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1. El Niño Southern Oscillation, monsoon anomaly, and childhood diarrheal disease morbidity in Nepal

   https://doi.org/10.1093/pnasnexus/pgac032  

   Adams, Nicholas ; Dhimal, Meghnath ; Mathews, Shifali ; Iyer, Veena ; Murtugudde, Raghu ; Liang, Xin-Zhong ; Haider, Muhiuddin ; Cruz-Cano, Raul ; Thu, Dang Thi Anh ; Hashim, Jamal Hisham ; et al ( March 2022 , PNAS Nexus)

   Climate change is adversely impacting the burden of diarrheal diseases. Despite significant reduction in global prevalence, diarrheal disease remains a leading cause of morbidity and mortality among young children in low- and middle-income countries. Previous studies have shown that diarrheal disease is associated with meteorological conditions but the role of large-scale climate phenomena such as El Niño-Southern Oscillation (ENSO) and monsoon anomaly is less understood. We obtained 13 years (2002–2014) of diarrheal disease data from Nepal and investigated how the disease rate is associated with phases of ENSO (El Niño, La Niña, vs. ENSO neutral) monsoon rainfall anomaly (below normal, above normal, vs. normal), and changes in timing of monsoon onset, and withdrawal (early, late, vs. normal). Monsoon season was associated with a 21% increase in diarrheal disease rates (Incident Rate Ratios [IRR]: 1.21; 95% CI: 1.16–1.27). El Niño was associated with an 8% reduction in risk while the La Niña was associated with a 32% increase in under-5 diarrheal disease rates. Likewise, higher-than-normal monsoon rainfall was associated with increased rates of diarrheal disease, with considerably higher rates observed in the mountain region (IRR 1.51, 95% CI: 1.19–1.92). Our findings suggest that under-5 diarrheal disease burden in Nepal ismore »significantly influenced by ENSO and changes in seasonal monsoon dynamics. Since both ENSO phases and monsoon can be predicted with considerably longer lead time compared to weather, our findings will pave the way for the development of more effective early warning systems for climate sensitive infectious diseases.

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2. Antibiotics and fecundability among female pregnancy planners: a prospective cohort study

   https://doi.org/10.1093/humrep/deab173  

   Crowe, Holly Michelle ; Wesselink, Amelia Kent ; Wise, Lauren Anne ; Wang, Tanran R ; Horsburgh, Charles Robert ; Mikkelsen, Ellen Margrethe ; Hatch, Elizabeth Elliott ( July 2021 , Human Reproduction)

   Abstract STUDY QUESTION To what extent is female preconception antibiotic use associated with fecundability? SUMMARY ANSWER Preconception antibiotic use overall was not appreciably associated with fecundability. WHAT IS KNOWN ALREADY Antibiotics are commonly used by women and are generally thought to be safe for use during pregnancy. However, little is known about possible effects of antibiotic use on fecundability, the per-cycle probability of conception. Previous research on this question has been limited to occupational rather than therapeutic exposure. STUDY DESIGN, SIZE, DURATION We analyzed data from an Internet-based preconception cohort study of 9524 female pregnancy planners aged 21–45 years residing in the USA and Canada who had been attempting to conceive for six or fewer cycles at study entry. Participants enrolled between June 2013 and September 2020 and completed baseline and bimonthly follow-up questionnaires for up to 12 months or until a reported pregnancy, whichever came first. The questions pertaining to antibiotic type and indication were added to the PRESTO questionnaires in March 2016. PARTICIPANTS/MATERIALS, SETTING, METHODS We assessed antibiotic use in the previous 4 weeks at baseline and on each follow-up questionnaire. Participants provided the name of the specific antibiotic and the indication for use. Antibiotics were classified based on active ingredientmore »(penicillins, macrolides, nitrofurantoin, nitroimidazole, cephalosporins, sulfonamides, quinolones, tetracyclines, lincosamides), and indications were classified by type of infection (respiratory, urinary tract, skin, vaginal, pelvic, and surgical). Participants reported pregnancy status on follow-up questionnaires. We used proportional probabilities regression to estimate fecundability ratios (FR), the per-cycle probability of conception comparing exposed with unexposed individuals, and 95% confidence intervals (CI), adjusting for sociodemographics, lifestyle factors, and reproductive history. MAIN RESULTS AND THE ROLE OF CHANCE Overall, women who used antibiotics in the past 4 weeks at baseline had similar fecundability to those who had not used antibiotics (FR: 0.98, 95% CI: 0.89–1.07). Sulfonamides and lincosamides were associated with slightly increased fecundability (FR: 1.39, 95% CI: 0.90–2.15, and FR: 1.58 95% CI: 0.96–2.60, respectively), while macrolides were associated with slightly reduced fecundability (FR: 0.70, 95% CI: 0.47–1.04). Analyses of the indication for antibiotic use suggest that there is likely some confounding by indication. LIMITATIONS, REASONS FOR CAUTION Findings were imprecise for some antibiotic classes and indications for use owing to small numbers of antibiotic users in these categories. There are likely heterogeneous effects of different combinations of indications and treatments, which may be obscured in the overall null results, but cannot be further elucidated in this analysis. WIDER IMPLICATIONS OF THE FINDINGS There is little evidence that use of most antibiotics is associated with reduced fecundability. Antibiotics and the infections they treat are likely associated with fecundability through differing mechanisms, resulting in their association with increased fecundability in some circumstances and decreased fecundability in others. STUDY FUNDING/COMPETING INTEREST(S) This study was supported through funds provided by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (R01-HD086742, R21-HD072326). L.A.W. has received in-kind donations from Swiss Precision Diagnostics, Sandstone Diagnostics, Fertility Friend, and Kindara for primary data collection in PRESTO. The other authors have no conflicts of interest to disclose. TRIAL REGISTRATION NUMBER N/A.« less
3. Epidemiology of the silent polio outbreak in Rahat, Israel, based on modeling of environmental surveillance data

   https://doi.org/10.1073/pnas.1808798115  

   Brouwer, Andrew F. ; Eisenberg, Joseph N. S. ; Pomeroy, Connor D. ; Shulman, Lester M. ; Hindiyeh, Musa ; Manor, Yossi ; Grotto, Itamar ; Koopman, James S. ; Eisenberg, Marisa C. ( October 2018 , Proceedings of the National Academy of Sciences)

   Israel experienced an outbreak of wild poliovirus type 1 (WPV1) in 2013–2014, detected through environmental surveillance of the sewage system. No cases of acute flaccid paralysis were reported, and the epidemic subsided after a bivalent oral polio vaccination (bOPV) campaign. As we approach global eradication, polio will increasingly be detected only through environmental surveillance. We developed a framework to convert quantitative polymerase chain reaction (qPCR) cycle threshold data into scaled WPV1 and OPV1 concentrations for inference within a deterministic, compartmental infectious disease transmission model. We used this approach to estimate the epidemic curve and transmission dynamics, as well as assess alternate vaccination scenarios. Our analysis estimates the outbreak peaked in late June, much earlier than previous estimates derived from analysis of stool samples, although the exact epidemic trajectory remains uncertain. We estimate the basic reproduction number was 1.62 (95% CI 1.04–2.02). Model estimates indicate that 59% (95% CI 9–77%) of susceptible individuals (primarily children under 10 years old) were infected with WPV1 over a little more than six months, mostly before the vaccination campaign onset, and that the vaccination campaign averted 10% (95% CI 1–24%) of WPV1 infections. As we approach global polio eradication, environmental monitoring with qPCR can bemore »used as a highly sensitive method to enhance disease surveillance. Our analytic approach brings public health relevance to environmental data that, if systematically collected, can guide eradication efforts.

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4. Repeat bleaching of a central Pacific coral reef over the past six decades (1960–2016)

   https://doi.org/10.1038/s42003-018-0183-7  

   Barkley, Hannah C. ; Cohen, Anne L. ; Mollica, Nathaniel R. ; Brainard, Russell E. ; Rivera, Hanny E. ; DeCarlo, Thomas M. ; Lohmann, George P. ; Drenkard, Elizabeth J. ; Alpert, Alice E. ; Young, Charles W. ; et al ( November 2018 , Communications Biology)

   The oceans are warming and coral reefs are bleaching with increased frequency and severity, fueling concerns for their survival through this century. Yet in the central equatorial Pacific, some of the world’s most productive reefs regularly experience extreme heat associated with El Niño. Here we use skeletal signatures preserved in long-lived corals on Jarvis Island to evaluate the coral community response to multiple successive heatwaves since 1960. By tracking skeletal stress band formation through the 2015-16 El Nino, which killed 95% of Jarvis corals, we validate their utility as proxies of bleaching severity and show that 2015-16 was not the first catastrophic bleaching event on Jarvis. Since 1960, eight severe (>30% bleaching) and two moderate (<30% bleaching) events occurred, each coinciding with El Niño. While the frequency and severity of bleaching on Jarvis did not increase over this time period, 2015–16 was unprecedented in magnitude. The trajectory of recovery of this historically resilient ecosystem will provide critical insights into the potential for coral reef resilience in a warming world.
5. Modeling and Cost Benefit Analysis to Guide Deployment of POC Diagnostics for Non-typhoidal Salmonella Infections with Antimicrobial Resistance

   https://doi.org/10.1038/s41598-019-47359-2  

   Manore, Carrie ; Graham, Todd ; Carr, Alexa ; Feryn, Alicia ; Jakhar, Shailja ; Mukundan, Harshini ; Highlander, Hannah Callender ( August 2019 , Scientific Reports)

   Invasive non-typhoidalSalmonella(NTS) is among the leading causes of blood stream infections in sub-Saharan Africa and other developing regions, especially among pediatric populations. Invasive NTS can be difficult to treat and have high case-fatality rates, in part due to emergence of strains resistant to broad-spectrum antibiotics. Furthermore, improper treatment contributes to increased antibiotic resistance and death. Point of care (POC) diagnostic tests that rapidly identify invasive NTS infection, and differentiate between resistant and non-resistant strains, may greatly improve patient outcomes and decrease resistance at the community level. Here we present for the first time a model for NTS dynamics in high risk populations that can analyze the potential advantages and disadvantages of four strategies involving POC diagnostic deployment, and the resulting impact on antimicrobial treatment for patients. Our analysis strongly supports the use of POC diagnostics coupled with targeted antibiotic use for patients upon arrival in the clinic for optimal patient and public health outcomes. We show that even the use of imperfect POC diagnostics can significantly reduce total costs and number of deaths, provided that the diagnostic gives results quickly enough that patients are likely to return or stay to receive targeted treatment.