COVID-19: decision-making in public health.

Against a background of stalling UK life expectancy, the COVID-19 pandemic necessitated a different way of working for public health to respond quickly to new and many demands. At the same time, public health teams had to ensure they did not concentrate on the immediate crisis at the expense of mitigating longer-term impacts of the pandemic. This was, and is, a major challenge with additional demands on an already hard-pressed workforce. This paper discusses the experience of a local public health department in responding to the pandemic and raises four key areas that influenced decisions and need to be considered in future. These are care homes issues, addressing all four harms of the pandemic, lessons for behaviour change and the need to strengthen Scotland's public health workforce.

Informing prevention of stillbirth and preterm birth in Malawi: development of a minimum dataset for health facilities participating in the DIPLOMATIC collaboration.

OBJECTIVE: The global research group, DIPLOMATIC (Using eviDence, Implementation science, and a clinical trial PLatform to Optimise MATernal and newborn health in low Income Countries), aims to reduce stillbirths and preterm births and optimise outcomes for babies born preterm. Minimum datasets for routine data collection in healthcare facilities participating in DIPLOMATIC (initially in Malawi) were designed to assist understanding of baseline maternal and neonatal care processes and outcomes, and facilitate evaluation of improvement interventions and pragmatic clinical trials. DESIGN: Published and grey literature was reviewed alongside extensive in-country consultation to define relevant clinical best practice guidance, and the existing local data and reporting infrastructure, to identify requirements for the minimum datasets. Data elements were subjected to iterative rounds of consultation with topic experts in Malawi and Scotland, the relevant Malawian professional bodies and the Ministry of Health in Malawi to ensure relevance, validity and feasibility. SETTING: Antenatal, maternity and specialist neonatal care in Malawi. RESULTS: The resulting three minimum datasets cover the maternal and neonatal healthcare journey for antenatal, maternity and specialist neonatal care, with provision for effective linkage of records for mother/baby pairs. They can facilitate consistent, precise recording of relevant outcomes (stillbirths, preterm births, neonatal deaths), risk factors and key care processes. CONCLUSIONS: Poor quality routine data on care processes and outcomes constrain healthcare system improvement. The datasets developed for implementation in DIPLOMATIC partner facilities reflect, and hence support delivery of, internationally agreed best practice for maternal and newborn care in low-income settings. Informed by extensive consultation, they are designed to integrate with existing local data infrastructure and reporting as well as meeting research data needs. This work provides a transferable example of strengthening data infrastructure to underpin a learning healthcare system approach in low-income settings.DIPLOMATIC is funded by the UK National Institute for Health Research.

Seasonal Influenza Vaccine Effectiveness in People With Asthma: A National Test-Negative Design Case-Control Study.

BACKGROUND: Influenza infection is a trigger of asthma attacks. Influenza vaccination can potentially reduce the incidence of influenza in people with asthma, but uptake remains persistently low, partially reflecting concerns about vaccine effectiveness (VE). METHODS: We conducted a test-negative designed case-control study to estimate the effectiveness of influenza vaccine in people with asthma in Scotland over 6 seasons (2010/2011 to 2015/2016). We used individual patient-level data from 223 practices, which yielded 1 830 772 patient-years of data that were linked with virological (n = 5910 swabs) data. RESULTS: Vaccination was associated with an overall 55.0% (95% confidence interval [CI], 45.8-62.7) risk reduction of laboratory-confirmed influenza infections in people with asthma over 6 seasons. There were substantial variations in VE between seasons, influenza strains, and age groups. The highest VE (76.1%; 95% CI, 55.6-87.1) was found in the 2010/2011 season, when the A(H1N1) strain dominated and there was a good antigenic vaccine match. High protection was observed against the A(H1N1) (eg, 2010/2011; 70.7%; 95% CI, 32.5-87.3) and B strains (eg, 2010/2011; 83.2%; 95% CI, 44.3-94.9), but there was lower protection for the A(H3N2) strain (eg, 2014/2015; 26.4%; 95% CI, -12.0 to 51.6). The highest VE against all viral strains was observed in adults aged 18-54 years (57.0%; 95% CI, 42.3-68.0). CONCLUSIONS: Influenza vaccination gave meaningful protection against laboratory-confirmed influenza in people with asthma across all seasons. Strategies to boost influenza vaccine uptake have the potential to substantially reduce influenza-triggered asthma attacks.

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.

Moving epidemic method (MEM) applied to virology data as a novel real time tool to predict peak in seasonal influenza healthcare utilisation. The Scottish experience of the 2017/18 season to date.

Scotland observed an unusual influenza A(H3N2)-dominated 2017/18 influenza season with healthcare services under significant pressure. We report the application of the moving epidemic method (MEM) to virology data as a tool to predict the influenza peak activity period and peak week of swab positivity in the current season. This novel MEM application has been successful locally and is believed to be of potential use to other countries for healthcare planning and building wider community resilience.

Effectiveness of Influenza Vaccines in Asthma: A Systematic Review and Meta-Analysis.

There is uncertainty about the effectiveness of influenza vaccination in persons with asthma and its impact on asthma outcomes, which may contribute to the suboptimal vaccination rates in persons with asthma. This systematic review and meta-analysis involved searching 12 international databases for randomized controlled trials (RCTs) and high-quality quasi-experimental and epidemiological studies (1970-2016). The risk of bias was low for 3 included RCTs. The quality of 3 included observational studies was moderate. The quality of evidence was very low for all study outcomes. Pooled vaccine effectiveness in 1825 persons with asthma from 2 test-negative design case-control studies was 45% (95% confidence interval [CI], 31%-56%) for laboratory-confirmed influenza. Pooled efficacy of live vaccines in reducing influenza was 81% (95% CI, 33%- 94%). Live vaccine reduced febrile illness by 72% (95% CI, 20%-90%). Influenza vaccine prevented 59%-78% of asthma attacks leading to emergency visits and/or hospitalizations. For persons with asthma, influenza vaccination may be effective in both reducing influenza infection and asthma attacks.

Evaluating the effectiveness, impact and safety of live attenuated and seasonal inactivated influenza vaccination: protocol for the Seasonal Influenza Vaccination Effectiveness II (SIVE II) study.

INTRODUCTION: Seasonal (inactivated) influenza vaccination is recommended for all individuals aged 65+ and in individuals under 65 who are at an increased risk of complications of influenza infection, for example, people with asthma. Live attenuated influenza vaccine (LAIV) was recommended for children as they are thought to be responsible for much of the transmission of influenza to the populations at risk of serious complications from influenza. A phased roll-out of the LAIV pilot programme began in 2013/2014. There is limited evidence for vaccine effectiveness (VE) in the populations targeted for influenza vaccination. The aim of this study is to examine the safety and effectiveness of the live attenuated seasonal influenza vaccine programme in children and the inactivated seasonal influenza vaccination programme among different age and at-risk groups of people. METHODS AND ANALYSIS: Test negative and cohort study designs will be used to estimate VE. A primary care database covering 1.25 million people in Scotland for the period 2000/2001 to 2015/2016 will be linked to the Scottish Immunisation Recall Service (SIRS), Health Protection Scotland virology database, admissions to Scottish hospitals and the Scottish death register. Vaccination status (including LAIV uptake) will be determined from the primary care and SIRS database. The primary outcome will be influenza-positive real-time PCR tests carried out in sentinel general practices and other healthcare settings. Secondary outcomes include influenza-like illness and asthma-related general practice consultations, hospitalisations and death. An instrumental variable analysis will be carried out to account for confounding. Self-controlled study designs will be used to estimate the risk of adverse events associated with influenza vaccination. ETHICS AND DISSEMINATION: We obtained approval from the National Research Ethics Service Committee, West Midlands-Edgbaston. The study findings will be presented at international conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN88072400; Pre-results.

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.

Effectiveness of influenza vaccination for preventing influenza-related complications in people with asthma: a systematic review protocol.

INTRODUCTION: Influenza vaccination is administered annually as a preventive measure against influenza infection and influenza-related complications in high-risk individuals, such as those with asthma. However, the effectiveness of influenza vaccination in people with asthma against influenza-related complications is still not well established. METHODS AND ANALYSIS: We will search the following databases: MEDLINE (Ovid), EMBASE (Ovid), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, Cochrane Database of Systematic Reviews (CDSR), Web of Science Core Collection, Science direct, WHO Library Information System (WHOLIS), Global Health Library and Chinese databases (CNKI, Wanfang and ChongQing VIP) from Jan 1970 to Jan 2016 for observational and experimental studies on effectiveness of influenza vaccine in people with asthma. The identification of studies will be complemented with the searching of the reference lists and citations, and contacting influenza vaccine manufacturers to identify unpublished or ongoing studies. Two reviewers will extract data and appraise the quality of each study independently. Separate meta-analyses will be undertaken for observational and experimental evidence using fixed-effect or random-effects models, as appropriate. ETHICS AND DISSEMINATION: Formal ethical approval is not required, as primary data will not be collected. The review will be disseminated in peer-reviewed publications and conference presentations.

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.

Assessing the risk of human granulocytic anaplasmosis and lyme borreliosis after a tick bite in Bavaria, Germany.

To date, only isolated incidences of human granulocytic anaplasmosis (HGA) have been reported in Europe. However, entomological studies in Bavaria, Germany showed a prevalence of Anaplasma phagocytophilum of between 2 and 9.5% in the tick vector Ixodes ricinus. In this study we assessed the risk of pathogenic A. phagocytophilum infection after a tick bite in Bavaria. The seroprevalence of anti-Borrelia burgdorferi sensu lato (s.l.) antibodies was investigated as an indicator of past exposure, seroconversion as actual exposure of participants to ticks. Patients with a tick bite in the preceding four weeks were recruited by participating doctors. Questionnaires on demographics, tick exposure and clinical signs were completed by patients and doctors, respectively. Two blood samples, taken at an interval of two weeks, were tested for antibodies against A. phagocytophilum and B. burgdorferi s.l. One of 107 recruited patients showed serological evidence of an acute infection of A. phagocytophilum but had no clinical signs. Four out of six patients with serological evidence of an acute B. burgdorferi s.l. infection, presented with erythema migrans. A seroprevalence of 7.5% for A. phagocytophilum and 13.1% for B. burgdorferi s.l. was detected. The comparatively high seroprevalence of B. burdorferi s.l. and A. phagocytophilum antibodies indicate frequent past exposure of participants to ticks. The finding of one acute infection of A. phagocytophilum in the absence of clinical signs, supports entomological evidence that the strains of A. phagocytophilum predominantly present in the Bavarian tick population may cause transient infections but are of low pathogenicity in humans.

Quantifying the association between bovine and human trypanosomiasis in newly affected sleeping sickness areas of Uganda.

BACKGROUND: Uganda has active foci of both chronic and acute HAT with the acute zoonotic form of disease classically considered to be restricted to southeast Uganda, while the focus of the chronic form of HAT was confined to the northwest of the country. Acute HAT has however been migrating from its traditional disease focus, spreading rapidly to new districts, a spread linked to movement of infected cattle following restocking. Cattle act as long-term reservoirs of human infective T. b. rhodesiense showing few signs of morbidity, yet posing a significant risk to human health. It is important to understand the relationship between infected cattle and infected individuals so that an appropriate response can be made to the risk posed to the community from animals infected with human pathogens in a village setting. METHODOLOGY/PRINCIPAL FINDINGS: This paper examines the relationship between human T. b. rhodesiense infection and human infective and non-human T. brucei s.l. circulating in cattle at village level in Kaberamaido and Dokolo Districts, Uganda. The study was undertaken in villages that had reported a case of sleeping sickness in the six months prior to sample collection and those villages that had never reported a case of sleeping sickness. CONCLUSIONS AND SIGNIFICANCE: The sleeping sickness status of the villages had a significant effect with higher odds of infection in cattle from case than from non-case villages for T. brucei s.l. (OR: 2.94, 95%CI: 1.38-6.24). Cattle age had a significant effect (p<0.001) on the likelihood of T. brucei s.l. infection within cattle: cattle between 18-36 months (OR: 3.51, 95%CI: 1.63-7.51) and cattle over 36 months (OR: 4.20, 95%CI: 2.08-8.67) had significantly higher odds of T. brucei s. l. infection than cattle under 18 months of age. Furthermore, village human sleeping sickness status had a significant effect (p<0.05) on the detection of T. b. rhodesiense in the village cattle herd, with significantly higher likelihood of T. b. rhodesiense in the village cattle of case villages (OR: 25, 95%CI: 1.2-520.71). Overall a higher than average T. brucei s.l. prevalence (>16.3%) in a village herd over was associated with significantly higher likelihood of T. b. rhodesiense being detected in a herd (OR: 25, 95%CI: 1.2-520.71).

Factors associated with acquisition of human infective and animal infective trypanosome infections in domestic livestock in Western Kenya.

BACKGROUND: Trypanosomiasis is regarded as a constraint on livestock production in Western Kenya where the responsibility for tsetse and trypanosomiasis control has increasingly shifted from the state to the individual livestock owner. To assess the sustainability of these localised control efforts, this study investigates biological and management risk factors associated with trypanosome infections detected by polymerase chain reaction (PCR), in a range of domestic livestock at the local scale in Busia, Kenya. Busia District also remains endemic for human sleeping sickness with sporadic cases of sleeping sickness reported. RESULTS: In total, trypanosome infections were detected in 11.9% (329) out of the 2773 livestock sampled in Busia District. Multivariable logistic regression revealed that host species and cattle age affected overall trypanosome infection, with significantly increased odds of infection for cattle older than 18 months, and significantly lower odds of infection in pigs and small ruminants. Different grazing and watering management practices did not affect the odds of trypanosome infection, adjusted by host species. Neither anaemia nor condition score significantly affected the odds of trypanosome infection in cattle. Human infective Trypanosoma brucei rhodesiense were detected in 21.5% of animals infected with T. brucei s.l. (29/135) amounting to 1% (29/2773) of all sampled livestock, with significantly higher odds of T. brucei rhodesiense infections in T. brucei s.l. infected pigs (OR =  4.3, 95%CI 1.5-12.0) than in T. brucei s.l. infected cattle or small ruminants. CONCLUSIONS: Although cattle are the dominant reservoir of trypanosome infection it is unlikely that targeted treatment of only visibly diseased cattle will achieve sustainable interruption of transmission for either animal infective or zoonotic human infective trypanosomiasis, since most infections were detected in cattle that did not exhibit classical clinical signs of trypanosomiasis. Pigs were also found to be reservoirs of infection for T. b. rhodesiense and present a risk to local communities.

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.