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Abstract Introduction Dravet syndrome (DS) is a rare, lifelong epileptic encephalopathy characterised by frequent and severe seizures associated with premature mortality. Typically diagnosed in infancy, patients also experience progressive behavioural, motor-function and cognitive decline. Twenty percent of patients do not reach adulthood. Quality of life (QoL) is impaired for both patients and their carers. Reducing convulsive seizure frequency, increasing convulsive seizure-free days (SFDs) and improving patient/carer QoL are primary treatment goals in DS. This study explored the relationship between SFDs and patients’ and carers’ QoL to inform a cost-utility analysis of fenfluramine (FFA). Methods In FFA registration studies, patients (or their carer proxies) completed the Paediatric QoL inventory (PedsQL). These data were mapped to EuroQol-5 Dimensions Youth version (EQ-5D-Y) to provide patient utilities. Carer utilities were collected using EQ-5D-5L and mapped to EQ-5D-3L to align patient and carer QoL on the same scale. Linear mixed-effects and panel regression models were tested and Hausman tests identified the most appropriate approach for each group. On this basis, a linear mixed-effects regression model was used to examine the relationships between patient EQ-5D-Y and clinically relevant variables (age, frequency of SFDs per 28 days, motor impairments and treatment dose). A linear panel regression model examined the relationship between SFDs and carer QoL. Results After adjustment for age and underlying comorbidities, the patient regression model showed that SFDs per 28 days was a significant predictor of QoL. Each additional patient-SFD increased utility by 0.005 (p

Locally tailored interventions for neglected tropical diseases (NTDs) are becoming increasingly important for ensuring that the World Health Organization (WHO) goals for control and elimination are reached. Mathematical models, such as those developed by the NTD Modelling Consortium, are able to offer recommendations on interventions but remain constrained by the data currently available. Data collection for NTDs needs to be strengthened as better data are required to indirectly inform transmission in an area. Addressing specific data needs will improve our modelling recommendations, enabling more accurate tailoring of interventions and assessment of their progress. In this collection, we discuss the data needs for several NTDs, specifically gambiense human African trypanosomiasis, lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminths (STH), trachoma, and visceral leishmaniasis. Similarities in the data needs for these NTDs highlight the potential for integration across these diseases and where possible, a wider spectrum of diseases.

Robust surveillance methods are needed for trachoma control and recrudescence monitoring, but existing methods have limitations. Here, we analyse data from nine trachoma-endemic populations and provide operational thresholds for interpretation of serological data in low-transmission and post-elimination settings. Analyses with sero-catalytic and antibody acquisition models provide insights into transmission history within each population. To accurately estimate sero-conversion rates (SCR) for trachoma in populations with high-seroprevalence in adults, the model accounts for secondary exposure to Chlamydia trachomatis due to urogenital infection. We estimate the population half-life of sero-reversion for anti-Pgp3 antibodies to be 26 (95% credible interval (CrI): 21-34) years. We show SCRs below 0.015 (95% confidence interval (CI): 0.0-0.049) per year correspond to a prevalence of trachomatous inflammation-follicular below 5%, the current threshold for elimination of active trachoma as a public health problem. As global trachoma prevalence declines, we may need cross-sectional serological survey data to inform programmatic decisions.

Despite great progress in eliminating trachoma from the majority of worldwide districts, trachoma control seems to have stalled in some endemic districts. Can mathematical models help suggest the way forward? We review specific achievements of models in trachoma control in the past. Models showed that, even with incomplete coverage, mass drug administration could eliminate disease through a spillover effect, somewhat analogous to how incomplete vaccine campaigns can eliminate disease through herd protection. Models also suggest that elimination can always be achieved if enough people are treated often enough with an effective enough drug. Other models supported the idea that targeting ages at highest risk or continued improvements in hygiene and sanitation can contribute meaningfully to trachoma control. Models of intensive targeting of a core group may point the way to final eradication even in areas with substantial transmission and within-community heterogeneity.

Introduction: Understanding human mixing patterns relevant to infectious diseases spread through close contact is vital for modelling transmission dynamics and optimisation of disease control strategies. Mixing patterns in low-income countries like Malawi are not well known. Methodology: We conducted a social mixing survey in urban Blantyre, Malawi between April and July 2021 (between the 2nd and 3rd wave of COVID-19 infections). Participants living in densely-populated neighbourhoods were randomly sampled and, if they consented, reported their physical and non-physical contacts within and outside homes lasting at least 5 min during the previous day. Age-specific mixing rates were calculated, and a negative binomial mixed effects model was used to estimate determinants of contact behaviour. Results: Of 1201 individuals enroled, 702 (58.5%) were female, the median age was 15 years (interquartile range [IQR] 5–32) and 127 (10.6%) were HIV-positive. On average, participants reported 10.3 contacts per day (range: 1–25). Mixing patterns were highly age-assortative, particularly those within the community and with skin-to-skin contact. Adults aged 20–49 y reported the most contacts (median:11, IQR: 8–15) of all age groups; 38% (95%CI: 16–63) more than infants (median: 8, IQR: 5–10), who had the least contacts. Household contact frequency increased by 3% (95%CI: 2–5) per additional household member. Unemployed participants had 15% (95%CI: 9–21) fewer contacts than other adults. Among long range (>30 m away from home) contacts, secondary school children had the largest median contact distance from home (257 m, IQR 78–761). HIV-positive status in adults >=18 years-old was not associated with changed contact patterns (rate ratio: 1.01, 95%CI: (0.91–1.12)). During this period of relatively low COVID-19 incidence in Malawi, 301 (25.1%) individuals stated that they had limited their contact with others due to COVID-19 precautions; however, their reported contacts were 8% (95%CI: 1–13) higher. Conclusion: In urban Malawi, contact rates, are high and age-assortative, with little reported behavioural change due to either HIV-status or COVID-19 circulation. This highlights the limits of contact-restriction-based mitigation strategies in such settings and the need for pandemic preparedness to better understand how contact reductions can be enabled and motivated.

The World Health Organization and its partners are aiming to eliminate trachoma as a public health problem by 2020. In this study, we compare forecasts of TF prevalence in 2011 for 7 different statistical and mechanistic models across 9 de-identified trachoma endemic districts, representing 4 unique trachoma endemic countries. We forecast TF prevalence between 1-6 years ahead in time and compare the 7 different models to the observed 2011 data using a log-likelihood score. An SIS model, including a district-specific random effect for the district-specific transmission coefficient, had the highest log-likelihood score across all 9 districts and was therefore the best performing model. While overall the deterministic transmission model was the least well performing model, although it did comparably well to the other models for 8 of 9 districts. We perform a statistically rigorous comparison of the forecasting ability of a range of mathematical and statistical models across multiple endemic districts between 1 and 6 years ahead of the last collected TF prevalence data point in 2011, assessing results against surveillance data. This study is a step towards making statements about likelihood and time to elimination with regard to the WHO GET2020 goals.

Abstract Background Herd protection through interruption of transmission has contributed greatly to the impact of pneumococcal conjugate vaccines (PCVs) and may enable the use of cost-saving reduced dose schedules. To aid PCV age targeting to achieve herd protection, we estimated which population age groups contribute most to vaccine serotype (VT) pneumococcal transmission. Methods We used transmission dynamic models to mirror pre-PCV epidemiology in England and Wales, Finland, Kilifi in Kenya and Nha Trang in Vietnam where data on carriage prevalence in infants, pre-school and school-aged children and adults as well as social contact patterns was available. We used Markov Chain Monte Carlo methods to fit the models and then extracted the per capita and population-based contribution of different age groups to VT transmission. Results We estimated that in all settings,

A rapid point-of-care (PoC) test as an adjunct to blood culture to aid the diagnosis of sepsis patients with bloodstream infections may decrease the use of broad-spectrum antibiotics and reduce rates of inappropriate antimicrobial therapy (IAAT) use. Through a decision tree model, taking the perspective of the Irish healthcare provider, the cost-effectiveness of such an intervention was evaluated against the current standard of care (SoC) in hospitalized adults in Ireland. The base-case scenario showed that using a rapid PoC test was cost-saving and life-saving, with €8188 saved per death averted. The results were sensitive to the length of hospital stay for patients with true-positive and true-negative results and to the length of stay (LOS) in the intensive care unit. The threshold analysis showed that even at lower sensitivities, the rapid PoC test could be cost-effective due to the substantial impact of starting earlier targeted and appropriate treatment in patients with bloodstream infection (BSI) and sepsis.

Human immunodeficiency virus (HIV) infected adults are at a higher risk of pneumococcal colonisation and disease, even while receiving antiretroviral therapy (ART). To help evaluate potential indirect effects of vaccination of HIV-infected adults, we assessed whether HIV-infected adults disproportionately contribute to household transmission of pneumococci. We constructed a hidden Markov model to capture the dynamics of pneumococcal carriage acquisition and clearance observed during a longitudinal household-based nasopharyngeal swabbing study, while accounting for sample misclassifications. Households were followed-up twice weekly for approximately 10 months each year during a three-year study period for nasopharyngeal carriage detection via real-time PCR. We estimated the effect of participant's age, HIV status, presence of a HIV-infected adult within the household and other covariates on pneumococcal acquisition and clearance probabilities. Of 1,684 individuals enrolled, 279 (16.6%) were younger children (

Locally tailored interventions for neglected tropical diseases (NTDs) are becoming increasingly important for ensuring that the World Health Organization (WHO) goals for control and elimination are reached. Mathematical models, such as those developed by the NTD Modelling Consortium, are able to offer recommendations on interventions but remain constrained by the data currently available. Data collection for NTDs needs to be strengthened as better data are required to indirectly inform transmission in an area. Addressing specific data needs will improve our modelling recommendations, enabling more accurate tailoring of interventions and assessment of their progress. In this collection, we discuss the data needs for several NTDs, specifically gambiense human African trypanosomiasis, lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminths (STH), trachoma, and visceral leishmaniasis. Similarities in the data needs for these NTDs highlight the potential for integration across these diseases and where possible, a wider spectrum of diseases.

Robust surveillance methods are needed for trachoma control and recrudescence monitoring, but existing methods have limitations. Here, Pinsent et al. analyse data from nine trachoma-endemic populations and provide operational thresholds for interpretation of serological data in low transmission and post-elimination settings.

The World Health Organization and its partners are aiming to eliminate trachoma as a public health problem by 2020. In this study, we compare forecasts of TF prevalence in 2011 for 7 different statistical and mechanistic models across 9 de-identified trachoma endemic districts, representing 4 unique trachoma endemic countries. We forecast TF prevalence between 1–6 years ahead in time and compare the 7 different models to the observed 2011 data using a log-likelihood score. An SIS model, including a district-specific random effect for the district-specific transmission coefficient, had the highest log-likelihood score across all 9 districts and was therefore the best performing model. While overall the deterministic transmission model was the least well performing model, although it did comparably well to the other models for 8 of 9 districts. We perform a statistically rigorous comparison of the forecasting ability of a range of mathematical and statistical models across multiple endemic districts between 1 and 6 years ahead of the last collected TF prevalence data point in 2011, assessing results against surveillance data. This study is a step towards making statements about likelihood and time to elimination with regard to the WHO GET2020 goals.

Background: Infant contact information (skin-to-skin contact between infants and others) is important to understand Streptococcus pneumoniae transmission patterns. A few studies have investigated infant contact patterns by asking the mother/guardian to record all contacts a child makes in one day. However, this approach does not capture contact behaviour in day-care. Our study describes the frequency and nature of physical contacts of infants in day-care to understand infant infection risk in day-care in Nha Trang, Vietnam. Methods: This cross-sectional study enrolled infants aged

Background: Infant contact information (skin-to-skin contact between infants and others) is important to understand Streptococcus pneumoniae transmission patterns. A few studies have investigated infant contact patterns by asking the mother/guardian to record all contacts a child makes in one day. However, this approach does not capture contact behaviour in day-care. Our study describes the frequency and nature of physical contacts of infants in day-care to understand infant infection risk in day-care in Nha Trang, central Vietnam. Methods: This cross-sectional study enrolled infants aged less than 12 months, attending 10 randomly selected day-care centres in Nha Trang. Physical contacts of each infant for one day at the day-care centre were observed and recorded. The mean number of contacts of infants and its factors were assessed using negative binomial regression. Results: In total 14 infants, aged 6 to 11 months, were enrolled, and a total of 96 contacts were observed. The mean number of contacts an infant made in one day was 6.9. Infants who walked independently (age-adjusted rate ratio 1.68, 95% confidence interval 1.06-2.68) and those cared for in a larger group (1.99, 1.42-2.79) had more contacts at day-care. About 50% of infants made contact with at least one person from a commune different from the infant’s, and 50% made contact with at least one other infant at day-care. Conclusion: This study found that day-care attendance may be one factor that increases contact rates of infants in Nha Trang and diversifies them in terms of age and geographical spread. In this study, day-care attendance not only increased contact rates beyond those usually experienced by young children cared at home but specifically increased the contact rates with other children and adults from other communes. Day-care may play a key role in the transmission of respiratory pathogens like Streptococcus pneumoniae to infants.

Abstract Quantitative analysis and mathematical models are useful tools in informing strategies to control or eliminate disease. Currently, there is an urgent need to develop these tools to inform policy to achieve the 2020 goals for neglected tropical diseases (NTDs). In this paper we give an overview of a collection of novel model-based analyses which aim to address key questions on the dynamics of transmission and control of nine NTDs: Chagas disease, visceral leishmaniasis, human African trypanosomiasis, leprosy, soil-transmitted helminths, schistosomiasis, lymphatic filariasis, onchocerciasis and trachoma. Several common themes resonate throughout these analyses, including: the importance of epidemiological setting on the success of interventions; targeting groups who are at highest risk of infection or re-infection; and reaching populations who are not accessing interventions and may act as a reservoir for infection,. The results also highlight the challenge of maintaining elimination ‘as a public health problem’ when true elimination is not reached. The models elucidate the factors that may be contributing most to persistence of disease and discuss the requirements for eventually achieving true elimination, if that is possible. Overall this collection presents new analyses to inform current control initiatives. These papers form a base from which further development of the models and more rigorous validation against a variety of datasets can help to give more detailed advice. At the moment, the models’ predictions are being considered as the world prepares for a final push towards control or elimination of neglected tropical diseases by 2020.