Economic interventions to improve population health: a scoping study of systematic reviews.

BACKGROUND: Recognizing the close relationship between poverty and health, national program managers, policy-makers and donors are increasingly including economic interventions as part of their core strategies to improve population health. However, there is often confusion among stakeholders about the definitions and operational differences between distinct types of economic interventions and financial instruments, which can lead to important differences in interpretation and expectations. METHODS: We conducted a scoping study to define and clarify concepts underlying key economic interventions - price interventions (taxes and subsidies), income transfer programs, incentive programs, livelihood support programs and health-related financial services - and map the evidence currently available from systematic reviews. RESULTS: We identified 195 systematic reviews on economic interventions published between 2005 and July 2015. Overall, there was an increase in the number of reviews published after 2010. The majority of reviews focused on price interventions, income transfer programs and incentive programs, with much less evidence available from systematic reviews on livelihood support programs and health-related financial services. We also identified a lack of evidence on: health outcomes in low income countries; unintended or perverse outcomes; implementation challenges; scalability and cost-effectiveness of economic interventions. CONCLUSIONS: We conclude that while more research is clearly needed to assess suitability and effectiveness of economic interventions in different contexts, before interventions are tested and further systematic reviews conducted, a consistent and accurate understanding of the fundamental differences in terminology and approaches is essential among researchers, public health policy makers and program planners.

Pilgrims and MERS-CoV: what's the risk?

The risk of Middle East Respiratory Syndrome Coronavirus spreading globally is worrying, given the annual mass gathering of the Hajj and the year-long influx of pilgrims undertaking the Umrah. Based on the incidence in Saudi Arabia since June 2012, the most likely scenario given recent pilgrim numbers is estimated to be one case per Hajj, and three Umrah pilgrims per year, but which could plausibly reach seven and ten pilgrims respectively. In addition to the 2015 Hajj, national surveillance systems should be on the alert for the low but long-lasting risk of infected pilgrims returning from the Umrah throughout the year.

The distribution of incubation and relapse times in experimental human infections with the malaria parasite Plasmodium vivax.

BACKGROUND: The distributions of incubation and relapse periods are key components of infectious disease models for the malaria parasite Plasmodium vivax; however, detailed distributions based upon experimental data are lacking. METHODS: Using a range of historical, experimental mosquito-transmitted human infections, Bayesian estimation with non-informative priors was used to determine parametric distributions that can be readily implemented for the incubation period and time-to-first relapse in P. vivax infections, including global subregions by parasite source. These analyses were complemented with a pooled analysis of observational human infection data with infections that included malaria chemoprophylaxis and long-latencies. The epidemiological impact of these distributional assumptions was explored using stochastic epidemic simulations at a fixed reproductive number while varying the underlying distribution of incubation periods. RESULTS: Using the Deviance Information Criteria to compare parameterizations, experimental incubation periods are most closely modeled with a shifted log-logistic distribution; a log-logistic mixture is the best fit for incubations in observational studies. The mixture Gompertz distribution was the best fit for experimental times-to-relapse among the tested parameterizations, with some variation by geographic subregions. Simulations suggest underlying distributional assumptions have critically important impacts on both the time-scale and total case counts within epidemics. CONCLUSIONS: These results suggest that the exponential and gamma distributions commonly used for modeling incubation periods and relapse times inadequately capture the complexity in the distributions of event times in P. vivax malaria infections. In future models, log-logistic and Gompertz distributions should be utilized for general incubation periods and relapse times respectively, and region-specific distributions should be considered to accurately model and predict the epidemiology of this important human pathogen.

Re-assessing the relationship between sporozoite dose and incubation period in Plasmodium vivax malaria: a systematic re-analysis.

Infections with the malaria parasite Plasmodium vivax are noteworthy for potentially very long incubation periods (6-9 months), which present a major barrier to disease elimination. Increased sporozoite challenge has been reported to be associated with both shorter incubation and pre-patent periods in a range of human challenge studies. However, this evidence base has scant empirical foundation, as these historical analyses were limited by available analytic methods, and provides no quantitative estimates of effect size. Following a comprehensive literature search, we re-analysed all identified studies using survival and/or logistic models plus contingency tables. We have found very weak evidence for dose-dependence at entomologically plausible inocula levels. These results strongly suggest that sporozoite dosage is not an important driver of long-latency. Evidence presented suggests that parasite strain and vector species have quantitatively greater impacts, and the potential existence of a dose threshold for human dose-response to sporozoites. Greater consideration of the complex interplay between these aspects of vectors and parasites are important for human challenge experiments, vaccine trials, and epidemiology towards global malaria elimination.

Quantifying effect of geographic location on epidemiology of Plasmodium vivax malaria.

Recent autochthonous transmission of Plasmodium vivax malaria in previously malaria-free temperate regions has generated renewed interest in the epidemiology of this disease. Accurate estimates of the incubation period and time to relapse are required for effective malaria surveillance; however, this information is currently lacking. By using historical data from experimental human infections with diverse P. vivax strains, survival analysis models were used to obtain quantitative estimates of the incubation period and time to first relapse for P. vivax malaria in broad geographic regions. Results show that Eurasian strains from temperate regions have longer incubation periods, and Western Hemisphere strains from tropical and temperate regions have longer times to relapse compared with Eastern Hemisphere strains. The diversity in these estimates of key epidemiologic parameters for P. vivax supports the need for elucidating local epidemiology to inform clinical follow-up and to build an evidence base toward global elimination of malaria.

Emerging infectious diseases in southeast Asia: regional challenges to control.

Southeast Asia is a hotspot for emerging infectious diseases, including those with pandemic potential. Emerging infectious diseases have exacted heavy public health and economic tolls. Severe acute respiratory syndrome rapidly decimated the region's tourist industry. Influenza A H5N1 has had a profound effect on the poultry industry. The reasons why southeast Asia is at risk from emerging infectious diseases are complex. The region is home to dynamic systems in which biological, social, ecological, and technological processes interconnect in ways that enable microbes to exploit new ecological niches. These processes include population growth and movement, urbanisation, changes in food production, agriculture and land use, water and sanitation, and the effect of health systems through generation of drug resistance. Southeast Asia is home to about 600 million people residing in countries as diverse as Singapore, a city state with a gross domestic product (GDP) of US$37,500 per head, and Laos, until recently an overwhelmingly rural economy, with a GDP of US$890 per head. The regional challenges in control of emerging infectious diseases are formidable and range from influencing the factors that drive disease emergence, to making surveillance systems fit for purpose, and ensuring that regional governance mechanisms work effectively to improve control interventions.

How prepared is Europe for pandemic influenza? Analysis of national plans.

BACKGROUND: The threat of a human pandemic of influenza has prompted urgent development of national preparedness plans. We assessed these plans, to judge Europe's preparedness for pandemic influenza. METHODS: Published national pandemic influenza preparedness plans from the European Union countries, the two acceding countries (Bulgaria and Romania), Norway, and Switzerland, were evaluated against criteria taken from a WHO checklist. Plans were eligible for inclusion if formally published between Jan 1, 2002, and Nov 30, 2005. FINDINGS: 21 national plans were eligible for inclusion for analysis. Although preparation for surveillance, planning and coordination, and communication were good, maintenance of essential services, putting plans into action, and public-health interventions were probably inadequate. Few countries have addressed in their plans the need for collaboration with adjacent countries, despite this being an acknowledged imperative. Similarly, plans for the timely distribution of available medical supplies are notably absent. INTERPRETATION: Governmental commitment in most European countries is strong, and levels of preparedness are broadly good. However, gaps in preparedness planning remain, and substantial variations exist between countries, with important implications for the region and nation states. Improved cooperation between countries may be needed to share experience, and to ensure coherence of approaches.

High coverage with HAART is required to substantially reduce the number of deaths from tuberculosis: system dynamics simulation.

We used a system dynamics simulation model of the transmission dynamics of drug-sensitive tuberculosis (DSTB), multidrug-resistant tuberculosis (MDRTB) and HIV to estimate the impact of coverage with highly active antiretroviral therapy (HAART) and different cure rates for MDRTB in settings of explosive HIV epidemics and high MDRTB levels. Population coverage levels at 0%, 25%, 50%, 75% and 100% for HAART, and 5% and 80% of MDRTB treatment cure rates were simulated over a 10-year period and cumulative deaths from tuberculosis and HIV-associated tuberculosis were estimated for populations with latent tuberculosis, DSTB, MDRTB, HIV and HIV-associated tuberculosis. Depending on levels of HAART population coverage, increasing MDRTB cure rates from 5% to 80% reduces cumulative tuberculosis deaths by 1% and 13%. High population coverage with HAART (75% or higher), allied with high MDRTB cure rates, reduces cumulative deaths by 60%, with limited impact below this level. High coverage with HAART is required to substantially reduce the number of deaths from tuberculosis.

Impact of joined-up HIV harm reduction and multidrug resistant tuberculosis control programmes in Estonia: System dynamics simulation model.

In Eastern Europe and Central Asia (ECA) the control of tuberculosis, multidrug resistant tuberculosis (MDRTB) and human immunodeficiency virus (HIV) poses important public health challenges. We used system dynamics simulation to determine impact on cumulative HIV/AIDS, tuberculosis and HIV-associated-tuberculosis deaths, over 20 years, of harm-reduction programmes to reduce needle-sharing and injection-frequency amongst injecting drug users (IDUs) and multidrug resistant tuberculosis (MDRTB) control in a population with an explosive HIV epidemic in IDUs and high MDRTB prevalence. We estimate that the number of HIV-associated-deaths will decline by 30% with effective harm-reduction programmes but double if these are ineffective. In our model, effective MDRTB and HIV control reduces cumulative tuberculosis deaths by 54%, cumulative MDRTB deaths 15-fold and cumulative HIV-associated-tuberculosis-deaths 2-fold. Effective MDRTB control, without effective harm-reduction programmes, only reduce tuberculosis deaths by 22%. However, effective harm-reduction programme with a poor MDRTB control reduce cumulative tuberculosis deaths by 34%, MDRTB by 14% and HIV-associated-tuberculosis by 56%. Even with good control programmes for drug sensitive TB, neglecting harm reduction and MDRTB control will result in 50% more tuberculosis-related deaths than if both are effectively addressed. Effective harm-reduction programmes reduces cumulative deaths from tuberculosis more substantively than effective MDRTB control. Our finding have important policy implications for communicable disease policies in post-Soviet countries, which need to substantially change if they are to effectively address the emerging HIV and MDRTB epidemics.

Risk factors that may be driving the emergence of drug resistance in tuberculosis patients treated in Yangon, Myanmar.

BACKGROUND: The majority of new tuberculosis cases emerging every year occur in low and middle-income countries where public health systems are often characterised by weak infrastructure and inadequate resources. This study investigates healthcare seeking behaviour, knowledge and treatment of tuberculosis patients in Myanmar-which is facing an acute drug-resistant tuberculosis epidemic-and identifies factors that may increase the risk of emergence of drug-resistant tuberculosis. METHODS: We randomly selected adult smear-positive pulmonary tuberculosis patients diagnosed between September 2014 and March 2015 at ten public township health centres in Yangon, the largest city in Myanmar. Data on patients' healthcare seeking behaviour, treatment at the township health centres, co-morbidities and knowledge was collected through patient interviews and extraction from hospital records. A retrospective descriptive cross-sectional analysis was conducted. RESULTS: Of 404 TB patients selected to participate in the study, 11 had died since diagnosis, resulting in 393 patients being included in the final analysis. Results indicate that a high proportion of patients (16%; 95% CI = 13-20) did not have a treatment supporter assigned to improve adherence to medication, with men being more likely to have no treatment supporter assigned. Use of private healthcare providers was very common; 59% (54-64) and 30.3% (25.9-35.0) of patients reported first seeking care at private clinics and pharmacies respectively. We found that 8% (6-11) of tuberculosis patients had confirmed diabetes. Most patients had some knowledge about tuberculosis transmission and the consequences of missing treatment. However, 5% (3-8) stated that they miss taking tuberculosis medicines at least weekly, and patients with no knowledge of consequences of missing treatment were more likely to miss doses. CONCLUSIONS: This study analysed healthcare seeking behaviour and treatment related practices of tuberculosis patients being managed under operational conditions in a fragile health system. Findings indicate that ensuring that treatment adherence support is arranged for all patients, monitoring of response to treatment among the high proportion of tuberculosis patients with diabetes and engagement with private healthcare providers could be strategies addressed to reduce the risk of emergence of drug-resistant tuberculosis.

Evidence to inform resource allocation for tuberculosis control in Myanmar: a systematic review based on the SYSRA framework.

Myanmar represents an extreme example of the difficulties in optimally allocating resources for maximum public health benefit, on the basis of limited information. At the recent Myanmar Health Forum 'Investing in Health' much of the discussion revolved around what to invest in, how health systems could be strengthened, and what research and capacity building areas the international donor community should prioritise for support. Funding for infectious disease control, particularly HIV and tuberculosis, is being channelled to the country at an unprecedented rate, but very little research has been conducted in recent years, and existing information has not yet been synthesised. This paper presents findings of the first systematic literature review on tuberculosis control and the health system in Myanmar, with the aim of informing the development of optimal research priorities and strategies. Medline and grey literature were searched for relevant papers. Inclusion criteria and analyses were structured to capture data on the Myanmar health system, healthcare delivery, financing, tuberculosis control indicators and information systems. A total of 77 papers were included in the analysis. The results indicate that there has been a large increase in the number of peer-reviewed articles published on tuberculosis in Myanmar over the past decade, although the absolute number of studies remains small. We identified several areas in which evidence to inform policy and resource allocation decisions is lacking, including research focused on rural and/or vulnerable populations, analyses of risk factors for TB and drug resistance that can inform prevention strategies and economic analyses for optimising resource allocation. The gaps in research to inform policy identified through this study may be relevant to other low resource settings with extremely limited research capacity.

Preventing emergence of drug resistant tuberculosis in Myanmar's transitioning health system.

Multidrug-resistant tuberculosis (MDR-TB) is a particular threat to the populations of resource-limited countries. Although inadequate treatment of TB has been identified as a major underlying cause of drug resistance, essential information to inform changes in health service delivery and policy is missing. We investigate factors that may be driving the emergence of MDR-TB in Myanmar, a country where investment and health system reforms are ongoing to address the unexplained, high occurrence of MDR-TB. We conducted a multi-centre, retrospective case-control study in 10 townships across Yangon. Cases were 202 GeneXpert-confirmed MDR-TB patients with a history of prior first-line treatment for TB. Controls were 404 previously untreated smear-microscopy confirmed TB patients who had no evidence of resistance to anti-TB drugs. Information on patient and health service factors was collected through face-to-face patient interviews and hospital record reviews. Multivariable logistic regression analysis indicated that the following TB patient groups are at higher risk of developing MDR-TB after initial TB treatment: those who have diabetes (aOR 2.10; 95% CI 1.17-3.76), those who missed taking drugs during the initial treatment more than once weekly (aOR 2.35; 95% CI 1.18-4.65) and those with a higher socioeconomic (aOR 1.99; 95% CI 1.09-3.63) or educational status (aOR 1.78; 95% CI1.01-3.13). Coinciding with a surge in funding to improve health in Myanmar, this study identifies practices of patients and healthcare organizations that can be addressed, and high-risk TB patient groups that can be prioritized for treatment support. Specifically, the study shows that TB patients who experience frequent, short interruptions in treatment and those with diabetes may require enhanced treatment support and monitoring by health services in order to prevent further generation of drug resistance.

Health-care system frailties and public health control of communicable disease on the European Union's new eastern border.

In May, 2004, the border of the European Union (EU) will shift eastward such that the new frontier will be made up by Ukraine, Belarus, and a considerably longer Russian border. Here, we discuss three issues: first, the factors that have contributed to the growth of communicable disease in Russia, Ukraine, and Belarus; second, how public health systems have responded to these challenges; and third, the implications for the EU as a whole. Since the break-up of the Soviet Union, Russia, Ukraine, and Belarus have witnessed substantial political, social, and economic changes. These events have been reflected in changes in the epidemiology of communicable diseases, including tuberculosis and HIV (ie, HIV-1). Moreover, public health systems, rooted in Soviet traditions, are struggling to respond effectively to the challenges of resurgent infectious diseases, such as tuberculosis, and newly emergent challenges such as HIV. The changing patterns of communicable diseases east of the EU's new border has implications for how the EU aids the strengthening of public health systems east of the new frontier. Transborder spread of communicable diseases also challenges communicable disease control systems within the EU. Concerted action is needed by member states and the EU, building on models of cooperation between institutions that have been successful in areas beyond health, if public health systems are to meet the emerging challenges to communicable disease control.

Impact of an effective multidrug-resistant tuberculosis control programme in the setting of an immature HIV epidemic: system dynamics simulation model.

This study sought to determine the impact of an effective programme of multidrug resistant tuberculosis control (MDRTB) on a population that is witnessing an explosive HIV epidemic among injecting drug users (IDUs), where the prevalence of MDRTB is already high. A transmission model was constructed that represents the dynamics of the drug-susceptible tuberculosis (DSTB), MDRTB and HIV spread among the adult population of Samara Oblast, Russia: from official notifications of tuberculosis and of HIV infection, estimates of MDRTB derived from surveillance studies, population data from official regional statistics, data on transmission probabilities from peer-reviewed publications and informed estimates, and policy-makers' estimates of IDU populations. Two scenarios of programme effectiveness for MDRTB were modelled and run over a period of 10 years to predict cumulative deaths. In a population of 3.3 million with a high prevalence of MDRTB, an emerging epidemic of HIV among IDUs, and a functioning directly observed therapy-short course (DOTS) programme, the model predicts that under low cure rates for MDRTB the expected cumulative deaths from tuberculosis will reach 6303 deaths including 1900 deaths from MDRTB at 10 years. Under high cure rate for MDRTB 4465 deaths will occur including 134 deaths from MDRTB. At 10 years there is little impact on HIV-infected populations from the MDRTB epidemic, but as the HIV epidemic matures the impact becomes substantial. When the model is extended to 20 years cumulative deaths from MDRTB become very high if cure rates for MDRTB are low and cumulative deaths in the HIV-infected population, likewise, are profoundly affected. In the presence of an immature HIV epidemic failure to actively control MDRTB may result in approximately a third more deaths than if effective treatment is given. As the HIV epidemic matures then the impact of MDRTB grows substantially if MDRTB control strategies are ineffective. The epidemiological starting point for these scenarios is present in many regions within the former Soviet Union and this analysis suggests control of MDRTB should be an urgent priority.

Implementing WHO DOTS strategy in the Russian Federation: stakeholder attitudes.

Russia has the ninth highest tuberculosis burden in the world. After a period of decline starting in the 1960s, the case notification rate tripled during the 1990s. Historically, case-finding, treatment and reporting practices in Russia have differed from those advocated by WHO and the international community: Directly Observed Therapy--short course (DOTS). By 2003, approximately 26% of the population in Russia was covered by the DOTS strategy. By contrast, the average coverage in the 22 high-burden countries is 61%. The reasons for this low rate in Russia have not been systematically examined. Using qualitative research methods we explored, in depth, the attitudes of key stakeholders involved in tuberculosis control to introduction of DOTS in a region of Russia. Six focus groups and 128 in depth interviews were held with clinicians, managers, policy-makers and patients. The results show negative attitude to change due to inadequate understanding of DOTS; perceived 'directiveness' of the 'externally developed' DOTS strategy and the standardized nature of the treatment regimen. The doctors, managers and patients saw that prolonged periods of hospitalisation (the traditional way of managing TB in Russia) was advantageous because treatment routines could be ensured, medical expertise was readily available, and other needs such as shelter and food were provided. Respondents felt that the patients were unlikely to adhere to treatment in the community. Cultural issues and capacity constraints, especially in laboratory equipment and personnel, would impede introduction and sustainability of the DOTS strategy.

Do mixed infections matter? Assessing virulence of mixed-clone infections in experimental human and murine malaria.

BACKGROUND: Malaria parasites within an individual infection often consist of multiple strains (clonal populations) of a single species, which have the potential to interact both with one another, and with the host immune system. Several effects of these interactions have been measured in different parasite systems including competition and mutualism; however, direct observation of these effects in human malaria has been limited by sampling complexities and inherent ethical limitations. METHODS: Using multiple complementary epidemiological models, we propose a suite of analyses to more fully utilize data from challenge experiments, and re-examine historical human challenge studies with mixed-strain Plasmodium vivax inocula. We then compare these results with murine model systems using mixed-strain Plasmodium yoelii or Plasmodium chabaudi, to explore the utility of these methods in fully utilizing these data, including the first quantitative estimates of effect sizes for mixed-strain parasitemia. These models also provide a method to assess consistency within these animal model systems. RESULTS: We find that amongst a limited set of P. vivax (incubation time) and P. yoelii infections (time-to-mortality), survival times at a study population-level are intermediate between each single-clone infection, and are not dominated by the more virulent clone; in P. vivax relapses, mixed clone infections also show intermediate survival curves. In these infections, the results strongly suggest that highly virulent clones have their virulence attenuated by the presence of less-virulent clones. The analysis of multiple experiments with P. chabaudi suggests greater nuances in the interactions between strains, and that mortality and time-to-event in mixed-strain infections are both indistinguishable from single infections with the more virulent strain. CONCLUSIONS: These divergent dynamics support earlier work that suggested drivers of virulence may differ in fundamental ways between malaria species that are reticulocyte-specific and those that readily infect all red blood cell stages which should be studied in greater detail. The effect sizes (magnitude of biological effects) from these analyses are significant, and suggest the potential for important gains in malaria control by greater incorporation of evolutionary epidemiology theory. Moreover, we suggest that using these epidemiological models may generally allow fuller use of data from experimentally challenging animal model experiments.

Communicable disease control programmes and health systems: an analytical approach to sustainability.

There is renewed concern over the sustainability of disease control programmes, and re-emergence of policy recommendations to integrate programmes with general health systems. However, the conceptualization of this issue has remarkably received little critical attention. Additionally, the study of programmatic sustainability presents methodological challenges. In this article, we propose a conceptual framework to support analyses of sustainability of communicable disease programmes. Through this work, we also aim to clarify a link between notions of integration and sustainability. As a part of development of the conceptual framework, we conducted a systematic literature review of peer-reviewed literature on concepts, definitions, analytical approaches and empirical studies on sustainability in health systems. Identified conceptual proposals for analysis of sustainability in health systems lack an explicit conceptualization of what a health system is. Drawing upon theoretical concepts originating in sustainability sciences and our review here, we conceptualize a communicable disease programme as a component of a health system which is viewed as a complex adaptive system. We propose five programmatic characteristics that may explain a potential for sustainability: leadership, capacity, interactions (notions of integration), flexibility/adaptability and performance. Though integration of elements of a programme with other system components is important, its role in sustainability is context specific and difficult to predict. The proposed framework might serve as a basis for further empirical evaluations in understanding complex interplay between programmes and broader health systems in the development of sustainable responses to communicable diseases.