Reply to Kloepfer and Gern: Independent studies suggest an arms race between influenza and rhinovirus: what next?

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Virus-virus interactions impact the population dynamics of influenza and the common cold

The human respiratory tract hosts a diverse community of cocirculating viruses that are responsible for acute respiratory infections. This shared niche provides the opportunity for virus–virus interactions which have the potential to affect individual infection risks and in turn influence dynamics of infection at population scales. However, quantitative evidence for interactions has lacked suitable data and appropriate analytical tools. Here, we expose and quantify interactions among respiratory viruses using bespoke analyses of infection time series at the population scale and coinfections at the individual host scale. We analyzed diagnostic data from 44,230 cases of respiratory illness that were tested for 11 taxonomically broad groups of respiratory viruses over 9 y. Key to our analyses was accounting for alternative drivers of correlated infection frequency, such as age and seasonal dependencies in infection risk, allowing us to obtain strong support for the existence of negative interactions between influenza and noninfluenza viruses and positive interactions among noninfluenza viruses. In mathematical simulations that mimic 2-pathogen dynamics, we show that transient immune-mediated interference can cause a relatively ubiquitous common cold-like virus to diminish during peak activity of a seasonal virus, supporting the potential role of innate immunity in driving the asynchronous circulation of influenza A and rhinovirus. These findings have important implications for understanding the linked epidemiological dynamics of viral respiratory infections, an important step towards improved accuracy of disease forecasting models and evaluation of disease control interventions

Seasonal influenza vaccine effectiveness in people with asthma: a national test-negative design case-control study

Financial support. The work was funded by the Chief Scientist Office of the Scottish Government under the grant (AUKCAR/14/03) and the NIHR–Health Technology Assessment (HTA) Programme (13/34/14) for the Seasonal Influenza Vaccination Effectiveness II (SIVE II) study. As principal investigator, C. R. S. received a grant for the SIVE-II project from the NIHR HTA. This work was carried out with the support of the Asthma UK Centre for Applied Research (AUK-AC-2012-01), the Farr Institute (MR/M501633/2), Health Data Research UK (an initiative funded by UK Research and Innovation, Department of Health and Social Care England and the devolved administrations and leading medical research charities), the European Union’s Horizon 2020 research and innovation programme (under grant agreement No 634446) and European Centre for Disease Prevention and Control (Influenza-Monitoring Vaccine Effectiveness). Acknowledgments. The authors thank and acknowledge all colleagues at the Asthma UK Centre for Applied Research for their support in this study. Disclaimer. The funding bodies had no role in the design of the study, review process, analysis, interpretation, or reporting of data. The views and opinions expressed herein are those of the authors and do not necessarily reflect those of the Health Technology Assessment Programme, National Institute for Health Research (NIHR), National Health Service, or the Department of Health. Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.Peer reviewedPublisher PDFPublisher PD

Effectiveness of seasonal influenza vaccine in preventing laboratory-confirmed influenza in primary care in the United Kingdom : 2014/15 end of season results

The 2014/15 influenza season in the United Kingdom (UK) was characterised by circulation of predominantly antigenically and genetically drifted influenza A(H3N2) and B viruses. A universal paediatric influenza vaccination programme using a quadrivalent live attenuated influenza vaccine (LAIV) has recently been introduced in the UK. This study aims to measure the end-of-season influenza vaccine effectiveness (VE), including for LAIV, using the test negative case–control design. The overall adjusted VE against all influenza was 34.3% (95% confidence interval (CI) 17.8 to 47.5); for A(H3N2) 29.3% (95% CI: 8.6 to 45.3) and for B 46.3% (95% CI: 13.9 to 66.5). For those aged under 18 years, influenza A(H3N2) LAIV VE was 35% (95% CI: −29.9 to 67.5), whereas for influenza B the LAIV VE was 100% (95% CI:17.0 to 100.0). Although the VE against influenza A(H3N2) infection was low, there was still evidence of significant protection, together with moderate, significant protection against drifted circulating influenza B viruses. LAIV provided non-significant positive protection against influenza A, with significant protection against B. Further work to assess the population impact of the vaccine programme across the UK is underway

Low effectiveness of seasonal influenza vaccine in preventing laboratory-confirmed influenza in primary care in the United Kingdom : 2014/15 mid-season results

In 2014/15 the United Kingdom experienced circulation of influenza A(H3N2) with impact in the elderly. Midseason vaccine effectiveness (VE) shows an adjusted VE of 3.4% (95% CI: −44.8 to 35.5) against primary care consultation with laboratory-confirmed influenza and −2.3% (95% CI: −56.2 to 33.0) for A(H3N2). The low VE reflects mismatch between circulating viruses and the 2014/15 northern hemisphere A(H3N2) vaccine strain. Early use of antivirals for prophylaxis and treatment of vulnerable populations remains important

The helicity amplitudes A1/2_{1/2} and A3/2_{3/2} for the D13(1520)_{13}(1520) resonance obtained from the γ⃗p⃗→pπ0\vec{\gamma} \vec{p} \to p \pi^0 reaction}

The helicity dependence of the $\vec{\gamma} \vec{p} \to p \pi^0$ reaction has been measured for the first time in the photon energy range from 550 to 790 MeV. The experiment, performed at the Mainz microtron MAMI, used a 4$\pi$-detector system, a circularly polarized, tagged photon beam, and a longitudinally polarized frozen-spin target. These data are predominantly sensitive to the $D_{13}(1520)$ resonance and are used to determine its parameters.Comment: 5 pages, 4 figure

Evaluating the impact of targeting livestock for the prevention of human and animal trypanosomiasis, at village level, in districts newly affected with T. b. rhodesiense in Uganda

Background: Uganda has suffered from a series of epidemics of Human African Trypanosomiasis (HAT), a tsetse transmitted disease, also known as sleeping sickness. The area affected by acute Trypanosoma brucei rhodesiense HAT (rHAT) has been expanding, driven by importation of infected cattle into regions previously free of the disease. These regions are also affected by African Animal Trypanosomiasis (AAT) demanding a strategy for integrated disease control.Methods: In 2008, the Public Private Partnership, Stamp Out Sleeping Sickness (SOS) administered a single dose of trypanocide to 31 486 head of cattle in 29 parishes in Dokolo and Kaberamaido districts. This study examines the impact of this intervention on the prevalence of rHAT and AAT trypanosomes in cattle from villages that had (HAT+ve) or had not (HAT-ve) experienced a recent case of rHAT. Cattle herds from 20 villages were sampled and screened by PCR, pre-intervention and 6-months post-intervention, for the presence or absence of: Trypanosoma brucei s.l.; human infective T. b. rhodesiense; Trypanosoma vivax; and Trypanosoma congolense savannah.Results: Post-intervention, there was a significant decrease in the prevalence of T. brucei s.l. and the human infective sub-species T. b. rhodesiense in village cattle across all 20 villages. The prevalence of T. b. rhodesiense was reduced from 2.4% to 0.74% (P < 0.0001), with the intervention showing greater impact in HAT-ve villages. The number of villages containing cattle harbouring human infective parasites decreased from 15/20 to 8/20, with T. b. rhodesiense infection mainly persisting within cattle in HAT+ve villages (six/eight). The proportion of T. brucei s.l. infections identified as human infective T. b. rhodesiense decreased after the intervention from 8.3% (95% CI = 11.1–5.9%) to 4.1% (95% CI = 6.8–2.3%). Villages that had experienced a recent human case (HAT+ve villages) showed a significantly higher prevalence for AAT both pre- and post-intervention. For AAT the prevalence of T. vivax was significantly reduced from 5.9% to 0.05% post-intervention while the prevalence of T. congolense increased from 8.0% to 12.2%.Conclusions: The intervention resulted in a significant decrease in the prevalence of T. brucei s.l., human infective T. b. rhodesiense and T. vivax infection in village cattle herds. The proportion of T. brucei s.l. that were human infective, decreased from 1:12 T. brucei s.l. infections before the intervention to 1:33 post-intervention. It is clearly more difficult to eliminate T. b. rhodesiense from cattle in villages that have experienced a human case. Evidence of elevated levels of AAT in livestock within village herds is a useful indicator of risk for rHAT in Uganda. Integrated veterinary and medical surveillance is key to successful control of zoonotic rHAT

First measurement of the Gerasimov-Drell-Hearn integral for Hydrogen from 200 to 800 MeV

A direct measurement of the helicity dependence of the total photoabsorption cross section on the proton was carried out at MAMI (Mainz) in the energy range 200 < E_gamma < 800 MeV. The experiment used a 4$\pi$ detection system, a circularly polarized tagged photon beam and a frozen spin target. The contributions to the Gerasimov-Drell-Hearn sum rule and to the forward spin polarizability $\gamma_0$ determined from the data are 226 \pm 5 (stat)\pm 12(sys) \mu b and -187 \pm 8 (stat)\pm 10(sys)10^{-6} fm^4, respectively, for 200 < E_\gamma < 800 MeV.Comment: 6 pages, 3 figures, 3 table

Managing Tsetse Transmitted Trypanosomosis by Insecticide Treated Nets - an Affordable and Sustainable Method for Resource Poor Pig Farmers in Ghana

An outbreak of tsetse-transmitted trypanosomiasis resulted in more than 50% losses of domestic pigs in the Eastern Region of Ghana (source: Veterinary Services, Accra; April 2007). In a control trial from May 4th–October 10th 2007, the efficacy of insecticide-treated mosquito fences to control tsetse was assessed. Two villages were selected – one serving as control with 14 pigsties and one experimental village where 24 pigsties were protected with insecticide treated mosquito fences. The 100 cm high, 150denier polyester fences with 100 mg/m2 deltamethrin and a UV protector were attached to surrounding timber poles and planks. Bi-monthly monitoring of tsetse densities with 10 geo-referenced bi-conical traps per village showed a reduction of more than 90% in the protected village within two months. Further reductions exceeding 95% were recorded during subsequent months. The tsetse population in the control village was not affected, only displaying seasonal variations. Fifty pigs from each village were ear-tagged and given a single curative treatment with diminazene aceturate (3.5 mg/kg bw) after their blood samples had been taken. The initial trypanosome prevalence amounted to 76% and 72% of protected and control animals, respectively, and decreased to 16% in protected as opposed to 84% in control pigs three months after intervention. After six months 8% of the protected pigs were infected contrasting with 60% in the control group

No Gold Standard Estimation of the Sensitivity and Specificity of Two Molecular Diagnostic Protocols for Trypanosoma brucei spp. in Western Kenya

African animal trypanosomiasis is caused by a range of tsetse transmitted protozoan parasites includingTrypanosoma vivax, Trypanosoma congolense and Trypansoma brucei. In Western Kenya and other parts of East Africa two subspecies of T. brucei, T.b. brucei and the zoonoticT.b. rhodesiense, co-circulate in livestock. A range of polymerase chain reactions (PCR) have been developed as important molecular diagnostic tools for epidemiological investigations of T. brucei s.l. in the animal reservoir and of its zoonotic potential. Quantification of the relative performance of different diagnostic PCRs is essential to ensure comparability of studies. This paper describes an evaluation of two diagnostic test systems for T. brucei using a T. brucei s.l. specific PCR [1] and a single nested PCR targeting the Internal Transcribed Spacer (ITS) regions of trypanosome ribosomal DNA [2]. A Bayesian formulation of the Hui-Walter latent class model was employed to estimate their test performance in the absence of a gold standard test for detecting T.brucei s.l. infections in ear-vein blood samples from cattle, pig, sheep and goat populations in Western Kenya, stored on Whatman FTA cards. The results indicate that the system employing the T. brucei s.l. specific PCR (Se1 = 0.760) had a higher sensitivity than the ITS-PCR (Se2 = 0.640); both have high specificity (Sp1 = 0.998; Sp2 = 0.997). The true prevalences for livestock populations were estimated (pcattle = 0.091, ppigs = 0.066, pgoats = 0.005, psheep = 0.006), taking into account the uncertainties in the specificity and sensitivity of the two test systems. Implications of test performance include the required survey sample size; due to its higher sensitivity and specificity, the T. brucei s.l. specific PCR requires a consistently smaller sample size than the ITS-PCR for the detection of T. brucei s.l. However the ITS-PCR is able to simultaneously screen samples for other pathogenic trypanosomes and may thus be, overall, a better choice of test in multi-organism studies