Persistence Of Plague Research Articles

Alternative lifestyles: A plague persistence hypothesis

AbstractSeveral explanations have been posited for how the plague bacterium (Yersinia pestis) reemerges during sylvatic cycles within the same foci over many years, and often without direct evidence of host die‐offs. One prevalent view is that transmission‐optimized Y. pestis bacteria, exhibiting epizootic/enzootic behavior, almost continually replicate and survive through repeated, linked, host‐centered propagation events. These bacteria, we will refer to as “r‐pestis” type ecotype(s), represent a limited number of phenotypic lineages exhibiting optimal transmissibility and high rates of reproduction. These attributes, it is thought, assure their durability through time. For continuous r‐pestis type expansions to be successful, adequate numbers of fleas and hosts must become infected to produce massive numbers of bacteria. In the process, host and flea numbers decline as they succumb to plague. Here we hypothesize that r‐pestis population expansions seed the environment and confront a unique, highly competitive local milieu, where natural selection favors new ecotypes that incorporate a range of emergent adaptive survival strategies. These newly adapted survivors we recognize as a range of “K‐pestis” ecotypes with greater durability and lower reproduction rates. These emergent K‐pestis forms may arise in succession or coexist for varying periods of time with r‐pestis ecotypes, and with other K‐pestis ecotypes. Among K‐pestis ecotypes, we hypothesize that through adaptive radiations, some persist within flea life stages, soil, organic waste, amoebae, plants, carcasses, hosts, or within niches yet to be characterized. In some settings, after a long quiet period, when favorable, K‐pestis bacteria may trigger a singular event where an r‐pestis transmission stream emerges precipitating another enzootic/epizootic progression. If this hypothesis withstands rigorous testing, then Y. pestis might represent an even more formidable, enduring, and adaptable foe, where unforeseen local events could trigger new epidemic and epizootic/enzootic events threatening humans and populations of other mammals, including those of conservation concern.

Rodent abundance, diversity and community structure in a bubonic plague endemic area, northern Tanzania

Abstract Rodent-borne diseases such as bubonic plague remain a significant threat to public health in tropical countries. In plague-endemic areas, little information exists on the factors triggering periodic bursts, thus rendering preparedness strategies for preventing the negative impacts of the deadly zoonosis difficult. In this study, we assessed how species richness, diversity, and community structure of rodents are associated with plague persistence in Mbulu District, Tanzania. Rodent data were collected using the removal trapping technique. We captured 610 rodents belonging to 12 species, with Mastomys natalensis recording highest abundance. There was significantly higher abundance and species richness in persistent than non-persistent plague locality. Also, house premises recorded significantly lower species richness than farm and forest habitats. Additionally, we found three broad rodent community structures that varied significantly between studied habitat types suggesting high rodent populations interaction at fine-scale resource abundance. The high abundance and diversity of plague-susceptible rodent reservoirs suggestively contribute to the plague persistence in the foci. These results may be useful to developing preparedness strategies in these areas to control plague outbreaks.

Human plague system associated with rodent diversity and other environmental factors.

Plague remains a threat to public health and is considered as a re-emerging infectious disease today. Rodents play an important role as major hosts in plague persistence and driving plague outbreaks in natural foci; however, few studies have tested the association between host diversity in ecosystems and human plague risk. Here we use zero-inflated generalized additive models to examine the association of species richness with human plague presence (where plague outbreaks could occur) and intensity (the average number of annual human cases when they occurred) in China during the Third Pandemic. We also account for transportation network density, annual precipitation levels and human population size. We found rodent species richness, particularly of rodent plague hosts, is positively associated with the presence of human plague. Further investigation shows that species richness of both wild and commensal rodent plague hosts are positively correlated with the presence, but only the latter correlated with the intensity. Our results indicated a positive relationship between rodent diversity and human plague, which may provide suggestions for the plague surveillance system.

Bubonic Plague Outbreak Investigation in the Endemic District of Tsiroanomandidy - Madagascar, October 2014

Background: Plague remains a major public health problem in Madagascar. Faced with reports of plague cases and deaths in Tsiroanomandidy district, we performed an investigation in October 2014.List of Abbreviations: BHCS: Basic Health Center; CDC: Control and prevention Diseases Center; DHS: District Health Service; IPM: Institut Pasteur de Madagascar; MOH: Ministry of Health; SMZ-TMP: Sulfamethoxazole Trimethoprim; WHO: World Health Organization Methods: We used the National plague control program case definition. We identified cases from outpatient registers and collected socio-demographic and clinical information. Plague circulation was determined through a retrospective environmental survey of rodents and vectors. Results: From August 1st to October 12th 2014, we identified 30 cases of which 13 deaths in 7 out of 17 municipalities; 18 were confirmed, 6 probable, and 6 suspected cases. The sex ratio (M/F) was 4:1. Yersinia pestis was isolated from Rattus rattus in one municipality. Flea index was 2.3. We collected 45 fleas through a trap set in a house 6 hours after insecticide spraying. Our aim was to describe the plague outbreak and to improve the national plague control strategies. Conclusion: The presence of infected flea and rodent maintain the persistence of plague in the municipalities investigated. There is a high risk of plague transmission to humans. This study showed that rodent and flea information are important for plague control strategies.

Cross-scale modeling of a vector-borne disease, from the individual to the metapopulation: The seasonal dynamics of sylvatic plague in Kazakhstan

Individual-based or population-level simulation approaches are often employed alternatively in eco-epidemiological modeling. In this paper, we introduce an original coupling approach applied to bubonic plague zoonotic infection in the Pre-Balkhash focus (central Asia), with main host Rhombomys opimus (Rodentia: Gerbillidae) and vector its associated ectoparasite flea Xenopsylla gerbilli minax. An Individual-Based Model (IBM) is first developed as a Multi-Agent System (MAS), addressing the seasonally forced internal dynamics of a typical burrow system based upon individual processes and interaction rules of the host-vector parasitoid system. Key population parameters and incidence functions are derived from simulations on the IBM and introduced in a second stochastic Population-Level Model (PLM), operating at the level of a metapopulation composed of interacting communities occupying burrow systems. The methodology facilitates knowledge integration and encourages bridging scales at which determinant contagion processes occur. Through simulations, we bring new insights about conditions for the local persistence of plague in a seasonally constrained environment. Under the seasonal scenario where half of the fleas overwinter in an active state, the introduction of the plague pathogen in spring in a metapopulation composed of 20 communities leads in one case out of two to epizootics surviving the first winter, while the infection has a 5% chance of passing the second winter. If the metapopulation is extended to 70 communities, simulations suggest the same 5% chance is estimated for plague persisting almost 4 years. Optimal vector community sizes or host dispersal intensities for the persistence of epizootics are also highlighted by sensitivity analyses.

Eighteenth century Yersinia pestis genomes reveal the long-term persistence of an historical plague focus.

The 14th-18th century pandemic of Yersinia pestis caused devastating disease outbreaks in Europe for almost 400 years. The reasons for plague's persistence and abrupt disappearance in Europe are poorly understood, but could have been due to either the presence of now-extinct plague foci in Europe itself, or successive disease introductions from other locations. Here we present five Y. pestis genomes from one of the last European outbreaks of plague, from 1722 in Marseille, France. The lineage identified has not been found in any extant Y. pestis foci sampled to date, and has its ancestry in strains obtained from victims of the 14th century Black Death. These data suggest the existence of a previously uncharacterized historical plague focus that persisted for at least three centuries. We propose that this disease source may have been responsible for the many resurgences of plague in Europe following the Black Death.

Plague Persistence in Western Europe: A Hypothesis

Historical sources documenting recurrent plagues of the “Second Pandemic” usually focus on urban epidemic mortality. Instead, plague persists in remote, rural hinterlands: areas less visible in the written sources of late medieval Europe. Plague spreads as fleas move from relatively resistant rodents, which serve as “maintenance hosts,” to an array of more susceptible rural mammals, now called “amplifying hosts.” Using sources relevant to plague in thinly populated Central and Western Alpine regions, this paper postulates that Alpine Europe could have been a region of plague persistence via its population of wild rodents, particularly the Alpine marmot.

Predicting small mammal and flea abundance using landform and soil properties in a plague endemic area in Lushoto District, Tanzania.

Small mammals particularly rodents, are considered the primary natural hosts of plague. Literature suggests that plague persistence in natural foci has a root cause in soils. The objective of this study was to investigate the relationship between on the one hand landforms and associated soil properties, and on the other hand small mammals and fleas in West Usambara Mountains in Tanzania, a plague endemic area. Standard field survey methods coupled with Geographical Information System (GIS) technique were used to examine landform and soils characteristics. Soil samples were analysed in the laboratory for physico-chemical properties. Small mammals were trapped on pre-established landform positions and identified to genus/species level. Fleas were removed from the trapped small mammals and counted. Exploration of landform and soil data was done using ArcGIS Toolbox functions and descriptive statistical analysis. The relationships between landforms, soils, small mammals and fleas were established by generalised linear regression model (GLM) operated in R statistics software. Results show that landforms and soils influence the abundance of small mammals and fleas and their spatial distribution. The abundance of small mammals and fleas increased with increase in elevation. Small mammal species richness also increases with elevation. A landform-soil model shows that available phosphorus, slope aspect and elevation were statistically significant predictors explaining richness and abundance of small mammals. Fleas' abundance and spatial distribution were influenced by hill-shade, available phosphorus and base saturation. The study suggests that landforms and soils have a strong influence on the richness and evenness of small mammals and their fleas' abundance hence could be used to explain plague dynamics in the area.

Socio-epidemiological determinants of 2002 plague outbreak in Himachal Pradesh, India: a qualitative study

BackgroundThis qualitative investigation was conducted to determine the socio-epidemiological factors related to the plague outbreak (2002) in Himachal Pradesh (HP), India.MethodsThe data for socio-epidemiological factors related to the plague outbreak (2002) in HP was obtained from residents through 150 in-depth Interviews (IDI) and 30 Focus Group Discussions (FGD) during six visits (from May 2011 to April 2012) by the research team. Natives, health officials and the nomadic population were interviewed. According to their opinion and viewpoints data was collected and their lifestyle and hunting practices were studied in detail. Tape recorders were used during various FGDs and IDIs. The interviews and FGDs were later transcribed and coded. In-depth analysis of the recorded data was done using an inductive thematic analysis approach.ResultsThe study reports that the outbreak in 2002 in a few villages of Himachal Pradesh was that of plague and it occurred by the contact of an index case with wild animals after hunting and de-skinning. The first wave of plague transmission which took 16 lives of residents was followed by a second wave of transmission in a ward of a tertiary care hospital where one visitor acquired it from relatives of the index case and succumbed. The life-style practices of residents (hunting behavior, long stay in caves and jungles, overcrowding in houses, poor hygiene and sanitation, belief in ‘God’ and faith healers for cure of diseases) was optimal for the occurrence and rapid spread of such a communicable disease. The man-rodent contact is intensified due to the practice of hunting in such a rodent-ridden environment. The residents harbor a strong belief that plague occurs due to the wrath of gods. Various un-reported outbreaks of plague were also observed by officials, residents and old folk. The persistence of plague in HP is favoured by its hilly terrain, inaccessible areas, inclement weather (snow) in winters, unhygienic lifestyle, hunting practices of residents, and treatment practices through faith healers.ConclusionsThis study suggests that the lifestyle of the natives of HP and other socio-epidemiological factors played a role in the outbreak of plague in that area.

Plague in Tanzania: An overview

Human plague remains a public health concern in Tanzania despite its quiescence in most foci for years, considering the recurrence nature of the disease. Despite the long-standing history of this problem, there have not been recent reviews of the current knowledge on plague in Tanzania. This work aimed at providing a current overview of plague in Tanzania in terms of its introduction, potential reservoirs, possible causes of plague persistence and repeated outbreaks in the country. Plague is believed to have been introduced to Tanzania from the Middle East through Uganda with the first authentication in 1886. Xenopsylla brasiliensis, X. cheopis, Dinopsyllus lypusus, and Pulex irritans are among potential vectors while Lophuromys spp, Praomys delectorum, Graphiurus murinus, Lemniscomys striatus, Mastomys natalensis, and Rattus rattus may be the potential reservoirs. Plague persistence and repeated outbreaks in Tanzania are likely to be attributable to a complexity of factors including cultural, socio-economical, environmental and biological. Minimizing or preventing people's proximity to rodents is probably the most effective means of preventing plague outbreaks in humans in the future. In conclusion, much has been done on plague diagnosis in Tanzania. However, in order to achieve new insights into the features of plague epidemiology in the country, and to reorganize an effective control strategy, we recommend broader studies that will include the ecology of the pathogen, vectors and potential hosts, identifying the reservoirs, dynamics of infection and landscape ecology.

Understanding the Persistence of Plague Foci in Madagascar

Plague, a zoonosis caused by Yersinia pestis, is still found in Africa, Asia, and the Americas. Madagascar reports almost one third of the cases worldwide. Y. pestis can be encountered in three very different types of foci: urban, rural, and sylvatic. Flea vector and wild rodent host population dynamics are tightly correlated with modulation of climatic conditions, an association that could be crucial for both the maintenance of foci and human plague epidemics. The black rat Rattus rattus, the main host of Y. pestis in Madagascar, is found to exhibit high resistance to plague in endemic areas, opposing the concept of high mortality rates among rats exposed to the infection. Also, endemic fleas could play an essential role in maintenance of the foci. This review discusses recent advances in the understanding of the role of these factors as well as human behavior in the persistence of plague in Madagascar.

Host Resistance, Population Structure and the Long-Term Persistence of Bubonic Plague: Contributions of a Modelling Approach in the Malagasy Focus

Although bubonic plague is an endemic zoonosis in many countries around the world, the factors responsible for the persistence of this highly virulent disease remain poorly known. Classically, the endemic persistence of plague is suspected to be due to the coexistence of plague resistant and plague susceptible rodents in natural foci, and/or to a metapopulation structure of reservoirs. Here, we test separately the effect of each of these factors on the long-term persistence of plague. We analyse the dynamics and equilibria of a model of plague propagation, consistent with plague ecology in Madagascar, a major focus where this disease is endemic since the 1920s in central highlands. By combining deterministic and stochastic analyses of this model, and including sensitivity analyses, we show that (i) endemicity is favoured by intermediate host population sizes, (ii) in large host populations, the presence of resistant rats is sufficient to explain long-term persistence of plague, and (iii) the metapopulation structure of susceptible host populations alone can also account for plague endemicity, thanks to both subdivision and the subsequent reduction in the size of subpopulations, and extinction-recolonization dynamics of the disease. In the light of these results, we suggest scenarios to explain the localized presence of plague in Madagascar.

Local persistence and extinction of plague in a metapopulation of great gerbil burrows, Kazakhstan

Speculation on how the bacterium Yersinia pestis re-emerges after years of absence in the Prebalkhash region in Kazakhstan has been ongoing for half a century, but the mechanism is still unclear. One of the theories is that plague persists in its reservoir host (the great gerbil) in so-called hotspots, i.e. small regions in which the conditions remain favourable for plague to persist during times where the conditions in the Prebalkhash region as a whole have become unfavourable for plague persistence. In this paper we use a metapopulation model that describes the dynamics of the great gerbil. With this model we study the minimum size of an individual hotspot and the combined size of multiple hotspots in the Prebalkhash region that would be required for Y. pestis to persist through an inter-epizootic period. We show that the combined area of hotspots required for plague persistence is so large that it would be unlikely to have been missed by existing plague surveillance. This suggests that persistence of plague in that region cannot solely be explained by the existence of hotspots, and therefore other hypotheses, such as survival in multiple host species, and persistence in fleas or in the soil should be considered as well.

Field evaluation of imidacloprid as a systemic approach to flea control in black-tailed prairie dogs, Cynomys ludovicianus

Epizootic outbreaks of sylvatic plague have dramatically influenced prairie dog (Cynomys sp.) populations across North America. While a great deal of debate surrounds the cause and persistence of plague, flea control can stop the spread of plague epizootic outbreaks and even increase prairie dog survival under non-epizootic conditions. We investigated a newly-developed imidacloprid-treated grain bait that could potentially reduce flea infestations and mitigate the effects of plague on black-tailed prairie dogs (C. ludovicianus). We used a study design involving randomly assigned experimental and control study plots to assess the effectiveness of the systemic flea control product. We observed a significant difference in flea prevalence and abundance between experimental and control sites on three of the four sites treated with a single application of imidacloprid-treated grain bait for up to 90 days post-treatment. We observed an even greater reduction in flea infestations following the double application of treatment bait on two of three additional experimental sites. While we were unable to reduce flea infestations to the extent reported for more commonly used topical insecticides containing deltamethrin, imidacloprid might still be effective at reducing the risk of plague and halting epizootics. In addition, this systemic product can be more rapidly applied than topical insecticides, providing managers with a tool to quickly reduce flea infestations. Future research is needed to evaluate the effectiveness of different application timing and rates, the utility of the product in limiting plague, and the potential effects on non-target species that might also consume the treated bait.

Modeling Susceptible Infective Recovered Dynamics and Plague Persistence in California Rodent–Flea Communities

Plague persists as an enzootic in several very different rodent-flea communities around the world. In California, a diversity of rodent-flea communities maintains the disease, and a single-host reservoir seems unlikely. Logistic regression of plague presence on climate and topographic variables predicts plague in many localities where it is absent. Thus, a dynamic community-based analysis was needed. Deterministic Susceptible Infective Recovered (SIR) models were adapted for plague and analyzed with an eye for insights concerning disease persistence. An R simulation program, Plaguesirs, was developed incorporating multihost and multivector SIR dynamics, demographic and environmental stochasticity, density dependence, and seasonal variation in birth and death. Flea-rodent utilization matrices allowed us to get transmission rates as well as flea carrying capacities. Rodent densities allowed us to estimate host carrying capacities, while maximum birth rates were mainly approximated through an examination of litter phenology and demography. We ran a set of simulations to assess the role of community structure in maintaining plague in a simulated version of Chuchupate campground in Ventura County. Although the actual campground comprises 10 rodent and 19 flea species, we focused on a subset suspected to act as a reservoir community. This included the vole Microtus californicus, the deer mouse Peromyscus maniculatus, the Ceratophyllid fleas Aetheca wagneri and Malareus telchinum, and the Leptopsyllid flea Peromyscopsylla hesperomys. The dynamics of 21 subsets of this community were simulated for 20 years. Single-rodent communities showed much lower disease persistence than two-rodent communities. However, so long as Malareus was present, endemicity was enhanced; removal of the other two fleas slightly increased disease persistence. Two critical features improved disease persistence: (1) host breeding season heterogeneity and (2) host population augmentation (due to two similar host species instead of one). Voles are winter-spring breeders compared to the spring-summer deer mice. While host synchronicity may enhance epidemics, host asynchronicity favors endemics.

MODELING PLAGUE PERSISTENCE IN HOST-VECTOR COMMUNITIES IN CALIFORNIA

Plague is an enzootic disease in the western United States, even though long-term persistent infections do not seem to occur. Enzootic persistence may occur as a function of dynamic interactions between flea vectors and transiently infected hosts, but the specific levels of vector competence, host competence, and transmission and recovery rates that would promote persistence and emergence among wild hosts and vectors are not known. We developed a mathematical model of enzootic plague in the western United States and implemented the model with the following objectives: 1) to use matrix manipulation within a classic susceptible-->infective-->resistant-->susceptible (SIRS) model framework to describe transmission of the plague bacterium Yersinia pestis among rodents and fleas in California, 2) to perform sensitivity analysis with model parameters and variables to indicate which values tended to dominate model output, and 3) to determine whether enzootic maintenance would be predicted with realistic parameter values obtained from the literature for Y. pestis in California rodents and fleas. The model PlagueSIRS was implemented in discrete time as a computer simulation incorporating environmental stochasticity and seasonality, by using matrix functions in the computer language R, allowing any number of rodent and flea species to interact through parasitism and disease transmission. Sensitivity analysis indicated that the model was sensitive to flea attack rate, host recovery rate, and rodent host carrying capacity but relatively insensitive to changes in the duration of latent infection in the flea, host and vector competence, flea recovery from infection, and host mortality attributable to plague. Realistic parameters and variable values did allow for the model to predict enzootic plague in some combinations, specifically when rodent species that were susceptible to infection but resistant to morbidity were parasitized by multiple poorly competent flea species, including some that were present year-round. This model could be extended to similar vectorborne disease systems and could be used iteratively with data collection in sylvatic plague studies to better understand plague persistence and emergence in nature.

Model Explains Bubonic Plague's Persistence

Science NewsVolume 158, Issue 17 p. 262-262 This Week Model explains bubonic plague's persistence John Travis, John TravisSearch for more papers by this author John Travis, John TravisSearch for more papers by this author First published: 01 July 2009 https://doi.org/10.2307/4018629AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume158, Issue1721 October 2000Pages 262-262 RelatedInformation

Seasonality of plague in early modern Europe: Swiss epidemic of 1628--1630.

The course of plague is markedly influenced by seasonal factors. A quantitative estimate of its seasonal distribution was made from parish death books of 38 communities in a small, diversified area of Switzerland for the epidemic period of 1628--1630. The temporal distribution of outbreaks was bimodal with maximal mortalities in the autumn-early winter seasons of two successive years. Of 43 peaks of mortality, 39 occurred between September and January; November was the month of highest frequency. Colder weather exerted a gradual limiting influence, but late-blooming community outbreaks continued at a high or maximal level as late as January. Evidence is presented that the temporal distribution of outbreaks affected the persistence of plague in the region. The seasonality of plague in Switzerland contrasts with the pattern in Great Britain, where midsummer epidemics prevailed.

Susceptibility of rodents to oral plague infection: a mechanism for the persistence of plague in inter-epidemic periods.

Oral infection of rodents with Pasteurella pestis has been demonstrated with both fully virulent and avirulent strains. Sustained rodent plague epizootics have been initiated and maintained in the absence of the classical flea vector. Transmission was due to cannibalism of the dying rodents by their healthy cagemates. Oral infection is considered to provide a plausible mechanism for the persistence of plague in an area where conditions are temporarily unsuitable for flea transmission.

Plague in South-East Asia: A brief historical summary and present geographical distribution

The paper presents a historical background and a summary of the situation of plague in South-East Asia. South-East Asia contributes at present over 90% of the total world incidence of plague. Two small outbreaks in Nepal can be considered as accidental in a wild plague focus due to intimate sharing of habitat by both man and rodents. No cases of human plague occurred in Thailand in the last 17 years (Fig. 6). In Indonesia the disease has been active again in a previously infected area after a silent period of 7 years (Fig. 5). In Burma and South Viet-Nam it continued to be active since its introduction almost 70 years ago (Figs. 7, 8, 9 and 10). Occasional increases in incidence due to new entrants in the areas in which zootic maintenance of plague is possible, and intermittent silent periods, are less evident in those two countries. The question whether the foci are “true” or not is rather academic if large numbers of cases in humans are observed year after year for 70 years. The facility with which it has spread in Viet-Nam in the last few years due to the state of war and consequent profound disturbances of the human and zootic habitats, should not obscure the fact that plague is neither new nor unexpected and that in 7 provinces (out of which 5 are coastal) the disease in humans occurred with perseverance and regularity. In others, quiescent periods are not unusual. The dispersal beyond the as yet not precisely defined “plague areas” might be temporary and plague might again retract to more limited areas ∗ ∗ The incomplete data gathered during the second world war and after and the change of names of towns and provinces have made the persistence of plague less evident to an external observer. . However, at present it continues to occur in 33 out of 46 provinces and autonomous towns of the Republic of Viet-Nam in spite of tremendous antiflea dustings and vaccination campaigns. The transformation of the habitats in such a way as to eliminate the opportunity for an epizootic maintenance is still a very distant hope. Studies of plague ecology in this part of the world are rare and are sensu stricto only starting now. Obviously, many questions could not have been answered at the time when infection was widely spread, when it involved a large portion of the country and large numbers of people. Also a certain historical perspective is necessary for this appraisal. The question of the existence of foci, that is to say of the true “natural” foci in South-East Asia has not been solved yet. It may be that the occurrence of plague in areas described are the last remnants of a slowly disappearing infection after the last pandemic, which started 70 years ago, which is in ecological terms, a very short period. The question of the nature of the foci will therefore be answered only after complex ecological studies have been carried out involving the pathogen, vector and host, and their dynamics and mutual relationship have been understood. While these studies are, no doubt, extremely important in order to assess the state of periodicity, the persistence and the future of the plague situation, there are many pressing practical public health problems which now require full attention.