Individual-based models provide modularity and structural flexibility necessary for modeling of infectious diseases at the within-host and population levels, but are challenging to implement. Levels of complexity can exceed the capacity and timescales for students and trainees in most academic institutions. Here we describe the process and advantages of a multi-disease framework approach developed with formal software support. The epidemiological modeling software, EMOD, has undergone a decade of software development. It is structured so that a majority of code is shared across disease modeling including malaria, HIV, tuberculosis, dengue, polio and typhoid. In additional to implementation efficiency, the sharing increases code usage and testing. The freely available codebase also includes hundreds of regression tests, scientific feature tests and component tests to help verify functionality and avoid inadvertent changes to functionality during future development. Here we describe the levels of detail, flexible configurability and modularity enabled by EMOD and the role of software development principles and processes in its development.
Typhoid fever is an acute systemic infectious disease responsible for an estimated 12-20 million illnesses and over 150 000 deaths annually. In March, 2018, a new recommendation was issued by WHO for the programmatic use of typhoid conjugate vaccines in endemic countries. Health economic analyses of typhoid vaccines have informed funding decisions and national policies regarding vaccine rollout. However, by focusing only on averted typhoid cases and their associated costs, traditional cost-effectiveness analyses might underestimate crucial benefits of typhoid vaccination programmes, because the potential effect of typhoid vaccines on the treatment of patients with non-specific acute febrile illnesses is not considered. For every true case of typhoid fever, three to 25 patients without typhoid disease are treated with antimicrobials unnecessarily, conservatively amounting to more than 50 million prescriptions per year. Antimicrobials for suspected typhoid might therefore be an important selective pressure for the emergence and spread of antimicrobial resistance globally. We propose that large-scale, more aggressive typhoid vaccination programmes-including catch-up campaigns in children up to 15 years of age, and vaccination in lower incidence settings-have the potential to reduce the overuse of antimicrobials and thereby reduce antimicrobial resistance in many bacterial pathogens. Funding bodies and national governments must therefore consider the potential for broad reductions in antimicrobial use and resistance in decisions related to the rollout of typhoid conjugate vaccines.
Background Typhoid fever remains a major cause of morbidity and mortality in low- and middle-income settings. In the last 10 years, several reports have described the reemergence of typhoid fever in southern and eastern Africa, associated with multidrug-resistant H58 Salmonella Typhi. Here, we identify risk factors for pediatric typhoid fever in a large epidemic in Blantyre, Malawi. Methods A case-control study was conducted between April 2015 and November 2016. Cases were recruited at a large teaching hospital, and controls were recruited from the community, matched by residential ward. Stepwise variable selection and likelihood ratio testing were used to select candidate risk factors for a final logistic regression model. Results Use of river water for cooking and cleaning was highly associated with risk of typhoid fever (odds ratio [OR], 4.6 [95% confidence interval {CI}, 1.7–12.5]). Additional risk factors included protective effects of soap in the household (OR, 0.6 [95% CI, .4–.98]) and >1 water source used in the previous 3 weeks (OR, 3.2 [95% CI, 1.6–6.2]). Attendance at school or other daycare was also identified as a risk factor (OR, 2.7 [95% CI, 1.4–5.3]) and was associated with the highest attributable risk (51.3%). Conclusions These results highlight diverse risk factors for typhoid fever in Malawi, with implications for control in addition to the provision of safe drinking water. There is an urgent need to improve our understanding of transmission pathways of typhoid fever, both to develop tools for detecting S. Typhi in the environment and to inform water, sanitation, and hygiene interventions.
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