Dennis Lai Chao

Recent advances in clinical prediction for diarrhoeal aetiology in low- and middle-income countries have revealed that the addition of weather data to clinical data improves predictive performance. However, the optimal source of weather data remains unclear. We aim to compare the use of model estimated satellite- and ground-based observational data...

Importance The MORDOR (Macrolides Oraux pour Réduire les Décès avec un Oeil sur la Résistance) trial demonstrated that mass azithromycin administration reduced mortality by 18% among children aged 1 to 59 months in Niger. The identification of high-risk subgroups to target with this intervention could reduce the risk of antimicrobial resistance. O...

Recent advances in clinical prediction for diarrheal etiology in low- and middle-income countries have revealed that addition of weather data improves predictive performance. However, the optimal source of weather data remains unclear. We aim to compare model estimated satellite- and ground-based observational data with weather station directly-obs...

Women's empowerment and contraceptive use are critical to achieving gender equality. The positive association between more empowered women and higher rates of contraceptive use has been well-established by cross-sectional research. However, there remains a gap in understanding the longitudinal relationship between contraceptive adoption and changes...

Objectives To estimate the fraction of anaemia attributable to malaria and sickle cell disease (SCD) among children aged 6–59 months in Nigeria. Design Cross-sectional analysis of data from Nigeria’s 2018 Demographic and Health Survey (DHS). Setting Nigeria. Participants 11 536 children aged 6–59 months from randomly selected households were eli...

Importance: Inappropriate use of antibiotics for diarrheal illness can result in adverse effects and increase in antimicrobial resistance. Objective: To determine whether the diarrheal etiology prediction (DEP) algorithm, which uses patient-specific and location-specific features to estimate the probability that diarrhea etiology is exclusively...

Introduction Anaemia is a major cause of morbidity and mortality among children in sub-Saharan Africa. Anaemia has many aetiologies best addressed by different treatments, so regional studies of the aetiology of anaemia may be required. Methods We analysed data from Nigeria’s 2018 Demographic and Health Survey (DHS) to study predictors of anaemia...

How COVID-19 vaccine is distributed within low- and middle-income countries has received little attention outside of equity or logistical concerns but may ultimately affect campaign impact in terms of infections, severe cases, or deaths averted. In this study we examined whether subnational (urban-rural) prioritization may affect the cumulative two...

Background: During the first year of the COVID-19 pandemic, the most effective way to reduce transmission and to protect oneself was to reduce contact with others. However, it is unclear how behavior changed, despite numerous surveys about peoples' attitudes and actions during the pandemic and public health efforts to influence behavior. Methods: W...

Mathematical modeling can be used to project the impact of mass vaccination on cholera transmission. Here, we discuss two examples for which indirect protection from mass vaccination needs to be considered. In the first, we show that non-vaccinees can be protected by mass vaccination campaigns. This additional benefit of indirect protection improve...

Background Child mortality from sickle cell disease in sub-Saharan Africa is presumed to be high but is not well quantified. This uncertainty contributes to the neglect of sickle cell disease and delays the prioritisation of interventions. In this study, we estimated the mortality of children in Nigeria with sickle cell disease, and the proportion...

Background: Child mortality from sickle cell disease in sub-Saharan Africa is presumed to be high but is not well quantified. This uncertainty contributes to the neglect of sickle cell disease and delays the prioritisation of interventions. In this study, we estimated the mortality of children in Nigeria with sickle cell disease, and the proportio...

Understanding the complex interplay between human behavior, disease transmission and non-pharmaceutical interventions during the COVID-19 pandemic could provide valuable insights with which to focus future public health efforts. Cell phone mobility data offer a modern measurement instrument to investigate human mobility and behavior at an unprecede...

How COVID-19 vaccine is distributed within low- and middle-income countries has received little attention outside of equity or logistical concerns but may ultimately affect campaign impact in terms of infections, severe cases, or deaths averted. In this study we examined whether subnational (urban-rural) prioritization may affect the cumulative two...

Traditional clinical prediction models focus on parameters of the individual patient. For infectious diseases, sources external to the patient, including characteristics of prior patients and seasonal factors, may improve predictive performance. We describe the development of a predictive model that integrates multiple sources of data in a principl...

As COVID-19 cases resurge in the United States, understanding the complex interplay between human behavior, disease transmission, and non-pharmaceutical interventions during the pandemic could provide valuable insights to focus future public health efforts. Cell-phone mobility data offers a modern measurement instrument to investigate human mobilit...

Traditional clinical prediction models focus on parameters of the individual patient. For infectious diseases, sources external to the patient, including characteristics of prior patients and seasonal factors, may improve predictive performance. We describe the development of a predictive model that integrates multiple sources of data in a principl...

A fundamental, clinical and scientific concern is how lytic bacteriophage, as well as antibiotics, impact diagnostic positivity. Cholera was chosen as a model disease to investigate this important question because cholera outbreaks enable large enrollment, field methods are well established, and the predatory relationship between lytic bacteriophag...

Background Cholera was introduced into Haiti in 2010. Since then, more than 820 000 cases and nearly 10 000 deaths have been reported. Oral cholera vaccine (OCV) is safe and effective, but has not been seen as a primary tool for cholera elimination due to a limited period of protection and constrained supplies. Regionally, epidemic cholera is conta...

Background: The novel coronavirus SARS-CoV-2 has rapidly spread across the globe and is poised to cause millions of deaths worldwide. There are currently no proven pharmaceutical treatments, and vaccines are likely over a year away. At present, non-pharmaceutical interventions (NPIs) are the only effective option to reduce transmission of the virus...

Background: Most of the world's sickle cell disease (SCD) burden is in Africa, where it is a major contributor to child morbidity and mortality. Despite the low cost of many preventive SCD interventions, insufficient resources have been allocated, and progress in alleviating the SCD burden has lagged behind other public-health efforts in Africa. T...

Background A fundamental clinical and scientific concern is how lytic bacteriophage, as well as antibiotics, impact diagnostic positivity. Methods Cholera was chosen as a model disease to investigate this important question. Patients with diarrheal disease were enrolled at two remote hospitals in Bangladesh. Diagnostic performance was assessed as...

Background Cholera was introduced into Haiti in 2010. Since, there have been over 820,000 reported cases and nearly 10,000 deaths. The year 2019 has seen the lowest reported number of cases since the epidemic began. Oral cholera vaccine (OCV) is safe and effective, but has generally not been seen as a primary tool for cholera elimination due to a l...

Background Pediatric diarrhea can be caused by a wide variety of pathogens, from bacteria to viruses to protozoa. Pathogen prevalence is often described as seasonal, peaking annually and associated with specific weather conditions. Although many studies have described the seasonality of diarrheal disease, these studies have occurred predominantly i...

Background: Pediatric diarrhea can be caused by a wide variety of pathogens, from bacteria to viruses to protozoa. Pathogen prevalence is often described as seasonal, peaking annually and associated with specific weather conditions. Although many studies have described the seasonality of diarrheal disease, these studies have occurred predominantly...

Background Cholera remains an important public health problem in major cities in Bangladesh, especially in slum areas. In response to growing interest among local policymakers to control this disease, this study estimated the impact and cost-effectiveness of preventive cholera vaccination over a ten-year period in a high-risk slum population in Dha...

Estimated average cost of treating a hospitalized cholera patient at the icddr,b hospital, 2013 (US$). (DOC)

Selected thanas of Dhaka for the analysis and their populations. (DOC)

UNICEF prices for one- and ten-dose vials of several EPI vaccines. (DOC)

Coverage rate estimates from past OCV campaigns. (DOC)

Mathematical modeling methodology and additional results. (DOC)

Background Oral cholera vaccine (OCV) is a feasible tool to prevent or mitigate cholera outbreaks. A better understanding of the vaccine’s efficacy among different age groups and how rapidly its protection wanes could help guide vaccination policy. Methods To estimate the level and duration of OCV efficacy, we re-analyzed data from a previously pub...

The 2014 West African Ebola Outbreak is the largest Ebola virus disease (EVD) epidemic ever recorded, not only in number of cases but also in geographical extent. Unlike previous EVD outbreaks, the large number of cases observed in major cities with international airports raised the concern about the possibility of exportation of the infection in c...

Dengue vaccines will soon provide a new tool for reducing dengue disease, but the effectiveness of widespread vaccination campaigns has not yet been determined. We developed an agent-based dengue model representing movement of and transmission dynamics among people and mosquitoes in Yucatán, Mexico, and simulated various vaccine scenarios to evalua...

Further details on synthetic population, transmission model, parameterization, effect of climate change on results, and prediction intervals for results. (PDF)

Many infectious diseases have seasonal outbreaks, which may be driven by cyclical environmental conditions (e.g., an annual rainy season) or human behavior (e.g., school calendars or seasonal migration). If a pathogen is only transmissible for a limited period of time each year, then seasonal outbreaks could infect fewer individuals than expected g...

In 1998, a cholera epidemic in east Africa reached the Comoros Islands, an archipelago in the Mozambique Channel that had not reported a cholera case for more than 20 years. In just a little over 1 year (between January 1998 and March 1999), Grande Comore, the largest island in the Union of the Comoros, reported 7,851 cases of cholera, about 3% of...

An individual's risk of infection from an infectious agent can depend on both the individual's own risk and protective factors and those of individuals in the same community. We hypothesize that an individual's exposure to an infectious agent is associated with the risks of infection of those living nearby, whether their risks are modified by pharm...

Background: The 2014 epidemic of Ebola virus disease in parts of west Africa defines an unprecedented health threat. We developed a model of Ebola virus transmission that integrates detailed geographical and demographic data from Liberia to overcome the limitations of non-spatial approaches in projecting the disease dynamics and assessing non-phar...

Killed, oral cholera vaccines have proven safe and effective, and several large-scale mass cholera vaccination efforts have demonstrated the feasibility of widespread deployment. This study uses a mathematical model of cholera transmission in Bangladesh to examine the effectiveness of potential vaccination strategies. We developed an age-structured...

The quick spread of an Ebola outbreak in West Africa has led a number of countries and airline companies to issue travel bans to the affected areas. Considering data up to 31 Aug 2014, we assess the impact of the resulting traffic reductions with detailed numerical simulations of the international spread of the epidemic. Traffic reductions are show...

Growing interest in mass vaccination with oral cholera vaccine in endemic and epidemic settings will require policymakers to evaluate how to allocate these vaccines in the most efficient manner. Because cholera, when treated properly, has a low case fatality rate, it may not be economically feasible to vaccinate an entire population. Using a new pu...

Background: The 2014 West African Ebola Outbreak is so far the largest and deadliest recorded in history. The affected countries, Sierra Leone, Guinea, Liberia, and Nigeria, have been struggling to contain and to mitigate the outbreak. The ongoing rise in confirmed and suspected cases, 2615 as of 20 August 2014, is considered to increase the risk o...

The 2009 H1N1 influenza pandemic provides a unique opportunity for detailed examination of the spatial dynamics of an emerging pathogen. In the US, the pandemic was characterized by substantial geographical heterogeneity: the 2009 spring wave was limited mainly to northeastern cities while the larger fall wave affected the whole country. Here we us...

Mathematical models have been used to study the dynamics of infectious disease outbreaks and predict the effectiveness of potential mass vaccination campaigns. However, models depend on simplifying assumptions to be tractable, and the consequences of making such assumptions need to be studied. Two assumptions usually incorporated by mathematical mo...

Mathematical modeling can be a valuable tool for studying infectious disease outbreak dynamics and simulating the effects of possible interventions. Here, we describe approaches to modeling cholera outbreaks and how models have been applied to explore intervention strategies, particularly in Haiti. Mathematical models can play an important role in...

Background: The mutations that confer resistance to antiviral agents are thought to be detrimental, or at best neutral, to influenza virus fitness. The fact that resistant influenza strains can circulate and sometimes replace sensitive strains is of great public health concern. Objectives: We used mathematical modeling to test various hypotheses...

Although there is no doubt that significant morbidity and mortality occur during annual influenza epidemics, the role of contextual circumstances, which catalyze seasonal influenza transmission, remains unclear. Weather conditions are believed to affect virus survival, efficiency of transmission and host immunity, but seasonality may also be driven...

Age distribution of the sample populations after partitioning for day-type and daily temperature. Top: regular workdays with low (less or equal than the median temperature, A1) and high (A2) temperatures, regular weekend days with low (B1) and high (B2) temperatures. Bottom: workdays during official holiday periods with low (C1) and high (C2) tempe...

R ratio confidence interval limits for different bootstrap sizes. The upper and lower limits of the 95% confidence intervals (CI) for the ratio of the estimated R 's for regular workdays with high and low precipitation. (TIFF)

Sensitivity of attack rates to vaccine efficacy. (PDF)

Background Dengue is a mosquito-borne infectious disease that constitutes a growing global threat with the habitat expansion of its vectors Aedes aegyti and A. albopictus and increasing urbanization. With no effective treatment and limited success of vector control, dengue vaccines constitute the best control measure for the foreseeable future. Wit...

Resistance to oseltamivir, the most widely used influenza antiviral drug, spread to fixation in seasonal influenza A(H1N1) between 2006 and 2009. This sudden rise in resistance seemed puzzling given the low overall level of the oseltamivir usage and the lack of a correlation between local rates of resistance and oseltamivir usage. We used a stochas...

Animation of a simulated pandemic H1N1 2009-like pandemic. The simulation was initialized with 1,000 infected individuals in Mexico City on March 29 with . Red dots on the map indicate cities with infected individuals, with the size of the dot proportional to prevalence. Light blue arcs indicate that an infected person travels to a city with no inf...

Animation of a simulated pandemic beginning in Hong Kong. The simulation was initialized with 1,000 infected individuals in Hong Kong on June 1 with . (MPG)

Influenza seasons in the model. Each row of symbols represents the seasonality of a single city over the course of a year, with the exception of the first row, which represents all cities north of Lahore, Pakistan. Cities labeled in red are Northern (above Tropic of Cancer), those in green are in the tropics, and those in blue are Southern. Red tri...

Sensitivity of the model results to the symptomatic vs healthy travel ratio. Top panel: The model was run for a pandemic H1N1-like scenario, starting on March 29 with 1,000 individuals infected with a strain with . The symptomatic to healthy travel ratio was varied from 0% to 100%. For each value of this ratio, the simulation was run 10 times, and...

Sensitivity of the model results to population age structure. Top panel: The model was run for a pandemic H1N1-like scenario, starting on March 29 with 1,000 individuals infected with a strain with . In the default scenario (in black), the fraction of children in the population of each country was based on [16]. In the alternative scenario (in red)...

Influenza season data from the literature. (PDF)

Attack rate with 95% bootstrapped CI for a single intervention for six different vaccination days considered and six different vaccination coverages for an epidemic starting in Hong Kong. Each panel represents a given number of vaccine doses available to distribute in the entire network: A) Two million doses. B) Four million doses. C) Five million...

Model parameters. (PDF)

Model. (PDF)

Pandemic simulations. (PDF)

Diagram of how vaccine roll-out occurs in the model. In the model, we target a set of age cohorts each year for vaccination. The numbers in the diagrams indicate the ages of the population cohorts in years. The numbers in black in each row indicate the cohorts targeted each year, while the numbers in red indicate those already protected by vaccine...

Fitting the model to the 1968–69 Hong Kong pandemic. Top panel: Estimates of R and the pandemic start date. We varied R in increments of 0.05 and the pandemic start date (day on which 1,000 people are infected in Hong Kong) in increments of one week. We ran the simulation twice for each combination of values and chose the results with the smaller e...

The effect of vaccination on influenza prevalence in the model by hemisphere. Top: For a 1968–1969-like pandemic, we assumed that it began with 1,000 infected individuals in Hong Kong on June 1 with R = 1.4 and vaccination occurred 180 days later in late November. Bottom: For a 2009-like pandemic, we assumed that the pandemic started with 1,000 inf...

Observed and simulated pandemic H1N1 2009 epidemic peaks. Observed data was from influenza A virology surveillance data from Flunet. (PDF)

Animation of simulated pandemics beginning in Mexico, with or without vaccination. The simulation was initialized with 1,000 infected individuals in Mexico City on April 1 with . The top panels show a map and the prevalence of infection when there is no vaccine available, while the bottom panels correspond to the simulation in which vaccine was adm...