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The emergence of successive Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) during 2020 to 2022, each exhibiting increased epidemic growth relative to earlier circulating variants, has created a need to understand the drivers of such growth. However, both pathogen biology and changing host characteristics-such as varying levels of immunity-can combine to influence replication and transmission of SARS-CoV-2 within and between hosts. Disentangling the role of variant and host in individual-level viral shedding of VOCs is essential to inform Coronavirus Disease 2019 (COVID-19) planning and response and interpret past epidemic trends. Using data from a prospective observational cohort study of healthy adult volunteers undergoing weekly occupational health PCR screening, we developed a Bayesian hierarchical model to reconstruct individual-level viral kinetics and estimate how different factors shaped viral dynamics, measured by PCR cycle threshold (Ct) values over time. Jointly accounting for both interindividual variation in Ct values and complex host characteristics-such as vaccination status, exposure history, and age-we found that age and number of prior exposures had a strong influence on peak viral replication. Older individuals and those who had at least 5 prior antigen exposures to vaccination and/or infection typically had much lower levels of shedding. Moreover, we found evidence of a correlation between the speed of early shedding and duration of incubation period when comparing different VOCs and age groups. Our findings illustrate the value of linking information on participant characteristics, symptom profile and infecting variant with prospective PCR sampling, and the importance of accounting for increasingly complex population exposure landscapes when analysing the viral kinetics of VOCs. Trial Registration: The Legacy study is a prospective observational cohort study of healthy adult volunteers undergoing weekly occupational health PCR screening for SARS-CoV-2 at University College London Hospitals or at the Francis Crick Institute (NCT04750356) (22,23). The Legacy study was approved by London Camden and Kings Cross Health Research Authority Research and Ethics committee (IRAS number 286469). The Legacy study was approved by London Camden and Kings Cross Health Research Authority Research and Ethics committee (IRAS number 286469) and is sponsored by University College London Hospitals. Written consent was given by all participants.
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COVID-19 , SARS-CoV-2 , Adulto , Humanos , SARS-CoV-2/genética , Teorema de Bayes , COVID-19/epidemiologia , Estudos ProspectivosRESUMO
BACKGROUND: Neglected tropical diseases are responsible for considerable morbidity and mortality in low-income populations. International efforts have reduced their global burden, but transmission is persistent and case-finding-based interventions rarely target asymptomatic individuals. METHODS: We develop a generic mathematical modeling framework for analyzing the dynamics of visceral leishmaniasis in the Indian sub-continent (VL), gambiense sleeping sickness (gHAT), and Chagas disease and use it to assess the possible contribution of asymptomatics who later develop disease (pre-symptomatics) and those who do not (non-symptomatics) to the maintenance of infection. Plausible interventions, including active screening, vector control, and reduced time to detection, are simulated for the three diseases. RESULTS: We found that the high asymptomatic contribution to transmission for Chagas and gHAT and the apparently high basic reproductive number of VL may undermine long-term control. However, the ability to treat some asymptomatics for Chagas and gHAT should make them more controllable, albeit over relatively long time periods due to the slow dynamics of these diseases. For VL, the toxicity of available therapeutics means the asymptomatic population cannot currently be treated, but combining treatment of symptomatics and vector control could yield a quick reduction in transmission. CONCLUSIONS: Despite the uncertainty in natural history, it appears there is already a relatively good toolbox of interventions to eliminate gHAT, and it is likely that Chagas will need improvements to diagnostics and their use to better target pre-symptomatics. The situation for VL is less clear, and model predictions could be improved by additional empirical data. However, interventions may have to improve to successfully eliminate this disease.
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Infecções Assintomáticas , Doença de Chagas , Leishmaniose Visceral , Modelos Teóricos , Doenças Negligenciadas , Humanos , Doenças Negligenciadas/prevenção & controle , Doenças Negligenciadas/epidemiologia , Doença de Chagas/transmissão , Doença de Chagas/prevenção & controle , Doença de Chagas/epidemiologia , Doença de Chagas/tratamento farmacológico , Infecções Assintomáticas/epidemiologia , Leishmaniose Visceral/prevenção & controle , Leishmaniose Visceral/epidemiologia , Leishmaniose Visceral/transmissão , Leishmaniose Visceral/tratamento farmacológico , Tripanossomíase Africana/prevenção & controle , Tripanossomíase Africana/epidemiologia , Tripanossomíase Africana/transmissão , Tripanossomíase Africana/tratamento farmacológico , Índia/epidemiologia , AnimaisRESUMO
BACKGROUND: Recurring COVID-19 waves highlight the need for tools able to quantify transmission risk, and identify geographical areas at risk of outbreaks. Local outbreak risk depends on complex immunity patterns resulting from previous infections, vaccination, waning and immune escape, alongside other factors (population density, social contact patterns). Immunity patterns are spatially and demographically heterogeneous, and are challenging to capture in country-level forecast models. METHODS: We used a spatiotemporal regression model to forecast subnational case and death counts and applied it to three EU countries as test cases: France, Czechia, and Italy. Cases in local regions arise from importations or local transmission. Our model produces age-stratified forecasts given age-stratified data, and links reported case counts to routinely collected covariates (e.g. test number, vaccine coverage). We assessed the predictive performance of our model up to four weeks ahead using proper scoring rules and compared it to the European COVID-19 Forecast Hub ensemble model. Using simulations, we evaluated the impact of variations in transmission on the forecasts. We developed an open-source RShiny App to visualise the forecasts and scenarios. RESULTS: At a national level, the median relative difference between our median weekly case forecasts and the data up to four weeks ahead was 25% (IQR: 12-50%) over the prediction period. The accuracy decreased as the forecast horizon increased (on average 24% increase in the median ranked probability score per added week), while the accuracy of death forecasts was more stable. Beyond two weeks, the model generated a narrow range of likely transmission dynamics. The median national case forecasts showed similar accuracy to forecasts from the European COVID-19 Forecast Hub ensemble model, but the prediction interval was narrower in our model. Generating forecasts under alternative transmission scenarios was therefore key to capturing the range of possible short-term transmission dynamics. DISCUSSION: Our model captures changes in local COVID-19 outbreak dynamics, and enables quantification of short-term transmission risk at a subnational level. The outputs of the model improve our ability to identify areas where outbreaks are most likely, and are available to a wide range of public health professionals through the Shiny App we developed.
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COVID-19 , Humanos , COVID-19/epidemiologia , Incidência , Surtos de Doenças , Saúde Pública , PrevisõesRESUMO
Understanding of spatiotemporal transmission of infectious diseases has improved significantly in recent years. Advances in Bayesian inference methods for individual-level geo-located epidemiological data have enabled reconstruction of transmission trees and quantification of disease spread in space and time, while accounting for uncertainty in missing data. However, these methods have rarely been applied to endemic diseases or ones in which asymptomatic infection plays a role, for which additional estimation methods are required. Here, we develop such methods to analyze longitudinal incidence data on visceral leishmaniasis (VL) and its sequela, post-kala-azar dermal leishmaniasis (PKDL), in a highly endemic community in Bangladesh. Incorporating recent data on VL and PKDL infectiousness, we show that while VL cases drive transmission when incidence is high, the contribution of PKDL increases significantly as VL incidence declines (reaching 55% in this setting). Transmission is highly focal: 85% of mean distances from inferred infectors to their secondary VL cases were <300 m, and estimated average times from infector onset to secondary case infection were <4 mo for 88% of VL infectors, but up to 2.9 y for PKDL infectors. Estimated numbers of secondary cases per VL and PKDL case varied from 0 to 6 and were strongly correlated with the infector's duration of symptoms. Counterfactual simulations suggest that prevention of PKDL could have reduced overall VL incidence by up to 25%. These results highlight the need for prompt detection and treatment of PKDL to achieve VL elimination in the Indian subcontinent and provide quantitative estimates to guide spatiotemporally targeted interventions against VL.
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Leishmaniose Cutânea/epidemiologia , Leishmaniose Visceral/epidemiologia , Infecções Assintomáticas/epidemiologia , Bangladesh/epidemiologia , Coinfecção/epidemiologia , Coinfecção/transmissão , Busca de Comunicante , Doenças Endêmicas/estatística & dados numéricos , Humanos , Incidência , Leishmaniose Cutânea/prevenção & controle , Leishmaniose Cutânea/transmissão , Leishmaniose Visceral/prevenção & controle , Leishmaniose Visceral/transmissão , Estudos LongitudinaisRESUMO
We estimate the potential remaining COVID-19 hospitalisation and death burdens in 19 European countries by estimating the proportion of each country's population that has acquired immunity to severe disease through infection or vaccination. Our results suggest many European countries could still face high burdens of hospitalisations and deaths, particularly those with lower vaccination coverage, less historical transmission and/or older populations. Continued non-pharmaceutical interventions and efforts to achieve high vaccination coverage are required in these countries to limit severe COVID-19 outcomes.
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COVID-19 , Europa (Continente)/epidemiologia , Hospitalização , Humanos , SARS-CoV-2 , VacinaçãoRESUMO
Routine asymptomatic testing strategies for COVID-19 have been proposed to prevent outbreaks in high-risk healthcare environments. We used simulation modeling to evaluate the optimal frequency of viral testing. We found that routine testing substantially reduces risk of outbreaks, but may need to be as frequent as twice weekly.
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COVID-19 , Atenção à Saúde , Surtos de Doenças/prevenção & controle , Instalações de Saúde , Humanos , SARS-CoV-2RESUMO
BACKGROUND: COVID-19 outbreaks have occurred in homeless shelters across the US, highlighting an urgent need to identify the most effective infection control strategy to prevent future outbreaks. METHODS: We developed a microsimulation model of SARS-CoV-2 transmission in a homeless shelter and calibrated it to data from cross-sectional polymerase chain reaction (PCR) surveys conducted during COVID-19 outbreaks in five homeless shelters in three US cities from March 28 to April 10, 2020. We estimated the probability of averting a COVID-19 outbreak when an exposed individual is introduced into a representative homeless shelter of 250 residents and 50 staff over 30 days under different infection control strategies, including daily symptom-based screening, twice-weekly PCR testing, and universal mask wearing. RESULTS: The proportion of PCR-positive residents and staff at the shelters with observed outbreaks ranged from 2.6 to 51.6%, which translated to the basic reproduction number (R0) estimates of 2.9-6.2. With moderate community incidence (~ 30 confirmed cases/1,000,000 people/day), the estimated probabilities of averting an outbreak in a low-risk (R0 = 1.5), moderate-risk (R0 = 2.9), and high-risk (R0 = 6.2) shelter were respectively 0.35, 0.13, and 0.04 for daily symptom-based screening; 0.53, 0.20, and 0.09 for twice-weekly PCR testing; 0.62, 0.27, and 0.08 for universal masking; and 0.74, 0.42, and 0.19 for these strategies in combination. The probability of averting an outbreak diminished with higher transmissibility (R0) within the simulated shelter and increasing incidence in the local community. CONCLUSIONS: In high-risk homeless shelter environments and locations with high community incidence of COVID-19, even intensive infection control strategies (incorporating daily symptom screening, frequent PCR testing, and universal mask wearing) are unlikely to prevent outbreaks, suggesting a need for non-congregate housing arrangements for people experiencing homelessness. In lower-risk environments, combined interventions should be employed to reduce outbreak risk.
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Teste de Ácido Nucleico para COVID-19/métodos , COVID-19/prevenção & controle , Simulação por Computador , Surtos de Doenças/prevenção & controle , Pessoas Mal Alojadas , Controle de Infecções/métodos , COVID-19/epidemiologia , Teste de Ácido Nucleico para COVID-19/estatística & dados numéricos , Cidades/epidemiologia , Cidades/estatística & dados numéricos , Simulação por Computador/estatística & dados numéricos , Estudos Transversais , Surtos de Doenças/estatística & dados numéricos , Pessoas Mal Alojadas/estatística & dados numéricos , Habitação/estatística & dados numéricos , Humanos , Controle de Infecções/estatística & dados numéricos , Programas de Rastreamento/métodos , Programas de Rastreamento/estatística & dados numéricos , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: On the Indian subcontinent, visceral leishmaniasis (VL) incidence is on track to reach elimination goals by 2020 in nearly all endemic districts. Although not included in official targets, previous data suggest post-kala-azar dermal leishmaniasis (PKDL) patients can act as an infection reservoir. METHODS: We conducted xenodiagnosis on 47 PKDL patients and 15 VL patients using laboratory-reared Phlebotomus argentipes. In direct xenodiagnosis, flies were allowed to feed on the patient's skin for 15 minutes. For indirect xenodiagnosis, flies were fed through a membrane on the patient's blood. Five days later, blood-fed flies were dissected and examined by microscopy and/or polymerase chain reaction (PCR). A 3-mm skin snip biopsy (PKDL) or venous blood (VL) was processed by quantitative PCR. RESULTS: Twenty-seven PKDL patients (57.4%) had positive results by direct and/or indirect xenodiagnosis. Direct was significantly more sensitive than indirect xenodiagnosis (55.3% vs 6.4%, P < .0001). Those with positive xenodiagnosis had median skin parasite loads >1 log10 unit higher than those with negative results (2.88 vs 1.66, P < .0001). In a multivariable model, parasite load, nodular lesions, and positive skin microscopy were significantly associated with positive xenodiagnosis. Blood parasite load was the strongest predictor for VL. Compared to VL, nodular PKDL was more likely and macular PKDL less likely to result in positive xenodiagnosis, but neither difference reached statistical significance. CONCLUSIONS: Nodular and macular PKDL, and VL, can be infectious to sand flies. Active PKDL case detection and prompt treatment should be instituted and maintained as an integral part of VL control and elimination programs.
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Reservatórios de Doenças , Transmissão de Doença Infecciosa , Insetos Vetores/parasitologia , Leishmania donovani/isolamento & purificação , Leishmaniose Cutânea/transmissão , Leishmaniose Visceral/transmissão , Psychodidae/parasitologia , Adulto , Animais , Feminino , Humanos , Insetos Vetores/fisiologia , Leishmaniose Cutânea/parasitologia , Leishmaniose Visceral/parasitologia , Masculino , Pessoa de Meia-Idade , Psychodidae/fisiologiaRESUMO
Background: Visceral leishmaniasis (VL) has been targeted by the World Health Organization (WHO) and 5 countries in the Indian subcontinent for elimination as a public health problem. To achieve this target, the WHO has developed guidelines consisting of 4 phases of different levels of interventions, based on vector control through indoor residual spraying of insecticide (IRS) and active case detection (ACD). Mathematical transmission models of VL are increasingly used for planning and assessing the efficacy of interventions and evaluating the intensity and timescale required to achieve the elimination target. Methods: This paper draws together the key policy-relevant conclusions from recent transmission modeling of VL, and presents new predictions for VL incidence under the interventions recommended by the WHO using the latest transmission models. Results: The model predictions suggest that the current WHO guidelines should be sufficient to reach the elimination target in areas that had medium VL endemicities (up to 5 VL cases per 10000 population per year) prior to the start of interventions. However, additional interventions, such as extending the WHO attack phase (intensive IRS and ACD), may be required to bring forward elimination in regions with high precontrol endemicities, depending on the relative infectiousness of different disease stages. Conclusions: The potential hurdle that asymptomatic and, in particular, post-kala-azar dermal leishmaniasis cases may pose to reaching and sustaining the target needs to be addressed. As VL incidence decreases, the pool of immunologically naive individuals will grow, creating the potential for new outbreaks.
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Erradicação de Doenças/legislação & jurisprudência , Inseticidas/administração & dosagem , Leishmaniose Visceral/prevenção & controle , Modelos Teóricos , Phlebotomus/parasitologia , Animais , Feminino , Humanos , Incidência , Índia/epidemiologia , Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/epidemiologia , Leishmaniose Visceral/transmissão , Políticas , Saúde Pública , Organização Mundial da SaúdeRESUMO
Generating autologous tissue grafts of a clinically useful volume requires efficient and controlled expansion of cell populations harvested from patients. Hollow fibre bioreactors show promise as cell expansion devices, owing to their potential for scale-up. However, further research is required to establish how to specify appropriate hollow fibre bioreactor operating conditions for expanding different cell types. In this study we develop a simple model for the growth of a cell layer seeded on the outer surface of a single fibre in a perfused hollow fibre bioreactor. Nutrient-rich culture medium is pumped through the fibre lumen and leaves the bioreactor via the lumen outlet or passes through the porous fibre walls and cell layer, and out via ports on the outer wall of the extra-capillary space. Stokes and Darcy equations for fluid flow in the fibre lumen, fibre wall, cell layer and extra-capillary space are coupled to reaction-advection-diffusion equations for oxygen and lactate transport through the bioreactor, and to a simple growth law for the evolution of the free boundary of the cell layer. Cells at the free boundary are assumed to proliferate at a rate that increases with the local oxygen concentration, and to die and detach from the layer if the local fluid shear stress or lactate concentration exceed critical thresholds. We use the model to predict operating conditions that maximise the cell layer growth for different cell types. In particular, we predict the optimal flow rate of culture medium into the fibre lumen and fluid pressure imposed at the lumen outlet for cell types with different oxygen demands and fluid shear stress tolerances, and compare the growth of the cell layer when the exit ports on the outside of the bioreactor are open with that when they are closed. Model simulations reveal that increasing the inlet flow rate and outlet fluid pressure increases oxygen delivery to the cell layer and, therefore, the growth rate of cells that are tolerant to high shear stresses, but may be detrimental for shear-sensitive cells. The cell layer growth rate is predicted to increase, and be less sensitive to the lactate tolerance of the cells, when the exit ports are opened, as the radial flow through the bioreactor is enhanced and the lactate produced by the cells cleared more rapidly from the cell layer.
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Reatores Biológicos , Técnicas de Cultura de Células , Modelos Biológicos , Animais , Bovinos , Linhagem Celular , Humanos , RatosAssuntos
Varicela/epidemiologia , Surtos de Doenças , Influenza Humana/epidemiologia , Caxumba/epidemiologia , Migrantes/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Prisões Locais , Masculino , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Adulto JovemRESUMO
Cutaneous leishmaniasis (CL) is a neglected tropical disease caused by Leishmania parasites, that can cause long-term chronic disabilities. The clinical presentation of CL varies in both type and severity. CL presents as three main clinical forms: localised lesions (localised cutaneous leishmaniasis, LCL); mucocutaneous leishmaniasis (MCL) that affects the mucosa of the nose or the mouth; or as disseminated not ulcerating nodules (diffuse cutaneous leishmaniasis, DCL). Here we recruited a cohort of CL patients in a newly established leishmaniasis treatment centre (LTC) in Lay Gayint, Northwest Ethiopia, and collected detailed demographic and clinical data. The results of our study show that more males than females present to the LTC to seek diagnosis and treatment. 70.2% of CL patients presented with LCL and 20.8% with MCL. A small number of patients presented with DCL, recidivans CL (a rare form of CL where new lesions appear on the edges of CL scars) or with a combination of different clinical presentations. The duration of illness varied from 1 month to 180 months. Over a third of CL patients had additional suspected CL cases in their household. Despite the majority of CL patients having heard about CL, only a minority knew about its transmission or that it could be treated. Most CL patients lived in areas where environmental factors known to be associated with the transmission of CL were present. This work highlights that CL is an important public health problem in Lay Gayint and emphasises the urgent need for more CL awareness campaigns, better health education and better disease management practices.
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Leishmaniose Cutânea , Humanos , Etiópia/epidemiologia , Masculino , Feminino , Adulto , Leishmaniose Cutânea/epidemiologia , Leishmaniose Cutânea/diagnóstico , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Cutânea/patologia , Adulto Jovem , Adolescente , Pessoa de Meia-Idade , Criança , Pré-Escolar , Idoso , Conhecimentos, Atitudes e Prática em Saúde , Estudos de CoortesRESUMO
Introduction: Visceral leishmaniasis (VL), a neglected tropical disease that causes substantial morbidity and mortality, is a serious health problem in Ethiopia. Infections are caused by Leishmania (L.) donovani parasites. Most individuals remain asymptomatic, but some develop VL, which is generally fatal if not treated. We identified the area of Metema-Humera in Northwest Ethiopia as a setting in which we could follow migrant workers when they arrived in an endemic area. The demographic characteristics of this population and factors associated with their risk of asymptomatic infection are poorly characterised. Methods: We divided our cohort into individuals who visited this area for the first time (first comers, FC) and those who had already been in this area (repeat comers, RC). We followed them from the beginning (Time 1, T1) to the end of the agricultural season (Time 2, T2), performing tests for sand fly bite exposure (anti-sand fly saliva antibody ELISA) and serology for Leishmania infection (rK39 rapid diagnostic test and the direct agglutination test) at each time point and collecting information on risk factors for infection. Results: Our results show that most migrant workers come from non-endemic areas, are male, young (median age of 20 years) and are farmers or students. At T1, >80% of them had been already exposed to sand fly bites, as shown by the presence of anti-saliva antibodies. However, due to seasonality of sand flies there was no difference in exposure between FC and RC, or between T1 and T2. The serology data showed that at T1, but not at T2, a significantly higher proportion of RC were asymptomatic. Furthermore, 28.6% of FC became asymptomatic between T1 and T2. Over the duration of this study, one FC and one RC developed VL. In multivariable logistic regression of asymptomatic infection at T1, only age and the number of visits to Metema/Humera were significantly associated with asymptomatic infection. Conclusion: A better understanding of the dynamics of parasite transmission and the risk factors associated with the development of asymptomatic infections and potentially VL will be essential for the development of new strategies to prevent leishmaniasis.
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Estimating the impact of vaccination and non-pharmaceutical interventions on COVID-19 incidence is complicated by several factors, including successive emergence of SARS-CoV-2 variants of concern and changing population immunity from vaccination and infection. We develop an age-structured multi-strain COVID-19 transmission model and inference framework to estimate vaccination and non-pharmaceutical intervention impact accounting for these factors. We apply this framework to COVID-19 waves in French Polynesia and estimate that the vaccination programme averted 34.8% (95% credible interval: 34.5-35.2%) of 223,000 symptomatic cases, 49.6% (48.7-50.5%) of 5830 hospitalisations and 64.2% (63.1-65.3%) of 1540 hospital deaths that would have occurred in a scenario without vaccination up to May 2022. We estimate the booster campaign contributed 4.5%, 1.9%, and 0.4% to overall reductions in cases, hospitalisations, and deaths. Our results suggest that removing lockdowns during the first two waves would have had non-linear effects on incidence by altering accumulation of population immunity. Our estimates of vaccination and booster impact differ from those for other countries due to differences in age structure, previous exposure levels and timing of variant introduction relative to vaccination, emphasising the importance of detailed analysis that accounts for these factors.
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COVID-19 , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , SARS-CoV-2 , Controle de Doenças Transmissíveis , Polinésia/epidemiologia , VacinaçãoRESUMO
As India comes closer to the elimination of visceral leishmaniasis (VL) as a public health problem, surveillance efforts and elimination targets must be continuously revised and strengthened. Mathematical modelling is a compelling research discipline for informing policy and programme design in its capacity to project incidence across space and time, the likelihood of achieving benchmarks, and the impact of different interventions. To gauge the extent to which modelling informs policy in India, this qualitative analysis explores how and whether policy makers understand, value, and reference recently produced VL modelling research. Sixteen semi-structured interviews were carried out with both users- and producers- of VL modelling research, guided by a knowledge utilisation framework grounded in knowledge translation theory. Participants reported that barriers to knowledge utilisation include 1) scepticism that models accurately reflect transmission dynamics, 2) failure of modellers to apply their analyses to specific programme operations, and 3) lack of accountability in the process of translating knowledge to policy. Political trust and support are needed to translate knowledge into programme activities, and employment of a communication intermediary may be a necessary approach to improve this process.
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Visceral leishmaniasis (VL) is declining in India and the World Health Organization's (WHO) 2020 'elimination as a public health problem' target has nearly been achieved. Intensified combined interventions might help reach elimination, but their impact has not been assessed. WHO's Neglected Tropical Diseases 2021-2030 roadmap provides an opportunity to revisit VL control strategies. We estimated the combined effect of a district-wide pilot of intensified interventions in the highly-endemic Vaishali district, where cases fell from 3,598 in 2012-2014 to 762 in 2015-2017. The intensified control approach comprised indoor residual spraying with improved supervision; VL-specific training for accredited social health activists to reduce onset-to-diagnosis time; and increased Information Education & Communication activities in the community. We compared the rate of incidence decrease in Vaishali to other districts in Bihar state via an interrupted time series analysis with a spatiotemporal model informed by previous VL epidemiological estimates. Changes in Vaishali's rank among Bihar's endemic districts in terms of monthly incidence showed a change pre-pilot (3rd highest out of 33 reporting districts) vs. during the pilot (9th) (p<1e-10). The rate of decline in Vaishali's incidence saw no change in rank at 11th highest, both pre-pilot & during the pilot. Counterfactual model simulations suggest an estimated median of 352 cases (IQR 234-477) were averted by the Vaishali pilot between January 2015 and December 2017, which was robust to modest changes in the onset-to-diagnosis distribution. Strengthening control strategies may have precipitated a substantial change in VL incidence in Vaishali and suggests this approach should be piloted in other highly-endemic districts.
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Leishmaniose Visceral , Humanos , Incidência , Índia/epidemiologia , Análise de Séries Temporais Interrompida , Leishmaniose Visceral/epidemiologia , Leishmaniose Visceral/prevenção & controleRESUMO
A key public health question during any disease outbreak when limited vaccine is available is who should be prioritized for early vaccination. Most vaccine prioritization analyses only consider variation in risk of infection and death by a single risk factor, such as age. We provide a more granular approach with stratification by demographics, risk factors, and location. We use this approach to compare the impact of different COVID-19 vaccine prioritization strategies on COVID-19 cases, deaths and disability-adjusted life years (DALYs) over the first 6 months of vaccine rollout, using California as a case example. We estimate the proportion of cases, deaths and DALYs averted relative to no vaccination for strategies prioritizing vaccination by a single risk factor and by multiple risk factors (e.g. age, location). When targeting by a single risk factor, we find that age-based targeting averts the most deaths (62% for 5 million individuals vaccinated) and DALYs (38%) and targeting essential workers averts the least deaths (31%) and DALYs (24%) over the first 6 months of rollout. However, targeting by two or more risk factors simultaneously averts up to 40% more DALYs. Our findings highlight the potential value of multiple-risk-factor targeting of vaccination against COVID-19 and other infectious diseases, but must be balanced with feasibility for policy.
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COVID-19RESUMO
The tau statistic τ uses geolocation and, usually, symptom onset time to assess global spatiotemporal clustering from epidemiological data. We test different methods that could bias the clustering range estimate based on the statistic or affect its apparent precision, by comparison with a baseline analysis of an open access measles dataset. From re-analysing this data we find evidence against no clustering and no inhibition, p -value ∈ [ 0 , 0 â 022 ] (global envelope test). We develop a tau-specific modification of the Loh & Stein spatial bootstrap sampling method, which gives bootstrap tau estimates with 24% lower sampling error and a 110% higher estimated clustering endpoint than previously published (61â 0 m vs. 29 m) and an equivalent increase in the clustering area of elevated disease odds by 342%. These differences could have important consequences for control efforts. Correct practice of graphical hypothesis testing of no clustering and clustering range estimation of the tau statistic are illustrated in the online Graphical abstract. We advocate proper implementation of this useful statistic, ultimately to reduce inaccuracies in control policy decisions made during disease clustering analysis.
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BACKGROUND: With visceral leishmaniasis (VL) incidence at its lowest level since the 1960s, increasing attention has turned to early detection and investigation of outbreaks. METHODS: Outbreak investigations were triggered by recognition of case clusters in the VL surveillance system established for the elimination program. Investigations included ascertainment of all VL cases by date of fever onset, household mapping and structured collection of risk factor data. RESULTS: VL outbreaks were investigated in 13 villages in 10 blocks of 7 districts. Data were collected for 20,670 individuals, of whom 272 were diagnosed with VL between 2012 and 2019. Risk was significantly higher among 10-19 year-olds and adults 35 or older compared to children younger than 10 years. Outbreak confirmation triggered vector control activities and heightened surveillance. VL cases strongly clustered in tolas (hamlets within villages) in which > 66% of residents self-identified as scheduled caste or scheduled tribe (SC/ST); 79.8% of VL cases occurred in SC/ST tolas whereas only 24.2% of the population resided in them. Other significant risk factors included being an unskilled non-agricultural laborer, migration for work in a brick kiln, living in a kuccha (mud brick) house, household crowding, habitually sleeping outside or on the ground, and open defecation. CONCLUSIONS: Our data highlight the importance of sensitive surveillance with triggers for case cluster detection and rapid, careful outbreak investigations to better respond to ongoing and new transmission. The strong association with SC/ST tolas suggests that efforts should focus on enhanced surveillance in these disadvantaged communities.
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Erradicação de Doenças/métodos , Surtos de Doenças/prevenção & controle , Leishmaniose Visceral/epidemiologia , Saúde Pública/métodos , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , Aglomeração , Características da Família , Feminino , Humanos , Incidência , Índia/epidemiologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto JovemRESUMO
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.