Nathan Lo

All Publications

• Nathan Lo-translating infectious disease models into policy. The Lancet. Infectious diseases Kirby, T. 2024; 24 (11): 1196

  View details for DOI 10.1016/S1473-3099(24)00678-9

  View details for PubMedID 39455239

• Review of the WHO guideline on preventive chemotherapy for public health control of strongyloidiasis. The Lancet. Infectious diseases Lo, N. C., Addiss, D. G., Buonfrate, D., Amor, A., Anegagrie, M., Bisoffi, Z., Bradbury, R. S., Keiser, J., Kepha, S., Khieu, V., Krolewiecki, A., Mbonigaba, J. B., Muñoz, J., Mutapi, F., Novela, V., Vaz Nery, S., Coffeng, L. E., de Vlas, S. J., Bartoszko, J., Moja, L., Mupfasoni, D., Montresor, A. 2024

  Abstract

  Strongyloidiasis is a soil-transmitted helminthiasis that is estimated to affect 300-600 million people across Asia, Africa, South and central America, and the Pacific. This neglected parasitic disease is most known for its ability to persist as a lifelong infection due to autoinfection and its risk of hyperinfection and disseminated disease during immunosuppression, which has a more than 60% case fatality. Despite the large global burden of strongyloidiasis, there have been no large-scale public health programmes or WHO guidelines directed towards its control and elimination. However, over the past decade, key scientific and policy changes along with requests from endemic countries have led to WHO incorporating strongyloidiasis into its 2021-30 roadmap and public health targets for control and elimination of neglected tropical diseases. In 2024, WHO published its first guideline on public health control of strongyloidiasis with a single recommendation: in endemic settings with a Strongyloides stercoralis infection prevalence of 5% or higher (measured either with Baermann or agar plate culture from stool specimens), WHO conditionally recommends mass drug administration with single-dose ivermectin (200 μg/kg; oral therapy) in all age groups from 5 years and older to reduce strongyloidiasis. This Review, written by the 2023-24 strongyloidiasis guidelines development group along with WHO colleagues and international experts, presents a summary of the recently published WHO guideline recommendation for strongyloidiasis, and the supporting evidence, considerations for public health implementation, and future research needs.

  View details for DOI 10.1016/S1473-3099(24)00595-4

  View details for PubMedID 39481419

• Comparing frequency of booster vaccination to prevent severe COVID-19 by risk group in the United States. Nature communications Park, H. J., Gonsalves, G. S., Tan, S. T., Kelly, J. D., Rutherford, G. W., Wachter, R. M., Schechter, R., Paltiel, A. D., Lo, N. C. 2024; 15 (1): 1883

  Abstract

  There is a public health need to understand how different frequencies of COVID-19 booster vaccines may mitigate the risk of severe COVID-19, while accounting for waning of protection and differential risk by age and immune status. By analyzing United States COVID-19 surveillance and seroprevalence data in a microsimulation model, here we show that more frequent COVID-19 booster vaccination (every 6-12 months) in older age groups and the immunocompromised population would effectively reduce the burden of severe COVID-19, while frequent boosters in the younger population may only provide modest benefit against severe disease. In persons 75+ years, the model estimated that annual boosters would reduce absolute annual risk of severe COVID-19 by 199 (uncertainty interval: 183-232) cases per 100,000 persons, compared to a one-time booster vaccination. In contrast, for persons 18-49 years, the model estimated that annual boosters would reduce this risk by 14 (10-19) cases per 100,000 persons. Those with prior infection had lower benefit of more frequent boosting, and immunocompromised persons had larger benefit. Scenarios with emerging variants with immune evasion increased the benefit of more frequent variant-targeted boosters. This study underscores the benefit of considering key risk factors to inform frequency of COVID-19 booster vaccines in public health guidance and ensuring at least annual boosters in high-risk populations.

  View details for DOI 10.1038/s41467-024-45549-9

  View details for PubMedID 38448400

  View details for PubMedCentralID 10014083

• Development of prediction models to identify hotspots of schistosomiasis in endemic regions to guide mass drug administration. Proceedings of the National Academy of Sciences of the United States of America Singer, B. J., Coulibaly, J. T., Park, H. J., Andrews, J. R., Bogoch, I. I., Lo, N. C. 2024; 121 (2): e2315463120

  Abstract

  Schistosomiasis is a neglected tropical disease affecting over 150 million people. Hotspots of Schistosoma transmission-communities where infection prevalence does not decline adequately with mass drug administration-present a key challenge in eliminating schistosomiasis. Current approaches to identify hotspots require evaluation 2-5 y after a baseline survey and subsequent mass drug administration. Here, we develop statistical models to predict hotspots at baseline prior to treatment comparing three common hotspot definitions, using epidemiologic, survey-based, and remote sensing data. In a reanalysis of randomized trials in 589 communities in five endemic countries, a regression model predicts whether Schistosoma mansoni infection prevalence will exceed the WHO threshold of 10% in year 5 ("prevalence hotspot") with 86% sensitivity, 74% specificity, and 93% negative predictive value (NPV; assuming 30% hotspot prevalence), and a regression model for Schistosoma haematobium achieves 90% sensitivity, 90% specificity, and 96% NPV. A random forest model predicts whether S. mansoni moderate and heavy infection prevalence will exceed a public health goal of 1% in year 5 ("intensity hotspot") with 92% sensitivity, 79% specificity, and 96% NPV, and a boosted trees model for S. haematobium achieves 77% sensitivity, 95% specificity, and 91% NPV. Baseline prevalence is a top predictor in all models. Prediction is less accurate in countries not represented in training data and for a third hotspot definition based on relative prevalence reduction over time ("persistent hotspot"). These models may be a tool to prioritize high-risk communities for more frequent surveillance or intervention against schistosomiasis, but prediction of hotspots remains a challenge.

  View details for DOI 10.1073/pnas.2315463120

  View details for PubMedID 38181058

• Infectiousness of SARS-CoV-2 breakthrough infections and reinfections during the Omicron wave. Nature medicine Tan, S. T., Kwan, A. T., Rodríguez-Barraquer, I., Singer, B. J., Park, H. J., Lewnard, J. A., Sears, D., Lo, N. C. 2023; 29 (2): 358-365

  Abstract

  Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infections in vaccinated individuals and reinfections in previously infected individuals have become increasingly common. Such infections highlight a broader need to understand the contribution of vaccination, including booster doses, and natural immunity to the infectiousness of individuals with SARS-CoV-2 infections, especially in high-risk populations with intense transmission, such as in prisons. Here we show that both vaccine-derived and naturally acquired immunity independently reduce the infectiousness of persons with Omicron variant SARS-CoV-2 infections in a prison setting. Analyzing SARS-CoV-2 surveillance data from December 2021 to May 2022 across 35 California state prisons with a predominately male population, we estimate that unvaccinated Omicron cases had a 36% (95% confidence interval (CI): 31-42%) risk of transmitting infection to close contacts, as compared to a 28% (25-31%) risk among vaccinated cases. In adjusted analyses, we estimated that any vaccination, prior infection alone and both vaccination and prior infection reduced an index case's risk of transmitting infection by 22% (6-36%), 23% (3-39%) and 40% (20-55%), respectively. Receipt of booster doses and more recent vaccination further reduced infectiousness among vaccinated cases. These findings suggest that, although vaccinated and/or previously infected individuals remain highly infectious upon SARS-CoV-2 infection in this prison setting, their infectiousness is reduced compared to individuals without any history of vaccination or infection. This study underscores benefit of vaccination to reduce, but not eliminate, transmission.

  View details for DOI 10.1038/s41591-022-02138-x

  View details for PubMedID 36593393

  View details for PubMedCentralID PMC9974584

• Review of 2022 WHO guidelines on the control and elimination of schistosomiasis. The Lancet. Infectious diseases Lo, N. C., Bezerra, F. S., Colley, D. G., Fleming, F. M., Homeida, M., Kabatereine, N., Kabole, F. M., King, C. H., Mafe, M. A., Midzi, N., Mutapi, F., Mwanga, J. R., Ramzy, R. M., Satrija, F., Stothard, J. R., Traoré, M. S., Webster, J. P., Utzinger, J., Zhou, X. N., Danso-Appiah, A., Eusebi, P., Loker, E. S., Obonyo, C. O., Quansah, R., Liang, S., Vaillant, M., Murad, M. H., Hagan, P., Garba, A. 2022; 22 (11): e327-e335

  Abstract

  Schistosomiasis is a helminthiasis infecting approximately 250 million people worldwide. In 2001, the World Health Assembly (WHA) 54.19 resolution defined a new global strategy for control of schistosomiasis through preventive chemotherapy programmes. This resolution culminated in the 2006 WHO guidelines that recommended empirical treatment by mass drug administration with praziquantel, predominately to school-aged children in endemic settings at regular intervals. Since then, school-based and community-based preventive chemotherapy programmes have been scaled-up, reducing schistosomiasis-associated morbidity. Over the past 15 years, new scientific evidence-combined with a more ambitious goal of eliminating schistosomiasis and an increase in the global donated supply of praziquantel-has highlighted the need to update public health guidance worldwide. In February, 2022, WHO published new guidelines with six recommendations to update the global public health strategy against schistosomiasis, including expansion of preventive chemotherapy eligibility from the predominant group of school-aged children to all age groups (2 years and older), lowering the prevalence threshold for annual preventive chemotherapy, and increasing the frequency of treatment. This Review, written by the 2018-2022 Schistosomiasis Guidelines Development Group and its international partners, presents a summary of the new WHO guideline recommendations for schistosomiasis along with their historical context, supporting evidence, implications for public health implementation, and future research needs.

  View details for DOI 10.1016/S1473-3099(22)00221-3

  View details for PubMedID 35594896

• COVID-19 Vaccination and Estimated Public Health Impact in California. JAMA network open Tan, S. T., Park, H. J., Rodríguez-Barraquer, I., Rutherford, G. W., Bibbins-Domingo, K., Schechter, R., Lo, N. C. 2022; 5 (4): e228526

  Abstract

  Despite widespread vaccination against COVID-19 in the United States, there are limited empirical data quantifying their public health impact in the population.To estimate the number of COVID-19 cases, hospitalizations, and deaths directly averted because of COVID-19 vaccination in California.This modeling study used person-level data provided by the California Department of Public Health (CDPH) on COVID-19 cases, hospitalizations, and deaths as well as COVID-19 vaccine administration from January 1, 2020, to October 16, 2021. A statistical model was used to estimate the number of COVID-19 cases that would have occurred in the vaccine era (November 29, 2020, to October 16, 2021) in the absence of vaccination based on the ratio of the number of cases among the unvaccinated (aged <12 years) and vaccine-eligible groups (aged ≥12 years) before vaccine introduction. Vaccine-averted COVID-19 cases were estimated by finding the difference between the projected and observed number of COVID-19 cases. Averted COVID-19 hospitalizations and deaths were assessed by applying estimated hospitalization and case fatality risks to estimates of vaccine-averted COVID-19 cases. As a sensitivity analysis, a second independent model was developed to estimate the number of vaccine-averted COVID-19 outcomes by applying published data on vaccine effectiveness to data on COVID-19 vaccine administration and estimated risk of COVID-19 over time.COVID-19 vaccination.Number of COVID-19 cases, hospitalizations, and deaths estimated to have been averted because of COVID-19 vaccination.There were 4 585 248 confirmed COVID-19 cases, 240 718 hospitalizations, and 70 406 deaths in California from January 1, 2020, to October 16, 2021, during which 27 164 680 vaccine-eligible individuals aged 12 years and older were reported to have received at least 1 dose of a COVID-19 vaccine in the vaccine era (79.5% of the eligible population). The primary model estimated that COVID-19 vaccination averted 1 523 500 (95% prediction interval [PI], 976 800-2 230 800) COVID-19 cases in California, corresponding to a 72% (95% PI, 53%-91%) relative reduction in cases because of vaccination. COVID-19 vaccination was estimated to have averted 72 930 (95% PI, 53 250-99 160) hospitalizations and 19 430 (95% PI, 14 840-26 230) deaths during the study period. The alternative model identified comparable findings.This study provides evidence of the public health benefit of COVID-19 vaccination in the United States and further supports the urgency for continued vaccination.

  View details for DOI 10.1001/jamanetworkopen.2022.8526

  View details for PubMedID 35452106

  View details for PubMedCentralID PMC9034409

• WHO guideline on control and elimination of human schistosomiasis WHO, .. World Health Organization. 2022
• Routine asymptomatic testing strategies for airline travel during the COVID-19 pandemic: a simulation study. The Lancet. Infectious diseases Kiang, M. V., Chin, E. T., Huynh, B. Q., Chapman, L. A., Rodriguez-Barraquer, I., Greenhouse, B., Rutherford, G. W., Bibbins-Domingo, K., Havlir, D., Basu, S., Lo, N. C. 2021

  Abstract

  BACKGROUND: Routine viral testing strategies for SARS-CoV-2 infection might facilitate safe airline travel during the COVID-19 pandemic and mitigate global spread of the virus. However, the effectiveness of these test-and-travel strategies to reduce passenger risk of SARS-CoV-2 infection and population-level transmission remains unknown.METHODS: In this simulation study, we developed a microsimulation of SARS-CoV-2 transmission in a cohort of 100000 US domestic airline travellers using publicly available data on COVID-19 clinical cases and published natural history parameters to assign individuals one of five health states of susceptible to infection, latent period, early infection, late infection, or recovered. We estimated a per-day risk of infection with SARS-CoV-2 corresponding to a daily incidence of 150 infections per 100000 people. We assessed five testing strategies: (1) anterior nasal PCR test within 3 days of departure, (2) PCR within 3 days of departure and 5 days after arrival, (3) rapid antigen test on the day of travel (assuming 90% of the sensitivity of PCR during active infection), (4) rapid antigen test on the day of travel and PCR test 5 days after arrival, and (5) PCR test 5 days after arrival. Strategies 2 and 4 included a 5-day quarantine after arrival. The travel period was defined as 3 days before travel to 2 weeks after travel. Under each scenario, individuals who tested positive before travel were not permitted to travel. The primary study outcome was cumulative number of infectious days in the cohort over the travel period without isolation or quarantine (population-level transmission risk), and the key secondary outcome was the number of infectious people detected on the day of travel (passenger risk of infection).FINDINGS: We estimated that in a cohort of 100000 airline travellers, in a scenario with no testing or screening, there would be 8357 (95% uncertainty interval 6144-12831) infectious days with 649 (505-950) actively infectious passengers on the day of travel. The pre-travel PCR test reduced the number of infectious days from 8357 to 5401 (3917-8677), a reduction of 36% (29-41) compared with the base case, and identified 569 (88% [76-92]) of 649 actively infectious travellers on the day of flight; the addition of post-travel quarantine and PCR reduced the number of infectious days to 2520 days (1849-4158), a reduction of 70% (64-75) compared with the base case. The rapid antigen test on the day of travel reduced the number of infectious days to 5674 (4126-9081), a reduction of 32% (26-38) compared with the base case, and identified 560 (86% [83-89]) actively infectious travellers; the addition of post-travel quarantine and PCR reduced the number of infectious days to 3124 (2356-495), a reduction of 63% (58-66) compared with the base case. The post-travel PCR alone reduced the number of infectious days to 4851 (3714-7679), a reduction of 42% (35-49) compared with the base case.INTERPRETATION: Routine asymptomatic testing for SARS-CoV-2 before travel can be an effective strategy to reduce passenger risk of infection during travel, although abbreviated quarantine with post-travel testing is probably needed to reduce population-level transmission due to importation of infection when travelling from a high to low incidence setting.FUNDING: University of California, San Francisco.

  View details for DOI 10.1016/S1473-3099(21)00134-1

  View details for PubMedID 33765417

• Influenza, Varicella, and Mumps Outbreaks in US Migrant Detention Centers. JAMA Lo, N. C., Nyathi, S., Chapman, L. A., Rodriguez-Barraquer, I., Kushel, M., Bibbins-Domingo, K., Lewnard, J. A. 2020

  View details for DOI 10.1001/jama.2020.20539

  View details for PubMedID 33119037

• Frequency of Routine Testing for Coronavirus Disease 2019 (COVID-19) in High-risk Healthcare Environments to Reduce Outbreaks. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Chin, E. T., Huynh, B. Q., Chapman, L. A., Murrill, M., Basu, S., Lo, N. C. 2020

  Abstract

  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.

  View details for DOI 10.1093/cid/ciaa1383

  View details for PubMedID 33570097

• Childhood vaccines and antibiotic use in low- and middle-income countries. Nature Lewnard, J. A., Lo, N. C., Arinaminpathy, N., Frost, I., Laxminarayan, R. 2020; 581 (7806): 94-99

  Abstract

  Vaccines may reduce the burden of antimicrobial resistance, in part by preventing infections for which treatment often includes the use of antibiotics1-4. However, the effects of vaccination on antibiotic consumption remain poorly understood-especially in low- and middle-income countries (LMICs), where the burden of antimicrobial resistance is greatest5. Here we show that vaccines that have recently been implemented in the World Health Organization's Expanded Programme on Immunization reduce antibiotic consumption substantially among children under five years of age in LMICs. By analysing data from large-scale studies of households, we estimate that pneumococcal conjugate vaccines and live attenuated rotavirus vaccines confer 19.7% (95% confidence interval, 3.4-43.4%) and 11.4% (4.0-18.6%) protection against antibiotic-treated episodes of acute respiratory infection and diarrhoea, respectively, in age groups that experience the greatest disease burden attributable to the vaccine-targeted pathogens6,7. Under current coverage levels, pneumococcal and rotavirus vaccines prevent 23.8 million and 13.6 million episodes of antibiotic-treated illness, respectively, among children under five years of age in LMICs each year. Direct protection resulting from the achievement of universal coverage targets for these vaccines could prevent an additional 40.0 million episodes of antibiotic-treated illness. This evidence supports the prioritization of vaccines within the global strategy to combat antimicrobial resistance8.

  View details for DOI 10.1038/s41586-020-2238-4

  View details for PubMedID 32376956

  View details for PubMedCentralID PMC7332418

• The 2016 California policy to eliminate nonmedical vaccine exemptions and changes in vaccine coverage: An empirical policy analysis. PLoS medicine Nyathi, S. n., Karpel, H. C., Sainani, K. L., Maldonado, Y. n., Hotez, P. J., Bendavid, E. n., Lo, N. C. 2019; 16 (12): e1002994

  Abstract

  Vaccine hesitancy, the reluctance or refusal to receive vaccination, is a growing public health problem in the United States and globally. State policies that eliminate nonmedical ("personal belief") exemptions to childhood vaccination requirements are controversial, and their effectiveness to improve vaccination coverage remains unclear given limited rigorous policy analysis. In 2016, a California policy (Senate Bill 277) eliminated nonmedical exemptions from school entry requirements. The objective of this study was to estimate the association between California's 2016 policy and changes in vaccine coverage.We used a quasi-experimental state-level synthetic control analysis and a county-level difference-in-differences analysis to estimate the impact of the 2016 California policy on vaccination coverage and prevalence of exemptions to vaccine requirements (nonmedical and medical). We used publicly available state-level data from the US Centers for Disease Control and Prevention on coverage of measles, mumps, and rubella (MMR) vaccination, nonmedical exemption, and medical exemption in children entering kindergarten. We used county-level data individually requested from state departments of public health on overall vaccine coverage and exemptions. Based on data availability, we included state-level data for 45 states, including California, from 2011 to 2017 and county-level data for 17 states from 2010 to 2017. The prespecified primary study outcome was MMR vaccination in the state analysis and overall vaccine coverage in the county analysis. In the state-level synthetic control analysis, MMR coverage in California increased by 3.3% relative to its synthetic control in the postpolicy period (top 2 of 43 states evaluated in the placebo tests, top 5%), nonmedical exemptions decreased by 2.4% (top 2 of 43 states evaluated in the placebo tests, top 5%), and medical exemptions increased by 0.4% (top 1 of 44 states evaluated in the placebo tests, top 2%). In the county-level analysis, overall vaccination coverage increased by 4.3% (95% confidence interval [CI] 2.9%-5.8%, p < 0.001), nonmedical exemptions decreased by 3.9% (95% CI 2.4%-5.4%, p < 0.001), and medical exemptions increased by 2.4% (95% CI 2.0%-2.9%, p < 0.001). Changes in vaccination coverage across counties after the policy implementation from 2015 to 2017 ranged from -6% to 26%, with larger increases in coverage in counties with lower prepolicy vaccine coverage. Results were robust to alternative model specifications. The limitations of the study were the exclusion of a subset of US states from the analysis and the use of only 2 years of postpolicy data based on data availability.In this study, implementation of the California policy that eliminated nonmedical childhood vaccine exemptions was associated with an estimated increase in vaccination coverage and a reduction in nonmedical exemptions at state and county levels. The observed increase in medical exemptions was offset by the larger reduction in nonmedical exemptions. The largest increases in vaccine coverage were observed in the most "high-risk" counties, meaning those with the lowest prepolicy vaccine coverage. Our findings suggest that government policies removing nonmedical exemptions can be effective at increasing vaccination coverage.

  View details for DOI 10.1371/journal.pmed.1002994

  View details for PubMedID 31869328

• State of deworming coverage and equity in low-income and middle-income countries using household health surveys: a spatiotemporal cross-sectional study. The Lancet. Global health Lo, N. C., Heft-Neal, S. n., Coulibaly, J. T., Leonard, L. n., Bendavid, E. n., Addiss, D. G. 2019

  Abstract

  Mass deworming against soil-transmitted helminthiasis, which affects 1 billion of the poorest people globally, is one of the largest public health programmes for neglected tropical diseases, and is intended to be equitable. However, the extent to which treatment programmes for deworming achieve equitable coverage across wealth class and sex is unclear and the public health metric of national deworming coverage does not include representation of equity. This study aims to measure both coverage and equity in global, national, and subnational deworming to guide future programmatic evaluation, investment, and metric design.We used nationally representative, geospatial, household data from Demographic and Health Surveys that measured mother-reported deworming in children of preschool age (12-59 months). Deworming was defined as children having received drugs for intestinal parasites in the previous 6 months before the survey. We estimated deworming coverage disaggregated by geography, wealth quintile, and sex, and computed an equity index. We examined trends in coverage and equity index across countries, within countries, and over time. We used a regression model to compute the household correlates of deworming and ecological correlates of equitable deworming.Our study included 820 883 children living in 50 countries from Africa, the Americas, Asia, and Europe that are endemic for soil-transmitted helminthiasis using 77 Demographic and Health Surveys from December, 2003, to October, 2017. In these countries, the mean deworming coverage in preschool children was estimated at 33·0% (95% CI 32·9-33·1). The subnational coverage ranged from 0·5% to 87·5%, and within-country variation was greater than between-country variation. Of the 31 countries reporting that they reached the WHO goal of more than 75% national coverage, 30 had inequity in deworming, with treatment concentrated in wealthier populations. We did not detect systematic differences in deworming equity by sex.Substantial inequities in mass deworming programmes are common as wealthier populations have consistently higher coverage than that of the poor, including in countries reporting to have reached the WHO goal of more than 75% national coverage. These inequities seem to be geographically heterogeneous, modestly improving over time, with no evidence of sex differences in inequity. Future reporting of deworming coverage should consider disaggregation by geography, wealth, and sex with incorporation of an equity index to complement the conventional public health metric of national deworming coverage.Bill & Melinda Gates Foundation, Stanford University Medical Scientist Training Program.

  View details for DOI 10.1016/S2214-109X(19)30413-9

  View details for PubMedID 31558383

• Comparison of Strategies and Incidence Thresholds for Vi Conjugate Vaccines Against Typhoid Fever: A Cost-effectiveness Modeling Study JOURNAL OF INFECTIOUS DISEASES Lo, N. C., Gupta, R., Stanaway, J. D., Garrett, D. O., Bogoch, I. I., Luby, S. P., Andrews, J. R. 2018; 218: S232–S242

  View details for DOI 10.1093/infdis/jix598

  View details for Web of Science ID 000463874100008

• Comparison of Strategies and Incidence Thresholds for Vi Conjugate Vaccines Against Typhoid Fever: A Cost-effectiveness Modeling Study. The Journal of infectious diseases Lo, N. C., Gupta, R. n., Stanaway, J. D., Garrett, D. O., Bogoch, I. I., Luby, S. P., Andrews, J. R. 2018

  Abstract

  Typhoid fever remains a major public health problem globally. While new Vi conjugate vaccines hold promise for averting disease, the optimal programmatic delivery remains unclear. We aimed to identify the strategies and associated epidemiologic conditions under which Vi conjugate vaccines would be cost-effective.We developed a dynamic, age-structured transmission and cost-effectiveness model that simulated multiple vaccination strategies with a typhoid Vi conjugate vaccine from a societal perspective. We simulated 10-year vaccination programs with (1) routine immunization of infants (aged <1 year) through the Expanded Program on Immunization (EPI) and (2) routine immunization of infants through the EPI plus a 1-time catch-up campaign in school-aged children (aged 5-14 years). In the base case analysis, we assumed a 0.5% case-fatality rate for all cases of clinically symptomatic typhoid fever and defined strategies as highly cost-effective by using the definition of a low-income country (defined as a country with a gross domestic product of $1045 per capita). We defined incidence as the true number of clinically symptomatic people in the population per year.Vi conjugate typhoid vaccines were highly cost-effective when administered by routine immunization activities through the EPI in settings with an annual incidence of >50 cases/100000 (95% uncertainty interval, 40-75 cases) and when administered through the EPI plus a catch-up campaign in settings with an annual incidence of >130 cases/100000 (95% uncertainty interval, 50-395 cases). The incidence threshold was sensitive to the typhoid-related case-fatality rate, carrier contribution to transmission, vaccine characteristics, and country-specific economic threshold for cost-effectiveness.Typhoid Vi conjugate vaccines would be highly cost-effective in low-income countries in settings of moderate typhoid incidence (50 cases/100000 annually). These results were sensitive to case-fatality rates, underscoring the need to consider factors contributing to typhoid mortality (eg, healthcare access and antimicrobial resistance) in the global vaccination strategy.

  View details for PubMedID 29444257

• Impact and cost-effectiveness of snail control to achieve disease control targets for schistosomiasis. Proceedings of the National Academy of Sciences of the United States of America Lo, N. C., Gurarie, D. n., Yoon, N. n., Coulibaly, J. T., Bendavid, E. n., Andrews, J. R., King, C. H. 2018

  Abstract

  Schistosomiasis is a parasitic disease that affects over 240 million people globally. To improve population-level disease control, there is growing interest in adding chemical-based snail control interventions to interrupt the lifecycle of Schistosoma in its snail host to reduce parasite transmission. However, this approach is not widely implemented, and given environmental concerns, the optimal conditions for when snail control is appropriate are unclear. We assessed the potential impact and cost-effectiveness of various snail control strategies. We extended previously published dynamic, age-structured transmission and cost-effectiveness models to simulate mass drug administration (MDA) and focal snail control interventions against Schistosoma haematobium across a range of low-prevalence (5-20%) and high-prevalence (25-50%) rural Kenyan communities. We simulated strategies over a 10-year period of MDA targeting school children or entire communities, snail control, and combined strategies. We measured incremental cost-effectiveness in 2016 US dollars per disability-adjusted life year and defined a strategy as optimally cost-effective when maximizing health gains (averted disability-adjusted life years) with an incremental cost-effectiveness below a Kenya-specific economic threshold. In both low- and high-prevalence settings, community-wide MDA with additional snail control reduced total disability by an additional 40% compared with school-based MDA alone. The optimally cost-effective scenario included the addition of snail control to MDA in over 95% of simulations. These results support inclusion of snail control in global guidelines and national schistosomiasis control strategies for optimal disease control, especially in settings with high prevalence, "hot spots" of transmission, and noncompliance to MDA.

  View details for PubMedID 29301964

• A call to strengthen the global strategy against schistosomiasis and soil-transmitted helminthiasis: the time is now. The Lancet. Infectious diseases Lo, N. C., Addiss, D. G., Hotez, P. J., King, C. H., Stothard, J. R., Evans, D. S., Colley, D. G., Lin, W., Coulibaly, J. T., Bustinduy, A. L., Raso, G., Bendavid, E., Bogoch, I. I., Fenwick, A., Savioli, L., Molyneux, D., Utzinger, J., Andrews, J. R. 2017; 17 (2): e64-e69

  Abstract

  In 2001, the World Health Assembly (WHA) passed the landmark WHA 54.19 resolution for global scale-up of mass administration of anthelmintic drugs for morbidity control of schistosomiasis and soil-transmitted helminthiasis, which affect more than 1·5 billion of the world's poorest people. Since then, more than a decade of research and experience has yielded crucial knowledge on the control and elimination of these helminthiases. However, the global strategy has remained largely unchanged since the original 2001 WHA resolution and associated WHO guidelines on preventive chemotherapy. In this Personal View, we highlight recent advances that, taken together, support a call to revise the global strategy and guidelines for preventive chemotherapy and complementary interventions against schistosomiasis and soil-transmitted helminthiasis. These advances include the development of guidance that is specific to goals of morbidity control and elimination of transmission. We quantify the result of forgoing this opportunity by computing the yearly disease burden, mortality, and lost economic productivity associated with maintaining the status quo. Without change, we estimate that the population of sub-Saharan Africa will probably lose 2·3 million disability-adjusted life-years and US$3·5 billion of economic productivity every year, which is comparable to recent acute epidemics, including the 2014 Ebola and 2015 Zika epidemics. We propose that the time is now to strengthen the global strategy to address the substantial disease burden of schistosomiasis and soil-transmitted helminthiasis.

  View details for DOI 10.1016/S1473-3099(16)30535-7

  View details for PubMedID 27914852

  View details for PubMedCentralID PMC5280090

• Public Health and Economic Consequences of Vaccine Hesitancy for Measles in the United States. JAMA pediatrics Lo, N. C., Hotez, P. J. 2017

  Abstract

  Routine childhood vaccination is declining in some regions of the United States due to vaccine hesitancy, which risks the resurgence of many infectious diseases with public health and economic consequences. There are ongoing policy debates on the state and national level, including legislation around nonmedical (personal-belief) exemptions for childhood vaccination and possibly a special government commission on vaccine safety, which may affect vaccine coverage.To estimate the number of measles cases in US children and the associated economic costs under scenarios of different levels of vaccine hesitancy, using the case example of measles, mumps, and rubella (MMR) vaccination and measles.Publicly available data from the US Centers for Disease Control and Prevention were used to simulate county-level MMR vaccination coverage in children (age 2-11 years) in the United States. A stochastic mathematical model was adapted for infectious disease transmission that estimated a distribution for outbreak size as it relates to vaccine coverage. Economic costs per measles case were obtained from the literature. The predicted effects of increasing the prevalence of vaccine hesitancy as well as the removal of nonmedical exemptions were estimated. The model was calibrated to annual measles cases in US children over recent years, and the model prediction was validated using an independent data set from England and Wales.Annual measles cases in the United States and the associated public sector costs.A 5% decline in MMR vaccine coverage in the United States would result in an estimated 3-fold increase in measles cases for children aged 2 to 11 years nationally every year, with an additional $2.1 million in public sector costs. The numbers would be substantially higher if unvaccinated infants, adolescents, and adult populations were also considered. There was variation around these estimates due to the stochastic elements of measles importation and sensitivity of some model inputs, although the trend was robust.This analysis predicts that even minor reductions in childhood vaccination, driven by vaccine hesitancy (nonmedical and personal belief exemptions), will have substantial public health and economic consequences. The results support an urgent need to address vaccine hesitancy in policy dialogues at the state and national level, with consideration of removing personal belief exemptions of childhood vaccination.

  View details for PubMedID 28738137

• Assessment of global guidelines for preventive chemotherapy against schistosomiasis and soil-transmitted helminthiasis: a cost-effectiveness modelling study LANCET INFECTIOUS DISEASES Lo, N. C., Lai, Y., Karagiannis-Voules, D., Bogoch, I. I., Coulibaly, J. T., Bendavid, E., Utzinger, J., Vounatsou, P., Andrews, J. R. 2016; 16 (9): 1065-1075

  Abstract

  WHO guidelines recommend annual treatment for schistosomiasis or soil-transmitted helminthiasis when prevalence in school-aged children is at or above a threshold of 50% and 20%, respectively. Separate treatment guidelines are used for these two helminthiases, and integrated community-wide treatment is not recommended. We assessed the cost-effectiveness of changing prevalence thresholds and treatment guidelines under an integrated delivery framework.We developed a dynamic, age-structured transmission and cost-effectiveness model that simulates integrated preventive chemotherapy programmes against schistosomiasis and soil-transmitted helminthiasis. We assessed a 5-year treatment programme with praziquantel (40 mg/kg per treatment) against schistosomiasis and albendazole (400 mg per treatment) against soil-transmitted helminthiasis at 75% coverage. We defined strategies as highly cost-effective if the incremental cost-effectiveness ratio was less than the World Bank classification for a low-income country (gross domestic product of US$1045 per capita). We calculated the prevalence thresholds for cost-effective preventive chemotherapy of various strategies, and estimated treatment needs for sub-Saharan Africa.Annual preventive chemotherapy against schistosomiasis was highly cost-effective in treatment of school-aged children at a prevalence threshold of 5% (95% uncertainty interval [UI] 1·7-5·2; current guidelines recommend treatment at 50% prevalence) and for community-wide treatment at a prevalence of 15% (7·3-18·5; current recommendation is unclear, some community treatment recommended at 50% prevalence). Annual preventive chemotherapy against soil-transmitted helminthiasis was highly cost-effective in treatment of school-aged children at a prevalence of 20% (95% UI 5·4-30·5; current guidelines recommend treatment at 20% prevalence) and the entire community at 60% (35·3-85·1; no guidelines available). When both helminthiases were co-endemic, prevalence thresholds using integrated delivery were lower. Using this revised treatment framework, we estimated that treatment needs would be six times higher than WHO guidelines for praziquantel and two times higher for albendazole. An additional 21·3% (95% Bayesian credible interval 20·4-22·2) of the population changed from receiving non-integrated treatment under WHO guidelines to integrated treatment (both praziquantel and albendazole). Country-specific economic differences resulted in heterogeneity around these prevalence thresholds.Annual preventive chemotherapy programmes against schistosomiasis and soil-transmitted helminthiasis are likely to be highly cost-effective at prevalences lower than WHO recommendations. These findings support substantial treatment scale-up, community-wide coverage, integrated treatment in co-endemic settings that yield substantial cost synergies, and country-specific treatment guidelines.Doris Duke Charitable Foundation, Mount Sinai Hospital-University Health Network AMO Innovation Fund, and Stanford University Medical Scholars Programme.

  View details for DOI 10.1016/S1473-3099(16)30073-1

  View details for Web of Science ID 000381655200036

  View details for PubMedID 27286968

• Abstinence Funding Was Not Associated With Reductions In HIV Risk Behavior In Sub-Saharan Africa HEALTH AFFAIRS Lo, N. C., Lowe, A., Bendavid, E. 2016; 35 (5): 856-863

  Abstract

  The President's Emergency Plan for AIDS Relief (PEPFAR) has been the largest funder of abstinence and faithfulness programming in sub-Saharan Africa, with a cumulative investment of over US $1.4 billion in the period 2004-13. We examined whether PEPFAR funding for abstinence and faithfulness programs, which aimed to reduce the risk of HIV transmission, was associated with a relative change in five outcomes indicative of high-risk sexual behavior: number of sexual partners in the past twelve months for men and for women, age at first sexual intercourse for men and for women, and teenage pregnancies. Using nationally representative surveys from twenty-two sub-Saharan African countries, we compared trends between people living in countries that received PEPFAR abstinence and faithfulness funding and those living in countries that did not in the period 1998-2013. We found no evidence to suggest that PEPFAR funding was associated with population-level reductions in any of the five outcomes. These results suggest that alternative funding priorities for HIV prevention may yield greater health benefits.

  View details for DOI 10.1377/hlthaff.2015.0828

  View details for Web of Science ID 000375796700015

  View details for PubMedID 27140992

• Comparison of community-wide, integrated mass drug administration strategies for schistosomiasis and soil-transmitted helminthiasis: a cost-effectiveness modelling study. The Lancet. Global health Lo, N. C., Bogoch, I. I., Blackburn, B. G., Raso, G., N'Goran, E. K., Coulibaly, J. T., Becker, S. L., Abrams, H. B., Utzinger, J., Andrews, J. R. 2015; 3 (10): e629-38

  Abstract

  More than 1·5 billion people are affected by schistosomiasis or soil-transmitted helminthiasis. WHO's recommendations for mass drug administration (MDA) against these parasitic infections emphasise treatment of school-aged children, using separate treatment guidelines for these two helminthiases groups. We aimed to evaluate the cost-effectiveness of expanding integrated MDA to the entire community in four settings in Côte d'Ivoire.We extended previously published, dynamic, age-structured models of helminthiases transmission to simulate costs and disability averted with integrated MDA (of praziquantel and albendazole) for schistosomiasis and soil-transmitted helminthiasis. We calibrated the model to data for prevalence and intensity of species-specific helminth infection from surveys undertaken in four communities in Côte d'Ivoire between March, 1997, and September, 2010. We simulated a 15-year treatment programme with 75% coverage in only school-aged children; school-aged children and preschool-aged children; adults; and the entire community. Treatment costs were estimated at US$0·74 for school-aged children and $1·74 for preschool-aged children and adults. The incremental cost-effectiveness ratio (ICER) was calculated in 2014 US dollars per disability-adjusted life-year (DALY) averted.Expanded community-wide treatment was highly cost effective compared with treatment of only school-aged children (ICER $167 per DALY averted) and WHO guidelines (ICER $127 per DALY averted), and remained highly cost effective even if treatment costs for preschool-aged children and adults were ten times greater than those for school-aged children. Community-wide treatment remained highly cost effective even when elimination of helminth infections was not achieved. These findings were robust across the four diverse communities in Côte d'Ivoire, only one of which would have received annual MDA for both schistosomiasis and soil-transmitted helminthiasis under the latest WHO guidelines. Treatment every 6 months was also highly cost effective in three out of four communities.Integrated, community-wide MDA programmes for schistosomiasis and soil-transmitted helminthiasis can be highly cost effective, even in communities with low disease burden in any helminth group. These results support an urgent need to re-evaluate current global guidelines for helminthiases control programmes to include community-wide treatment, increased treatment frequency, and consideration for lowered prevalence thresholds for integrated treatment.Stanford University Medical Scholars Programme, Mount Sinai Hospital-University Health Network AMO Innovation Fund.

  View details for DOI 10.1016/S2214-109X(15)00047-9

  View details for PubMedID 26385302

• Cost-effectiveness and public health impact of typhoid conjugate vaccine introduction strategies in Bangladesh. Vaccine Weyant, C., Hooda, Y., Munira, S. J., Lo, N. C., Ryckman, T., Tanmoy, A. M., Kanon, N., Seidman, J. C., Garrett, D., Saha, S. K., Goldhaber-Fiebert, J. D., Saha, S., Andrews, J. R. 2024

  Abstract

  Typhoid fever causes substantial morbidity and mortality in Bangladesh. The government of Bangladesh plans to introduce typhoid conjugate vaccines (TCV) in its expanded program on immunization (EPI) schedule. However, the optimal introduction strategy in addition to the costs and benefits of such a program are unclear.We extended an existing mathematical model of typhoid transmission to integrate cost data, clinical incidence data, and recently conducted serosurveys in urban, semi-urban, and rural areas. In our primary analysis, we evaluated the status quo (i.e., no vaccination) and eight vaccine introduction strategies including routine and 1-time campaign strategies, which differed by age groups targeted and geographic focus. Model outcomes included clinical incidence, seroincidence, deaths, costs, disability-adjusted life years (DALYs), and incremental cost-effectiveness ratios (ICERs) for each strategy. We adopted a societal perspective, 10-year model time horizon, and 3 % annual discount rate. We performed probabilistic, one-way, and scenario sensitivity analyses including adopting a healthcare perspective and alternate model time horizons.We projected that all TCV strategies would be cost saving compared to the status quo. The preferred strategy was a nationwide introduction of TCV at 9-12 months of age with a single catch-up campaign for children ages 1-15, which was cost saving compared to all other strategies and the status quo. In the 10 years following implementation, we projected this strategy would avert 3.77 million cases (95 % CrI: 2.60 - 5.18), 11.31 thousand deaths (95 % CrI: 3.77 - 23.60), and save $172.35 million (95 % CrI: -14.29 - 460.59) compared to the status quo. Our findings were broadly robust to changes in parameter values and willingness-to-pay thresholds.We projected that nationwide TCV introduction with a catch-up campaign would substantially reduce typhoid incidence and very likely be cost saving in Bangladesh.

  View details for DOI 10.1016/j.vaccine.2024.03.035

  View details for PubMedID 38531727

• Determining herd immunity thresholds for hepatitis A virus transmission to inform vaccination strategies among people who inject drugs in 16 U.S. States. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Yang, J., Lo, N. C., Dankwa, E. A., Donnelly, C. A., Gupta, R., Montgomery, M. P., Weng, M. K., Martin, N. K. 2023

  Abstract

  BACKGROUND: Widespread outbreaks of person-to-person transmission of hepatitis A virus (HAV), particularly among people who inject drugs (PWID), continue across the United States and globally. However, the herd immunity threshold and vaccination coverage required to prevent outbreaks is unknown. We aimed to use surveillance data and dynamic modeling to estimate herd immunity thresholds among PWID in 16 U.S. states.METHODS: We used a previously published dynamic transmission model of HAV transmission, calibrated to surveillance data from outbreaks involving PWID in 16 states. Using state-level calibrated models, we estimated the basic reproduction number (R0) and herd immunity threshold for PWID in each state. We performed a meta-analysis of herd immunity thresholds to determine the critical vaccination coverage required to prevent most HAV outbreaks among PWID.RESULTS: Estimates of R0 for HAV infection ranged from 2.2 (95% CI 1.9-2.5) for North Carolina to 5.0 (95% CI 4.5-5.6) for West Virginia. Corresponding herd immunity thresholds ranged from 55% (95% CI 47-61%) for North Carolina to 80% (95% CI 78-82%) for West Virginia. Based on the meta-analysis, we estimated a pooled herd immunity threshold of 64% (95% CI 61-68%, 90% prediction interval 52-76%) among PWID. Using the prediction interval upper bound (76%) and assuming 95% vaccine efficacy, we estimate a vaccination coverage of 80% could prevent most HAV outbreaks.CONCLUSIONS: Hepatitis A vaccination programs in the United States may need to achieve vaccination coverage of at least 80% among PWID in order to prevent most HAV outbreaks among this population.

  View details for DOI 10.1093/cid/ciad552

  View details for PubMedID 37738564

• Predicting the Public Health Impact of Bivalent Vaccines and Nirmatrelvir-Ritonavir Against Coronavirus Disease 2019. Open forum infectious diseases Park, H. J., Tan, S. T., León, T. M., Jain, S., Schechter, R., Lo, N. C. 2023; 10 (9): ofad415

  Abstract

  Uptake of coronavirus disease 2019 (COVID-19) bivalent vaccines and the oral medication nirmatrelvir-ritonavir (Paxlovid) has remained low across the United States. Assessing the public health impact of increasing uptake of these interventions in key risk groups can guide further public health resources and policy and determine what proportion of severe COVID-19 is avertable with these interventions.This modeling study used person-level data from the California Department of Public Health on COVID-19 cases, hospitalizations, deaths, and vaccine administration from 23 July 2022 to 23 January 2023. We used a quasi-Poisson regression model calibrated to recent historical data to predict future COVID-19 outcomes and modeled the impact of increasing uptake (up to 70% coverage) of bivalent COVID-19 vaccines and nirmatrelvir-ritonavir during acute illness in different risk groups. Risk groups were defined by age (≥50, ≥65, ≥75 years) and vaccination status (everyone, primary series only, previously vaccinated). We predicted the number of averted COVID-19 cases, hospitalizations, and deaths and number needed to treat (NNT).The model predicted that increased uptake of bivalent COVID-19 boosters and nirmatrelvir-ritonavir (up to 70% coverage) in all eligible persons could avert an estimated 15.7% (95% uncertainty interval [UI], 11.2%-20.7%; NNT: 17 310) and 23.5% (95% UI, 13.1%-30.0%; NNT: 67) of total COVID-19-related deaths, respectively. In the high-risk group of persons ≥65 years old alone, increased uptake of bivalent boosters and nirmatrelvir-ritonavir could avert an estimated 11.9% (95% UI, 8.4%-15.1%; NNT: 2757) and 22.8% (95% UI, 12.7%-29.2%; NNT: 50) of total COVID-19-related deaths, respectively.These findings suggest that prioritizing uptake of bivalent boosters and nirmatrelvir-ritonavir among older age groups (≥65 years) would be most effective (based on NNT) but would not address the entire burden of severe COVID-19.

  View details for DOI 10.1093/ofid/ofad415

  View details for PubMedID 37674629

  View details for PubMedCentralID PMC10478155

• Outbreaks in U.S. Migrant Detention Centers - A Vaccine-Preventable Cause of Health Inequity. The New England journal of medicine Lo, N. C., Gonsalves, G. S. 2023

  View details for DOI 10.1056/NEJMp2304716

  View details for PubMedID 37602574

• Public health impact and cost-effectiveness of screening for active tuberculosis disease or infection among children in South Africa. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Brough, J., Martinez, L., Hatherill, M., Zar, H. J., Lo, N. C., Andrews, J. R. 2023

  Abstract

  Although tuberculosis disease is a leading cause of global childhood mortality, there remain major gaps in diagnosis, treatment and prevention in children, as tuberculosis control programs rely predominantly on presentation of symptomatic children or contact tracing. We assessed the public health impact and cost-effectiveness of age-based routine screening and contact tracing in children in South Africa.We used a deterministic mathematical model to evaluate age-based routine screening in 1-year increments from ages 0 to 5, with and without contact tracing and preventive treatment. Screening incorporated symptom history and tuberculin skin testing, with chest X-ray and GeneXpert Ultra for confirmatory testing. We projected tuberculosis cases, deaths, disability-adjusted life years (DALYs) and costs (2021 U.S. Dollars) and evaluated the incremental cost-effectiveness ratios (ICERs) comparing each intervention.Routine screening at age 2 with contact tracing and preventive treatment averted 11,900 tuberculosis cases (95% confidence interval (CI), 6,160-15,730), 1,360 deaths (95% CI, 260-3,800), and 40,000 DALYs (95% CI, 13,000-100,000) in the South Africa pediatric population over 1 year compared with the status quo. This combined strategy was cost-effective (ICER $9,050 per DALY; 95% CI, 2,890-22,920) and remained cost-effective above an annual risk of infection of 1.6%. For annual risk of infection between 0.8% and 1.6%, routine screening at age 2 was the dominant strategy.Routine screening for tuberculosis among young children combined with contact tracing and preventive treatment would have a large public health impact and be cost-effective in preventing pediatric tuberculosis deaths in high incidence settings like South Africa.

  View details for DOI 10.1093/cid/ciad449

  View details for PubMedID 37542465

• A sustainable way to control the parasitic disease schistosomiasis. Nature Lo, N. C., Arnold, B. 2023

  View details for DOI 10.1038/d41586-023-02178-4

  View details for PubMedID 37438627

  View details for PubMedCentralID 6785807

• Perspective on Schistosomiasis Drug Discovery: Highlights from a Schistosomiasis Drug Discovery Workshop at Wellcome Collection, London, September 2022. ACS infectious diseases Caldwell, N., Afshar, R., Baragaña, B., Bustinduy, A. L., Caffrey, C. R., Collins, J. J., Fusco, D., Garba, A., Gardner, M., Gomes, M., Hoffmann, K. F., Hsieh, M., Lo, N. C., McNamara, C. W., Nono, J. K., Padalino, G., Read, K. D., Roestenberg, M., Spangenberg, T., Specht, S., Gilbert, I. H. 2023; 9 (5): 1046-1055

  Abstract

  In September 2022, the Drug Discovery Unit at the University of Dundee, UK, organised an international meeting at the Wellcome Collection in London to explore the current clinical situation and challenges associated with treating schistosomiasis. The aim of this meeting was to discuss the need for new treatments in view of the clinical situation and to ascertain what the key requirements would be for any potential new anti-schistosomals. This information will be essential to inform ongoing drug discovery efforts for schistosomiasis. We also discussed the potential drug discovery pathway and associated criteria for progressing compounds to the clinic. To date, praziquantel (PZQ) is the only drug available to treat all species causing schistosomiasis, but it is often unable to completely clear parasites from an infected patient, partially due to its inactivity against juvenile worms. PZQ-mediated mass drug administration campaigns conducted in endemic areas (e.g., sub-Saharan Africa, where schistosomiasis is primarily prevalent) have contributed to reducing the burden of disease but will not eliminate the disease as a public health problem. The potential for Schistosoma to develop resistance towards PZQ, as the sole treatment available, could become a concern. Consequently, new anthelmintic medications are urgently needed, and this Perspective aims to capture some of the learnings from our discussions on the key criteria for new treatments.

  View details for DOI 10.1021/acsinfecdis.3c00081

  View details for PubMedID 37083395

  View details for PubMedCentralID PMC10186373

• Burden of Typhoid and Paratyphoid Fever in India. The New England journal of medicine John, J., Bavdekar, A., Rongsen-Chandola, T., Dutta, S., Gupta, M., Kanungo, S., Sinha, B., Srinivasan, M., Shrivastava, A., Bansal, A., Singh, A., Koshy, R. M., Jinka, D. R., Thomas, M. S., Alexander, A. P., Thankaraj, S., Ebenezer, S. E., Karthikeyan, A. S., Kumar, D., Njarekkattuvalappil, S. K., Raju, R., Sahai, N., Veeraraghavan, B., Murhekar, M. V., Mohan, V. R., Natarajan, S. K., Ramanujam, K., Samuel, P., Lo, N. C., Andrews, J., Grassly, N. C., Kang, G. 2023; 388 (16): 1491-1500

  Abstract

  In 2017, more than half the cases of typhoid fever worldwide were projected to have occurred in India. In the absence of contemporary population-based data, it is unclear whether declining trends of hospitalization for typhoid in India reflect increased antibiotic treatment or a true reduction in infection.From 2017 through 2020, we conducted weekly surveillance for acute febrile illness and measured the incidence of typhoid fever (as confirmed on blood culture) in a prospective cohort of children between the ages of 6 months and 14 years at three urban sites and one rural site in India. At an additional urban site and five rural sites, we combined blood-culture testing of hospitalized patients who had a fever with survey data regarding health care use to estimate incidence in the community.A total of 24,062 children who were enrolled in four cohorts contributed 46,959 child-years of observation. Among these children, 299 culture-confirmed typhoid cases were recorded, with an incidence per 100,000 child-years of 576 to 1173 cases in urban sites and 35 in rural Pune. The estimated incidence of typhoid fever from hospital surveillance ranged from 12 to 1622 cases per 100,000 child-years among children between the ages of 6 months and 14 years and from 108 to 970 cases per 100,000 person-years among those who were 15 years of age or older. Salmonella enterica serovar Paratyphi was isolated from 33 children, for an overall incidence of 68 cases per 100,000 child-years after adjustment for age.The incidence of typhoid fever in urban India remains high, with generally lower estimates of incidence in most rural areas. (Funded by the Bill and Melinda Gates Foundation; NSSEFI Clinical Trials Registry of India number, CTRI/2017/09/009719; ISRCTN registry number, ISRCTN72938224.).

  View details for DOI 10.1056/NEJMoa2209449

  View details for PubMedID 37075141

• Evaluation of the US Definitions for Coronavirus Disease 2019 Community Risk Levels. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Mokhtar, S., Parpia, A. S., Lo, N. C., Ndeffo-Mbah, M. L. 2023; 76 (8): 1496-1499

  Abstract

  The US Centers for Disease Control and Prevention (CDC) defines a county metric of coronavirus disease 2019 (COVID-19) community levels to inform public health measures. We find that the COVID-19 community levels vary frequently over time, which may not be optimal for decision making. Alternative metric formulations that do not compromise predictive ability are shown to reduce variability.

  View details for DOI 10.1093/cid/ciac922

  View details for PubMedID 36433715

  View details for PubMedCentralID PMC10110267

• Comparison of model predictions of typhoid conjugate vaccine public health impact and cost-effectiveness. Vaccine Burrows, H., Antillón, M., Gauld, J. S., Kim, J. H., Mogasale, V., Ryckman, T., Andrews, J. R., Lo, N. C., Pitzer, V. E. 2022

  Abstract

  Models are useful to inform policy decisions on typhoid conjugate vaccine (TCV) deployment in endemic settings. However, methodological choices can influence model-predicted outcomes. To provide robust estimates for the potential public health impact of TCVs that account for structural model differences, we compared four dynamic and one static mathematical model of typhoid transmission and vaccine impact. All models were fitted to a common dataset of age-specific typhoid fever cases in Kolkata, India. We evaluated three TCV strategies: no vaccination, routine vaccination at 9 months of age, and routine vaccination at 9 months with a one-time catch-up campaign (ages 9 months to 15 years). The primary outcome was the predicted percent reduction in symptomatic typhoid cases over 10 years after vaccine introduction. For three models with economic analyses (Models A-C), we also compared the incremental cost-effectiveness ratios (ICERs), calculated as the incremental cost (US$) per disability-adjusted life-year (DALY) averted. Routine vaccination was predicted to reduce symptomatic cases by 10-46 % over a 10-year time horizon under an optimistic scenario (95 % initial vaccine efficacy and 19-year mean duration of protection), and by 2-16 % under a pessimistic scenario (82 % initial efficacy and 6-year mean protection). Adding a catch-up campaign predicted a reduction in incidence of 36-90 % and 6-35 % in the optimistic and pessimistic scenarios, respectively. Vaccine impact was predicted to decrease as the relative contribution of chronic carriers to transmission increased. Models A-C all predicted routine vaccination with or without a catch-up campaign to be cost-effective compared to no vaccination, with ICERs varying from $95-789 per DALY averted; two models predicted the ICER of routine vaccination alone to be greater than with the addition of catch-up campaign. Despite differences in model-predicted vaccine impact and cost-effectiveness, routine vaccination plus a catch-up campaign is likely to be impactful and cost-effective in high incidence settings such as Kolkata.

  View details for DOI 10.1016/j.vaccine.2022.12.032

  View details for PubMedID 36586741

• Contribution and quality of mathematical modeling evidence in World Health Organization guidelines: A systematic review. Epidemics Lo, N. C., Andrejko, K., Shukla, P., Baker, T., Sawin, V. I., Norris, S. L., Lewnard, J. A. 2022; 39: 100570

  Abstract

  Mathematical modeling studies are frequently conducted to guide policy in global health. However, the contribution of mathematical modeling studies to World Health Organization (WHO) guideline recommendations, and the quality of evidence contributed by these studies remains unknown. We conducted a systematic review of the WHO Guidelines Review Committee database to identify guideline recommendations that included evidence from mathematical modeling studies since inception of the Guidelines Review Committee on 1 December, 2007. We included WHO guideline recommendations citing a mathematical modeling study in the primary evidence base. We defined a mathematical model as a framework that predicted epidemiologic, health or economic impact of an intervention or decision in the clinical or public health context. The primary outcome was inclusion of evidence from mathematical modeling studies in a guideline recommendation. We evaluated each unique modeling study across multiple domains of quality. Between 1 December 2007 and 1 April 2019, the WHO Guidelines Review Committee approved 154 guidelines providing 1619 guideline recommendations. Mathematical modeling studies informed 46 WHO guidelines (29.9%) and 101 unique guideline recommendations (6.2%). Modeling evidence addressed topics related to infectious diseases in 38 guidelines (82.6%) and 81 recommendations (80.2%), most commonly for HIV and tuberculosis. Evidence from modeling studies was assessed in the GRADE evidence profile for 12 recommendations (12.9%) and GRADE evidence-to-decision framework for 45 recommendations (44.6%). Modeling-informed recommendations were more likely than other recommendations within the same guidelines to be issued with a "conditional" rather than "strong" strength of recommendation (53.5% versus 37.8%), and the evidence underlying modeling-informed recommendations was more likely to be assessed as very low quality (41.6% versus 24.1%). Upon review of individual modeling studies, we estimated that 33.8% of models performed a calibration, 29.4% of models performed a validation of results, and 20.6% of models reported a change in the study conclusion in the sensitivity analysis. While policy recommendations in WHO guidelines are informed by evidence from modeling studies, the validity of modeling studies included in guidelines development is heterogeneous. Quality assessment is needed to support the evaluation and incorporation of evidence from mathematical modeling studies in guidelines development.

  View details for DOI 10.1016/j.epidem.2022.100570

  View details for PubMedID 35569248

• Risk factor targeting for vaccine prioritization during the COVID-19 pandemic SCIENTIFIC REPORTS Chapman, L. C., Shukla, P., Rodriguez-Barraquer, I., Shete, P. B., Leon, T. M., Bibbins-Domingo, K., Rutherford, G. W., Schechter, R., Lo, N. C. 2022; 12 (1): 3055

  Abstract

  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.

  View details for DOI 10.1038/s41598-022-06971-5

  View details for Web of Science ID 000760421800009

  View details for PubMedID 35197495

  View details for PubMedCentralID PMC8866501

• Predicting covid-19 outcomes. BMJ (Clinical research ed.) Habib, A. R., Lo, N. C. 2022; 376: o354

  View details for DOI 10.1136/bmj.o354

  View details for PubMedID 35177413

• Geographic Pattern of Typhoid Fever in India: A Model-Based Estimate of Cohort and Surveillance Data. The Journal of infectious diseases Cao, Y., Karthikeyan, A. S., Ramanujam, K., Raju, R., Krishna, S., Kumar, D., Ryckman, T., Mohan, V. R., Kang, G., John, J., Andrews, J. R., Lo, N. C. 2021; 224 (Supplement_5): S475-S483

  Abstract

  Typhoid fever remains a major public health problem in India. Recently, the Surveillance for Enteric Fever in India program completed a multisite surveillance study. However, data on subnational variation in typhoid fever are needed to guide the introduction of the new typhoid conjugate vaccine in India.We applied a geospatial statistical model to estimate typhoid fever incidence across India, using data from 4 cohort studies and 6 hybrid surveillance sites from October 2017 to March 2020. We collected geocoded data from the Demographic and Health Survey in India as predictors of typhoid fever incidence. We used a log linear regression model to predict a primary outcome of typhoid incidence.We estimated a national incidence of typhoid fever in India of 360 cases (95% confidence interval [CI], 297-494) per 100 000 person-years, with an annual estimate of 4.5 million cases (95% CI, 3.7-6.1 million) and 8930 deaths (95% CI, 7360-12 260), assuming a 0.2% case-fatality rate. We found substantial geographic variation of typhoid incidence across the country, with higher incidence in southwestern states and urban centers in the north.There is a large burden of typhoid fever in India with substantial heterogeneity across the country, with higher burden in urban centers.

  View details for DOI 10.1093/infdis/jiab187

  View details for PubMedID 35238365

• Addendum needed on COVID-19 travel study - Authors' reply. The Lancet. Infectious diseases Kiang, M. V., Chin, E. T., Huynh, B. Q., Chapman, L. A., Lo, N. C. 2021

  View details for DOI 10.1016/S1473-3099(21)00562-4

  View details for PubMedID 34536351

• Comparison of infection control strategies to reduce COVID-19 outbreaks in homeless shelters in the United States: a simulation study. BMC medicine Chapman, L. A., Kushel, M., Cox, S. N., Scarborough, A., Cawley, C., Nguyen, T. Q., Rodriguez-Barraquer, I., Greenhouse, B., Imbert, E., Lo, N. C. 2021; 19 (1): 116

  Abstract

  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.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.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.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.

  View details for DOI 10.1186/s12916-021-01965-y

  View details for PubMedID 33962621

  View details for PubMedCentralID PMC8103431

• Comparison of World Health Organization and Demographic and Health Surveys data to estimate sub-national deworming coverage in pre-school aged children. PLoS neglected tropical diseases Lo, N. C., Gupta, R., Addiss, D. G., Bendavid, E., Heft-Neal, S., Mikhailov, A., Montresor, A., Mbabazi, P. S. 2020; 14 (8): e0008551

  Abstract

  BACKGROUND: The key metric for monitoring the progress of deworming programs in controlling soil-transmitted helminthiasis (STH) is national drug coverage reported to the World Health Organization (WHO). There is increased interest in utilizing geographically-disaggregated data to estimate sub-national deworming coverage and equity, as well as gender parity. The Demographic and Health Surveys (DHS) offer a potential source of sub-national data. This study aimed to compare deworming coverage routinely reported to WHO and estimated by DHS in pre-school aged children to inform global STH measurement and evaluation.METHODOLOGY: We compared sub-national deworming coverage in pre-school aged children reported to WHO and estimated by DHS aligned geospatially and temporally. We included data from Burundi (2016-2017), Myanmar (2015-2016), and the Philippines (2017) based on data availability. WHO provided data on the date and sub-national coverage per mass drug administration reported by Ministries of Health. DHS included maternally-reported deworming status within the past 6 months for each child surveyed. We estimated differences in sub-national deworming coverage using WHO and DHS data, and performed sensitivity analyses.PRINCIPAL FINDINGS: We compared data on pre-school aged children from 13 of 18 districts in Burundi (N = 6,835 in DHS), 11 of 15 districts in Myanmar (N = 1,462 in DHS) and 16 of 17 districts in the Philippines (N = 7,594 in DHS) following data exclusion. The national deworming coverages estimated by DHS in Burundi, Myanmar, and the Philippines were 75.5% (95% CI: 73.7%-77.7%), 47.0% (95% CI: 42.7%-51.3%), and 48.0% (95% CI: 46.0%-50.0%), respectively. The national deworming coverages reported by WHO in Burundi, Myanmar, and the Philippines were 80.1%, 93.6% and 75.7%, respectively. The mean absolute differences in district-level coverage reported to WHO and estimated by DHS in Burundi, Myanmar, and the Philippines were 9.5%, 41.5%, and 24.6%, respectively. Across countries, coverage reported to WHO was frequently higher than DHS estimates (32 of 40 districts). National deworming coverage from DHS estimates were similar by gender within countries.CONCLUSIONS AND SIGNIFICANCE: Agreement of deworming coverage reported to WHO and estimated by DHS data was heterogeneous across countries, varying from broadly compatible in Burundi to largely discrepant in Myanmar. DHS data could complement deworming data reported to WHO to improve data monitoring practices and serve as an independent sub-national source of coverage data.

  View details for DOI 10.1371/journal.pntd.0008551

  View details for PubMedID 32804925

• Projected geographic disparities in healthcare worker absenteeism from COVID-19 school closures and the economic feasibility of child care subsidies: a simulation study. BMC medicine Chin, E. T., Huynh, B. Q., Lo, N. C., Hastie, T., Basu, S. 2020; 18 (1): 218

  Abstract

  BACKGROUND: School closures have been enacted as a measure of mitigation during the ongoing coronavirus disease 2019 (COVID-19) pandemic. It has been shown that school closures could cause absenteeism among healthcare workers with dependent children, but there remains a need for spatially granular analyses of the relationship between school closures and healthcare worker absenteeism to inform local community preparedness.METHODS: We provide national- and county-level simulations of school closures and unmet child care needs across the USA. We develop individual simulations using county-level demographic and occupational data, and model school closure effectiveness with age-structured compartmental models. We perform multivariate quasi-Poisson ecological regressions to find associations between unmet child care needs and COVID-19 vulnerability factors.RESULTS: At the national level, we estimate the projected rate of unmet child care needs for healthcare worker households to range from 7.4 to 8.7%, and the effectiveness of school closures as a 7.6% and 8.4% reduction in fewer hospital and intensive care unit (ICU) beds, respectively, at peak demand when varying across initial reproduction number estimates by state. At the county level, we find substantial variations of projected unmet child care needs and school closure effects, 9.5% (interquartile range (IQR) 8.2-10.9%) of healthcare worker households and 5.2% (IQR 4.1-6.5%) and 6.8% (IQR 4.8-8.8%) reduction in fewer hospital and ICU beds, respectively, at peak demand. We find significant positive associations between estimated levels of unmet child care needs and diabetes prevalence, county rurality, and race (p<0.05). We estimate costs of absenteeism and child care and observe from our models that an estimated 76.3 to 96.8% of counties would find it less expensive to provide child care to all healthcare workers with children than to bear the costs of healthcare worker absenteeism during school closures.CONCLUSIONS: School closures are projected to reduce peak ICU and hospital demand, but could disrupt healthcare systems through absenteeism, especially in counties that are already particularly vulnerable to COVID-19. Child care subsidies could help circumvent the ostensible trade-off between school closures and healthcare worker absenteeism.

  View details for DOI 10.1186/s12916-020-01692-w

  View details for PubMedID 32664927

• Application of Schistosomiasis Consortium for Operational Research and Evaluation Study Findings to Refine Predictive Modeling of Schistosoma mansoni and Schistosoma haematobium Control in Sub-Saharan Africa. The American journal of tropical medicine and hygiene King, C. H., Yoon, N., Wang, X., Lo, N. C., Alsallaq, R., Ndeffo-Mbah, M., Li, E., Gurarie, D. 2020; 103 (1_Suppl): 97-104

  Abstract

  An essential mission of the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) was to help inform global health practices related to the control and elimination of schistosomiasis. To provide more accurate, evidence-based projections of the most likely impact of different control interventions, whether implemented alone or in combination, SCORE supported mathematical modeling teams to provide simulations of community-level Schistosoma infection outcomes in the setting of real or hypothetical programs implementing multiyear mass drug administration (MDA) for parasite control. These models were calibrated using SCORE experience with Schistosoma mansoni and Schistosoma haematobium gaining and sustaining control studies, and with data from comparable programs that used community-based or school-based praziquantel MDA in other parts of sub-Saharan Africa. From 2010 to 2019, models were developed and refined, first to project the likely SCORE control outcomes, and later to more accurately reflect impact of MDA across different transmission settings, including the role of snail ecology and the impact of seasonal rainfall on snail abundance. Starting in 2014, SCORE modeling projections were also compared with the models of colleagues in the Neglected Tropical Diseases Modelling Consortium. To explore further possible improvement to program-based control, later simulations examined the cost-effectiveness of combining MDA with environmental snail control, and the utility of early impact assessment to more quickly identify persistent hot spots of transmission. This article provides a nontechnical summary of the 11 SCORE-related modeling projects and provides links to the original open-access articles describing model development and projections relevant to schistosomiasis control policy.

  View details for DOI 10.4269/ajtmh.19-0852

  View details for PubMedID 32400357

  View details for PubMedCentralID PMC7351296

• Scientific and ethical basis for social-distancing interventions against COVID-19. The Lancet. Infectious diseases Lewnard, J. A., Lo, N. C. 2020; 20 (6): 631-633

  View details for DOI 10.1016/S1473-3099(20)30190-0

  View details for PubMedID 32213329

  View details for PubMedCentralID PMC7118670

• The risk of tuberculosis in children after close exposure: a systematic review and individual-participant meta-analysis LANCET Martinez, L., Cords, O., Horsburgh, C., Andrews, J. R., Pediat TB Contact Studies 2020; 395 (10228): 973–84

  View details for Web of Science ID 000521744600028

• Neglected Tropical Diseases: Public Health Control Programs and Mass Drug Administration Hunter's Tropical Medicine and Emerging Infectious Diseases Lo, N. C., Hotez, P. J. 2020
• Improving public health control of schistosomiasis with a modified WHO strategy: a model-based comparison study. The Lancet. Global health Li, E. Y., Gurarie, D., Lo, N. C., Zhu, X., King, C. H. 2019; 7 (10): e1414-e1422

  Abstract

  Schistosomiasis is endemic in many low-income and middle-income countries. To reduce infection-associated morbidity, WHO has published guidelines for control of schistosomiasis based on targeted mass drug administration (MDA) and, in 2017, on supplemental snail control. We compared the current WHO guideline-based strategies from 2012 to an alternative, adaptive decision making framework for control in heterogeneous environments, to estimate their predicted relative effectiveness and time to achievement of defined public health goals.In this model-based comparison study, we adapted an established transmission model for Schistosoma infection that couples local human and snail populations and includes aspects of snail ecology and parasite biology. We calibrated the model using data from high-risk, moderate-risk, and lower-risk rural villages in Kenya, and then simulated control via MDA. We compared 2012 WHO guidelines with a modified adaptive strategy that tested a lower-prevalence threshold for MDA and shorter intervals between implementation, evaluation, and modification. We also explored the addition of snail control to this modified strategy. The primary outcomes were the proportion of simulations that achieved the WHO targets in children aged 5-14 years of less than 5% (2020 morbidity control goal) and less than 1% (2025 elimination as a public health problem goal) heavy infection and the mean duration of treatment required to achieve these goals.In high-risk communities (80% baseline prevalence), current WHO strategies for MDA were not predicted to achieve morbidity control (<5% prevalence of heavy infections) in 80% of simulations over a 10-year period, whereas the modified adaptive strategy was predicted to achieve this goal in over 50% of simulations within 5 years. In low-risk and moderate-risk communities, current WHO guidelines from 2012 were predicted to achieve morbidity control in most simulations (96% in low-risk and 41% for moderate-risk), although the proposed adaptive strategy reached this goal in a shorter period (mean reduction of 5 years). The model predicted that the addition of snail control to the proposed adaptive strategy would achieve morbidity control in all high-risk communities, and 54% of communities could reach the goal for elimination as a public health problem (<1% heavy infection) within 7 years.The modified adaptive decision making framework is predicted to be more effective than the current WHO guidelines in reaching 2025 public health goals, especially for high-prevalence regions. Modifications in current guidelines could reduce the time and resources needed for countries who are currently working on achieving public health goals against schistosomiasis.University of Georgia Research Foundation, The Bill & Melinda Gates Foundation, and the Medical Scientist Training Program at Stanford University School of Medicine.

  View details for DOI 10.1016/S2214-109X(19)30346-8

  View details for PubMedID 31537371

  View details for PubMedCentralID PMC7024988

• Paediatric tuberculosis transmission outside the household: challenging historical paradigms to inform future public health strategies LANCET RESPIRATORY MEDICINE Martinez, L., Lo, N. C., Cords, O., Hill, P. C., Khan, P., Hatherill, M., Mandalakas, A., Kay, A., Croda, J., Horsburgh, C., Zar, H. J., Andrews, J. R. 2019; 7 (6): 544–52

  View details for DOI 10.1016/S2213-2600(19)30137-7

  View details for Web of Science ID 000468488400022

• Clinical evaluation for morbidity associated with soil-transmitted helminth infection in school-age children on Pemba Island, Tanzania. PLoS neglected tropical diseases Bogoch, I. I., Speich, B. n., Lo, N. C., Moser, W. n., Croll, D. n., Ali, S. M., Ame, S. M., Utzinger, J. n., Andrews, J. R., Keiser, J. n. 2019; 13 (7): e0007581

  Abstract

  More than 1.5 billion people are infected with soil-transmitted helminths (Ascaris lumbricoides, hookworm, Strongyloides stercoralis, and Trichuris trichiura), causing an estimated global burden in excess of 3 million disability-adjusted life years. However, the relationship between soil-transmitted helminth infection, adverse health consequences, and beneficial effects of deworming are not well understood.We pursued a detailed longitudinal clinical evaluation of school-age children to evaluate morbidity associated with soil-transmitted helminth infection and responses to treatment. This exploratory study was embedded into a randomized controlled trial. Overall, 434 children, aged 7-14 years, underwent a detailed medical history, physical examination, stool microscopy for soil-transmitted helminths, and hemoglobin (Hb) measurement at baseline. Medical history and stool examination were repeated at 3 and 18 weeks posttreatment. Additionally, Hb measurement was performed at the 18-week treatment follow-up. Logistic regression was employed to assess clinical factors associated with soil-transmitted helminth infection at baseline, and longitudinal data analysis to examine change in health outcomes following treatment over time.All enrolled children were infected with T. trichiura, and randomized into four different treatment interventions. None of the medical history, physical examination, and laboratory (i.e., Hb) findings were associated with A. lumbricoides, hookworm, or S. stercoralis infection at baseline. A composite of physical exam findings for anemia, including pallor of the conjunctiva, nail beds, and palmar creases predicted lower Hb values (-3.8 g/dl, 95% confidence interval (CI): -6.9, -0.6 g/dl). When examining longitudinal trends, we did not find improvements to Hb or face Wong-Baker Likert scale among children with soil-transmitted helminth infection compared to those without infection, although there was a slight trend toward improving Hb values after treating hookworm infection.Our study demonstrates the challenges of measuring morbidity in the context of soil-transmitted helminth infection and treatment, thus confirming the mainly subtle morbidity effects of infection.

  View details for DOI 10.1371/journal.pntd.0007581

  View details for PubMedID 31306433

• Antibacterial mass drug administration for child mortality reduction: Opportunities, concerns, and possible next steps. PLoS neglected tropical diseases Bogoch, I. I., Utzinger, J. n., Lo, N. C., Andrews, J. R. 2019; 13 (5): e0007315

  View details for DOI 10.1371/journal.pntd.0007315

  View details for PubMedID 31120903

• Modulation of Antibody Responses to the V1V2 and V3 Regions of HIV-1 Envelope by Immune Complex Vaccines FRONTIERS IN IMMUNOLOGY Hioe, C. E., Kumar, R., Upadhyay, C., Jan, M., Fox, A., Itri, V., Peachman, K. K., Rao, M., Liu, L., Lo, N. C., Tuen, M., Jiang, X., Kong, X., Zolla-Pazner, S. 2018; 9

  View details for DOI 10.3389/fimmu.2018.02441

  View details for Web of Science ID 000448355300001

• Typhoid conjugate vaccines: a new tool in the fight against antimicrobial resistance. The Lancet. Infectious diseases Andrews, J. R., Baker, S., Marks, F., Alsan, M., Garrett, D., Gellin, B. G., Saha, S. K., Qamar, F. N., Yousafzai, M. T., Bogoch, I. I., Antillon, M., Pitzer, V. E., Kim, J., John, J., Gauld, J., Mogasale, V., Ryan, E. T., Luby, S. P., Lo, N. C. 2018

  Abstract

  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.

  View details for PubMedID 30170987

• Review of the 2017 WHO Guideline: Preventive chemotherapy to control soil-transmitted helminth infections in at-risk population groups. An opportunity lost in translation. PLoS neglected tropical diseases Savioli, L. n., Albonico, M. n., Daumerie, D. n., Lo, N. C., Stothard, J. R., Asaolu, S. n., Tchuem Tchuenté, L. A., Anderson, R. M. 2018; 12 (4): e0006296

  View details for PubMedID 29698486

  View details for PubMedCentralID PMC5919405

• Deworming in pre-school age children: A global empirical analysis of health outcomes. PLoS neglected tropical diseases Lo, N. C., Snyder, J. n., Addiss, D. G., Heft-Neal, S. n., Andrews, J. R., Bendavid, E. n. 2018; 12 (5): e0006500

  Abstract

  There is debate over the effectiveness of deworming children against soil-transmitted helminthiasis (STH) to improve health outcomes, and current evidence may be limited in study design and generalizability. However, programmatic deworming continues throughout low and middle-income countries.We performed an empirical evaluation of the relationship between deworming in pre-school age children (ages 1-4 years) within the previous 6 months, as proxy-reported by the mother, and health outcomes of weight, height, and hemoglobin. We used nationally representative cross-sectional data from 45 countries using the Demographic and Health Surveys (DHS) during the period 2005-2016. We used logistic regression with coarsened exact matching, fixed effects for survey and year, and person-level covariates. We included data on 325,115 children in 45 STH-endemic countries from 66 DHS surveys. Globally in STH-endemic countries, children who received deworming treatment were less likely to be stunted (1.2 percentage point decline from mean of 36%; 95% CI [-1.9, -0.5%]; p<0.001), but we did not detect consistent associations between deworming and anemia or weight. In sub-Saharan Africa, we found that children who received deworming treatment were less likely to be stunted (1.1 percentage point decline from mean of 36%; 95% CI [-2.1, -0.2%]; p = 0.01) and less likely to have anemia (1.8 percentage point decline from mean of 58%; 95% CI [-2.8, -0.7%]; p<0.001), but we did not detect consistent associations between deworming and weight. These findings were robust across multiple statistical models, and we did not find consistently measurable associations with data from non-endemic settings.Among pre-school age children, we detected a robust and consistent association between deworming and reduced stunting, with additional evidence for reduced anemia in sub-Saharan Africa. We did not find a consistent relationship between deworming and improved weight. This global empirical analysis provides evidence to support the deworming of pre-school age children.

  View details for PubMedID 29852012

• Invasive Pomacea snails as important intermediate hosts of Angiostrongylus cantonensis in Laos, Cambodia and Vietnam: implications for outbreaks of eosinophilic meningitis. Acta tropica Lv, S. n., Guo, Y. H., Nguyen, H. M., Sinuon, M. n., Sayasone, S. n., Lo, N. C., Zhou, X. N., Andrews, J. R. 2018

  Abstract

  The rat lungworm Angiostrongylus cantonensis causes human eosinophilic meningitis and it is endemic in Southeast Asia, but little is known about its distribution in Laos, Cambodia and Vietnam. We conducted a multi-country survey for A. cantonensis in these countries to estimate its prevalence in snails along the Mekong River and the east coast of Vietnam. We identified Angiostrongylus species by morphological and molecular analysis. We found A. cantonensis in the invasive snail, Pomacea spp. The wide accessibility of Pomacea snails, along with their infection by A. cantonensis, indicates that this snail species could be used in surveillance for preventing outbreaks of eosinophilic meningitis.

  View details for PubMedID 29574000

• The human-snail transmission environment shapes long term schistosomiasis control outcomes: Implications for improving the accuracy of predictive modeling. PLoS neglected tropical diseases Gurarie, D. n., Lo, N. C., Ndeffo-Mbah, M. L., Durham, D. P., King, C. H. 2018; 12 (5): e0006514

  Abstract

  Schistosomiasis is a chronic parasitic trematode disease that affects over 240 million people worldwide. The Schistosoma lifecycle is complex, involving transmission via specific intermediate-host freshwater snails. Predictive mathematical models of Schistosoma transmission have often chosen to simplify or ignore the details of environmental human-snail interaction in their analyses. Schistosome transmission models now aim to provide better precision for policy planning of elimination of transmission. This heightens the importance of including the environmental complexity of vector-pathogen interaction in order to make more accurate projections.We propose a nonlinear snail force of infection (FOI) that takes into account an intermediate larval stage (miracidium) and snail biology. We focused, in particular, on the effects of snail force of infection (FOI) on the impact of mass drug administration (MDA) in human communities. The proposed (modified) model was compared to a conventional model in terms of their predictions. A longitudinal dataset generated in Kenya field studies was used for model calibration and validation. For each sample community, we calibrated modified and conventional model systems, then used them to model outcomes for a range of MDA regimens. In most cases, the modified model predicted more vigorous post-MDA rebound, with faster relapse to baseline levels of infection. The effect was pronounced in higher risk communities. When compared to observed data, only the modified system was able to successfully predict persistent rebound of Schistosoma infection.The observed impact of varying location-specific snail inputs sheds light on the diverse MDA response patterns noted in operational research on schistosomiasis control, such as the recent SCORE project. Efficiency of human-to-snail transmission is likely to be much higher than predicted by standard models, which, in practice, will make local elimination by implementation of MDA alone highly unlikely, even over a multi-decade period.

  View details for PubMedID 29782500

• Mobile phone and handheld microscopes for public health applications. The Lancet. Public health Bogoch, I. I., Lundin, J., Lo, N. C., Andrews, J. R. 2017; 2 (8): e355

  View details for DOI 10.1016/S2468-2667(17)30120-2

  View details for PubMedID 29253476

• The Perils of Trumping Science in Global Health - The Mexico City Policy and Beyond. New England journal of medicine Lo, N. C., Barry, M. 2017

  View details for DOI 10.1056/NEJMp1701294

  View details for PubMedID 28225666

• Mobile-phone and handheld microscopy for neglected tropical diseases. PLoS neglected tropical diseases Rajchgot, J. n., Coulibaly, J. T., Keiser, J. n., Utzinger, J. n., Lo, N. C., Mondry, M. K., Andrews, J. R., Bogoch, I. I. 2017; 11 (7): e0005550

  View details for PubMedID 28683127

• Schistosoma haematobium Egg Excretion does not Increase after Exercise: Implications for Diagnostic Testing. The American journal of tropical medicine and hygiene Coulibaly, J. T., Andrews, J. R., Lo, N. C., N'Goran, E. K., Utzinger, J. n., Keiser, J. n., Bogoch, I. I. 2017

  Abstract

  Children are frequently invited to exercise before micturition, as it is believed that this will result in higher Schistosoma haematobium egg excretion, and hence, increases sensitivity of microscopic diagnoses. However, the evidence of this recommendation is scant. In the study presented here, 257 children, aged 2-15 years from south Côte d'Ivoire, provided urine samples for microscopy on consecutive days; one sample without prior exercise and one sample after exercise. Comparing the same individuals without and with prior exercise, sample positivity for S. haematobium (25.7% versus 23.0%, P = 0.31) and mean egg counts (10.2 eggs/10 mL versus 8.5 eggs/10 mL, P = 0.45) did not differ. Exercise before urine collection does not appear to increase S. haematobium egg excretion.

  View details for PubMedID 29260647

• Comparison of sensitivity and faecal egg counts of Mini-FLOTAC using fixed stool samples and Kato-Katz technique for the diagnosis of Schistosoma mansoni and soil-transmitted helminths ACTA TROPICA Coulibaly, J. T., Ouattara, M., Becker, S. L., Lo, N. C., Keiser, J., N'Goran, E. K., Ianniellog, D., Rinaldi, L., Cringoli, G., Utzinger, J. 2016; 164: 107-116

  Abstract

  Accurate diagnostic tools for human helminthiasis are crucial for epidemiological surveys, improved patient management, and evaluation of community-based intervention studies. However, the diagnosis of intestinal schistosomiasis and soil-transmitted helminthiasis heavily relies on stool microscopy using the Kato-Katz technique, which has a low sensitivity. The Mini-FLOTAC method is an alternative microscopy-based technique, but its diagnostic performance using sodium acetate-acetic acid-formalin-(SAF)-fixed stool specimens has not been validated. The fixation of stool samples for later examination in a laboratory may reduce logistical and financial barriers of prevalence surveys by not requiring field laboratories. We compared the diagnostic accuracy of the Kato-Katz technique using fresh stool samples with the Mini-FLOTAC technique, employing matched stool samples that were fixed in SAF. Three consecutive stool samples from 149 school-aged children in Côte d'Ivoire were subjected to quintuplicate Kato-Katz thick smears examined on the same day. From the remaining stool, approximately 2g was fixed in 10ml of SAF for about 3 months, and then subjected to the Mini-FLOTAC method, using two flotation solutions (FS2 and FS7). The combined results of multiple Kato-Katz and Mini-FLOTAC readings revealed prevalences of Schistosoma mansoni, Trichuris trichiura and hookworm of 99.3%, 72.5% and 7.4%, respectively. Employing a Bayesian latent class analysis to estimate the true sensitivity of the diagnostic approaches, the sensitivity of Mini-FLOTAC using FS2 was 50.1% (95% Bayesian credible interval (BCI): 30.9-70.2%) for hookworm and 68.0% (95% BCI: 34.9-93.5%) for T. trichiura. When applying Mini-FLOTAC using FS7, the sensitivity was 89.9% (95% BCI: 86.9-97.4%) for S. mansoni, 37.2% (95% BCI: 17.2-60.6%) for hookworm and 67.7% (95% BCI: 33.0-93.0%) for T. trichiura. The specificity ranged from 80.1-95.0% in all Mini-FLOTAC tests. Mini-FLOTAC revealed higher arithmetic mean faecal egg counts (FECs) than the Kato-Katz technique. We found a significant correlation in FECs between Kato-Katz and Mini-FLOTAC for S. mansoni and T. trichiura. We conclude that Mini-FLOTAC shows reasonable diagnostic accuracy when using stool samples fixed in SAF for 3 months, and may be an alternative to multiple Kato-Katz thick smears.

  View details for DOI 10.1016/j.actatropica.2016.08.024

  View details for Web of Science ID 000389087700017

• Evaluation of a Urine Pooling Strategy for the Rapid and Cost-Efficient Prevalence Classification of Schistosomiasis. PLoS neglected tropical diseases Lo, N. C., Coulibaly, J. T., Bendavid, E., N'Goran, E. K., Utzinger, J., Keiser, J., Bogoch, I. I., Andrews, J. R. 2016; 10 (8)

  Abstract

  A key epidemiologic feature of schistosomiasis is its focal distribution, which has important implications for the spatial targeting of preventive chemotherapy programs. We evaluated the diagnostic accuracy of a urine pooling strategy using a point-of-care circulating cathodic antigen (POC-CCA) cassette test for detection of Schistosoma mansoni, and employed simulation modeling to test the classification accuracy and efficiency of this strategy in determining where preventive chemotherapy is needed in low-endemicity settings.We performed a cross-sectional study involving 114 children aged 6-15 years in six neighborhoods in Azaguié Ahoua, south Côte d'Ivoire to characterize the sensitivity and specificity of the POC-CCA cassette test with urine samples that were tested individually and in pools of 4, 8, and 12. We used a Bayesian latent class model to estimate test characteristics for individual POC-CCA and quadruplicate Kato-Katz thick smears on stool samples. We then developed a microsimulation model and used lot quality assurance sampling to test the performance, number of tests, and total cost per school for each pooled testing strategy to predict the binary need for school-based preventive chemotherapy using a 10% prevalence threshold for treatment.The sensitivity of the urine pooling strategy for S. mansoni diagnosis using pool sizes of 4, 8, and 12 was 85.9%, 79.5%, and 65.4%, respectively, when POC-CCA trace results were considered positive, and 61.5%, 47.4%, and 30.8% when POC-CCA trace results were considered negative. The modeled specificity ranged from 94.0-97.7% for the urine pooling strategies (when POC-CCA trace results were considered negative). The urine pooling strategy, regardless of the pool size, gave comparable and often superior classification performance to stool microscopy for the same number of tests. The urine pooling strategy with a pool size of 4 reduced the number of tests and total cost compared to classical stool microscopy.This study introduces a method for rapid and efficient S. mansoni prevalence estimation through examining pooled urine samples with POC-CCA as an alternative to widely used stool microscopy.

  View details for DOI 10.1371/journal.pntd.0004894

  View details for PubMedID 27504954

  View details for PubMedCentralID PMC4978437

• Improving helminth treatment access: costs and opportunities. The Lancet. Infectious diseases Lo, N. C., Andrews, J. R., Bogoch, I. I. 2016; 16 (7): 762-4

  View details for DOI 10.1016/S1473-3099(16)30049-4

  View details for PubMedID 27352742

• Cost-effectiveness of community-wide treatment for helminthiasis--Authors' reply. The Lancet. Global health Lo, N. C., Bogoch, I. I., Utzinger, J., Andrews, J. R. 2016; 4 (3): e157-8

  View details for DOI 10.1016/S2214-109X(15)00278-8

  View details for PubMedID 26848087

• Strategies for last mile implementation of global health technologies. The Lancet. Global health Chao, T. E., Lo, N. C., Mody, G. N., Sinha, S. R. 2014; 2 (9): e497-8

  View details for DOI 10.1016/S2214-109X(14)70253-0

  View details for PubMedID 25304406

• Interaction of Shiga Toxin with the A-domains and Multimers of von Willebrand Factor JOURNAL OF BIOLOGICAL CHEMISTRY Lo, N. C., Turner, N. A., Cruz, M. A., Moake, J. 2013; 288 (46): 33118-33123

  Abstract

  Shiga toxin (Stx) produced by enterohemorrhagic Escherichia coli causes diarrhea-associated hemolytic-uremic syndrome (DHUS), a severe renal thrombotic microangiopathy. We investigated the interaction between Stx and von Willebrand Factor (VWF), a multimeric plasma glycoprotein that mediates platelet adhesion, activation, and aggregation. Stx bound to ultra-large VWF (ULVWF) secreted from and anchored to stimulated human umbilical vein endothelial cells, as well as to immobilized VWF-rich human umbilical vein endothelial cell supernatant. This Stx binding was localized to the A1 and A2 domain of VWF monomeric subunits and reduced the rate of ADAMTS-13-mediated cleavage of the Tyr(1605)-Met(1606) peptide bond in the A2 domain. Stx-VWF interaction and the associated delay in ADAMTS-13-mediated cleavage of VWF may contribute to the pathophysiology of DHUS.

  View details for DOI 10.1074/jbc.M113.487413

  View details for Web of Science ID 000328841700027

  View details for PubMedID 24097977

  View details for PubMedCentralID PMC3829160

• The Aging of Biomedical Research in the United States PLOS ONE Matthews, K. R., Calhoun, K. M., Lo, N., Ho, V. 2011; 6 (12)

  Abstract

  In the past 30 years, the average age of biomedical researchers has steadily increased. The average age of an investigator at the National Institutes of Health (NIH) rose from 39 to 51 between 1980 and 2008. The aging of the biomedical workforce was even more apparent when looking at first-time NIH grantees. The average age of a new investigator was 42 in 2008, compared to 36 in 1980. To determine if the rising barriers at NIH for entry in biomedical research might impact innovative ideas and research, we analyzed the research and publications of Nobel Prize winners from 1980 to 2010 to assess the age at which their pioneering research occurred. We established that in the 30-year period, 96 scientists won the Nobel Prize in medicine or chemistry for work related to biomedicine, and that their groundbreaking research was conducted at an average age of 41-one year younger than the average age of a new investigator at NIH. Furthermore, 78% of the Nobel Prize winners conducted their research before the age of 51, the average age of an NIH principal investigator. This suggested that limited access to NIH might inhibit research potential and novel projects, and could impact biomedicine and the next generation scientists in the United States.

  View details for DOI 10.1371/journal.pone.0029738

  View details for Web of Science ID 000300676300082

  View details for PubMedID 22216352

  View details for PubMedCentralID PMC3247288