Long-term impact of rotavirus vaccination on all-cause and rotavirus-specific gastroenteritis and strain distribution in Central Kenya: An 11-year interrupted time-series analysis.

BACKGROUND: Kenya introduced a monovalent rotavirus vaccine administered orally at 6 and 10 weeks of age into her National Immunization Program in July 2014. The study evaluated the long-term impact of the vaccine on hospitalization for all-cause and rotavirus-specific acute gastroenteritis (AGE) and strain epidemiology in Kenya. METHODS: Data on all-cause and rotavirus-specific AGE and strain distribution were derived from an eleven-year hospital-based surveillance of AGE among children aged <5 years at Kiambu County Teaching and Referral Hospital (KCTRH) in Central Kenya between 2009 and 2020. Fecal samples were screened for group A rotavirus using ELISA and genotyped using multiplex semi-nested RT-PCR. Trends in all-cause and rotavirus-related AGE and strain distribution were compared between the pre-vaccine (July 2009-June 2014), early post-vaccine (July 2014-June 2016) and late post-vaccine (February 2019-October 2020) periods. RESULTS: Rotavirus-specific AGE was detected at 27.5% (429/1546, 95% CI: 25.5-30.1%) in the pre-vaccine period; 13.8% (91/658, 95% CI: 11.3-16.6%) in the early post-vaccine period (July 2014-June 2016); and 12.0% (229/1916, 95% CI: 10.6-13.5%) in the late post-vaccine period (February 2019-October 2020). This amounted to a decline of 49.8% (95% CI: 34.6%-63.7%) in rotavirus-specific AGE in the early post-vaccine period and 53.4% (95% CI: 41.5-70.3%) in the late post-vaccine period when compared to the pre-vaccine period. All-cause AGE hospitalizations declined by 40.2% (95% CI: 30.8%-50.2%) and 75.3% (95% CI: 65.9-83.1%) in the early post-vaccine and late post-vaccine periods, respectively, when compared to the pre-vaccine period. G3P [8] was the predominant strain in the late post-vaccine period, replacing G1P[8] which had predominated in the pre-vaccine and early post-vaccine periods. Additionally, we detected considerable proportions of uncommon strains G3P[6] (4.8%) and G12P[6] (3.5%) in the post-vaccine era. CONCLUSION: Rotavirus vaccination has resulted in a significant decline in all-cause and rotavirus-specific AGE, and thus, provides strong evidence for public health policy makers in Kenya to support the sustained use of the rotavirus vaccine in routine immunization. However, the shift in strain dominance and age distribution of rotavirus AGE in the post-vaccine era underscores the need for continued surveillance to assess any possible vaccine-induced selective pressure that could diminish the vaccine effectiveness over time.

Factors influencing parental COVID-19 vaccination willingness for children in Japan.

Objectives: This study aims to investigate the factors influencing parental willingness in COVID-19 vaccination for children in Japan in light of the introduction of pediatric vaccines. Methods: An online survey was conducted in February 2022, coinciding with the imminent start of pediatric COVID-19 vaccinations in Japan. It assessed attitudes toward vaccine uptake and included questions about health-related attributes, psychological considerations, and sources of COVID-19 information. Data from 2,419 respondents who had children under the age of 12 were analyzed using multinomial logistic regression to identify factors associated with parental willingness towards COVID-19 vaccination for children. The outcomes were "agree" (in favor of vaccination), "not sure" (undecided), with "disagree" (against vaccination) as the reference category. Results: Among participants supportive of vaccination ("agree" compared to the "disagree" reference), salient determinants included: gender (Men in reference to women: odds ratio [OR] 1.54; 95 % confidence interval [CI] 1.11-2.15), highest educational level (Junior College/Vocational in reference to under high school: OR 0.61; 95 % CI 0.40-0.93, Bachelor's /Master's/Doctoral degree in reference to under high school: OR 0.59; 95 % CI 0.42-0.84), perception of benefits of COVID-19 vaccination (Significant in reference to Insignificant: OR 2.04; 95 % CI 1.26-3.28), perception of risks of COVID-19 vaccination (Significant in reference to Insignificant: OR 0.28; 95 % CI 0.19-0.42, Neutral in reference to Insignificant: OR 0.48; 95 % CI 0.33-0.71), the number of referenced information sources utilized for COVID-19 was associated with attitudes towards children's vaccination (OR 1.02; 95 % CI 1.00-1.04). Conclusion: The study highlights the multifaceted factors influencing parents' COVID-19 vaccination attitudes for their children, encompassing socioeconomic, health, psychological, and informational aspects. Factors like cautious information gathering, vaccine concerns and diverse referenced information sources impact willingness. To facilitate informed decision-making, essential measures include government risk communication, widespread vaccine information dissemination, and enhancing parents' health information accessibility and evaluation skills are important.

A pilot study of dimeticone oils versus sodium carbonate treatment for tungiasis: A randomized cohort trial in Homa Bay County, Kenya.

BACKGROUND: Tungiasis is a cutaneous parasitosis caused by the female flea Tunga penetrans. Two-component dimeticone (NYDA) is the only treatment for tungiasis recommended by the World Health Organization; however, this topical drug is not available in Kenya. In Western Kenya, sodium carbonate is commonly used in the treatment of tungiasis. This study evaluated the 7-day cure rates for tungiasis by comparing sodium carbonate and NYDA treatments in Homa Bay County, Kenya. METHODOLOGY/PRINCIPAL FINDINGS: This was a randomized, observer-blinded, parallel-treatment cohort trial. Twenty-three eligible children with 126 flea infections were matched and randomized. All participants received both treatments, with one treatment on each foot. We recorded all health conditions/information, including inflammation scores and adverse events. Observations were performed on days 3, 5, and 7 using a digital microscope to confirm dead or live fleas based on the viability signs. Twenty-three children aged 3-13 years were analyzed. The proportion of dead fleas on day 7 was higher after NYDA treatment than after 5% sodium carbonate treatment (87% versus 64%, respectively, P = 0.01) NYDA. Median survival was 5 days for both treatments; NYDA had significantly higher trend of flea non-viability rate than 5% sodium carbonate (P<0.01). There were no significant differences in the inflammation score or pain/itchiness between the two treatments. On the last day, 14 children indicated their preference for NYDA in future treatment of tungiasis, whereas nine children preferred the 5% sodium carbonate solution. CONCLUSIONS/SIGNIFICANCE: NYDA was significantly more effective than 5% sodium carbonate for tungiasis treatment. Both treatments were safe but the children preferred NYDA more. Future studies with more participants and an extended observation period are warranted to confirm our findings. The findings suggest that NYDA should be made more available in tungiasis endemic area. TRIAL REGISTRATION: UMIN-CTR; UMIN 000044320.

Photoreceptors inhibit pathological retinal angiogenesis through transcriptional regulation of Adam17 via c-Fos.

Pathological retinal angiogenesis profoundly impacts visual function in vascular eye diseases, such as retinopathy of prematurity (ROP) in preterm infants and age-related macular degeneration in the elderly. While the involvement of photoreceptors in these diseases is recognized, the underlying mechanisms remain unclear. This study delved into the pivotal role of photoreceptors in regulating abnormal retinal blood vessel growth using an oxygen-induced retinopathy (OIR) mouse model through the c-Fos/A disintegrin and metalloprotease 17 (Adam17) axis. Our findings revealed a significant induction of c-Fos expression in rod photoreceptors, and c-Fos depletion in these cells inhibited pathological neovascularization and reduced blood vessel leakage in the OIR mouse model. Mechanistically, c-Fos directly regulated the transcription of Adam17 a shedding protease responsible for the production of bioactive molecules involved in inflammation, angiogenesis, and cell adhesion and migration. Furthermore, we demonstrated the therapeutic potential by using an adeno-associated virus carrying a rod photoreceptor-specific short hairpin RNA against c-fos which effectively mitigated abnormal retinal blood vessel overgrowth, restored retinal thickness, and improved electroretinographic (ERG) responses. In conclusion, this study highlights the significance of photoreceptor c-Fos in ROP pathology, offering a novel perspective for the treatment of this disease.

SOCS3 regulates pathological retinal angiogenesis through modulating SPP1 expression in microglia and macrophages.

Pathological ocular angiogenesis has long been associated with myeloid cell activation. However, the precise cellular and molecular mechanisms governing the intricate crosstalk between the immune system and vascular changes during ocular neovascularization formation remain elusive. In this study, we demonstrated that the absence of the suppressor of cytokine signaling 3 (SOCS3) in myeloid cells led to a substantial accumulation of microglia and macrophage subsets during the neovascularization process. Our single-cell RNA sequencing data analysis revealed a remarkable increase in the expression of the secreted phosphoprotein 1 (Spp1) gene within these microglia and macrophages, identifying subsets of Spp1-expressing microglia and macrophages during neovascularization formation in angiogenesis mouse models. Notably, the number of Spp1-expressing microglia and macrophages exhibited further elevation during neovascularization in mice lacking myeloid SOCS3. Moreover, our investigation unveiled the Spp1 gene as a direct transcriptional target gene of signal transducer and activator of transcription 3. Importantly, pharmaceutical activation of SOCS3 or blocking of SPP1 resulted in a significant reduction in pathological neovascularization. In conclusion, our study highlights the pivotal role of the SOCS3/STAT3/SPP1 axis in the regulation of pathological retinal angiogenesis.

Clinical utility and safety of a trapezoid-shaped electrode placement for evaluating the mesio-basal temporal lobe during epilepsy surgery.

A trapezoid-shaped electrode (TSE) is used for detecting epileptogenicity in patients with temporal lobe epilepsy (TLE). However, the utility and safety associated with TSE placement have not been reported. In this study, we evaluated the safety and usefulness of TSE by analyzing the seizure detection, surgical outcomes and complications in patients with TLE who underwent intracranial electrodes (ICE) placement. Between April 2000 and August 2019, 50 patients with TLE who underwent 51 ICE placement procedures were examined. A TSE with eight contacts covering the parahippocampal gyrus and basal temporal lobe was used. Among the 37 patients who underwent TSE placement, 26 and 11 patients were diagnosed with mesial TLE (mTLE) and extra-mTLE, respectively. The 14 remaining patients without TSE placement were diagnosed with extra-mTLE. Seizure freedom was achieved in 73% (19/26) of mTLE patients detected by TSE and 50% (14/24) of extra-mTLE patients.Good seizure outcomes (Engel class I and II) were observed in 81% (21/26) patients with mTLE and 67% (16/24) patients with extra-mTLE. Radiographic complications were observed in 20% (10/50) patients who underwent ICE placement. Although 6% (3/50) patients showed transient neurological deficits, none were permanent. The electrodes responsible for the occurrence of complications included nine grid electrodes and one TSE. The complication rate after TSE placement was 3% (1/37). More than 64 electrode contacts and male sex, not TSE placement, were identified as significant risk factors for developing complications. This study demonstrated the usefulness and safety of TSE for evaluating mTLE in patients undergoing ICE placement.

Environmental detection of eumycetoma pathogens using multiplex real-time PCR for soil DNA in Sennar State, Sudan.

BACKGROUND: Mycetoma is a chronic disease affecting the skin and subcutaneous tissue endemic in the tropical and subtropical regions. Several bacteria and fungi can cause mycetoma, but fungal mycetoma (eumycetoma) is challenging because the treatment requires a combination of a long-term antifungal agent and surgery. Although the transmission route has not yet been elucidated, infection from the soil is a leading hypothesis. However, there are few soil investigation studies, and the geographical distribution of mycetoma pathogens is not well documented. Here, we used multiplex real-time PCR technology to identify three fungal species from soil samples. METHODS: In total, 64 DNA samples were extracted from soil collected in seven villages in an endemic area in Sennar State, Sudan, in 2019. Primers and fluorescent probes specifically targeting the ribosomal DNA of Madurella mycetomatis, Falciformispora senegalensis, and F. tompkinsii were designed. RESULTS: Multiplex real-time PCR was performed and identified the major pathogen, M. mycetomatis that existed in most sites (95%). In addition, two other pathogens were identified from some sites. This is the first report on the use of this technique for identifying the eumycetoma causative microorganisms. CONCLUSIONS: This study demonstrated that soil DNA investigation can elucidate the risk area of mycetoma-causative agents. The results will contribute to the design of prevention measures, and further large-scale studies may be effective in understanding the natural habitats of mycetoma pathogens.

Comparison of sxx commercially-available dna polymerases for direct ccr / Comparacao de seis polimerases de DNA disponiveis comercialmente para o PCR direto

SUMMARY The use of a “direct PCR” DNA polymerase enables PCR amplification without any prior DNA purification from blood samples due to the enzyme's resistance to inhibitors present in blood components. Such DNA polymerases are now commercially available. We compared the PCR performance of six direct PCR-type DNA polymerases (KOD FX, Mighty Amp, Hemo KlenTaq, Phusion Blood II, KAPA Blood, and BIOTAQ) in dried blood eluted from a filter paper with TE buffer. GoTaq Flexi was used as a standard DNA polymerase. PCR performance was evaluated by a nested PCR technique for detecting Plasmodium falciparum genomic DNA in the presence of the blood components. Although all six DNA polymerases showed resistance to blood components compared to the standard Taq polymerase, the KOD FX and BIOTAQ DNA polymerases were resistant to inhibitory blood components at concentrations of 40%, and their PCR performance was superior to that of other DNA polymerases. When the reaction mixture contained a mild detergent, only KOD FX DNA polymerase retained the original amount of amplified product. These results indicate that KOD FX DNA polymerase is the most resistant to inhibitory blood components and/or detergents. Thus, KOD FX DNA polymerase could be useful in serological studies to simultaneously detect antibodies and DNA in eluents for antibodies. KOD FX DNA polymerase is thus not limited to use in detecting malaria parasites, but could also be employed to detect other blood-borne pathogens. .

RESUMO O propósito deste estudo foi avaliar 6 polimerases de DNA disponíveis comercialmente que são resistentes aos inibidores do PCR para uma amplificação potencial de DNA de amostras de sangue total. O DNA genômico do parasita humano da malária, Plasmodium falciparum, foi analisado sob condições que incluíram os componentes inibidores do sangue extraído de sangue ressacado em papel de filtro. Nossos resultados sugerem que a polimerase KOD FX DNA é superior a outras polimerases. .