ResearchPad - epidemiology-and-global-health https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Local emergence in Amazonia of <i>Plasmodium falciparum k13</i> C580Y mutants associated with <i>in vitro</i> artemisinin resistance]]> https://www.researchpad.co/article/elastic_article_7263 All recommended treatments against malaria include a drug called artemisinin or some of its derivatives. However, there are concerns that Plasmodium falciparum, the parasite that causes most cases of malaria, will eventually develop widespread resistance to the drug. A strain of P. falciparum partially resistant to artemisinin was seen in Cambodia in 2008, and it has since spread across Southeast Asia. The resistance appears to be frequently linked to a mutation known as pfk13 C580Y.

Southeast Asia and Amazonia are considered to be hotspots for antimalarial drug resistance, and the pfk13 C580Y mutation was detected in the South American country of Guyana in 2010. To examine whether the mutation was still circulating in this part of the world, Mathieu et al. collected and analyzed 854 samples across Guyana between 2016 and 2017. Overall, 1.6% of the samples had the pfk13 C580Y mutation, but this number was as high as 8.8% in one region. Further analyses revealed that the mutation in Guyana had not spread from Southeast Asia, but that it had occurred in Amazonia independently.

To better understand the impact of the pfk13 C580Y mutation, Mathieu et al. introduced this genetic change into non-resistant parasites from a country neighbouring Guyana. As expected, the mutation made P. falciparum highly resistant to artemisinin, but it also slowed the growth rate of the parasite. This disadvantage may explain why the mutation has not spread more rapidly through Guyana in recent years.

Artemisinin and its derivatives are always associated with other antimalarial drugs to slow the development of resistance; there are concerns that reduced susceptibility to artemisinin leads to the parasites becoming resistant to the partner drugs. Further research is needed to evaluate how the pfk13 C580Y mutation affects the parasite’s response to the typical combination of drugs that are given to patients.

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<![CDATA[Quantifying antibiotic impact on within-patient dynamics of extended-spectrum beta-lactamase resistance]]> https://www.researchpad.co/article/N7ecc8fa1-20b8-4271-9018-7ac9004c16bc Bacteria that are resistant to antibiotics are a growing global health crisis. One type of antibiotic resistance arises when certain bacteria that can produce enzymes called extended-spectrum beta-lactamases (or ESBLs for short) become more common in the gut. These enzymes stop important antibiotics, like penicillin, from working. However, exactly which antibiotics and treatment durations contribute to the emergence of this antibiotic resistance remain unknown.

Now, Niehus et al. find certain antibiotics that are associated with an increase in the number of gut bacteria carrying antibiotic resistance genes for ESBL enzymes. First, rectal swabs collected from 133 patients from three European hospitals were analysed to measure the total gut bacteria and the number of genes for ESBL enzymes. These samples had been collected at several time points including when the patient was first admitted to hospital, then every two to three days during their stay, and finally when they were discharged.

Combining the analysis of the samples with details of the patients’ charts showed that treatment with two antibiotics: cefuroxime and ceftriaxone, was linked to an increase in ESBL genes in the gut bacteria. Other antibiotics – namely, meropenem, piperacillin-tazobactam and oral ciprofloxacin – were associated with a decrease in the number of bacteria with ESBL genes. Niehus et al. then performed further analysis to see if different treatment regimens affected how long patients were carrying gut bacteria with ESBL genes. This predicted that a longer course of meropenem, 14 days rather than 5 days, would shorten the length of time patients carried ESBL-resistant bacteria in their guts by 70%, although this effect will likely depend on the location of the hospital and the local prevalence of other types of antibiotic resistance.

This analysis reveals new details about how antibiotic treatment can affect ESBL resistance genes. More studies are needed to understand how antibiotics affect other antibiotic resistance genes and how resistant bacteria spread. This will help scientists understand how much specific antibiotic regimens contribute to antibiotic resistance. It may also help scientists develop new antibiotic treatment strategies that reduce antibiotic resistance.

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<![CDATA[Impact of community piped water coverage on re-infection with urogenital schistosomiasis in rural South Africa]]> https://www.researchpad.co/article/Na9993ddb-20e8-4c4c-b531-5728d4ec080d

Previously, we demonstrated that coverage of piped water in the seven years preceding a parasitological survey was strongly predictive of Schistosomiasis haematobium infection in a nested cohort of 1976 primary school children (Tanser, 2018). Here, we report on the prospective follow up of infected members of this nested cohort (N = 333) for two successive rounds following treatment. Using a negative binomial regression fitted to egg count data, we found that every percentage point increase in piped water coverage was associated with 4.4% decline in intensity of re-infection (incidence rate ratio = 0.96, 95% CI: 0.93–0.98, p=0.004) among the treated children. We therefore provide further compelling evidence in support of the scaleup of piped water as an effective control strategy against Schistosoma haematobium transmission.

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<![CDATA[The hazards of smoking and the benefits of cessation: a critical summation of the epidemiological evidence in high-income countries]]> https://www.researchpad.co/article/N15a46ae5-d451-44b5-a4b2-f5f1b038b884

In high-income countries, the biggest cause of premature death, defined as death before 70 years, is smoking of manufactured cigarettes. Smoking-related disease was responsible for about 41 million deaths in the United States, United Kingdom and Canada, cumulatively, from 1960 to 2020. Every million cigarettes smoked leads to one death in the US and Canada, but slightly more than one death in the UK. The 21st century hazards reveal that smokers who start smoking early in adult life and do not quit lose a decade of life expectancy versus non-smokers. Cessation, particularly before age 40 years, yields large reductions in mortality risk. Up to two-thirds of deaths among smokers are avoidable at non-smoking death rates, and former smokers have about only a quarter of the excess risk of death compared to current smokers. The gap between scientific and popular understanding of smoking hazards is surprisingly large.

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<![CDATA[Estimated effectiveness of symptom and risk screening to prevent the spread of COVID-19]]> https://www.researchpad.co/article/Nd9a70b08-55d1-4b16-8192-d6313d99d300

Traveller screening is being used to limit further spread of COVID-19 following its recent emergence, and symptom screening has become a ubiquitous tool in the global response. Previously, we developed a mathematical model to understand factors governing the effectiveness of traveller screening to prevent spread of emerging pathogens (Gostic et al., 2015). Here, we estimate the impact of different screening programs given current knowledge of key COVID-19 life history and epidemiological parameters. Even under best-case assumptions, we estimate that screening will miss more than half of infected people. Breaking down the factors leading to screening successes and failures, we find that most cases missed by screening are fundamentally undetectable, because they have not yet developed symptoms and are unaware they were exposed. Our work underscores the need for measures to limit transmission by individuals who become ill after being missed by a screening program. These findings can support evidence-based policy to combat the spread of COVID-19, and prospective planning to mitigate future emerging pathogens.

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<![CDATA[Zika seroprevalence declines and neutralizing antibodies wane in adults following outbreaks in French Polynesia and Fiji]]> https://www.researchpad.co/article/Nfa69b771-086e-4b27-9c50-be01056a8592

It has been commonly assumed that Zika virus (ZIKV) infection confers long-term protection against reinfection, preventing ZIKV from re-emerging in previously affected areas for several years. However, the long-term immune response to ZIKV following an outbreak remains poorly documented. We compared results from eight serological surveys before and after known ZIKV outbreaks in French Polynesia and Fiji, including cross-sectional and longitudinal studies. We found evidence of a decline in seroprevalence in both countries over a two-year period following first reported ZIKV transmission. This decline was concentrated in adults, while high seroprevalence persisted in children. In the Fiji cohort, there was also a significant decline in neutralizing antibody titres against ZIKV, but not against dengue viruses that circulated during the same period.

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<![CDATA[A meta-analysis of threats to valid clinical inference in preclinical research of sunitinib]]> https://www.researchpad.co/article/5989dac5ab0ee8fa60bb2020

Poor study methodology leads to biased measurement of treatment effects in preclinical research. We used available sunitinib preclinical studies to evaluate relationships between study design and experimental tumor volume effect sizes. We identified published animal efficacy experiments where sunitinib monotherapy was tested for effects on tumor volume. Effect sizes were extracted alongside experimental design elements addressing threats to valid clinical inference. Reported use of practices to address internal validity threats was limited, with no experiments using blinded outcome assessment. Most malignancies were tested in one model only, raising concerns about external validity. We calculate a 45% overestimate of effect size across all malignancies due to potential publication bias. Pooled effect sizes for specific malignancies did not show apparent relationships with effect sizes in clinical trials, and we were unable to detect dose–response relationships. Design and reporting standards represent an opportunity for improving clinical inference.

DOI: http://dx.doi.org/10.7554/eLife.08351.001

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<![CDATA[Epidemiology and burden of multidrug-resistant bacterial infection in a developing country]]> https://www.researchpad.co/article/5989db07ab0ee8fa60bc8efb

Little is known about the excess mortality caused by multidrug-resistant (MDR) bacterial infection in low- and middle-income countries (LMICs). We retrospectively obtained microbiology laboratory and hospital databases of nine public hospitals in northeast Thailand from 2004 to 2010, and linked these with the national death registry to obtain the 30-day mortality outcome. The 30-day mortality in those with MDR community-acquired bacteraemia, healthcare-associated bacteraemia, and hospital-acquired bacteraemia were 35% (549/1555), 49% (247/500), and 53% (640/1198), respectively. We estimate that 19,122 of 45,209 (43%) deaths in patients with hospital-acquired infection due to MDR bacteria in Thailand in 2010 represented excess mortality caused by MDR. We demonstrate that national statistics on the epidemiology and burden of MDR in LMICs could be improved by integrating information from readily available databases. The prevalence and mortality attributable to MDR in Thailand are high. This is likely to reflect the situation in other LMICs.

DOI: http://dx.doi.org/10.7554/eLife.18082.001

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<![CDATA[Resistome diversity in cattle and the environment decreases during beef production]]> https://www.researchpad.co/article/5989db03ab0ee8fa60bc7443

Antimicrobial resistant determinants (ARDs) can be transmitted from livestock systems through meat products or environmental effluents. The public health risk posed by these two routes is not well understood, particularly in non-pathogenic bacteria. We collected pooled samples from 8 groups of 1741 commercial cattle as they moved through the process of beef production from feedlot entry through slaughter. We recorded antimicrobial drug exposures and interrogated the resistome at points in production when management procedures could potentially influence ARD abundance and/or transmission. Over 300 unique ARDs were identified. Resistome diversity decreased while cattle were in the feedlot, indicating selective pressure. ARDs were not identified in beef products, suggesting that slaughter interventions may reduce the risk of transmission of ARDs to beef consumers. This report highlights the utility and limitations of metagenomics for assessing public health risks regarding antimicrobial resistance, and demonstrates that environmental pathways may represent a greater risk than the food supply.

DOI: http://dx.doi.org/10.7554/eLife.13195.001

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<![CDATA[The effects of a deleterious mutation load on patterns of influenza A/H3N2's antigenic evolution in humans]]> https://www.researchpad.co/article/5989dacfab0ee8fa60bb5759

Recent phylogenetic analyses indicate that RNA virus populations carry a significant deleterious mutation load. This mutation load has the potential to shape patterns of adaptive evolution via genetic linkage to beneficial mutations. Here, we examine the effect of deleterious mutations on patterns of influenza A subtype H3N2's antigenic evolution in humans. By first analyzing simple models of influenza that incorporate a mutation load, we show that deleterious mutations, as expected, act to slow the virus's rate of antigenic evolution, while making it more punctuated in nature. These models further predict three distinct molecular pathways by which antigenic cluster transitions occur, and we find phylogenetic patterns consistent with each of these pathways in influenza virus sequences. Simulations of a more complex phylodynamic model further indicate that antigenic mutations act in concert with deleterious mutations to reproduce influenza's spindly hemagglutinin phylogeny, co-circulation of antigenic variants, and high annual attack rates.

DOI: http://dx.doi.org/10.7554/eLife.07361.001

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<![CDATA[Skin deep]]> https://www.researchpad.co/article/5989dacbab0ee8fa60bb4204

Trypanosome parasites are hiding in human skin, a discovery that may undermine efforts to eliminate sleeping sickness by 2020.

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<![CDATA[What makes an eLife paper in epidemiology and global health?]]> https://www.researchpad.co/article/5989dab7ab0ee8fa60bad54d

The best papers provide evidence that can be used to make changes that improve the health and lives of people around the world.

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<![CDATA[Ebola virus disease in the Democratic Republic of the Congo, 1976-2014]]> https://www.researchpad.co/article/5989da20ab0ee8fa60b7e92d

The Democratic Republic of the Congo has experienced the most outbreaks of Ebola virus disease since the virus' discovery in 1976. This article provides for the first time a description and a line list for all outbreaks in this country, comprising 996 cases. Compared to patients over 15 years old, the odds of dying were significantly lower in patients aged 5 to 15 and higher in children under five (with 100% mortality in those under 2 years old). The odds of dying increased by 11% per day that a patient was not hospitalised. Outbreaks with an initially high reproduction number, R (>3), were rapidly brought under control, whilst outbreaks with a lower initial R caused longer and generally larger outbreaks. These findings can inform the choice of target age groups for interventions and highlight the importance of both reducing the delay between symptom onset and hospitalisation and rapid national and international response.

DOI: http://dx.doi.org/10.7554/eLife.09015.001

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<![CDATA[Fighting an old disease with next-generation sequencing]]> https://www.researchpad.co/article/5989daa8ab0ee8fa60ba8269

Whole genome sequencing has revealed that most cases of tuberculosis in a high-incidence setting in Malawi were caused by just one lineage of the bacterium responsible for the disease.

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<![CDATA[Species-wide whole genome sequencing reveals historical global spread and recent local persistence in Shigella flexneri]]> https://www.researchpad.co/article/5989d9efab0ee8fa60b6dd98

Shigella flexneri is the most common cause of bacterial dysentery in low-income countries. Despite this, S. flexneri remains largely unexplored from a genomic standpoint and is still described using a vocabulary based on serotyping reactions developed over half-a-century ago. Here we combine whole genome sequencing with geographical and temporal data to examine the natural history of the species. Our analysis subdivides S. flexneri into seven phylogenetic groups (PGs); each containing two-or-more serotypes and characterised by distinct virulence gene complement and geographic range. Within the S. flexneri PGs we identify geographically restricted sub-lineages that appear to have persistently colonised regions for many decades to over 100 years. Although we found abundant evidence of antimicrobial resistance (AMR) determinant acquisition, our dataset shows no evidence of subsequent intercontinental spread of antimicrobial resistant strains. The pattern of colonisation and AMR gene acquisition suggest that S. flexneri has a distinct life-cycle involving local persistence.

DOI: http://dx.doi.org/10.7554/eLife.07335.001

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<![CDATA[Mycobacterium ulcerans dynamics in aquatic ecosystems are driven by a complex interplay of abiotic and biotic factors]]> https://www.researchpad.co/article/5989da89ab0ee8fa60b9d2ed

Host–parasite interactions are often embedded within complex host communities and can be influenced by a variety of environmental factors, such as seasonal variations in climate or abiotic conditions in water and soil, which confounds our understanding of the main drivers of many multi-host pathogens. Here, we take advantage of a combination of large environmental data sets on Mycobacterium ulcerans (MU), an environmentally persistent microorganism associated to freshwater ecosystems and present in a large variety of aquatic hosts, to characterize abiotic and biotic factors driving the dynamics of this pathogen in two regions of Cameroon. We find that MU dynamics are largely driven by seasonal climatic factors and certain physico-chemical conditions in stagnant and slow-flowing ecosystems, with an important role of pH as limiting factor. Furthermore, water conditions can modify the effect of abundance and diversity of aquatic organisms on MU dynamics, which suggests a different contribution of two MU transmission routes for aquatic hosts (trophic vs environmental transmission) depending on local abiotic factors.

DOI: http://dx.doi.org/10.7554/eLife.07616.001

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<![CDATA[Epidemiological dynamics of Ebola outbreaks]]> https://www.researchpad.co/article/5989daf2ab0ee8fa60bc1bf1

Ebola is a deadly virus that causes frequent disease outbreaks in the human population. In this study, we analyse its rate of new introductions, case fatality ratio, and potential to spread from person to person. The analysis is performed for all completed outbreaks and for a scenario where these are augmented by a more severe outbreak of several thousand cases. The results show a fast rate of new outbreaks, a high case fatality ratio, and an effective reproductive ratio of just less than 1.

DOI: http://dx.doi.org/10.7554/eLife.03908.001

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<![CDATA[Updates to the zoonotic niche map of Ebola virus disease in Africa]]> https://www.researchpad.co/article/5989db47ab0ee8fa60bd8e01

As the outbreak of Ebola virus disease (EVD) in West Africa is now contained, attention is turning from control to future outbreak prediction and prevention. Building on a previously published zoonotic niche map (Pigott et al., 2014), this study incorporates new human and animal occurrence data and expands upon the way in which potential bat EVD reservoir species are incorporated. This update demonstrates the potential for incorporating and updating data used to generate the predicted suitability map. A new data portal for sharing such maps is discussed. This output represents the most up-to-date estimate of the extent of EVD zoonotic risk in Africa. These maps can assist in strengthening surveillance and response capacity to contain viral haemorrhagic fevers.

DOI: http://dx.doi.org/10.7554/eLife.16412.001

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<![CDATA[Variation in natural exposure to anopheles mosquitoes and its effects on malaria transmission]]> https://www.researchpad.co/article/5b49d3bb463d7e343a08d40a

Variation in biting frequency by Anopheles mosquitoes can explain some of the heterogeneity in malaria transmission in endemic areas. In this study in Burkina Faso, we assessed natural exposure to mosquitoes by matching the genotype of blood meals from 1066 mosquitoes with blood from residents of local households. We observed that the distribution of mosquito bites exceeded the Pareto rule (20/80) in two of the three surveys performed (20/85, 76, and 96) and, at its most pronounced, is estimated to have profound epidemiological consequences, inflating the basic reproduction number of malaria by 8-fold. The distribution of bites from sporozoite-positive mosquitoes followed a similar pattern, with a small number of individuals within households receiving multiple potentially infectious bites over the period of a few days. Together, our findings indicate that heterogeneity in mosquito exposure contributes considerably to heterogeneity in infection risk and suggest significant variation in malaria transmission potential.

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<![CDATA[Mapping Ebola in wild animals for better disease control]]> https://www.researchpad.co/article/5989da3aab0ee8fa60b87c72

Identifying the regions where wild animal populations could transmit the Ebola virus should help with efforts to prepare at-risk areas for future outbreaks.

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