Immune cell signatures and inflammatory mediators: unraveling their genetic impact on chronic kidney disease through Mendelian randomization.

Prior research has established associations between immune cells, inflammatory proteins, and chronic kidney disease (CKD). Our Mendelian randomization study aims to elucidate the genetic causal relationships among these factors and CKD. We applied Mendelian randomization using genetic variants associated with CKD from a large genome-wide association study (GWAS) and inflammatory markers from a comprehensive GWAS summary. The causal links between exposures (immune cell subtypes and inflammatory proteins) and CKD were primarily analyzed using the inverse variance-weighted, supplemented by sensitivity analyses, including MR-Egger, weighted median, weighted mode, and MR-PRESSO. Our analysis identified both absolute and relative counts of CD28 + CD45RA + CD8 + T cell (OR = 1.01; 95% CI = 1.01-1.02; p < 0.001, FDR = 0.018) (OR = 1.01; 95% CI = 1.00-1.01; p < 0.001, FDR = 0.002), CD28 on CD39 + CD8 + T cell(OR = 0.97; 95% CI = 0.96-0.99; p < 0.001, FDR = 0.006), CD16 on CD14-CD16 + monocyte (OR = 1.02; 95% CI = 1.01-1.03; p < 0.001, FDR = 0.004) and cytokines, such as IL-17A(OR = 1.11, 95% CI = 1.06-1.16, p < 0.001, FDR = 0.001), and LIF-R(OR = 1.06, 95% CI = 1.02-1.10, p = 0.005, FDR = 0.043) that are genetically predisposed to influence the risk of CKD. Moreover, the study discovered that CKD itself may causatively lead to alterations in certain proteins, including CST5(OR = 1.16, 95% CI = 1.09-1.24, p < 0.001, FDR = 0.001). No evidence of reverse causality was found for any single biomarker and CKD. This comprehensive MR investigation supports a genetic causal nexus between certain immune cell subtypes, inflammatory proteins, and CKD. These findings enhance the understanding of CKD's immunological underpinnings and open avenues for targeted treatments.

Identification of common genes of rhinovirus single/double­stranded RNA­induced asthma deterioration by bioinformatics analysis.

Rhinovirus (RV) is the most common respiratory virus affecting humans. The majority of asthma deteriorations are triggered by RV infections. However, whether the effects of RV single- and double-stranded RNA on asthma deterioration have common target genes needs to be further studied. In the present study, two datasets (GSE51392 and GSE30326) were used to screen for common differentially expressed genes (cDEGs). The molecular function, signaling pathways, interaction networks, hub genes, key modules and regulatory molecules of cDEGs were systematically analyzed using online tools such as Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, STRING and NetworkAnalyst. Finally, the hub genes STAT1 and IFIH1 were verified in clinical samples using reverse transcription-quantitative PCR (RT-qPCR). A total of 85 cDEGs were identified. Function analysis revealed that cDEGs served an important role in the innate immune response to viruses and its regulation. Signal transducer and activator of transcription 1 (STAT1), interferon induced with helicase C domain 1 (IFIH1), interferon regulatory factor 7 (IRF7), DExD/H box helicase 58 (DDX58) and interferon-stimulating gene 15 (ISG15) were detected to be hub genes based on the protein-protein interactions and six topological algorithms. A key module involved in influenza A, the Toll-like receptor signaling pathway, was identified using Cytoscape software. The hub genes were regulated by GATA-binding factor 2 and microRNA-146a-5p. In addition, RT-qPCR indicated that the expression levels of the hub genes STAT1 and IFIH1 were low during asthma deterioration compared with post-treatment recovery samples. The present study enhanced the understanding of the mechanism of RV-induced asthma deterioration.

A smart cysteine-activated and heavy-atom-free nano-photosensitizer for photodynamic therapy to treat cancers.

A smart and heavy-atom-free photoinactive nano-photosensitizer capable of being activated by cysteine at the tumor site to generate highly photoactive nano-photosensitizers that show strong NIR absorption and fluorescence with a good singlet oxygen quantum yield (16.8%) for photodynamic therapy is reported.

Dual-wavelength responsive CuS@COF nanosheets for high-performance photothermal/photodynamic combination treatments.

Photothermal therapy (PTT) makes it difficult to achieve good performance on tumor treatments due to insufficient photothermal conversion efficiency, etc. Combining PTT with photodynamic therapy (PDT) and other therapeutic tools can significantly enhance the tumor-killing ability and has been widely used in the development of therapeutic platforms. Copper sulfide nanoparticle (CuS NP) photothermal reagents have the advantages of low toxicity and simple synthesis; therefore, combining CuS NPs with PDT photosensitizers is an effective strategy to construct a PTT/PDT combination therapeutic platform. However, PDT photosensitizers and photothermal agents generally assembled through hydrophobic interaction, suffer from low coating efficiency or the risk of drug leakage, thus seriously restricting their applications. To address these challenges, CuS NPs with excellent photothermal conversion performance were selected as the core material to prepare CuS@COF nanosheets through a dual-ligand assistant strategy with 4,7-bis(4-aminophenyl)-2,1,3-benzothiadiazole (BTD) and 2,4,6-trihydroxybenzene-1,3,5-tricarbaldehyde (TP). As a PTT/PDT combination therapeutic platform, CuS@COF nanosheets possess a porous TP-BDT-based COF shell, and it can sufficiently contact oxygen to provide high singlet oxygen (1O2) yield under 505 nm laser irradiation. Upon illumination with a 1064 nm laser, CuS@COF nanosheets can effectively convert the photon energy into thermal energy with a photothermal conversion efficiency of 63.4%. The results of the CCK8 experiment showed that the phototoxicity of the PTT/PDT combination treatment reached 85.1%, which was much higher than the effect of a single treatment. It was also confirmed in vivo that the tumor inhibition effect of the PDT/PTT combination treatment group was much greater than that of the single treatment group.

Toward reaching hepatitis B goals: hepatitis B epidemiology and the impact of two decades of vaccination, Georgia, 2021.

BackgroundGeorgia has adopted the World Health Organization European Region's and global goals to eliminate viral hepatitis. A nationwide serosurvey among adults in 2015 showed 2.9% prevalence for hepatitis B virus (HBV) surface antigen (HBsAg) and 25.9% for antibodies against HBV core antigen (anti-HBc). HBV infection prevalence among children had previously not been assessed.AimWe aimed to assess HBV infection prevalence among children and update estimates for adults in Georgia.MethodsThis nationwide cross-sectional serosurvey conducted in 2021 among persons aged ≥ 5 years used multi-stage stratified cluster design. Participants aged 5-20 years were eligible for hepatitis B vaccination as infants. Blood samples were tested for anti-HBc and, if positive, for HBsAg. Weighted proportions and 95% confidence intervals (CI) were calculated for both markers.ResultsAmong 5-17 year-olds (n = 1,473), 0.03% (95% CI: 0-0.19) were HBsAg-positive and 0.7% (95% CI: 0.3-1.6) were anti-HBc-positive. Among adults (n = 7,237), 2.7% (95% CI: 2.3-3.4) were HBsAg-positive and 21.7% (95% CI: 20.4-23.2) anti-HBc-positive; HBsAg prevalence was lowest (0.2%; 95% CI: 0.0-1.5) among 18-23-year-olds and highest (8.6%; 95% CI: 6.1-12.1) among 35-39-year-olds.ConclusionsHepatitis B vaccination in Georgia had remarkable impact. In 2021, HBsAg prevalence among children was well below the 0.5% hepatitis B control target of the European Region and met the ≤ 0.1% HBsAg seroprevalence target for elimination of mother-to-child transmission of HBV. Chronic HBV infection remains a problem among adults born before vaccine introduction. Screening, treatment and preventive interventions among adults, and sustained high immunisation coverage among children, can help eliminate hepatitis B in Georgia by 2030.

Immunogenicity of novel oral poliovirus vaccine type 2 administered concomitantly with bivalent oral poliovirus vaccine: an open-label, non-inferiority, randomised, controlled trial.

BACKGROUND: Novel oral poliovirus vaccine type 2 (nOPV2) was developed by modifying the Sabin strain to increase genetic stability and reduce risk of seeding new circulating vaccine-derived poliovirus type 2 outbreaks. Bivalent oral poliovirus vaccine (bOPV; containing Sabin types 1 and 3) is the vaccine of choice for type 1 and type 3 outbreak responses. We aimed to assess immunological interference between nOPV2 and bOPV when administered concomitantly. METHODS: We conducted an open-label, non-inferiority, randomised, controlled trial at two clinical trial sites in Dhaka, Bangladesh. Healthy infants aged 6 weeks were randomly assigned (1:1:1) using block randomisation, stratified by site, to receive nOPV2 only, nOPV2 plus bOPV, or bOPV only, at the ages of 6 weeks, 10 weeks, and 14 weeks. Eligibility criteria included singleton and full term (≥37 weeks' gestation) birth and parents intending to remain in the study area for the duration of study follow-up activities. Poliovirus neutralising antibody titres were measured at the ages of 6 weeks, 10 weeks, 14 weeks, and 18 weeks. The primary outcome was cumulative immune response for all three poliovirus types at the age of 14 weeks (after two doses) and was assessed in the modified intention-to-treat population, which was restricted to participants with adequate blood specimens from all study visits. Safety was assessed in all participants who received at least one dose of study product. A non-inferiority margin of 10% was used to compare single and concomitant administration. This trial is registered with ClinicalTrials.gov, NCT04579510. FINDINGS: Between Feb 8 and Sept 26, 2021, 736 participants (244 in the nOPV2 only group, 246 in the nOPV2 plus bOPV group, and 246 in the bOPV only group) were enrolled and included in the modified intention-to-treat analysis. After two doses, 209 (86%; 95% CI 81-90) participants in the nOPV2 only group and 159 (65%; 58-70) participants in the nOPV2 plus bOPV group had a type 2 poliovirus immune response; 227 (92%; 88-95) participants in the nOPV2 plus bOPV group and 229 (93%; 89-96) participants in the bOPV only group had a type 1 response; and 216 (88%; 83-91) participants in the nOPV2 plus bOPV group and 212 (86%; 81-90) participants in the bOPV only group had a type 3 response. Co-administration was non-inferior to single administration for types 1 and 3, but not for type 2. There were 15 serious adverse events (including three deaths, one in each group, all attributable to sudden infant death syndrome); none were attributed to vaccination. INTERPRETATION: Co-administration of nOPV2 and bOPV interfered with immunogenicity for poliovirus type 2, but not for types 1 and 3. The blunted nOPV2 immunogenicity we observed would be a major drawback of using co-administration as a vaccination strategy. FUNDING: The US Centers for Disease Control and Prevention.

Combined therapy of local recombinant human interferon α1b injection and acupuncture on verruca vulgaris: a retrospective study.

Verruca vulgaris is always stubborn to treat. We applied a new combined therapy of local recombinant human interferon alpha 1b (rhIFNα1b) injection plus acupuncture on verruca vulgaris recently to evaluate the efficacy and safety of the combined therapy. The retrospective study was conducted in The First Hospital of China Medical University from 2018 to 2020. Patients with verruca vulgaris were included. Combined therapy with local rhIFNα1b injection plus acupuncture was set as treatment group, rhIFNα1b injection and carbon dioxide (CO2) laser were set as control groups. A total of 2415 patients were included in the study. The cure rates were 81.85%, 85.93%, and 100% in combined group, rhIFNα1b group, and CO2 laser group, separately. All lesions cured in combined group were located on hands or feet, while majority of lesions cured in other groups were located on other sites. For patients with medium/big single lesion or 6-9 lesions, less treatment times were needed in combined group than rhIFNα1b group. For patients with small single, two to five or more than ten lesions, the treatment times of combined group and rhIFNα1b group were comparable. All patients complained of pain in varying degrees when local injection or laser irradiation. Compared with CO2 laser group, more fever, less swelling or scar was reported in combined group. In conclusion, combined therapy of local rhIFNα1b plus acupuncture was beneficial for verruca vulgaris with limited adverse effects. The therapy was more acceptable by younger female patients with verruca vulgaris.

Tetanus and Diphtheria Seroprotection among Children Younger Than 15 Years in Nigeria, 2018: Who Are the Unprotected Children?

Serological surveys provide an objective biological measure of population immunity, and tetanus serological surveys can also assess vaccination coverage. We undertook a national assessment of immunity to tetanus and diphtheria among Nigerian children aged <15 years using stored specimens collected during the 2018 Nigeria HIV/AIDS Indicator and Impact Survey, a national cross-sectional household-based survey. We used a validated multiplex bead assay to test for tetanus and diphtheria toxoid-antibodies. In total, 31,456 specimens were tested. Overall, 70.9% and 84.3% of children aged <15 years had at least minimal seroprotection (≥0.01 IU/mL) against tetanus and diphtheria, respectively. Seroprotection was lowest in the north west and north east zones. Factors associated with increased tetanus seroprotection included living in the southern geopolitical zones, urban residence, and higher wealth quintiles (p < 0.001). Full seroprotection (≥0.1 IU/mL) was the same for tetanus (42.2%) and diphtheria (41.7%), while long-term seroprotection (≥1 IU/mL) was 15.1% for tetanus and 6.0% for diphtheria. Full- and long-term seroprotection were higher in boys compared to girls (p < 0.001). Achieving high infant vaccination coverage by targeting specific geographic areas and socio-economic groups and introducing tetanus and diphtheria booster doses in childhood and adolescence are needed to achieve lifelong protection against tetanus and diphtheria and prevent maternal and neonatal tetanus.

Programmatic Effectiveness of a Pediatric Typhoid Conjugate Vaccine Campaign in Navi Mumbai, India.

BACKGROUND: The World Health Organization recommends vaccines for prevention and control of typhoid fever, especially where antimicrobial-resistant typhoid circulates. In 2018, the Navi Mumbai Municipal Corporation (NMMC) implemented a typhoid conjugate vaccine (TCV) campaign. The campaign targeted all children aged 9 months through 14 years within NMMC boundaries (approximately 320 000 children) over 2 vaccination phases. The phase 1 campaign occurred from 14 July 2018 through 25 August 2018 (71% coverage, approximately 113 420 children). We evaluated the phase 1 campaign's programmatic effectiveness in reducing typhoid cases at the community level. METHODS: We established prospective, blood culture-based surveillance at 6 hospitals in Navi Mumbai and offered blood cultures to children who presented with fever ≥3 days. We used a cluster-randomized (by administrative boundary) test-negative design to estimate the effectiveness of the vaccination campaign on pediatric typhoid cases. We matched test-positive, culture-confirmed typhoid cases with up to 3 test-negative, culture-negative controls by age and date of blood culture and assessed community vaccine campaign phase as an exposure using conditional logistic regression. RESULTS: Between 1 September 2018 and 31 March 2021, we identified 81 typhoid cases and matched these with 238 controls. Cases were 0.44 times as likely to live in vaccine campaign communities (programmatic effectiveness, 56%; 95% confidence interval [CI], 25% to 74%; P = .002). Cases aged ≥5 years were 0.37 times as likely (95% CI, .19 to .70; P = .002) and cases during the first year of surveillance were 0.30 times as likely (95% CI, .14 to .64; P = .002) to live in vaccine campaign communities. CONCLUSIONS: Our findings support the use of TCV mass vaccination campaigns as effective population-based tools to combat typhoid fever.

Co-administration of Oral Cholera Vaccine With Oral Polio Vaccine Among Bangladeshi Young Children: A Randomized Controlled Open Label Trial to Assess Interference.

BACKGROUND: Cholera remains a public health threat for low- and middle-income countries, particularly in Asia and Africa. Shanchol™, an inactivated oral cholera vaccine (OCV) is currently in use globally. OCV and oral poliovirus vaccines (OPV) could be administered concomitantly, but the immunogenicity and safety of coadministration among children aged 1-3 years is unknown. METHODS: We undertook an open-label, randomized, controlled, inequality trial in Dhaka city, Bangladesh. Healthy children aged 1-3 years were randomly assigned to 1 of 3 groups: bivalent OPV (bOPV)-alone, OCV-alone, or combined bOPV + OCV and received vaccines on the day of enrollment and 28 days later. Blood samples were collected on the day of enrollment, day 28, and day 56. Serum poliovirus neutralizing antibodies and vibriocidal antibodies against Vibrio cholerae O1 were assessed using microneutralization assays. RESULTS: A total of 579 children aged 1‒3 years were recruited, 193 children per group. More than 90% of the children completed visits at day 56. Few adverse events following immunization were recorded and were equivalent among study arms. On day 28, 60% (90% confidence interval: 53%-67%) and 54% (46%-61%) of participants with co-administration of bOPV + OCV responded to polioviruses type 1 and 3, respectively, compared to 55% (47%-62%) and 46% (38%-53%) in the bOPV-only group. Additionally, >50% of participants showed a ≥4-fold increase in vibriocidal antibody titer responses on day 28, comparable to the responses observed in OCV-only arm. CONCLUSIONS: Co-administration of bOPV and OCV is safe and effective in children aged 1-3 years and can be cost-beneficial. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT03581734).

Seroprevalence of poliovirus antibodies in Nigeria: refining strategies to sustain the eradication effort.

Introduction: in 2016, a switch from trivalent oral poliovirus vaccine (OPV) (containing serotypes 1,2,3) to bivalent OPV (types 1,3) was implemented globally. We assessed the seroprevalence of poliovirus antibody levels in selected Nigerian states, before and after the switch, documented poliovirus type2 outbreak responses conducted and ascertained factors associated with immunity gaps based on seroprevalence rates. Methods: we conducted a secondary analysis of stored serum samples from the 2018 Nigeria National HIV/AIDS Indicator and Impact Survey. Serum from 1,185 children aged 0-119 months residing in one southern and four northern states were tested for serotype-specific PV neutralizing antibodies; seropositivity was a reciprocal titer ≥8. We conducted regression analysis to determine sociodemographic risk factors associated with low seroprevalence using SAS 9.4. Results: children aged 24-119 months (pre-switch cohort) had seroprevalence against PV1, PV2, and PV3, of 97.3% (95% CI:96.4-98.2), 93.8% (95% CI:92.2-95.5), and 91.3% (95% CI:89.2-93.4), while children aged <24 months (post-switch) had seroprevalence of 86.0% (95% CI:81.2-90.8), 55.6% (95% CI: 47.7-63.4), and 77.2% (95% CI:71.0-83.4) respectively. Regression analysis showed age <24 months was associated with lower seroprevalence against all PV serotypes, (p<0.0001); females had lower seroprevalence against PV1 (p=0.0184) and PV2 (p=0.0354); northern states lower seroprevalence against PV1 (p=0.0039), while well-water source lower seroprevalence against PV3 (p=0.0288). Conclusion: this study showed high seroprevalence rates against PV 1, 2, and 3 in pre-switch children (aged 24-119 months). However, post-switch children (<24 months) had low immunity against PV2 despite outbreak responses. Strategies to increase routine immunization coverage and high-quality polio campaigns can increase immunity against polio virus.

Prognostic Value of Serum Cholinesterase Levels for In-Hospital Mortality among Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Cholinesterase (ChE) is associated with the pathogenesis of chronic obstructive pulmonary disease (COPD), including chronic airway inflammation and oxidation/antioxidant imbalance. However, the relationship between serum ChE levels and survival outcomes of patients hospitalized with acute exacerbations of COPD (AECOPD) is unknown. In this retrospective single-center study, we investigated the ability of the serum ChE level to predict in-hospital death in patients hospitalized with AECOPD. The clinicopathological data, including serum ChE levels as well as clinical and biochemical indicators were extracted for 477 patients from the hospital records and analyzed. Our results demonstrated that AECOPD patients with lower serum ChE levels were associated with increased mortality, frequent hospitalization due to acute exacerbations (AE) in the past year, and longer hospital stay. The optimal cutoff value for the serum ChE level was 4323 U/L. The area under the ROC curve (AUC) values for predicting in-hospital mortality based on the serum ChE level was 0.79 (95% confidence interval (CI), 0.72-0.85). Multivariate logistic regression analysis demonstrated that serum ChE level ≤ 4323 U/L (odds ratio (OR) 9.09, 95% CI 3.43-28.3, p < 0.001), age-adjusted Charlson comorbidity index (aCCI), and the number of hospitalizations due to AE in the past year were independent risk factors for predicting the in-hospital mortality of AECOPD patients. In conclusion, our study demonstrated that low serum ChE levels were associated with significantly higher in-hospital mortality rates of patients hospitalized with AECOPD. Therefore, serum ChE level is a promising prognostic predictor of hospitalized AECOPD patients.

Tracking Autophagy Process with a TBET and AIE-Based Ratiometric Two-Photon Viscosity Probe.

Autophagy is a cellular self-degrading process that plays a key role in cellular health and functioning. Since autophagy disorder is related to many diseases, it is highly important to detect autophagy. This study aimed to establish a dual-sensing mechanism-based ratiometric viscosity-sensitive lysosome-targeted two-photon fluorescent probe Vis-sun to track the autophagy process (the increase in lysosome viscosity during autophagy) by combining through bond energy transfer (TBET) and aggregation-induced emission (AIE). The introduction of TBET not only overcame the interference of background signals but also achieved the baseline separation of two emission peaks, thus reducing the crosstalk between emissions, as well as the noninvasive bio-sensing of biological targets and long-term real-time tracer imaging by introducing AIE. In vitro experiments showed that the fluorescence intensity at 485 nm decreased gradually on increasing the volume ratio of water to tetrahydrofuran (Vwater/VTHF), while the fluorescence intensity at 605 nm increased significantly. Also, the fluorescence signal was maximized when the water content reached 100%. At the same time, the probe exhibited a significant dependence on the ambient viscosity. Therefore, the dynamic monitoring of lysosome viscosity during autophagy and the in situ imaging of autophagy fluctuations during stroke-induced neuroinflammation were successfully achieved by implementing Vis-sun lysosome anchoring with morpholine.

Tracking autophagy process with a through bond energy transfer-based ratiometric two-photon viscosity probe.

Autophagy is a self-degradation process in cells, which is of vital significance to the health and operation of organisms. Due to the increase of lysosomal viscosity during autophagy, viscosity probes that specifically accumulate in lysosome are powerful tools for monitoring autophagy and investigating related diseases. However, there is still a lack of viscosity-sensitive ratiometric autophagy probes, which restricts the tracking of autophagy with high accuracy in complex physiological environment. Herein, a viscosity-responsive, lysosome targeted two-photon fluorescent probe Lyso-Vis was designed based on through bond energy transfer (TBET) mechanism. The TBET-based probe achieved the separation of two emission baselines, which greatly improved the resolution and reliability of sensing and imaging. Under 810 nm two-photon excitation, the emission intensity ratio of the red and green channel increased with a viscosity dependent manner. Lyso-Vis not only for the first time realized ratiometric sensing of lysosomal viscosity during autophagy process, but also visualized the association of autophagy with inflammation and stroke, and it was applied to explore the activation and inhibition of autophagy during stroke in mice.

Near-Infrared in and out: Observation of Autophagy during Stroke via a Lysosome-Targeting Two-Photon Viscosity-Dependent Probe.

Fluorescence imaging using probes with two-photon excitation and near-infrared emission is currently the most popular in situ method for monitoring biological species or events, with a large imaging depth, low background fluorescence, low optical damage, and high spatial and temporal resolution. Nevertheless, current fluorescent dyes with near-infrared emission still have some disadvantages such as poor water solubility, low fluorescence quantum yield, and small two-photon absorption cross sections. These drawbacks are mainly caused by the structural characteristics of dyes with large conjugation surfaces but lacking strong and rigid structures. Herein, a lysosome-targeted and viscosity-sensitive probe (NCIC-VIS) is designed and synthesized. The protonation of morpholine not only helps anchor NCIC-VIS to the lysosome but also significantly enhances its water solubility. More importantly, its viscosity can increase the rigid structure of NCIC-VIS, which will improve the fluorescence quantum yield and the two-photon absorption cross section due to the imposed restrictions on molecular torsion. Based on the abovementioned characteristics, the real-time imaging of cellular autophagy (could increase the viscosity of lysosomes) was realized using NCIC-VIS. The results demonstrated that the level of autophagy was significantly enhanced in mice during stroke, while the inhibition of oxidative stress significantly reduced the degree of autophagy. The study corroborates that oxidative stress induced by stroke can lead to the development of autophagy.

A multi center real world observation to evaluate the efficacy of cryotherapy versus local hyperthermia for the treatment of plane warts.

Most plane warts are recalcitrant to treatment. Both cryotherapy and local hyperthermia have been applied to treat plane warts. However, no direct comparative study on their respective efficacy and safety has ever been performed. To assess the efficacy and safety of local hyperthermia at 43 ± 1°C versus liquid nitrogen cryotherapy for plane warts. Sequential patients with plane warts entered the study, either receiving cryotherapy or local hyperthermia therapy at the discretion of the patients and the recommendations of consultants. Cryotherapy with liquid nitrogen was delivered in two sessions 2 weeks apart, while local hyperthermia was delivered on three consecutive days, plus two similar treatments 10 ± 3 days later. The temperature over the treated skin surface was set at 43 ± 1°C for 30 min in each session. The primary outcome was the clearance rates of the lesions 6 months after treatment. Among the 194 participants enrolled, 183 were included in the analysis at 6 months. Local hyperthermia and cryotherapy achieved clearance rates of 35.56% (48/135) and 31.25% (15/48), respectively (p = 0.724); recurrence rates of 16.67% (8/48) and 53.33% (8/15) (p = 0.01); and adverse events rates of 20.74% (28/135) and 83.33% (40/48), respectively (p < 0.001). Cryotherapy had a higher pain score (p < 0.001) and a longer healing time (p < 0.001). Local hyperthermia at 43°C and cryotherapy had similar efficacy for plane warts. Local hyperthermia had a safer profile than cryotherapy but it required more treatment visits during a treatment course. More patients preferred local hyperthermia due to its treatment friendly nature.

Cost of human papillomavirus vaccine delivery at district and health facility levels in Zimbabwe: A school-based vaccination program targeting multiple cohorts.

BACKGROUND: After a pilot project in 2014-15 Zimbabwe introduced the human papillomavirus (HPV) vaccine nationally in 2018 for girls aged 10-14 years through a primarily school-based vaccination campaign with two doses administered at 12-month intervals. In 2019, a first dose was delivered to a new cohort of girls in grade 5 of girls age 10 years if out-of-school (OOS), along with a second dose to the 2018 multiple cohorts. Additional effort was made to identify and mobilize OOS girls by Village Health Workers (VHWs) in the community. Zimbabwe reported 1,569,905 doses of HPV vaccine administered during the 2018 and 2019 campaigns. This analysis evaluated the cost of Zimbabwe's national HPV vaccine introduction. METHODS: A retrospective, incremental, ingredients-based cost analysis from the provider perspective was conducted in 2018 and 2019. Financial and economic cost data were collected at district and health facility levels using a two-stage cluster sampling approach and four cost dimensions: program activity, resource input, payer, and administrative level. Costs are presented in 2020 US$ in total and per dose. RESULTS: The total weighted costs for combined district and health facility administrative levels were US$ 828,731 (financial) and US$ 2,060,943 (economic). For service delivery, the total weighted cost per dose was US$ 0.16 (financial) and US$ 0.59 (economic). The program activities with the largest share of total weighted financial cost were training (37% of total) and service delivery (30%), while the largest shares of total weighted economic costs were service delivery (45%) and training (19%). Efforts by VHWs to reach OOS girls resulted in an additional US$ 2.99 in financial cost per dose and US$ 7.79 in economic cost per dose. CONCLUSION: The service delivery cost per dose was lower than that documented in the pilot program cost analysis in Zimbabwe and studies elsewhere, reflecting a campaign delivery approach that spread fixed costs over a large vaccination cohort. The additional cost of reaching OOS girls with the HPV vaccine was documented for the first time in low- and middle-income countries, which may provide information on potential costs for other countries.

Multiple cohort HPV vaccination in Zimbabwe: 2018-2019 program feasibility, awareness, and acceptability among health, education, and community stakeholders.

INTRODUCTION: Zimbabwe introduced human papillomavirus (HPV) vaccine nationally in May 2018, targeting multiple cohorts (girls aged 10-14 years) through a school-based vaccination campaign. One year later, the second dose was administered to the multiple cohorts concurrently with the first dose given to a new single cohort of girls in grade 5. We conducted cross-sectional surveys among health workers, school personnel, and community members to assess feasibility of implementation, training, social mobilization, and community acceptability. METHODS: Thirty districts were selected proportional to the volume of the HPV vaccine doses delivered in 2018; two health facilities were randomly selected within each district. One health worker, school health coordinator, village health worker, and community leader were surveyed at each selected health facility and surrounding area during January-February 2020, using standard questionnaires. Descriptive analysis was completed across groups. RESULTS: There were 221 interviews completed. Over 60% of health workers reported having enough staff to carry out vaccination sessions in schools while maintaining routine vaccination services in health facilities. All school health coordinators felt the HPV vaccine should be delivered in schools in the future. Knowledge of the correct target cohort eligibility decreased from 91% in 2018 to 50% in 2020 among health workers. Understanding of HPV infection and use of HPV vaccine for cervical cancer prevention was above 90% for all respondents. Forty-two percent of respondents reported hearing rumors about the HPV vaccine, primarily regarding infertility and safety. CONCLUSIONS: Findings demonstrate the presence of highly knowledgeable staff at health facilities and schools, strong community acceptance, and a school-based HPV program considered feasible to implement in Zimbabwe. However, misunderstandings regarding target eligibility and rumors persist, which can impact vaccine uptake and coverage. Continued social mobilization efforts to maintain community demand and training on eligibility were recommended. Integration, partnerships, and resource mobilization are also needed to ensure program sustainability.

Cost of human papillomavirus vaccine delivery in a single-age cohort, routine-based vaccination program in Senegal.

INTRODUCTION: In 2018, Senegal introduced human papillomavirus (HPV) vaccine into its routine immunization program for all nine-year-old girls nationwide. We evaluated the costs of Senegal's introduction of HPV vaccine via this delivery approach. METHODS: We conducted a retrospective, incremental, ingredients-based cost evaluation from the provider perspective. The study timeframe included Senegal's first planning meeting in 2018 through data collection in early 2020. We collected costs from all involved units at the national and regional levels. A multi-stage cluster sampling approach was used to obtain a nationally representative sample of districts and health facilities. Weights were applied to costs from sampled units to estimate costs across all units. The cost evaluation was based on four dimensions: program activity, resource input, payer, and administrative level. Total costs were divided by the number of HPV doses administered to determine cost per dose and per dimension. RESULTS: Excluding vaccine program activity costs, the total financial and economic delivery costs of Senegal's HPV vaccination program were US$ 1,152,351 and US$ 2,838,466, respectively (US$ 3.07 and US$ 7.56 per dose, respectively). A total of 375,608 HPV vaccine doses were administered during the cost evaluation. Training and per diem represented the largest shares of financial costs. Service delivery and personnel time accounted for the largest shares of economic costs. By administrative level, district and health facility levels had the largest shares of financial and economic costs, respectively. Senegal's Ministry of Health accounted for the largest share of financial and economic costs. Including vaccine program activity costs (US$ 4.68/per dose), the total financial cost was US$ 2,911,343 (US$ 7.75 per dose). CONCLUSION: This cost evaluation can support Senegal's future vaccine introductions and inform other countries planning to introduce HPV vaccine nationwide. These findings support previous costing studies which anticipated potential economies of scale during the transition from HPV vaccine pilot demonstration projects to national introduction.