent oral poliovirus vaccine (tOPV); (2) monovalent OPV 2 (mOPV2); (3) tOPV together with a dose of inactivated poliovirus vaccine (IPV); or (4) mOPV2 with monovalent high-potency IPV type 2. Stool and blood samples were collected and assessed for presence of PV2 (stool) and anti-polio antibodies (sera). RESULTS: We analyzed data from 265 children seronegative for PV2. Seroconversion to PV2 was achieved in 48, 76, 98 and 100% in Groups 1-4 respectively. mOPV2 was more immunogenic than tOPV alone (p < 0.001); and OPV in combination with IPV was more immunogenic than OPV alone (p < 0.001). There were 33%, 67%, 20% and 43% PV2 excretors in Groups 1-4 respectively. mOPV2 resulted in more prevalent shedding of PV2 than when tOPV was used (p < 0.001); and tOPV together with IPV resulted in lower excretion of PV2 than tOPV alone (p = 0.046). CONCLUSION: mOPV2 was a more potent vaccine than tOPV. Adding IPV to OPV improved immunological response; adding IPV also seemed to have shortened the duration of PV2 shedding. mIPV2 did not provide measurable improvement of immune response when compared to conventional IPV. WHO recommendation to use mOPV2 as a vaccine of first choice in cVDPV2 outbreak response was supported by our findings. Clinical Trial registry number: NCT02189811.

Removal of intracardiac fractured port-A catheter utilizing an existing forearm peripheral intravenous access site in the cath lab.

The intravenous port-A catheters are widely used for long-term central venous access in cancer patients. Spontaneous fracture and migration of implanted port catheters is a known complication and necessitates immediate removal. Percutaneous retrieval of intravascular foreign body has become a common practice and is commonly performed through central venous access, mostly using femoral, subclavian, or internal jugular veins. Although the percutaneous approach is relatively safe, it can lead to potential iatrogenic complications. We report the first case report of percutaneous removal of intravascular foreign body using forearm peripheral intravenous access.

Current liver biopsy practices for suspected parenchymal liver diseases in the United States: the evolving role of radiologists.

OBJECTIVE: The aim of this study was to determine current liver biopsy practices in the United States. METHODS: We mailed a questionnaire to 260 randomly selected members of the American Association for the Study of Liver Diseases. Statistical analysis was conducted using the chi2 test. RESULTS: A total of 128 members (49%) responded, with 106 responses suitable for inclusion. Of the respondents, 25% had a radiologist perform >50% of their patients' liver biopsies, whereas 38% personally performed all their patients' biopsies. During training, 87% of respondents were taught to perform liver biopsy using the "blind" technique, 2% with ultrasound (US) guidance, and 11% both. A total of 76% used US guidance during liver biopsy. More private practitioners than those practicing in academic centers used the "blind" technique (35% vs 18%; p = 0.02) and referred >50% of their patients for liver biopsy to Radiology (36% vs 17%; p = 0.01); desire for real-time US guidance was the main reason in 43% of cases. Of the respondents, 75% used US for safety reasons; 77% of those who did not use US believed that it was unnecessary. Overall, 87% of respondents indicated that patient safety was the most important issue during liver biopsy; only 2% thought that personal convenience and cost-effectiveness were most important. CONCLUSIONS: Respondents' chief concern was patient safety, and most used US for this reason. Private practitioners were less likely than those practicing in academic centers to use US guidance and were more likely to refer patients to Radiology.