Understanding the persistence of measles: reconciling theory, simulation and observation

Ever since the pattern of localized extinction associated with measles was discovered by Bartlett in 1957, many models have been developed in an attempt to reproduce this phenomenon. Recently, the use of constant infectious and incubation periods, rather than the more convenient exponential forms, has been presented as a simple means of obtaining realistic persistence levels. However, this result appears at odds with rigorous mathematical theory; here we reconcile these differences. Using a deterministic approach, we parameterize a variety of models to fit the observed biennial attractor, thus determining the level of seasonality by the choice of model. We can then compare fairly the persistence of the stochastic versions of these models, using the 'best-fit' parameters. Finally, we consider the differences between the observed fade-out pattern and the more theoretically appealing 'first passage time'.     

Seasonality in the infection and invasion of Marteilioides chungmuensis in the Pacific oyster Crassostrea gigas

The protozoan parasite Marteilioides chungmuensis causes irregular enlargement of the ovary in the Pacific oyster Crassostrea gigas. The parasite invades the oyster through the epithelial tissue of the labial palp, replicates in the connective tissue, and then moves to the gonad, producing spores inside the oocytes. In this study the seasonality and invasion period of the parasite into the host was investigated over a 1 yr cycle. Uninfected 1 and 0 yr old (spat) oysters were placed in an epizootic area every month from July 2004 to July 2005 and September 2005 to March 2006, respectively, and left for 1 mo. Labial palps and gonad were sampled monthly and examined for infection by nested PCR and histological observations. Prevalence of infection detected by PCR was 70% or higher from August to October, but declined sharply in November and reached 7% or lower from February to April. To explain the low detection rate in winter, 1 yr old uninfected oysters were placed in an epizootic area in winter (water temperature: 8 to 10 degrees C) for 2 wk and then transferred to M. chungmuensis-free seawater at 24 degrees C. Although prevalence of infection was ca. 7% before transfer to heated seawater, levels of 87% were detected after 1 wk. After a 3 wk exposure to heated seawater, parasites were found in host oocytes by histological observation. It was concluded that the low prevalence in winter was due to insufficient replication of M. chungmuensis at low seawater temperatures, resulting in levels not detectable by nested PCR, and not to the absence of invasion.     

Seasonality of Batrachochytrium dendrobatidis infection in direct-developing frogs suggests a mechanism for persistence

Batrachochytrium dendrobatidis (Bd), a disease-causing amphibian-specific fungus, is widely distributed in Puerto Rico, but is restricted to elevations above 600 m. The effect of this pathogen in the wild was studied by monitoring Eleutherodactylus coqui and E. portoricensis in 2 upland forests at El Yunque, a site characterized by historic population declines in the presence of chytridiomycosis. We tested a potential synergistic interaction between climate and Bd by measuring prevalence of infection and level of infection per individual sampled (number of zoospores), across the dry and wet seasons for 2 yr (between 2005 and 2007). Infection levels in adult frogs were significantly higher during the dry season in both species studied, suggesting a cyclic pattern of dry/ cool-wet/warm climate-driven synergistic interaction. These results are consistent with ex situ experiments in which E. coqui infected with Bd were more susceptible to chytridiomycosis when subjected to limited water treatments resembling drought. Long-term data on the prevalence of Bd in the populations studied versus intensity of infection in individual frogs provided contradictory information. However, the conflicting nature of these data was essential to understand the status of Bd in the species and geographical area studied. We conclude that in Puerto Rico, Bd is enzootic, and vulnerability of eleutherodactylid frogs to this pathogen is related to seasonal climatic variables. Our data suggest a mechanism by which this disease can persist in tropical frog communities without decimation of its hosts, but that complex interactions during severe droughts may lead to population crashes.     

Structural explanation for the effect of humidity on persistence of airborne virus: Seasonality of influenza

Seasonal variation of infectious diseases is one of the oldest observations in epidemiology, most particularly for Influenza and other respiratory viral infections. The reason for this seasonality is poorly understood, despite the profound importance of these infections as communicable diseases capable of causing global epidemics. Environmental factors including relative humidity, vapor pressure and temperature are known to affect seasonal virus survival and transmission. Immunological status of the host and evolution of the virus have also been proposed to be the reason behind the cyclic recurrence. The molecular basis of these effects or their interplay with biological factors has not been reported before. Here a theoretical analysis shows that the structure of the viral envelope determines its persistence and transmission in various environmental conditions. Physico-chemical properties of the virus particles and their interaction with atmospheric processes along with the availability and susceptibility of hosts generates the conspicuous seasonality prevalent in the temperate zones and the apparent lack of it in the tropics. Additionally this model can estimate virus transmission in different weather conditions. This model may help to determine the right actions effective in preventing outbreaks of the flu-like respiratory viruses.     

Replication and persistence of measles virus in defined subpopulations of human leukocytes.

Replication of Edmonston strain measles virus was studied in several human lymphoblast lines, as well as in defined subpopulations of circulating human leukocytes. It was found that measles virus can productively infect T cells, B cells, and monocytes from human blood. These conclusions were derived from infectious center studies on segregated cell populations, as well as from ultrastructural analyses on cells labeled with specific markers. In contrast, mature polymorphonuclear cells failed to synthesize measles virus nucleocapsids even after infection at a relatively high multiplicity of infection. Measles virus replicated more efficiently in lymphocytes stimulated with mitogens than in unstimulated cells. However, both phytohemagglutinin and pokeweed mitogen had a negligible stimulatory effect on viral synthesis in purified populations of monocytes. In all instances the efficiency of measles virus replication by monocytes was appreciably less than that of mitogenically stimulated lymphocytes or of continuously culture lymphoblasts. Under standard conditions of infection, all of the surveyed lymphoblast lines produced equivalent amounts of measles virus regardless of the major histocompatibility (HL-A) haplotype. Hence, no evidence was found that the HL-A3,7 haplotype conferred either an advantage or disadvantage with respect to measles virus synthesis in an immunologically neutral environment. A persistent infection with measles virus could be established in both T and B lymphoblasts. The release of infectious virus from such persistently infected cells was stable over a period of several weeks and was approximately 100-fold less than peak viral titers obtained in each respective line after acute infection.     

Composite temporal strategies in pathogen evolution: balancing invasion and persistence

There is ongoing interest in the conditions that favor the evolution of acute, highly transmissible infections in contrast to chronic ones. Earlier studies typically consider the evolution of a trait that is constant over the lifetime of an infection. However, for many pathogens, such traits can vary over this course. Here, we address the evolution of temporal patterns in limited host population sizes, where a trade-off between invasion and persistence can arise. This is of particular relevance to questions on the evolution of acuteness and chronicity. We ask whether population dynamics of transmission at the between-host level could lead pathogen adaptation to favor temporal strategies during the course of infection. To do this, we consider an infection to be composed of multiple stages, allowing each of these to evolve independently under a transmission–duration trade-off. We only consider selection taking place on the between-host level and examine the balance of invasion and persistence (i.e., maximizing replication vs. minimizing vulnerability to extinction), using several fitness-related measures. We find that a composite strategy that is ordered in time can confer higher fitness than any single, constant, strategy. We discuss the relevance of these results for the ordered expression of var genes in Plasmodium falciparum, as well as for infections that characteristically have several stages as in some bacterial pathogens.     

The invasion, persistence and spread of infectious diseases within animal and plant communities

Recent theoretical and empirical studies of the population biology of infectious diseases have helped to improve our understanding of the major factors that influence the three phases of a successful invasion, namely initial establishment, persistence in the longer term and spread to other host communities. Of central importance in all three phases is the magnitude of the basic reproductive rate or transmission potential of the parasite. The value of this parameter is determined by a variety of biological properties of the association between an individual parasite and its host and the interaction between their populations. The recent epidemic of acquired immunodeficiency syndrome (AIDS) in North America and Europe is employed to illustrate the factors that promote disease establishment and spread. The frequency distribution of the number of different sexual partners per unit of time within homosexual communities is shown to be of central importance with respect to future trends in the incidence of AIDS. Broader aspects of pathogen invasion are examined by reference to simple mathematical models of three species associations, which mirror parasite introduction into resident predator-prey, host-parasite and competitive interactions. Many outcomes are possible, depending on the values of the numerous parameters that influence multi-species population interactions. Pathogen invasion is shown to have far-reaching implications for the structure and stability of ecological communities.     

Host cell invasion by Trypanosoma cruzi: a unique strategy that promotes persistence

The intracellular protozoan parasite Trypanosoma cruzi is the causative agent of Chagas' disease, a serious disorder that affects millions of people in Latin America. Despite the development of lifelong immunity following infections, the immune system fails to completely clear the parasites, which persist for decades within host tissues. Cardiomyopathy is one of the most serious clinical manifestations of the disease, and a major cause of sudden death in endemic areas. Despite decades of study, there is still debate about the apparent preferential tropism of the parasites for cardiac muscle, and its role in the pathology of the disease. In this review, we discuss these issues in light of recent observations, which indicate that T. cruzi invades host cells by subverting a highly conserved cellular pathway for the repair of plasma membrane lesions. Plasma membrane injury and repair is particularly prevalent in muscle cells, suggesting that the mechanism used by the parasites for cell invasion may be a primary determinant of tissue tropism, intracellular persistence, and Chagas' disease pathology.     

Seasonality and reproduction in aphids

Aphids are short-lived and occupy habitats which vary in quality in both time and space. They exploit their ephemerally nutritious habitats by rapidly producing many small offspring when conditions are good, and fewer, larger offspring when conditions are poor, at which time they also divert more of their resources into fat storage. Aphids of each of the generations which make up a life cycle have specific reproductive strategies adapted to the conditions they are most likely to encounter, that is they anticipate the predictable seasonal trends in habitat quality.     

Seasonality and photoperiodism in fungi

This review gives a retrospective of what is known about photoperiodism in fungi, which is largely based on reports about seasonal spore concentrations. Relatively few species have been investigated under laboratory conditions, so that our knowledge whether seasonal reproduction in fungi is mainly a direct response to environmental conditions or whether it involves a photoperiodic machinery with memory capacities and a relationship to the circadian system is extremely limited. To form a basis for further experimental endeavors into fungal photoperiodism, we review the reports about endogenous rhythms and photobiology. Finally, we will look at the possibilities of using the fungal circadian model system of Neurospora crassa for future work on photoperiodism.     

Seasonality of toxoplasmosis]

The indices of seasonal changes in the proportion of population allergopositive to toxoplasmosis were determined by analyzing the results of intracutaneous tests made in 61,324 pregnant women in Novokuznetsk between 1964 and 1974. Indices exceeding the average monthly level were registered in March-July and in September-October. Taking into account the modal term during which allergization develops in a patient from the moment of toxoplasmic invasion, a high risk of toxoplasmosis infection is likely to be present mainly during winter and spring (December-May), as well as summer (July-August) periods. Researchers should pay attention to the nature of the seasonal prevalence of the epidemic process of toxoplasmosis.     

Seasonality of MRSA infections

Using MRSA isolates submitted to our hospital microbiology laboratory January 2001–March 2010 and the number of our emergency department (ED) visits, quarterly community-associated (CA) and hospital-associated (HA) MRSA infections were modeled using Poisson regressions. For pediatric patients, approximately 1.85x (95% CI 1.45x–2.36x, adj. p<0.0001) as many CA-MRSA infections per ED visit occurred in the second two quarters as occurred in the first two quarters. For adult patients, 1.14x (95% CI 1.01x–1.29x, adj.p = 0.03) as many infections per ED visit occurred in the second two quarters as in the first two quarters. Approximately 2.94x (95% CI 1.39x–6.21x, adj.p = 0.015) as many HA-MRSA infections per hospital admission occurred in the second two quarters as occurred in the first two quarters for pediatric patients. No seasonal variation was observed among adult HA-MRSA infections per hospital admission. We demonstrated seasonality of MRSA infections and provide a summary table of similar observations in other studies.     

Seasonality and variability of the interestrous interval in the bitch

Records from two breeding colonies (A and B) located near each other were analyzed for this experiment. Colony A consisted of 19 bitches (8 Maltese, 5 Yorkshire, 3 Lhasa Apso, and 3 Bouvier des Flandres), while Colony B consisted of 48 Beagle bitches. A total of 126 interestrous intervals (141 estrous cycles) from Colony A were reviewed to quantitate the variability of the interestrous interval. Analysis of variance showed that the degree of variation of the estrous cycle length within bitches (65%) was about twice the degree of variation of means of the estrous cycle length among bitches (35%). It was found that the estrous cycle length is extremely variable, and it cannot be used to predict the next estrus in a single bitch, although some bitches were very consistent. The seasonal and monthly distribution of estrous cycles throughout the year was also analyzed from bitches kept in Colonies A and B for a total of 210 estrous cycles. The data were collected over a four-year period. A seasonal pattern was observed when the cumulative distributions over years were analyzed. A higher frequency of estrous cycles was observed during winter and summer. This seasonality pattern was not observed when individual years were analyzed separately. However, the overall probability that an estrus would occur at any month of the year was the same for each month (1 12 ) when cumulative distribution over years were analyzed.     

Modelling the Dynamics of Bluetongue Disease and the Effect of Seasonality

We present mathematical models for the midge-borne disease bluetongue, with cattle and sheep as hosts. The models take the form of delay differential equations and incorporate the incubation time of bluetongue in cattle, sheep and midges, and also the larval developmental time of midges. Recovery in cattle and sheep is also included. Both an autonomous and a periodic model are considered, to take account of seasonality. For both models we present conditions for the disease-free state to be linearly stable, and a detailed interpretation of those conditions. The results of simulations are also presented. Important findings include the need for prompt diagnosis of latent infection and appropriate action before the animal turns infectious, and the need for measures that reduce insect bites.     

Seasonality of births in Croatia

The aim of this paper was to investigate seasonal fluctuations of the number of births in Croatia. Vital registration data from the years 1970-2002 was used for analysis of the quarterly data (from the years 1970-1997), and monthly data (from the years 1998-2002). Both data sets were smoothed, using seasonal variation removal for quarterly data, and T4253H smoothing for monthly data. Edwards test and Ratchet circular scan tests were used in analysis. The results showed an increase in the summer birth proportion and decrease in the spring birth proportion, distorted during the wartime period (1991-1995). Monthly analysis reveals highest birth proportion in Croatia during July-September period, with peak date moving towards the end of summer, and reaching stability in the beginning of September during the years 2000-2002. This presumes highest conception rate during the beginning of the Christmas holiday season. Secondary peak in January was found in some years, which presumably sets second period of increased conception rate into the Easter holiday season, supporting the observation of the holiday-related birth peaks. Both quarterly and monthly data indicate a birth pattern that does not resemble either European, or American seasonal pattern. Regional analysis showed lack of seasonality in the capital city of Zagreb and either intermittent or stable seasonality pattern in the rest of the country.