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The force of infection, or the rate at which susceptible individuals become infected, is an important public health measure for assessing the extent of outbreaks and the impact of control programs. We present Bayesian methods for estimating force of infection using serological surveys of infections which produce a lasting immune response, accounting for imperfections of the test, and uncertainty in such imperfections. In this estimation, the sensitivity and specificity can either be fixed, or belief distributions of their values can be elicited to allow for uncertainty. We analyse data from two published serological studies of dengue, one in Colombo, Sri Lanka, with a single survey and one in Medellin, Colombia, with repeated surveys in the same individuals. For the Colombo study, we illustrate how the inferred force of infection increases as the sensitivity decreases, and the reverse for specificity. When 100% sensitivity and specificity are assumed, the results are very similar to those from a standard analysis with binomial regression. For the Medellin study, the elicited distribution for sensitivity had a lower mean and higher variance than the one for specificity. Consequently, taking uncertainty in sensitivity into account resulted in a wide credible interval for the force of infection. These methods can make more realistic estimates of force of infection, and help inform the choice of serological tests for future serosurveys.

Dengue fever is a major public health concern in many parts of the tropics and subtropics. The first dengue vaccine has already been licensed in six countries. Given the growing interests in the effective use of the vaccine, it is critical to understand the economic burden of dengue fever to guide decision-makers in setting health policy priorities. A standardized cost-of-illness study was conducted in three dengue endemic countries: Vietnam, Thailand, and Colombia. In order to capture all costs during the entire period of illness, patients were tested with rapid diagnostic tests on the first day of their clinical visits, and multiple interviews were scheduled until the patients recovered from the current illness. Various cost items were collected such as direct medical and non-medical costs, indirect costs, and non-out-of-pocket costs. In addition, socio-economic factors affecting disease severity were also identified by adopting a logit model. We found that total cost per episode ranges from $141 to $385 for inpatient and from $40 to $158 outpatient, with Colombia having the highest and Thailand having the lowest. The percentage of the private economic burden of dengue fever was highest in the low-income group and lowest in the high-income group. The logit analyses showed that early treatment, higher education, and better knowledge of dengue disease would reduce the probability of developing more severe illness. The cost of dengue fever is substantial in the three dengue endemic countries. Our study findings can be used to consider accelerated introduction of vaccines into the public and private sector programs and prioritize alternative health interventions among competing health problems. In addition, a community would be better off by propagating the socio-economic factors identified in this study, which may prevent its members from developing severe illness in the long run.

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.

Dengue fever is a rapidly growing public health problem in many parts of the tropics and sub-tropics in the world. While there are existing studies on the economic burden of dengue fever in some of dengue-endemic countries, cost components are often not standardized, making cross-country comparisons challenging. Furthermore, no such studies have been available in Africa. A patient-specific survey questionnaire was developed and applied in Burkina Faso, Kenya, and Cambodia in a standardized format. Multiple interviews were carried out in order to capture the entire cost incurred during the period of dengue illness. Both private (patient's out-of-pocket) and public (non-private) expenditure were accessed to understand how the economic burden of dengue is distributed between private and non-private payers. A substantial number of dengue-confirmed patients were identified in all three countries: 414 in Burkina Faso, 149 in Kenya, and 254 in Cambodia. The average cost of illness for dengue fever was $26 (95% CI $23-$29) and $134 (95% CI $119-$152) per inpatient in Burkina Faso and Cambodia, respectively. In the case of outpatients, the average economic burden per episode was $13 (95% CI $23-$29) in Burkina Faso and $23 (95% CI $19-$28) in Kenya. Compared to Cambodia, public contributions were trivial in Burkina Faso and Kenya, reflecting that a majority of medical costs had to be directly borne by patients in the two countries. The cost of illness for dengue fever is significant in the three countries. In particular, the current study sheds light on the potential economic burden of the disease in Burkina Faso and Kenya where existing evidence is sparse in the context of dengue fever, and underscores the need to achieve Universal Health Coverage. Given the availability of the current (CYD-TDV) and second-generation dengue vaccines in the near future, our study outcomes can be used to guide decision makers in setting health policy priorities.

The rise in dengue fever cases and the absence of dengue vaccines will likely cause governments to consider various types of effective means for controlling the disease. Given strong public interests in potential dengue vaccines, it is essential to understand the private economic benefits of dengue vaccines for accelerated introduction of vaccines into the public sector program and private markets of high-risk countries. A contingent valuation study for a hypothetical dengue vaccine was administered to 400 households in a multi-country setting: Vietnam, Thailand, and Colombia. All respondents received a description of the hypothetical dengue vaccine scenarios of 70% or 95% effectiveness for 10 or 30 years with a three dose series. Five price points were determined after pilot tests in order to reflect different local situations such as household income levels and general perceptions towards dengue fever. We adopted either Poisson or negative binomial regression models to calculate average willingness-to-pay (WTP), as well as median WTP. We found that there is a significant demand for dengue vaccines. The parametric median WTP is $26.4 ($8.8 per dose) in Vietnam, $70.3 ($23.4 per dose) in Thailand, and $23 ($7.7 per dose) in Colombia. Our study also suggests that respondents place more value on vaccinating young children than school age children and adults. Knowing that dengue vaccines are not yet available, our study provides critical information to both public and private sectors. The study results can be used to ensure broad coverage with an affordable price and incorporated into cost benefit analyses, which can inform prioritization of alternative health interventions at the national level.

Cancer stem cells (CSCs) are a tumour subpopulation whose capacity for self-renewal, differentiation and proliferation generates unfavourable patient outcomes, including therapeutic resistance and metastasis. Much research has focused on the generation, biomarkers and therapeutic resistance of CSCs, as well as the development of CSC-targeted therapies. Reviews to date have either addressed general CSC characteristics or focused on CSCs from a well-studied cancer. Increasingly, specific treatment plans based on identification of molecular features and biomarkers of a patient’s cancer, rather than classification according to tissue origin or bulk tumour properties, are leading to better patient outcomes. Here, we compare CSC characteristics, specifically their biomarkers and molecular features, and identify those that are common to a number of cancers. Identification of CSC markers that suggest therapeutic strategies has led to several successful in vitro and animal tests, recommending clinical trials of treatments with potentially enhanced therapeutic benefits, especially for recurring cancers.

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. 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. 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. 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.

Dengue is a major public health problem in Thailand, but data are often focused on certain dengue-endemic areas. Methods: To better understand dengue epidemiology and clinical characteristics in Thailand, a fever surveillance study was conducted among patients aged 1-55 years, who presented with non-localized febrile illness at Bang Phae Community Hospital in Ratchaburi province, Thailand from October 2011 to September 2016. Among 951 febrile episodes, 130 were dengue-confirmed. Individuals aged 10-14 years were mostly affected, followed by those 15-19 years-of-age, with about 15% of dengue-confirmed cases from adults 25 years and older. There were annual peaks of dengue occurrence between June-November. Most prevalent serotype in circulation was DENV-2 in 2012, DENV-3 in 2014, and DENV-4 & -3 in 2015. Among dengue cases, 65% were accurately detected using the dengue NS1 RDT. Detection rate was similar between secondary and primary dengue cases where 66% of secondary vs. 60% of primary dengue cases had positive results on the NS1 RDT. Among dengue cases, 66% were clinically diagnosed with suspected dengue or DHF, prior to lab confirmation. Dengue was positively associated with rash, headache, hematemesis and alterations to consciousness, when compared to non-dengue. Dengue patients were 10.6 times more likely to be hospitalized, compared to non-dengue cases. Among dengue cases, 95 were secondary and 35 were primary infections. There were 8 suspected DHF cases and all were identified to be secondary dengue. Secondary dengue cases were 3.5 times more likely to be hospitalized compared to primary dengue cases. Although the majority of our dengue-positive patients were secondary dengue cases, with few patients showing manifestations of DHF, our dengue cases were mostly mild disease. Even among children < 10 years-of-age, 61% had secondary infection and the rate of secondary infection increased with age. While the majority of dengue-confirmed cases were children, almost three-quarters of dengue-confirmed cases in this study were secondary dengue. Our study results consistent with previous data from the country confirm the hyperendemic transmission of DENV in Thailand, even in the non-epidemic years. With various interventions becoming available for dengue prevention and control, including dengue vaccines, decision-making on future implementation strategies should be based on such burden of disease data.

Hepatitis E virus (HEV) causes acute jaundice and poses an important public health problem in low- and middle-income countries. Limited surveillance capacity and suboptimal access to diagnostics leads to under-reporting of HEV infections in affected countries, including Nepal. Serum antibodies against HEV are indicative of past infection. We analyzed existing samples from a nationally representative serosurvey to describe the geospatial distribution and factors associated with HEV seroprevalence in Nepal, as a proxy for infection. A nationally representative cross-sectional serosurvey of 3,922 individuals ≥2 years old from 975 households spread across 65 wards throughout Nepal was conducted between November 2021 and January 2022. Bio-banked samples were tested for anti-HEV IgG. Seroprevalence and its 95% confidence interval were estimated by age, sex, ecological region, municipality type, and other waterborne-disease related risk factors. Bayesian geostatistical models were fitted to observed seroprevalence data and used to generate high-resolution maps of seroprevalence across Nepal. Available samples from 3,707 participants were tested for anti-HEV IgG, and 3,703 were used for final analysis. We found 20.8% (95% CI: 19.5-22.2) of participants had evidence of prior HEV infection. HEV seroprevalence increased with age, and was higher in males (23.5%, 95% CI: 21.5-25.5) than in females (18.6%, 95% CI: 16.9-20.3). Seroprevalence in hilly (28.9%, 95% CI: 26.6-31.2) and mountain (24.6%, 95% CI: 18.8-30.5) regions were significantly higher than in terai (14.2%, 95% CI: 12.7-15.8). While there was no significant difference between urban and rural populations, the predicted seroprevalence was highest in Kathmandu, the capital of Nepal, reaching seroprevalence of 50% in some selected area. No statistically significant differences were found for wealth quintile, water source, and toilet facility. This study provides population-based serologic evidence that HEV is endemic in Nepal, with the greatest risk of infection in Kathmandu.

A new species of caprellid, Aciconulatinggiensis (Amphipoda, Senticaudata, Caprellidae) was discovered from Pulau Tinggi, Sultan Iskandar Marine Park (SIMP), South China Sea, Malaysia. The new Malaysian species can be distinguished from the other Aciconula species by the combination of the following characters: 1. the presence of a very small suture between head and pereonite 1; 2. antenna 1 flagellum with 4 articles; 3. inner lobe of lower lip unilobed; 4. gnathopod 2 palm of propodus with a large proximal projection (stretching from the proximal margin of the palm to nearly mid-way of palm); 5. pereopods 3–4 with 2 articles (article 1 subrectangular, article 2 conical or tapering at the tip with 1 plumose seta and 2 normal setae) and; 6. pereopod 5 covered with relatively dense and long setae. An updated identification key for the five known species in the genus, including information on the respective geographical distribution and habitat, is presented.