Guinea worm disease – the final chapter?

The global campaign for the eradication of dracunculiasis has succeeded in reducing the incidence of guinea worm disease by >99% in the past 20 years. This has been accomplished by the provision of safe drinking water supplies, filtration of drinking water, chemical control of intermediate hosts, case containment and, crucially, local health-education initiatives.     

Why is dracunculiasis eradication taking so long?

The long time needed for global eradication of dracunculiasis (Guinea worm disease) was not anticipated at the outset. The successful eradication of smallpox in 10 years compares with the target date set in 1985 for dracunculiasis eradication - 1995. Seventeen years after that date, transmission continues. Why? Various factors are responsible, mainly lack of resources, or resources ineffectively used. The example of Ghana, where the programme stagnated for a decade, sheds light on this delay. When more resources were put into Ghana's programme in 2007, transmission of the disease was interrupted in 3 years. The variable success of dracunculiasis eradication in different countries provides lessons for future disease eradication programmes.     

Global eradication of Guinea worm

Little more than a decade ago, it was estimated that over three million cases of dracunculiasis occurred worldwide. Since then, the numbers have fallen dramatically, thanks to the water supply initiatives of the 1980s and, more recently, the national guinea worm eradication programmes implemented in a score of endemic countries. Hervé Periès and Sandy Cairncross discuss how eradication will require the containment of cases in the remaining endemic areas, together with the simultaneous strengthening of surveillance to permit the certification of eradication. This aim requires existing strategies to be adapted to maintain their efficacy and also to improve their sustainability and cost-effectiveness. Sudan with its civil war, and more than a hundred thousand reported cases, remains a major obstacle to rapid achievement of the goal.     

The role of research in viral disease eradication and elimination programs: lessons for malaria eradication

By examining the role research has played in eradication or regional elimination initiatives for three viral diseases--smallpox, poliomyelitis, and measles--we derive nine cross-cutting lessons applicable to malaria eradication. In these initiatives, some types of research commenced as the programs began and proceeded in parallel. Basic laboratory, clinical, and field research all contributed notably to progress made in the viral programs. For each program, vaccine was the lynchpin intervention, but as the programs progressed, research was required to improve vaccine formulations, delivery methods, and immunization schedules. Surveillance was fundamental to all three programs, whilst polio eradication also required improved diagnostic methods to identify asymptomatic infections. Molecular characterization of pathogen isolates strengthened surveillance and allowed insights into the geographic source of infections and their spread. Anthropologic, sociologic, and behavioural research were needed to address cultural and religious beliefs to expand community acceptance. The last phases of elimination and eradication became increasingly difficult, as a nil incidence was approached. Any eradication initiative for malaria must incorporate flexible research agendas that can adapt to changing epidemiologic contingencies and allow planning for posteradication scenarios.     

The DIOS framework for optimizing infectious disease surveillance: Numerical methods for simulation and multi-objective optimization of surveillance network architectures

Infectious disease surveillance systems provide vital data for guiding disease prevention and control policies, yet the formalization of methods to optimize surveillance networks has largely been overlooked. Decisions surrounding surveillance design parameters—such as the number and placement of surveillance sites, target populations, and case definitions—are often determined by expert opinion or deference to operational considerations, without formal analysis of the influence of design parameters on surveillance objectives. Here we propose a simulation framework to guide evidence-based surveillance network design to better achieve specific surveillance goals with limited resources. We define evidence-based surveillance design as an optimization problem, acknowledging the many operational constraints under which surveillance systems operate, the many dimensions of surveillance system design, the multiple and competing goals of surveillance, and the complex and dynamic nature of disease systems. We describe an analytical framework—the Disease Surveillance Informatics Optimization and Simulation (DIOS) framework—for the identification of optimal surveillance designs through mathematical representations of disease and surveillance processes, definition of objective functions, and numerical optimization. We then apply the framework to the problem of selecting candidate sites to expand an existing surveillance network under alternative objectives of: (1) improving spatial prediction of disease prevalence at unmonitored sites; or (2) estimating the observed effect of a risk factor on disease. Results of this demonstration illustrate how optimal designs are sensitive to both surveillance goals and the underlying spatial pattern of the target disease. The findings affirm the value of designing surveillance systems through quantitative and adaptive analysis of network characteristics and performance. The framework can be applied to the design of surveillance systems tailored to setting-specific disease transmission dynamics and surveillance needs, and can yield improved understanding of tradeoffs between network architectures.     

Assessing Progress towards Public Health,Human Rights,and International Development Goals Using Frontier Analysis

Indicators to measure progress towards achieving public health, human rights, and international development targets, such as 100% access to improved drinking water or zero maternal mortality ratio, generally focus on status (i.e., level of attainment or coverage) or trends in status (i.e., rates of change). However, these indicators do not account for different levels of development that countries experience, thus making it difficult to compare progress between countries. We describe a recently developed new use of frontier analysis and apply this method to calculate country performance indices in three areas: maternal mortality ratio, poverty headcount ratio, and primary school completion rate. Frontier analysis is used to identify the maximum achievable rates of change, defined by the historically best-performing countries, as a function of coverage level. Performance indices are calculated by comparing a country’s rate of change against the maximum achievable rate at the same coverage level. A country’s performance can be positive or negative, corresponding to progression or regression, respectively. The calculated performance indices allow countries to be compared against each other regardless of whether they have only begun to make progress or whether they have almost achieved the target. This paper is the first to use frontier analysis to determine the maximum achievable rates as a function of coverage level and to calculate performance indices for public health, human rights, and international development indicators. The method can be applied to multiple fields and settings, for example health targets such as cessation in smoking or specific vaccine immunizations, and offers both a new approach to analyze existing data and a new data source for consideration when assessing progress achieved.     

Humble origins for a successful strategy: complete enrolment in early Cambrian olenellid trilobites

Trilobites are typified by the behavioural and morphological ability to enrol their bodies, most probably as a defence mechanism against adverse environmental conditions or predators. Although most trilobites could enrol at least partially, there is uncertainty about whether olenellids—among the most phylogenetically and stratigraphically basal representatives—could perform this behaviour because of their poorly caudalized trunk and scarcity of coaptative devices. Here, we report complete—but not encapsulating—enrolment for the olenellid genus Mummaspis from the early Cambrian Mural Formation in Alberta, the earliest direct evidence of this strategy in the fossil record of polymerid trilobites. Complete enrolment in olenellids was achieved through a combination of ancestral morphological features, and thus provides new information on the character polarity associated with this key trilobite adaptation.     

Therapeutic antibodies,vaccines and antibodyomes

The potential for antibodies to act as “magic bullets” for treatment of human disease was recognized a century ago, but its full realization has began to occur only during the last decade. A key to their current success is the ability to make libraries of antibodies/B cells, isolate a single species, and engineer it to be safe, efficacious and of high quality. Despite this progress, major challenges to the effective prevention, diagnosis and treatment of a vast majority of diseases remain. Limited success in the development of effective vaccines against diseases such as AIDS and cancer reflects our incomplete understanding of how antibodies are generated and function. Only a miniscule number of antibodies are characterized out of the universe of antibodies generated by the immune system. Knowledge of antibodyomes—the complete sets of antibodies—could help solve these and other challenges.Key words: antibodies, therapeutics, vaccines, antibodyome, biologicals     

British Regional Heart Study: geographic variations in cardiovascular mortality,and the role of water quality

In a study of regional variations in cardiovascular mortality in Great Britain during 1969-73 based on 253 towns the possible contributions of drinking water quality, climate, air pollution, blood groups, and socioeconomic factors were evaluated. A twofold range in mortality from stroke and ischaemic heart disease was apparent, the highest mortality being in the west of Scotland and the lowest in south-east England. A multifactorial approach identified five principal factors that substantially explained this geographic variation in cardiovascular mortality—namely, water hardness, rainfall, temperature, and two social factors (percentage of manual workers and car ownership). After adjustment for other factors cardiovascular mortality in areas with very soft water, around 0·25 mmol/l (calcium carbonate equivalent 25 mg/l), was estimated to be 10-15% higher than that in areas with medium-hard water, around 1·7 mmol/l (170 mg/l), while any further increase in hardness beyond 1·7 mmol/l did not additionally lower cardiovascular mortality.Thus a negative relation existed between water hardness and cardiovascular mortality, although climate and socioeconomic conditions also appeared to be important influences. Cross-sectional and prospective surveys of 7500 middle-aged men from 24 towns are in progress and will permit further exploration of these geographic differences, especially with regard to personal risk factors such as blood pressure, blood lipid concentrations, and cigarette smoking.     

Rabies in the Baltic States: Decoding a Process of Control and Elimination

Rabies is a fatal zoonosis that still causes nearly 70, 000 human deaths every year. In Europe, the oral rabies vaccination (ORV) of red foxes (Vulpes vulpes) was developed in the late 1970s and has demonstrated its effectiveness in the eradication of the disease in Western and some Central European countries. Following the accession of the three Baltic countries—Estonia, Latvia and Lithuania—to the European Union in 2004, subsequent financial support has allowed the implementation of regular ORV campaigns since 2005–2006. This paper reviews ten years of surveillance efforts and ORV campaigns in these countries resulting in the near eradication of the disease. The various factors that may have influenced the results of vaccination monitoring were assessed using generalized linear models (GLMs) on bait uptake and on herd immunity. As shown in previous studies, juveniles had lower bait uptake level than adults. For the first time, raccoon dogs (Nyctereutes procyonoides) were shown to have significantly lower bait uptake proportion compared with red foxes. This result suggests potentially altered ORV effectiveness in this invasive species compared to the red foxes. An extensive phylogenetic analysis demonstrated that the North-East European (NEE) rabies phylogroup is endemic in all three Baltic countries. Although successive oral vaccination campaigns have substantially reduced the number of detected rabies cases, sporadic detection of the C lineage (European part of Russian phylogroup) underlines the risk of reintroduction via westward spread from bordering countries. Vaccine induced cases were also reported for the first time in non-target species (Martes martes and Meles meles).     

Control of Taenia solium taeniasis/cysticercosis: from research towards implementation

Theoretically, considering the biology of its transmission and reservoirs, global eradication of Taenia solium taeniasis and cysticercosis is feasible. Recently much progress has been made in research on diagnosis, treatment and prevention of human taeniasis and porcine cysticercosis, although more operational research is still needed. In spite of this, global eradication of T. solium infection is still unlikely in the near future. Major obstacles to practical implementation of control measures include low levels of sanitation and health education amongst endemic populations, ineffective health services infrastructure and inadequate socioeconomic development in these areas. The continued public health impact of neurocysticercosis, especially fatalities and epilepsy, force us to identify improved options for control. In order to implement control measures in highly endemic areas the active involvement of medical services in controlling T. solium infection and more effective collaboration between medical and veterinary services is necessary. A switch is suggested from total reliance on meat inspection to active diagnosis and treatment of human taeniasis, protection of pigs against infection, promotion of health education and improved surveillance preparing chemotherapeutic and/or sanitary interventions. This could be implemented in areas where active transmission causes substantial morbidity and mortality provided there is the political will, social support, better financing and an effective organizational framework.     

A New Approach to Bacterial Vaccines

Immunizing antigens against only 10 bacterial diseases—cholera, diphtheria, paratyphoid, pertussis, plague, scarlet fever, staphylococcal disease, tetanus, tuberculosis and typhoid—have been licensed for sale in Canada and the United States. Convincing evidence of efficacy is available for only four of these—diphtheria and tetanus toxoids, and pertussis and typhoid vaccines.The principles which determine the efficacy of different immunizing antigens are not always the same. Toxoids, for example, stimulate the formation of antitoxin-producing mechanisms which can neutralize toxins produced by invading organisms, thereby rendering them harmless. Conversely, vaccines stimulate the formation of antibacterial mechanisms which stop the growth of organisms before they can produce disease.Use of enzyme-lysed vaccines for prevention of staphylococcal disease represents a new approach in vaccine research. Animal tests have shown lysed vaccines to be 10 to 100 times less toxic, and about eight times more effective, than whole bacterial vaccines. Studies with lysed vaccines for other diseases are now in progress.     

Quantifying the Impact of Expanded Age Group Campaigns for Polio Eradication

A priority of the Global Polio Eradication Initiative (GPEI) 2013–2018 strategic plan is to evaluate the potential impact on polio eradication resulting from expanding one or more Supplementary Immunization Activities (SIAs) to children beyond age five-years in polio endemic countries. It has been hypothesized that such expanded age group (EAG) campaigns could accelerate polio eradication by eliminating immunity gaps in older children that may have resulted from past periods of low vaccination coverage. Using an individual-based mathematical model, we quantified the impact of EAG campaigns in terms of probability of elimination, reduction in polio transmission and age stratified immunity levels. The model was specifically calibrated to seroprevalence data from a polio-endemic region: Zaria, Nigeria. We compared the impact of EAG campaigns, which depend only on age, to more targeted interventions which focus on reaching missed populations. We found that EAG campaigns would not significantly improve prospects for polio eradication; the probability of elimination increased by 8% (from 24% at baseline to 32%) when expanding three annual SIAs to 5–14 year old children and by 18% when expanding all six annual SIAs. In contrast, expanding only two of the annual SIAs to target hard-to-reach populations at modest vaccination coverage—representing less than one tenth of additional vaccinations required for the six SIA EAG scenario—increased the probability of elimination by 55%. Implementation of EAG campaigns in polio endemic regions would not improve prospects for eradication. In endemic areas, vaccination campaigns which do not target missed populations will not benefit polio eradication efforts.     

Epidemiology of Cholera in the Philippines

Background

Despite being a cholera-endemic country, data on cholera in the Philippines remain sparse. Knowing the areas where cholera is known to occur and the factors that lead to its occurrence will assist in planning preventive measures and disaster mitigation.

Methods

Using sentinel surveillance data, PubMed and ProMED searches covering information from 2008–2013 and event-based surveillance reports from 2010–2013, we assessed the epidemiology of cholera in the Philippines. Using spatial log regression, we assessed the role of water, sanitation and population density on the incidence of cholera.

Results and Discussion

We identified 12 articles from ProMED and none from PubMed that reported on cholera in the Philippines from 2008 to 2013. Data from ProMed and surveillance revealed 42,071 suspected and confirmed cholera cases reported from 2008 to 2013, among which only 5,006 were confirmed. 38 (47%) of 81 provinces and metropolitan regions reported at least one confirmed case of cholera and 32 (40%) reported at least one suspected case. The overall case fatality ratio in sentinel sites was 0.62%, but was 2% in outbreaks. All age groups were affected. Using both confirmed and suspected cholera cases, the average annual incidence in 2010–2013 was 9.1 per 100,000 population. Poor access to improved sanitation was consistently associated with higher cholera incidence. Paradoxically, access to improved water sources was associated with higher cholera incidence using both suspected and confirmed cholera data sources. This finding may have been due to the breakdown in the infrastructure and non-chlorination of water supplies, emphasizing the need to maintain public water systems.

Conclusion

Our findings confirm that cholera affects a large proportion of the provinces in the country. Identifying areas most at risk for cholera will support the development and implementation of policies to minimize the morbidity and mortality due to this disease.     

Beyond Lassa Fever: Systemic and structural barriers to disease detection and response in Sierra Leone

BackgroundLassa fever (LF) often presents clinically as undifferentiated febrile illness. Lassa Fever cases in Sierra Leone have been falling since the 2014–2016 Ebola epidemic. Data from other LF endemic countries suggest that this is not a true reflection of local epidemiological decline, but rather a function of either health seeking behaviour or the health/referral system. In Sierra Leone, many other diseases present with a similar early clinical picture, including COVID-19 and Marburg Disease (which has recently emerged in neighbouring Guinea). This empirical study explores the implementation of health system processes associated with International Health Regulations (IHR) requirements for early detection and timely and effective responses to the spread of febrile disease, through the case study of LF in Sierra Leone.Methodology/Principal findingsThis study used a qualitative approach to analyse local policy and guidance documents, key informant interviews with policy and practice actors, and focus group discussions and in-depth interviews with health care workers (HCWs) and community health workers (CHWs) in Kenema District to examine the ways in which undifferentiated fever surveillance and response policies and processes were implemented in the post-Ebola period. Multiple challenges were identified, including: issues with the LF case definition, approaches to differential diagnosis, specimen transport and the provision of results, and ownership of laboratory data. These issues lead to delays in diagnosis, and potentially worse outcomes for individual patients, as well as affecting the system’s ability to respond to outbreak-prone disease.Conclusions/SignificanceIdentification of ways to improve the system requires balancing vertical disease surveillance programmes against other population health needs. Therefore, health system challenges to early identification of LF specifically have implications for the effectiveness of the wider Integrated Disease Surveillance and Response (IDSR) system in Sierra Leone more generally. Sentinel surveillance or improved surveillance at maternity facilities would help improve viral haemorrhagic fever (VHF) surveillance, as well as knowledge of LF epidemiology. Strengthening surveillance for vertical disease programmes, if correctly targeted, could have downstream benefits for COVID-19 surveillance and response as well as the wider health system—and therefore patient outcomes more generally.     

Disease Surveillance on Complex Social Networks

As infectious disease surveillance systems expand to include digital, crowd-sourced, and social network data, public health agencies are gaining unprecedented access to high-resolution data and have an opportunity to selectively monitor informative individuals. Contact networks, which are the webs of interaction through which diseases spread, determine whether and when individuals become infected, and thus who might serve as early and accurate surveillance sensors. Here, we evaluate three strategies for selecting sensors—sampling the most connected, random, and friends of random individuals—in three complex social networks—a simple scale-free network, an empirical Venezuelan college student network, and an empirical Montreal wireless hotspot usage network. Across five different surveillance goals—early and accurate detection of epidemic emergence and peak, and general situational awareness—we find that the optimal choice of sensors depends on the public health goal, the underlying network and the reproduction number of the disease (R₀). For diseases with a low R₀, the most connected individuals provide the earliest and most accurate information about both the onset and peak of an outbreak. However, identifying network hubs is often impractical, and they can be misleading if monitored for general situational awareness, if the underlying network has significant community structure, or if R₀ is high or unknown. Taking a theoretical approach, we also derive the optimal surveillance system for early outbreak detection but find that real-world identification of such sensors would be nearly impossible. By contrast, the friends-of-random strategy offers a more practical and robust alternative. It can be readily implemented without prior knowledge of the network, and by identifying sensors with higher than average, but not the highest, epidemiological risk, it provides reasonably early and accurate information.     

Spatially Explicit Modeling of Schistosomiasis Risk in Eastern China Based on a Synthesis of Epidemiological,Environmental and Intermediate Host Genetic Data

Schistosomiasis japonica is a major parasitic disease threatening millions of people in China. Though overall prevalence was greatly reduced during the second half of the past century, continued persistence in some areas and cases of re-emergence in others remain major concerns. As many regions in China are approaching disease elimination, obtaining quantitative data on Schistosoma japonicum parasites is increasingly difficult. This study examines the distribution of schistosomiasis in eastern China, taking advantage of the fact that the single intermediate host serves as a major transmission bottleneck. Epidemiological, population-genetic and high-resolution ecological data are combined to construct a predictive model capable of estimating the probability that schistosomiasis occurs in a target area (“spatially explicit schistosomiasis risk”). Results show that intermediate host genetic parameters are correlated with the distribution of endemic disease areas, and that five explanatory variables—altitude, minimum temperature, annual precipitation, genetic distance, and haplotype diversity—discriminate between endemic and non-endemic zones. Model predictions are correlated with human infection rates observed at the county level. Visualization of the model indicates that the highest risks of disease occur in the Dongting and Poyang lake regions, as expected, as well as in some floodplain areas of the Yangtze River. High risk areas are interconnected, suggesting the complex hydrological interplay of Dongting and Poyang lakes with the Yangtze River may be important for maintaining schistosomiasis in eastern China. Results demonstrate the value of genetic parameters for risk modeling, and particularly for reducing model prediction error. The findings have important consequences both for understanding the determinants of the current distribution of S. japonicum infections, and for designing future schistosomiasis surveillance and control strategies. The results also highlight how genetic information on taxa that constitute bottlenecks to disease transmission can be of value for risk modeling.     

Unconscious mental imagery

Historically, mental imagery has been defined as an experiential state—as something necessarily conscious. But most behavioural or neuroimaging experiments on mental imagery—including the most famous ones—do not actually take the conscious experience of the subject into consideration. Further, recent research highlights that there are very few behavioural or neural differences between conscious and unconscious mental imagery. I argue that treating mental imagery as not necessarily conscious (as potentially unconscious) would bring much needed explanatory unification to mental imagery research. It would also help us to reassess some of the recent aphantasia findings inasmuch as at least some subjects with aphantasia would be best described as having unconscious mental imagery.This article is part of the theme issue ‘Offline perception: voluntary and spontaneous perceptual experiences without matching external stimulation’.     

Application of techniques for the quantitative analysis of complex surveillance systems to disease and wildlife management

Scenario tree modelling and associated methods provide tools to quantify the combined value of multiple complex surveillance activities over time. The outputs of this analysis are an estimate of the sensitivity of a surveillance system, and the cumulative probability of disease freedom that surveillance provides over time. The ability to quantify the performance of complex surveillance systems provides a number of new opportunities in the design and application of search and detection activities. One of these is the ability to objectively compare alternative detection strategies. The sensitivity of a strategy (the probability that the target biota would be detected, given that they are present at a defined level) may be balanced against cost and practicality considerations to determine the most effective strategy for a given situation. The paper provides an example of the comparison of two surveillance strategies (structured surveys and abattoir surveillance) for disease detection in animal health (Classical Swine Fever). These techniques may also play an important role in the certification of success in pest eradication operations. The ability to use multiple sources of evidence to evaluate success means that a higher level of confidence can often be achieved at lower cost. Examples of the application of scenario tree modelling in plant health and invasive pests are provided to illustrate its use within eradication programs.