Role of healthcare workers in early epidemic spread of Ebola: policy implications of prophylactic compared to reactive vaccination policy in outbreak prevention and control

Ebola causes severe illness in humans and has epidemic potential. How to deploy vaccines most effectively is a central policy question since different strategies have implications for ideal vaccine profile. More than one vaccine may be needed. A vaccine optimised for prophylactic vaccination in high-risk areas but when the virus is not actively circulating should be safe, well tolerated, and provide long-lasting protection; a two- or three-dose strategy would be realistic. Conversely, a reactive vaccine deployed in an outbreak context for ring-vaccination strategies should have rapid onset of protection with one dose, but longevity of protection is less important. In initial cases, before an outbreak is recognised, healthcare workers (HCWs) are at particular risk of acquiring and transmitting infection, thus potentially augmenting early epidemics. We hypothesise that many early outbreak cases could be averted, or epidemics aborted, by prophylactic vaccination of HCWs. This paper explores the potential impact of prophylactic versus reactive vaccination strategies of HCWs in preventing early epidemic transmissions. To do this, we use the limited data available from Ebola epidemics (current and historic) to reconstruct transmission trees and illustrate the theoretical impact of these vaccination strategies. Our data suggest a substantial potential benefit of prophylactic versus reactive vaccination of HCWs in preventing early transmissions. We estimate that prophylactic vaccination with a coverage >99% and theoretical 100% efficacy could avert nearly two-thirds of cases studied; 75% coverage would still confer clear benefit (40% cases averted), but reactive vaccination would be of less value in the early epidemic. A prophylactic vaccination campaign for front-line HCWs is not a trivial undertaking; whether to prioritise long-lasting vaccines and provide prophylaxis to HCWs is a live policy question. Prophylactic vaccination is likely to have a greater impact on the mitigation of future epidemics than reactive strategies and, in some cases, might prevent them. However, in a confirmed outbreak, reactive vaccination would be an essential humanitarian priority. The value of HCW Ebola vaccination is often only seen in terms of personal protection of the HCW workforce. A prophylactic vaccination strategy is likely to bring substantial additional benefit by preventing early transmission and might abort some epidemics. This has implications both for policy and for the optimum product profile for vaccines currently in development

Risk factors for mortality from imported falciparum malaria in the United Kingdom over 20 years: an observational study

Objectives To determine which travellers with malaria are at greatest risk of dying, highlighting factors which can be used to target health messages to travellers. Design Observational study based on 20 years of UK national data. Setting National register of malaria cases. Participants 25 054 patients notified with Plasmodium falciparum malaria, of whom 184 died, between 1987 and 2006. Main outcome measures Comparison between those with falciparum malaria who died and non-fatal cases, including age, reason for travel, country of birth, time of year diagnosed, malaria prophylaxis used. Results Mortality increased steadily with age, with a case fatality of 25/548 (4.6%) in people aged >65 years, adjusted odds ratio 10.68 (95% confidence interval 6.4 to 17.8), P<0.001 compared with 18–35 year olds. There were no deaths in the ≤5 year age group. Case fatality was 3.0% (81/2740 cases) in tourists compared with 0.32% (26/8077) in travellers visiting friends and relatives (adjusted odds ratio 8.2 (5.1 to 13.3), P<0.001). Those born in African countries with endemic malaria had a case fatality of 0.4% (36/8937) compared with 2.4% (142/5849) in others (adjusted odds ratio 4.6 (3.1 to 9.9), P<0.001). Case fatality was particularly high from the Gambia. There was an inverse correlation in mortality between region of presentation and number of cases seen in the region (R2=0.72, P<0.001). Most delay in fatal cases was in seeking care. Conclusions Most travellers acquiring malaria are of African heritage visiting friends and relatives. In contrast the risks of dying from malaria once acquired are highest in the elderly, tourists, and those presenting in areas in which malaria is seldom seen. Doctors often do not think of these as high risk groups for malaria; for this reason they are important groups to target in pre-travel advice

Violent video games and morality: a meta-ethical approach

This paper considers what it is about violent video games that leads one reasonably minded person to declare "That is immoral" while another denies it. Three interpretations of video game content a re discussed: reductionist, narrow, and broad. It is argued that a broad interpretation is required for a moral objection to be justified. It is further argued that understanding the meaning of moral utterances – like "x is immoral" – is important to an understanding of why there is a lack of moral consensus when it comes to the content of violent video games. Constructive ecumenical expressivism is presented as a means of explaining what it is that we are doing when we make moral pronouncements and why, when it comes to video game content, differing moral attitudes abound. Constructive ecumenical expressivism is also presented as a means of illuminating what would be required for moral consensus to be achieved

Knowledge and malaria treatment practices using artemisinin combination therapy (ACT) in Malawi: survey of health professionals

<p>Abstract</p> <p>Background</p> <p>Malaria still remains a life-threatening disease worldwide causing between 190 and 311 million cases of malaria in 2008. Due to increased resistance to sulphadoxine-pyrimethamine (SP), the Ministry of Health in Malawi, as in many sub-Saharan African countries, changed the malaria treatment policy to use artemisinin-based combination therapy (ACT). In order to optimize the correct use of this drug, and protect against the development of the parasite's resistance, it is important to assess the knowledge and practices of medical practitioners on the use of ACT and its impact on adherence to new treatment policy guidelines.</p> <p>Methods</p> <p>A cross-sectional survey was conducted to assess the knowledge and perceptions of Malawian medical doctors and pharmacists on the use of ACT and the drivers of treatment choice and clinical treatment decisions. Medical doctors and pharmacists who are involved in managing malaria patients in Malawi were recruited and a self-administered questionnaire was used to obtain information on socio-demographic characteristics of the study participants, knowledge on ACT, source of information on ACT and methods used to decide on the treatment of patients with malaria.</p> <p>Results</p> <p>Most of the participants (95.7%) know at least one form of ACT, 67.4% reported that different forms of ACT have different characteristics, 77.3% reported that there are special formulations for children. The most commonly mentioned ACT was artemether-lumefantrine (AL), by 94.6% of the participants and 75.0% of the participants indicated that they prefer to prescribe AL. 73.9% of participants had ever received information on ACT. However, only 31.5% had received training on management of malaria using ACT. There were 71.7% respondents who had heard of ACT causing side effects. Only 25.0% of the participants had received training on how to report SAEs.</p> <p>Conclusion</p> <p>It was found that most of the participants know about ACT and treatment guidelines for malaria. However, most of the participants have not received any training on how to use ACT and how to report adverse effects arising from the use of ACT. There is need for more training of health care professionals to ensure correct and effective use of ACT.</p

Anthropometric indices of Gambian children after one or three annual rounds of mass drug administration with azithromycin for trachoma control.

BACKGROUND: Mass drug administration (MDA) with azithromycin, carried out for the control of blinding trachoma, has been linked to reduced mortality in children. While the mechanism behind this reduction is unclear, it may be due, in part, to improved nutritional status via a potential reduction in the community burden of infectious disease. To determine whether MDA with azithromycin improves anthropometric indices at the community level, we measured the heights and weights of children aged 1 to 4 years in communities where one (single MDA arm) or three annual rounds (annual MDA arm) of azithromycin had been distributed. METHODS: Data collection took place three years after treatment in the single MDA arm and one year after the final round of treatment in the annual MDA arm. Mean height-for-age, weight-for-age and weight-for-height z scores were compared between treatment arms. RESULTS: No significant differences in mean height-for-age, weight-for-age or weight-for-height z scores were found between the annual MDA and single MDA arms, nor was there a significant reduction in prevalence of stunting, wasting or underweight between arms. CONCLUSIONS: Our data do not provide evidence that community MDA with azithromycin improved anthropometric outcomes of children in The Gambia. This may suggest reductions in mortality associated with azithromycin MDA are due to a mechanism other than improved nutritional status

The quest for universal access to effective malaria treatment: how can the AMFm contribute?

Access to quality assured artemisinin-based combination therapy (ACT) has remained very low in most malaria endemic countries. A number of reasons, including unaffordable prices, have contributed to the low accessibility to these life-saving medicines. The Affordable Medicines Facility-Malaria (AMFm) is a mechanism to increase access to quality assured ACT. The AMFm will use price signals and a combination of public and private sector channels to achieve multiple public health objectives: replacing older and increasingly ineffective anti-malarial medicines, such as chloroquine and sulphadoxine-pyrimethamine with ACT, displacing oral artemisinin monotherapies from the market, and prolonging the lifespan of ACT by reducing the likelihood of resistance to artemisinin

Travel-related schistosomiasis, strongyloidiasis, filariasis, and toxocariasis: the risk of infection and the diagnostic relevance of blood eosinophilia

<p>Abstract</p> <p>Background</p> <p>This study prospectively assessed the occurrence of clinical and subclinical schistosomiasis, strongyloidiasis, filariasis, and toxocariasis, and the screening value of eosinophilia in adult short-term travelers to helminth-endemic countries.</p> <p>Methods</p> <p>Visitors of a pre-travel health advice centre donated blood samples for serology and blood cell count before and after travel. Samples were tested for eosinophilia, and for antibodies against schistosomiasis, strongyloidiasis, filariasis, and toxocariasis. Previous infection was defined as seropositivity in pre- and post-travel samples. Recent infection was defined as a seroconversion. Symptoms of parasitic disease were recorded in a structured diary.</p> <p>Results</p> <p>Previous infection was found in 112 of 1207 subjects: schistosomiasis in 2.7%, strongyloidiasis in 2.4%, filariasis in 3.4%, and toxocariasis in 1.8%. Recent schistosomiasis was found in 0.51% of susceptible subjects at risk, strongyloidiasis in 0.25%, filariasis in 0.09%, and toxocariasis in 0.08%. The incidence rate per 1000 person-months was 6.4, 3.2, 1.1, and 1.1, respectively. Recent infections were largely contracted in Asia. The positive predictive value of eosinophilia for diagnosis was 15% for previous infection and 0% for recent infection. None of the symptoms studied had any positive predictive value.</p> <p>Conclusion</p> <p>The chance of infection with schistosomiasis, strongyloidiasis, filariasis, and toxocariasis during one short-term journey to an endemic area is low. However, previous stay leads to a cumulative risk of infection. Testing for eosinophilia appeared to be of no value in routine screening of asymptomatic travelers for the four helminthic infections. Findings need to be replicated in larger prospective studies.</p

Exploring provider and community responses to the new malaria diagnostic and treatment regime in Solomon Islands

<p>Abstract</p> <p>Background</p> <p>Improvements in availability and accessibility of artemisinin-based combination therapy (ACT) for malaria treatment and the emergence of multi-drug-resistant parasites have prompted many countries to adopt ACT as the first-line drug. In 2009, Solomon Islands (SI) likewise implemented new national treatment guidelines for malaria. The ACT, Coartem^®(artemether-lumefantrine) is now the primary pharmacotherapy in SI for <it>Plasmodium falciparum </it>malaria, <it>Plasmodium vivax </it>malaria or mixed infections. Targeted treatment is also recommended in the new treatment regime through maintenance of quality microscopy services and the introduction of Rapid Diagnostic Tests (RDTs). Ascertaining the factors that influence community and provider acceptance of and adherence to the new treatment regime will be vital to improving the effectiveness of this intervention and reducing the risk of development of drug resistance.</p> <p>Methods</p> <p>In order to understand community and prescriber perceptions and acceptability of the new diagnostic and treatment interventions, 12 focus group discussions (FGDs) and 12 key informant interviews (KII) were carried out in rural and urban villages of Malaita Province, Solomon Islands four months subsequent to roll out of these interventions.</p> <p>Results</p> <p>Lack of access to microscopy or distrust in the accuracy of diagnostic tools were reported by some participants as reasons for the ongoing practice of presumptive treatment of malaria. Lack of confidence in RDT accuracy has negatively impacted its acceptability. Coartem^®had good acceptability among most participants, however, some rural participants questioned its effectiveness due to lack of side effects and the larger quantity of tablets required to be taken. Storing of left over medication for subsequent fever episodes was reported as common.</p> <p>Conclusion</p> <p>To address these issues, further training and supportive supervision of healthcare workers will be essential, as will the engagement of influential community members in health promotion activities to improve acceptability of RDTs and adherence to the new treatment regime. Exploring the extent of these issues beyond the study population must be a priority for malaria programme managers. Practices such as presumptive treatment and the taking of sub-curative doses are of considerable concern for both the health of individuals and the increased risk it poses to the development of parasite resistance to this important first-line treatment against malaria.</p

Safety and efficacy of dihydroartemisinin-piperaquine versus artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in Zambian children

<p>Abstract</p> <p>Background</p> <p>Malaria in Zambia remains a public health and developmental challenge, affecting mostly children under five and pregnant women. In 2002, the first-line treatment for uncomplicated malaria was changed to artemether-lumefantrine (AL) that has proved to be highly efficacious against multidrug resistant <it>Plasmodium falciparum</it>.</p> <p>Objective</p> <p>The study objective was to determine whether dihydroartemisinin-piperaquine (DHA/PQP) had similar efficacy, safety and tolerability as AL for the treatment of children with uncomplicated <it>P. falciparum </it>malaria in Ndola, Zambia.</p> <p>Methods</p> <p>Between 2005 and 2006, 304 children (6-59 months old) with uncomplicated <it>P. falciparum </it>were enrolled, randomized to AL (101) or DHA/PQP (203) and followed up for 42 days. Outcome of treatment was defined according to the standard WHO classification, i.e. early treatment failure (ETF), late clinical failure (LCF, late parasitological failure (LPF) and adequate clinical and parasitological response (ACPR). Recurrent infections were genotyped to distinguish between recrudescence and new infection.</p> <p>Results</p> <p>No ETF was observed. At day 28, PCR-uncorrected ACPR was 92% in the DHA/PQP and 74% in the AL arm (OR: 4.05; 95%CI: 1.89-8.74; p < 0.001). Most failure were new infections and PCR-corrected ACPR was similar in the two study arms (OR: 0.69; 95%CI: 0.22-2.26; p = 0.33). Similar results were observed for day 42, i.e. higher PCR-uncorrected ACPR for DHA/PQP, mainly due to the difference observed up to day 28, while the PCR-corrected ACPR was similar: DHA/PQP: 93% (179/192), AL: 93% (84/90), (OR: 0.92; 95%CI: 0.30-2.64; p = 0.85). Except for cough, more frequent in the DHA/PQP arm (p = 0.04), there were no differences between treatment arms in the occurrence of adverse events. Two serious adverse events were probably associated to AL treatment.</p> <p>Conclusion</p> <p>DHA/PQP was as efficacious, safe and well tolerated in treatment of uncomplicated malaria as AL, though in the latter group more new infections during the follow up were observed. DHA/PQP seems a potential candidate to be used as an alternative first-line or rescue treatment in Zambia.</p> <p>Trial Registration</p> <p><a href="http://www.controlled-trials.com/ISRCTN16263443">ISRCTN16263443</a>, at <url>http://www.controlled-trials.com/isrctn</url></p