Seroepidemiological Reconstruction of Long-term Chikungunya Virus Circulation in Burkina Faso and Gabon.

Chikungunya virus (CHIKV) is a major public health concern worldwide. However, infection levels are rarely known, especially in Africa. We recruited individuals from Ouagadougou, Burkina Faso and Lambaréné, Gabon (age range, 1-55 years), tested their blood for CHIKV antibodies, and used serocatalytic models to reconstruct epidemiological histories. In Ouagadougou, 291 of 999 (29.1%) individuals were seropositive, ranging from 2% among those aged <10 years to 66% in those aged 40-55 years. We estimated there were 7 outbreaks since the 1970s but none since 2001, resulting in 600 000 infections in the city, none of which were reported. However, we could not definitively conclude whether infections were due to CHIKV or o'nyong-nyong, another alphavirus. In Lambaréné, 117 of 427 (27%) participants were seropositive. Our model identified a single outbreak sometime since 2007, consistent with the only reported CHIKV outbreak in the country. These findings suggest sporadic outbreaks in these settings and that the burden remains undetected or incorrectly attributed.

Family-based treatment takes longer for adolescents with mental health comorbidities: findings from a community mental health service.

Children and adolescents diagnosed with an eating disorder often meet the diagnosis of another mental health disorder. In addition to eating disorders, individuals with comorbid disorders have higher suicide rates and more severe and chronic eating disorder symptoms. The present research aimed to investigate the influence of comorbid conditions on the treatment outcomes of children and adolescents that attended a public community mental health service. It was hypothesised that the patients with comorbidities would have a more extended treatment duration, slower rates of weight restoration, more hospital admissions for medical compromise, and poorer functioning than those without comorbidities. Data from 78 past patients at the Eating Disorder Program in Queensland, Australia, were analysed. Patients with comorbidities demonstrated similar recovery rates to those without comorbidities. However, those with comorbid conditions had longer episodes of treatment. The study's results support using Family Based Treatment for patients with and without comorbidities. The implications of the findings for public mental health services and directions for future research are discussed.

Changes in variability during intervention for childhood apraxia of speech: implications for therapy.

Typically developing children are variable in their speech production with decreasing variability indicating mastery of speech. Excessive variability which does not change over time may be an indication of unstable motor plans as often seen in children with childhood apraxia of speech (CAS). Dynamic Systems Theory (DST) provides a framework for understanding the role of variability in speech development and disorder. There are few studies that explore the impact of therapy on speech variability. This work explores the impact of therapy on perceptual speech production variability. It is a post-hoc analysis of data collected in two intervention studies of a motor-based treatment approach with children with CAS and explores DST variability effects in speech skill acquisition based on the case data from those studies. There were six participants in total across the two studies. Findings were mixed showing some non-linear changes in variability with larger changes in variability observed in participants who engaged in more extensive therapy. However, the pattern of variability change was not consistent across the participants. These findings suggest that targeting variability in therapy may be an effective way to improve the speech of children with CAS. A model for utilising variability in therapy is presented.

Emergency department childhood anaphylaxis presentations in regional/remote Australia.

AIM: Explore the prevalence of childhood anaphylaxis and clinical presentation of anaphylaxis in children across two regional emergency departments over a 7-year period. METHODS: Retrospective audit of all children (0-18 years) presenting to emergency from 1 January 2010 to 31 December 2016 with anaphylaxis, defined by Australasian Society of Clinical Immunology and Allergy definitions and doctor diagnosis. RESULTS: Seven hundred and twenty-four patients were identified with allergic diagnosis, 60% were diagnosed with non-anaphylaxis allergic reactions or unspecified urticaria and 40% with anaphylaxis (n = 286). Annual prevalence of anaphylaxis remained stable over the study period (M = 30.9/10 000 cases, range: 20.8-48.3/10 000). Gender distribution was equal, median age was 9.48 years (interquartile range = 4-15). Most (71%) arrived by private transport. 23% had a prior history of anaphylaxis. Food triggers (44%) were the most common cause of anaphylaxis. Insect bites/stings triggers occurred in 21%. Patients were promptly assessed (average wait time = 13 min), 16% received prior adrenaline injections. Adrenaline was administered in 26% and 20% were admitted to hospital. On discharge, 29% had a follow-up plan, 9% received an allergy clinic referral, 6% anaphylaxis action plan, 26% adrenaline autoinjector prescriptions and allergy testing performed in 6%. CONCLUSIONS: We found a relatively low prevalence of overall childhood anaphylaxis in a regional area. The two most common causes of anaphylaxis in this population (food and bites/stings) recorded increased prevalence providing an opportunity for further study. Significant gaps in evidence-based care of anaphylaxis were noted, demonstrating the need for improved recognition and treatment guideline implementation in regional areas.

Pathogens That Cause Acute Febrile Illness Among Children and Adolescents in Burkina Faso, Madagascar, and Sudan.

BACKGROUND: The etiology and optimal clinical management of acute febrile illness (AFI) is poorly understood. METHODS: Blood samples taken from study participants with acute fever (≥37.5°C) or a history of fever and recruited into the previous Typhoid Fever Surveillance in Africa (TSAP) study were evaluated using a polymerase chain reaction (PCR)-based TaqMan-Array Card designed to detect a panel of bacterial, viral, and parasitic pathogens. Clinical metadata were also assessed. RESULTS: A total of 615 blood samples available for analysis originated from Burkina Faso (n = 53), Madagascar (n = 364), and Sudan (n = 198) and were taken from participants ranging in age from 0-19 years. Through the TaqMan-Array Card, at least 1 pathogen was detected in 62% (33 of 53), 24% (86 of 364), and 60% (118 of 198) of specimens from Burkina Faso, Madagascar, and Sudan, respectively. The leading identified pathogen overall was Plasmodium spp., accounting for 47% (25 of 53), 2.2% (8 of 364), and 45% (90 of 198) of AFI at the respective sites. In Madagascar, dengue virus was the most prevalent pathogen (10.2%). Overall, 69% (357 of 516) of patients with clinical diagnoses of malaria, respiratory infection, or gastrointestinal infection were prescribed a World Health Organization guideline-recommended empiric antibiotic, whereas only 45% (106 of 237) of patients with pathogens detected were treated with an antibiotic exerting likely activity. CONCLUSIONS: A PCR approach for identifying multiple bacterial, viral, and parasitic pathogens in whole blood unveiled a diversity of previously undetected pathogens in AFI cases and carries implications for the appropriate management of this common syndrome.

Estimating the Force of Infection for Dengue Virus Using Repeated Serosurveys, Ouagadougou, Burkina Faso.

Because of limited data on dengue virus in Burkina Faso, we conducted 4 consecutive age-stratified longitudinal serologic surveys, ≈6 months apart, among persons 1-55 years of age, during June 2015-March 2017, which included a 2016 outbreak. The seroconversion rate before the serosurvey enrollment was estimated by binomial regression, taking age as the duration of exposure, and assuming constant force of infection (FOI) over age and calendar time. We calculated FOI between consecutive surveys and rate ratios for potentially associated characteristics based on seroconversion using the duration of intervals. Among 2,897 persons at enrollment, 66.3% were IgG-positive, and estimated annual FOI was 5.95%. Of 1,269 enrollees participating in all 4 serosurveys, 438 were IgG-negative at enrollment. The annualized FOI ranged from 10% to 20% (during the 2016 outbreak). Overall, we observed high FOI for dengue. These results could support decision-making about control and preventive measures for dengue.

Maternal autoimmunity and inflammation are associated with childhood tics and obsessive-compulsive disorder: Transcriptomic data show common enriched innate immune pathways.

Although genetic variation is a major risk factor of neurodevelopmental disorders, environmental factors during pregnancy and early life are also important in disease expression. Animal models demonstrate that maternal inflammation causes fetal neuroinflammation and neurodevelopmental deficits, and brain transcriptomics of neurodevelopmental disorders in humans show upregulated differentially expressed genes are enriched in immune pathways. We prospectively recruited 200 sequentially referred children with tic disorders/obsessive-compulsive disorder (OCD), 100 autoimmune neurological controls, and 100 age-matched healthy controls. A structured interview captured the maternal and family history of autoimmune disease and other pro-inflammatory states. Maternal blood and published Tourette brain transcriptomes were analysed for overlapping enriched pathways. Mothers of children with tics/OCD had a higher rate of autoimmune disease compared with mothers of children with autoimmune neurological conditions (p = 0.054), and mothers of healthy controls (p = 0.0004). Autoimmunity was similarly elevated in first- and second-degree maternal relatives of children with tics/OCD (p < 0.0001 and p = 0.014 respectively). Other pro-inflammatory states were also more common in mothers of children with tics/OCD than controls (p < 0.0001). Upregulated differentially expressed genes in maternal autoimmune disease and Tourette brain transcriptomes were commonly enriched in innate immune processes. Pro-inflammatory states, including autoimmune disease, are more common in the mothers and families of children with tics/OCD. Exploratory transcriptome analysis indicates innate immune signalling may link maternal inflammation and childhood tics/OCD. Targeting inflammation may represent preventative strategies in pregnancy and treatment opportunities for children with neurodevelopmental disorders.

Epidemiology and genetic diversity of circulating dengue viruses in Medellin, Colombia: a fever surveillance study.

BACKGROUND: Dengue fever is a major public health problem in Colombia. A fever surveillance study was conducted for evaluation of the clinical, epidemiological, and molecular patterns of dengue, prior to Chikungunya and Zika epidemics. METHODS: In November 2011-February 2014, a passive facility-based surveillance was implemented in Santa Cruz Hospital, Medellin, and enrolled eligible febrile patients between 1 and 65 years-of-age. Acute and convalescent blood samples were collected 10-21 days apart and tested for dengue using IgM/IgG ELISA. RNA was extracted for serotyping using RT-PCR on acute samples and genotyping was performed by sequencing. RESULTS: Among 537 febrile patients enrolled during the study period, 29% (n = 155) were identified to be dengue-positive. Only 7% of dengue cases were hospitalized, but dengue-positive patients were 2.6 times more likely to be hospitalized, compared to non-dengue cases, based on a logistic regression. From those tested with RT-PCR (n = 173), 17 were dengue-confirmed based on PCR and/or virus isolation showing mostly DENV-3 (n = 9) and DENV-4 (n = 7) with 1 DENV-1. Genotyping results showed that: DENV-1 isolate belongs to the genotype V or American/African genotype; DENV-3 isolates belong to genotype III; and DENV-4 isolates belong to the II genotype and specifically to the IIb sub-genotype or linage. CONCLUSIONS: Our surveillance documented considerable dengue burden in Santa Cruz comuna during non-epidemic years, and genetic diversity of circulating DENV isolates, captured prior to Chikungunya epidemic in 2014 and Zika epidemic in 2015. Our study findings underscore the need for continued surveillance and monitoring of dengue and other arboviruses and serve as epidemiological and molecular evidence base for future studies to assess changes in DENV transmission in Medellin, given emerging and re-emerging arboviral diseases in the region.

Look at Mummy: challenges in training parents to deliver a home treatment program for childhood apraxia of speech in a rural Canadian community.

INTRODUCTION: Children requiring speech pathology services in rural and remote locations face many barriers in accessing adequate services. This has particular consequences for children who need intensive treatment for therapy to be effective, such those with childhood apraxia of speech (CAS). Parent training has been used to overcome speech pathology service delivery barriers for a range of other communication disorders. However, the effectiveness of training parents to deliver a motor-based treatment for CAS within rural and remote contexts has not been evaluated. This study examined the effectiveness and feasibility of training parents in a rural community to use the treatment approach of dynamic temporal and tactile cueing (DTTC) in order to provide more intensive treatment sessions at home. METHODS: The study used an experimental single case across behaviours design and parent interviews to evaluate outcomes both quantitatively and qualitatively. The study included four parent-child dyads from a mixed socioeconomic rural community in Canada. Child participants ranged in age from 3 years to 8 years. Child treatment outcomes were measured using an improvement rate difference (IRD) calculation based on percentage of phonemes correct. Fidelity to the treatment protocol was measured using a fidelity score. RESULTS: All parents reported challenges in carrying out the program due to social and behavioural challenges. Parents also reported benefits such as being able to spend more time with their child and learning some useful cueing techniques. Only one of the four participants had a moderate effect size for his target words (IRD=57%). CONCLUSION: While training parents to deliver DTTC may be effective for some parent-child dyads, clinicians are advised that parent training may not be suitable for all families, and parents in rural and remote communities may face particular social circumstances that make following through with an intensive treatment program difficult.

Monoclonal antibody-based capture ELISA in the diagnosis of previous dengue infection.

BACKGROUND: Dengue is an important mosquito-borne disease. There is currently only one licensed vaccine for dengue prevention. The vaccine provides higher efficacy in pre-vaccination dengue-seropositive persons but a higher risk of subsequent more severe dengue in dengue-seronegative persons. It is recommended that the dengue vaccine may be given in dengue-seropositive individuals or as mass vaccination without individual pre-vaccination screening in areas where the dengue seroprevalence is > 80% in children aged 9 years. We evaluated a dengue specific immunoglobulin G monoclonal antibody-based capture enzyme-linked immunosorbent assay (MAb-ELISA) in the diagnosis of previous dengue infection using serum samples from the cohort study in Ratchaburi Province, Thailand. METHODS: The MAb-ELISA was compared to 70% plaque reduction neutralization test (PRNT70) in 453 serum samples from children aged 3-11 years in Ratchaburi Province, Thailand. RESULTS: The sensitivity and specificity of MAb-ELISA at the positive to negative (P/N) ratio cut-off level of > 3 were both 0.91 in the diagnosis of previous dengue infection, compared to PRNT70. The false positivity was mainly in Japanese encephalitis (JE) seropositive subjects. CONCLUSIONS: This research provides evidence that MAb-ELISA is useful for dengue seroprevalence study and dengue pre-vaccination screening. JE seropositivity was the major cause of false positive result in the study population.

Burden of dengue among febrile patients at the time of chikungunya introduction in Piedecuesta, Colombia.

OBJECTIVE: To estimate the age-specific incidence of symptomatic dengue and chikungunya in Colombia. METHOD: A passive facility-based fever surveillance study was conducted among individuals with undifferentiated fever. Confirmatory diagnostics included serological and molecular tests in paired samples, and surveillance's underreporting was assessed using capture-recapture methods. RESULTS: Of 839 febrile participants 686 completed the study. There were 33.2% (295/839) dengue infections (51% primary infections), and 35.9% (191/532) of negative dengue cases there were chikungunya cases. On average, dengue cases were younger (median = 18 years) than chikungunya cases (median = 25 years). Thrombocytopaenia and abdominal pain were the main dengue predictors, while presence of rash was the main predictor for chikungunya diagnosis. Underreporting of dengue was 31%; the estimated expansion factors indicate an underreporting rate of dengue cases of threefold for all cases and of almost sixfold for inpatients. CONCLUSIONS: These findings highlight the ongoing coexistence of both arboviruses, a distinct clinical profile of each condition in the study area that could be used by clinicians to generate a differential diagnosis, and the presence of underreporting, mostly among hospitalised cases.

Early warning signal for dengue outbreaks and identification of high risk areas for dengue fever in Colombia using climate and non-climate datasets.

BACKGROUND: Dengue has been prevalent in Colombia with high risk of outbreaks in various locations. While the prediction of dengue epidemics will bring significant benefits to the society, accurate forecasts have been a challenge. Given competing health demands in Colombia, it is critical to consider the effective use of the limited healthcare resources by identifying high risk areas for dengue fever. METHODS: The Climate Risk Factor (CRF) index was constructed based upon temperature, precipitation, and humidity. Considering the conditions necessary for vector survival and transmission behavior, elevation and population density were taken into account. An Early Warning Signal (EWS) model was developed by estimating the elasticity of the climate risk factor function to detect dengue epidemics. The climate risk factor index was further estimated at the smaller geographical unit (5 km by 5 km resolution) to identify populations at high risk. RESULTS: From January 2007 to December 2015, the Early Warning Signal model successfully detected 75% of the total number of outbreaks 1 ~ 5 months ahead of time, 12.5% in the same month, and missed 12.5% of all outbreaks. The climate risk factors showed that populations at high risk are concentrated in the Western part of Colombia where more suitable climate conditions for vector mosquitoes and the high population level were observed compared to the East. CONCLUSIONS: This study concludes that it is possible to detect dengue outbreaks ahead of time and identify populations at high risk for various disease prevention activities based upon observed climate and non-climate information. The study outcomes can be used to minimize potential societal losses by prioritizing limited healthcare services and resources, as well as by conducting vector control activities prior to experiencing epidemics.

A systematic review of the economic impact of rapid diagnostic tests for dengue.

BACKGROUND: Dengue fever is rapidly expanding geographically, with about half of the world's population now at risk. Among the various diagnostic options, rapid diagnostic tests (RDTs) are convenient and prompt, but limited in terms of accuracy and availability. METHODS: A systematic review was conducted of published data on the use of RDTs for dengue with respect to their economic impact. The search was conducted with combinations of key search terms, including "((Dengue[Title]) AND cost/economic)" and "rapid diagnostic test/assay (or point-of-care)". Articles with insufficient report on cost/economic aspect of dengue RDTs, usually on comparison of different RDTs or assessment of novel rapid diagnostic tools, were excluded. This review has been registered in the PROSPERO International prospective register of systematic reviews (registry #: CRD42015017775). RESULTS: Eleven articles were found through advanced search on Pubmed. From Embase and Web of Science, two and 14 articles were obtained, respectively. After removal of duplicate items, title screening was done on 21 published works and 12 titles, including 2 meeting abstracts, were selected for abstract review. For full-text review, by two independent reviewers, 5 articles and 1 meeting abstract were selected. Among these, the abstract was referring to the same study results as one of the articles. After full text review, two studies (two articles and one abstract) were found to report on cost-wise or economic benefits of dengue RDTs and were selected for data extraction. One study found satisfactory performance of IgM-based Panbio RDT, concluding that it would be cost-effective in endemic settings. The second study was a modeling analysis and showed that a dengue RDT would not be advantageous in terms of cost and effectiveness compared to current practice of antibiotics prescription for acute febrile illness. CONCLUSIONS: Despite growing use of RDTs in research and clinical settings, there were limited data to demonstrate an economic impact. The available two studies reached different conclusions on the cost-effectiveness of dengue RDTs, although only one of the two studies reported outcomes from cost-effectiveness analysis of dengue and the other was considering febrile illness more generally. Evidence of such an impact would require further quantitative economic studies.

Impact of time to treatment of oseltamivir on influenza hospitalization cost among Korean children.

BACKGROUND: Although oseltamivir is a common influenza treatment, there is a lack of data on the economic benefits of timely oseltamivir treatment. METHODS: From February 2004 through June 2007, 116 hospitalized children ≤ 15 years of age with laboratory-confirmed influenza who received oseltamivir were identified via retrospective medical chart review. Demographic, clinical, and cost data were abstracted and multivariate linear regression was used to assess the association between oseltamivir time to treatment and treatment-related costs among hospitalized children with laboratory-confirmed influenza. RESULTS: Overall, 28% (n = 33) of patients were treated with oseltamivir ≥ day 3 of admission. Rapid influenza diagnostic test was used in a significantly lower proportion of patients treated with oseltamivir ≥ day 3 of admission compared with those who received oseltamivir earlier. On multivariate linear regression, initiation of oseltamivir ≥ day 3 of admission was associated with a 60.84% increase (95%CI: 32.59-95.11) in treatment-related hospital costs, compared with initiation on admission. CONCLUSION: Delayed initiation of oseltamivir was found to be associated with increased treatment-related hospital costs among children hospitalized with laboratory-confirmed influenza.

The association between influenza treatment and hospitalization-associated outcomes among Korean children with laboratory-confirmed influenza.

There are limited data evaluating the relationship between influenza treatment and hospitalization duration. Our purpose assessed the association between different treatments and hospital stay among Korean pediatric influenza patients. Total 770 children ≤ 15 yr-of-age hospitalized with community-acquired laboratory-confirmed influenza at three large urban tertiary care hospitals were identified through a retrospective medical chart review. Demographic, clinical, and cost data were extracted and a multivariable linear regression model was used to assess the associations between influenza treatment types and hospital stay. Overall, there were 81% of the patients hospitalized with laboratory-confirmed influenza who received antibiotic monotherapy whereas only 4% of the patients received oseltamivir monotherapy. The mean treatment-related charges for hospitalizations treated with antibiotics, alone or with oseltamivir, were significantly higher than those treated with oseltamivir-only (P < 0.001). Influenza patients treated with antibiotics-only and antibiotics/oseltamivir combination therapy showed 44.9% and 28.2%, respectively, longer duration of hospitalization compared to those treated with oseltamivir-only. Patients treated with antibiotics, alone or combined with oseltamivir, were associated with longer hospitalization and significantly higher medical charges, compared to patients treated with oseltamivir alone. In Korea, there is a need for more judicious use of antibiotics, appropriate use of influenza rapid testing.

HYDIN variants cause primary ciliary dyskinesia in the Finnish population.

INTRODUCTION: Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterized by chronic respiratory tract infections and in some cases laterality defects and infertility. The symptoms of PCD are caused by malfunction of motile cilia, hair-like organelles protruding out of the cell. Thus far, disease causing variants in over 50 genes have been identified and these variants explain around 70% of all known cases. Population specific genetics underlying PCD has been reported highlighting the importance of characterizing gene variants in different populations for development of gene-based diagnostics and management. METHODS: Whole exome sequencing was used to identify disease causing variants in Finnish PCD cohort. The effect of the identified HYDIN variants on cilia structure and function was confirmed by high-speed video analysis, immunofluorescence and electron tomography. RESULTS: In this study, we identified three Finnish PCD patients carrying homozygous loss-of-function variants and one patient with compound heterozygous variants within HYDIN. The functional studies showed defects in the axonemal central pair complex. All patients had clinical PCD symptoms including chronic wet cough and recurrent airway infections, associated with mostly static airway cilia. CONCLUSION: Our results are consistent with the previously identified important role of HYDIN in the axonemal central pair complex and improve specific diagnostics of PCD in different national populations.

Statistical considerations on real time and extended controlled temperature conditions (ECTC) stability data analysis of vaccines.

BACKGROUND: Although maintaining vaccines in a strict cold chain has cost and logistical implications in low- and middle-income countries, only a few vaccines have obtained approval for extended controlled temperature conditions (ECTC) application, which permits the administration of vaccines after storage outside of the cold chain for a defined period. We developed a methodology to evaluate stability data and calculate minimum release potency (MRP) in support of ECTC application. METHODS: The methodology is focused on statistical considerations consisting of stability data collection, statistical analysis plan, statistical modelling, and statistical report. It uses mock stability data from a hypothetical product and may serve as a helpful guide for other products. The statistical data analysis is performed using the R program which is an open-source program and validated using the SAS software. RESULTS: We developed a stability data testing scheme that included 24 lots with six-time points for up to 24 months under real-time and real condition (RT) in the cold chain samples stored at 2-8 °C and 12 lots with six timepoints for 14 days under ECTC samples stored at 40 °C. The log-transformed stability data met the linear regression assumptions and were poolable from representative lots with no significant lot variation. The linear regression analysis model with a common slope and intercept confirmed the stable antigen content over time under RT and ECTC by the mean regression line and 95% confidence interval. Based on the fitted models and the estimated coefficients, the antigen content value of 966 was derived as the MRP under RT for 24 months followed by 14 days under ECTC. CONCLUSION: The presented framework of statistical considerations, with practical methods and R program codes to perform statistical analysis, may serve as a guide for developing the CTC data for a vaccine's stability evaluation prospectively.

Single Ad26.COV2.S booster dose following two doses of BBIBP-CorV vaccine against SARS-CoV-2 infection in adults: Day 28 results of a phase 1/2 open-label trial.

BACKGROUND: The inactivated COVID-19 whole-virus vaccine BBIBP-CorV has been extensively used worldwide. Heterologous boosting after primary vaccination can induce higher immune responses against SARS-CoV-2 than homologous boosting. The safety and immunogenicity after 28 days of a single Ad26.COV2.S booster dose given at different intervals after 2 doses of BBIBP-CorV are presented. METHODS: This open-label phase 1/2 trial was conducted in healthy adults in Thailand who had completed 2-dose primary vaccination with BBIBP-CorV. Participants received a single booster dose of Ad26.COV2.S (5 × 1010 virus particles) 90-240 days (Group A1; n = 360) or 45-75 days (Group A2; n = 66) after the second BBIBP-CorV dose. Safety and immunogenicity were assessed over 28 days. Binding IgG antibodies to the full-length pre-fusion Spike and anti-nucleocapsid proteins of SARS-CoV-2 were measured by enzyme-linked immunosorbent assay. The SARS-CoV-2 pseudovirus neutralization assay and live virus microneutralization assay were used to quantify the neutralizing activity of antibodies against ancestral SARS-CoV-2 (Wuhan-Hu-1) and the delta (B.1.617.2) and omicron (B.1.1.529/BA.1 and BA.2) variants. The cell-mediated immune response was measured using a quantitative interferon (IFN)-γ release assay in whole blood. RESULTS: Solicited local and systemic adverse events (AEs) on days 0-7 were mostly mild, as were unsolicited vaccine-related AEs during days 0-28, with no serious AEs. On day 28, anti-Spike binding antibodies increased from baseline by 487- and 146-fold in Groups A1 and A2, and neutralizing antibodies against ancestral SARS-CoV-2 by 55- and 37-fold, respectively. Humoral responses were strongest against ancestral SARS-CoV-2, followed by the delta, then the omicron BA.2 and BA.1 variants. T-cell-produced interferon-γ increased approximately 10-fold in both groups. CONCLUSIONS: A single heterologous Ad26.COV2.S booster dose after two BBIBP-CorV doses was well tolerated and induced robust humoral and cell-mediated immune responses measured at day 28 in both interval groups. CLINICAL TRIALS REGISTRATION: NCT05109559.

Dengue virus seroprevalence study in Bangphae district, Ratchaburi, Thailand: A cohort study in 2012-2015.

BACKGROUND: To determine the seroprevalence and transmission dynamics of dengue virus (DENV), age-stratified longitudinal serological surveys were conducted in Bangphae district, Ratchaburi province, Thailand, for 3 years between April 2012 and April 2015. METHODOLOGY: The surveys enrolled 2012 healthy children and adults between 1 and 55 years-of-age, and a longitudinal serosurvey of six repeated bleeds of the same cohort of individuals was conducted every 8 months for the first 2 years (M0, M8, M16) and every half a year (M24, M30, M36) for the rest of the study period. All samples were tested using in-house indirect sandwich dengue IgG ELISA to determine DENV antibody titer, and 640 paired samples which showed rising of DENV IgG titers in paired serum were further tested using in-house neutralization assay, Plaque Reduction Neutralization Test (PRNT50). PRINCIPAL FINDINGS: When compared against the gold standard based on the results of PRNT50, sensitivity and specificity of indirect ELISA were found to be both about 85%. The overall DENV IgG positivity determined by ELISA was 74.3% in 2012 and increased to 79.4% by the final sample collection in 2015. In our study sample, more than 98% of subjects older than 25 years were found to be seropositive. Among 518 IgG negative subjects at enrollment, the seroconversion rates were measured in paired bleeds; the rates (between successive visits, approximately 6 months) ranged between 4.8% (between M16 and M24) and 14.7% (between M0 and M8). The dominant serotype of primary DENV infection cases based on seroconversion was identified from the PRNT results and it was DENV-2. CONCLUSIONS: Our study documented high levels of seroprevalence and rate of transmission. Given the importance of the serostatus and disease burden in consideration for dengue vaccine introduction, our data could be used in decision-making on implementation of various dengue control and preventive measures.

CFAP300 mutation causing primary ciliary dyskinesia in Finland.

Primary ciliary dyskinesia (PCD) is a rare genetic condition characterized by chronic respiratory tract infections and in some cases laterality defects and infertility. The symptoms of PCD are caused by malfunction of motile cilia, hair-like organelles protruding out of the cell that are responsible for removal of mucus from the airways and organizing internal organ positioning during embryonic development. PCD is caused by mutations in genes coding for structural or assembly proteins in motile cilia. Thus far mutations in over 50 genes have been identified and these variants explain around 70% of all known cases. Population specific genetics underlying PCD has been reported, thus highlighting the importance of characterizing gene variants in different populations for development of gene-based diagnostics. In this study, we identified a recurrent loss-of-function mutation c.198_200delinsCC in CFAP300 causing lack of the protein product. PCD patients homozygous for the identified CFAP300 mutation have immotile airway epithelial cilia associated with missing dynein arms in their ciliary axonemes. Furthermore, using super resolution microscopy we demonstrate that CFAP300 is transported along cilia in normal human airway epithelial cells suggesting a role for CFAP300 in dynein complex transport in addition to preassembly in the cytoplasm. Our results highlight the importance of CFAP300 in dynein arm assembly and improve diagnostics of PCD in Finland.