Aggressive or moderate drug therapy for infectious diseases? Trade-offs between different treatment goals at the individual and population levels.

Antimicrobial resistance is one of the major public health threats of the 21st century. There is a pressing need to adopt more efficient treatment strategies in order to prevent the emergence and spread of resistant strains. The common approach is to treat patients with high drug doses, both to clear the infection quickly and to reduce the risk of de novo resistance. Recently, several studies have argued that, at least in some cases, low-dose treatments could be more suitable to reduce the within-host emergence of antimicrobial resistance. However, the choice of a drug dose may have consequences at the population level, which has received little attention so far. Here, we study the influence of the drug dose on resistance and disease management at the host and population levels. We develop a nested two-strain model and unravel trade-offs in treatment benefits between an individual and the community. We use several measures to evaluate the benefits of any dose choice. Two measures focus on the emergence of resistance, at the host level and at the population level. The other two focus on the overall treatment success: the outbreak probability and the disease burden. We find that different measures can suggest different dosing strategies. In particular, we identify situations where low doses minimize the risk of emergence of resistance at the individual level, while high or intermediate doses prove most beneficial to improve the treatment efficiency or even to reduce the risk of resistance in the population.

Thunderstorm asthma: revealing a hidden at-risk population.

BACKGROUND: Epidemic thunderstorm asthma (ETSA) refers to large-scale acute bronchospasm events associated with thunderstorm. The most serious episode ever recorded occurred in Melbourne, Australia, in November 2016, where more than 3500 patients were treated in hospitals and 10 died. Previous work has been focused primarily on patient presentations to emergency departments. The prevalence of individuals with milder, non-emergent symptoms and who may be at risk of more serious episodes in the future has not previously been explored. AIM: To characterise the nature and extent of respiratory symptoms in healthcare workers during the Melbourne ETSA event. METHODS: A survey was conducted among staff and volunteers across Eastern Health, distributed on the intranet homepage, by email and by word of mouth. Anonymous survey questions were constructed to assess prior and current diagnoses of relevance, symptoms, and demography. RESULTS: There were 515 participants (80% female, n = 411) of approximately 9000 potential respondents (~6% response rate) who completed the survey; 132 (25.6%) had symptoms suggestive of asthma during the Melbourne ETSA event, the majority of whom did not seek professional medical help. Notably, of those with ETSA-like symptoms, only 58 (43.9%) had a history of asthma, while 97 (73.5%) had a history of allergic rhinitis. Specifically, a history of allergic rhinitis (OR 2.77, P < 0.001), a history of asthma (OR 1.67, P = 0.037) and being of self-identified Asian ethnicity (OR 3.24, P < 0.001) were all strong predictors of ETSA-like symptoms. Being predominantly indoors was not protective. CONCLUSIONS: Our study provides evidence of the presence of a large cohort of sufferers during the Melbourne ETSA event of 2016 that did not come to the attention of medical services, implying a potentially hidden and significant susceptible population. Further research should help clarify the true prevalence of vulnerability in the general population, with important public health implications.

Evolutionary view of the AIDS process.

It is generally accepted that human immunodeficiency virus (HIV) is the etiological agent of acquired immune deficiency syndrome. According to this claim, HIV was transferred to humans from contact with monkeys around 35-50 years ago. However, this claim has not been sufficiently confirmed epidemiologically. The spread and incubation period of the plague epidemic has led to the theory that the Black Death was caused by hemorrhagic viruses. Having examined detailed historical data, we have concluded that the bacterium Yersenia pestis was an infectious agent in the epidemic, together with another agent which we suggest was HIV. Our considerations were mainly based on the existence of the CCR5 delta 32 mutation, which protects against HIV infection and has been present in the Caucasian population for over 2000 years. The combination of two infectious agents led to the devastation of the Black Death, the removal of HIV carriers, and an increase in the number of CCR5Δ32 mutations in the Caucasian population. In sub-Saharan Africa, this epidemic and subsequent sanitation process did not occur, which explains the much higher level of HIV genetic information in this part of the world.

The Melbourne epidemic thunderstorm asthma event 2016: an investigation of environmental triggers, effect on health services, and patient risk factors.

BACKGROUND: A multidisciplinary collaboration investigated the world's largest, most catastrophic epidemic thunderstorm asthma event that took place in Melbourne, Australia, on Nov 21, 2016, to inform mechanisms and preventive strategies. METHODS: Meteorological and airborne pollen data, satellite-derived vegetation index, ambulance callouts, emergency department presentations, and data on hospital admissions for Nov 21, 2016, as well as leading up to and following the event were collected between Nov 21, 2016, and March 31, 2017, and analysed. We contacted patients who presented during the epidemic thunderstorm asthma event at eight metropolitan health services (each including up to three hospitals) via telephone questionnaire to determine patient characteristics, and investigated outcomes of intensive care unit (ICU) admissions. FINDINGS: Grass pollen concentrations on Nov 21, 2016, were extremely high (>100 grains/m3). At 1800 AEDT, a gust front crossed Melbourne, plunging temperatures 10°C, raising humidity above 70%, and concentrating particulate matter. Within 30 h, there were 3365 (672%) excess respiratory-related presentations to emergency departments, and 476 (992%) excess asthma-related admissions to hospital, especially individuals of Indian or Sri Lankan birth (10% vs 1%, p<0·0001) and south-east Asian birth (8% vs 1%, p<0·0001) compared with previous 3 years. Questionnaire data from 1435 (64%) of 2248 emergency department presentations showed a mean age of 32·0 years (SD 18·6), 56% of whom were male. Only 28% had current doctor-diagnosed asthma. 39% of the presentations were of Asian or Indian ethnicity (25% of the Melbourne population were of this ethnicity according to the 2016 census, relative risk [RR] 1·93, 95% CI 1·74-2·15, p <0·0001). Of ten individuals who died, six were Asian or Indian (RR 4·54, 95% CI 1·28-16·09; p=0·01). 35 individuals were admitted to an intensive care unit, all had asthma, 12 took inhaled preventers, and five died. INTERPRETATION: Convergent environmental factors triggered a thunderstorm asthma epidemic of unprecedented magnitude, tempo, and geographical range and severity on Nov 21, 2016, creating a new benchmark for emergency and health service escalation. Asian or Indian ethnicity and current doctor-diagnosed asthma portended life-threatening exacerbations such as those requiring admission to an ICU. Overall, the findings provide important public health lessons applicable to future event forecasting, health care response coordination, protection of at-risk populations, and medical management of epidemic thunderstorm asthma. FUNDING: None.

Confronting the new epidemic: Integrated care for opioid use disorders.

The inaugural Collaborative Family Health Care (CFHA) regional conference took place March 17, 2017, in St. Louis, Missouri. The conference theme was opioid use disorders and the potential of medication-assisted treatment using team-based care to address this epidemic. The conference ended with an emphasis on the importance of and strategies for self-care among caregivers working with this population and their families. This intensive meeting was crafted as a proof in concept for CFHA; however, the content was timely with regard to its importance in health care as well as compelling in the opportunity for collaborative care to offer an effective approach. In this article, the authors highlight five impotance topics: (1) opioid use disorders should be addressed in primary care; (2) a team is essential; (3) harm reduction; (4) sustaining self through mindful practice and self-compassion; and (5) medication-assisted treatment. (PsycINFO Database Record

Turkish and Japanese Mycobacterium tuberculosis sublineages share a remote common ancestor.

Two geographically distant M. tuberculosis sublineages, Tur from Turkey and T3-Osaka from Japan, exhibit partially identical genotypic signatures (identical 12-loci MIRU-VNTR profiles, distinct spoligotyping patterns). We investigated T3-Osaka and Tur sublineages characteristics and potential genetic relatedness, first using MIRU-VNTR locus analysis on 21 and 25 samples of each sublineage respectively, and second comparing Whole Genome Sequences of 8 new samples to public data from 45 samples uncovering human tuberculosis diversity. We then tried to date their Most Recent Common Ancestor (MRCA) using three calibrations of SNP accumulation rate (long-term=0.03SNP/genome/year, derived from a tuberculosis ancestor of around 70,000years old; intermediate=0.2SNP/genome/year derived from a Peruvian mummy; short-term=0.5SNP/genome/year). To disentangle between these scenarios, we confronted the corresponding divergence times with major human history events and knowledge on human genetic divergence. We identified relatively high intrasublineage diversity for both T3-Osaka and Tur. We definitively proved their monophyly; the corresponding super-sublineage (referred to as "T3-Osa-Tur") shares a common ancestor with T3-Ethiopia and Ural sublineages but is only remotely related to other Euro-American sublineages such as X, LAM, Haarlem and S. The evolutionary scenario based on long-term evolution rate being valid until T3-Osa-Tur MRCA was not supported by Japanese fossil data. The evolutionary scenario relying on short-term evolution rate since T3-Osa-Tur MRCA was contradicted by human history and potential traces of past epidemics. T3-Osaka and Tur sublineages were found likely to have diverged between 800y and 2000years ago, potentially at the time of Mongol Empire. Altogether, this study definitively proves a strong genetic link between Turkish and Japanese tuberculosis. It provides a first hypothesis for calibrating TB Euro-American lineage molecular clock; additional studies are needed to reliably date events corresponding to intermediate depths in tuberculosis phylogeny.

HIV/AIDS prevention, faith, and spirituality among black/African American and Latino communities in the United States: strengthening scientific faith-based efforts to shift the course of the epidemic and reduce HIV-related health disparities.

Black/African American and Latino communities are disproportionately affected by the domestic HIV/AIDS epidemic. Blacks/African Americans and Latinos are also more likely to report a formal, religious, or faith affiliation when compared with non-Hispanic whites. As such, faith leaders and their institutions have been identified in the National HIV/AIDS Strategy as having a vital role to serve in reducing: (1) HIV-related health disparities and (2) the number of new HIV infections by promoting non-judgmental support for persons living with and at risk for HIV/AIDS and by serving as trusted information resources for their congregants and communities. We describe faith doctrines and faith-science partnerships that are increasing in support of faith-based HIV prevention and service delivery activities and discuss the vital role of these faith-based efforts in highly affected black/African American and Latino communities.

[Current data and trends on methicillin-resistant Staphylococcus aureus (MRSA)]. / Aktuelle Daten und Trends zu Methicillin-resistenten Staphylococcus aureus (MRSA).

Nosocomial infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are a problem in hospital settings worldwide. The National Reference Centre for Staphylococci performs molecular typing on a representative sample set of MRSA isolates from German hospitals for assessing long-term trends thus following the dynamics of emergence and spread of MRSA clones. The article focuses on recent data concerning antibiotic resistance and epidemic MRSA in nosocomial settings and also reflects the impact of community-acquired MRSA and MRSA from zoonotic reservoirs. Identifying common and newly emerging clones is an on-going challenge in the changing epidemiology of MRSA and prevention of further spread needs molecular surveillance.

Cigarette smoking as part of a syndemic among young men who have sex with men ages 13-29 in New York City.

The prevalence of cigarette smoking among young men who have sex with men (YMSM) is significantly higher than among their heterosexual peers. We undertook an analysis to examine cigarette smoking in relation to demographic factors and other risk behaviors among 580 YMSM, ages 13-29, in New York City. Cross-sectional data were collected as part of larger study of risk behaviors using palm devices and targeted active recruitment strategies across all five boroughs of the city. Multivariate modeling suggests that Asian or Pacific Islander and White YMSM are more likely to report cigarette smoking than other racial and ethnic groups, as are men reporting a middle class socioeconomic status. In addition, smoking was related to the likelihood of using a variety of illicit substances, as well as alcohol and pharmaceuticals without a prescription, during the period of assessment. YMSM who smoke cigarettes reported a greater number of casual sex partners and a greater number of transactional sex partners than non-smokers. Episodic analysis of sexual behaviors with casual partners indicated that smokers were more likely to engage in illicit drug and alcohol use immediately before or during sex than did non-smokers. These findings are understood as part of a larger syndemic among YMSM, and suggest that smoking prevention and cessation programs should be embedded as part of larger more holistic health and wellness programs targeting YMSM.