Mathematical models of mosquito-borne pathogen transmission originated in the early twentieth century to provide insights into how to most effectively combat malaria. The foundations of the Ross–Macdonald theory were established by 1970. Since then, there has been a growing interest in reducing the public health burden of mosquito-borne pathogens and an expanding use of models to guide their control. To assess how theory has changed to confront evolving public health challenges, we compiled a bibliography of 325 publications from 1970 through 2010 that included at least one mathematical model of mosquito-borne pathogen transmission and then used a 79-part questionnaire to classify each of 388 associated models according to its biological assumptions. As a composite measure to interpret the multidimensional results of our survey, we assigned a numerical value to each model that measured its similarity to 15 core assumptions of the Ross–Macdonald model. Although the analysis illustrated a growing acknowledgement of geographical, ecological and epidemiological complexities in modelling transmission, most models during the past 40 years closely resemble the Ross–Macdonald model. Modern theory would benefit from an expansion around the concepts of heterogeneous mosquito biting, poorly mixed mosquito-host encounters, spatial heterogeneity and temporal variation in the transmission process.

The study of several Escherichia coli intestinal commensal isolates per individual in 265 healthy human subjects belonging to seven populations distributed worldwide showed that the E. coli population is highly structured, with major differences between the tropical and temperate populations.Escherichia coli is a commensal inhabitant of the intestinal tracts of healthy humans and many animal species, but it can also cause a wide range of diseases, ranging from diarrhea to extraintestinal infections (8). As it has been proposed that pathogenic E. coli strains are derived from commensal strains by the acquisition of chromosomal or extrachromosomal virulence operons (19), identifying the factors that shape the genetic structure of commensal strains might help us understand the emergence of virulence. E. coli can be considered to have a clonal genetic structure with a low level of recombination (7, 10). Four main phylogenetic groups, A, B1, B2, and D, constitute the bulk of the species (15). A few authors have examined commensal strains from humans (3-5, 13) using population genetics molecular tools (for a pioneer review, see reference 14). A significant locale-specific distribution among groups A, B1, B2, and D has been observed in human commensal strains in three geographically distinct human populations (French, Croatian, and Malian) (9).To gain insight into the composition of the E. coli human commensal microbiota, we characterized the relative abundance of E. coli phylogenetic groups in a large collection of 1,740 isolates from 265 subjects belonging to seven populations spread over three continents and compared the results to those of previous studies using the same approach.Bacterial isolates. Isolates were collected between 1999 and 2001 from seven human populations composed of healthy adult subjects of both sexes from 15 to 65 years of age, except when otherwise stated. The populations were the following: (i) 27 subjects living in the Paris area (mainland France, Europe), (ii) 21 university students living in Brest (Brittany, mainland France), (iii) 25 bank and insurance workers (BIW) living in seven distinct areas of Brittany (mainland France), (iv) 25 pig farmers (PF) living in the same seven areas as the BIW, (v) 93 ethnically homogeneous Wayampi Amerindians living in three villages of southern French Guyana (South America) with no modern sanitary or hygienic facilities, (vi) 46 women living in Cotonou (Benin, Africa), and (vii) 28 subjects living in Bogotá (Colombia, South America). The individuals in the BIW and PF populations in Brittany were matched for county of residence, age (20 to 60 years), and sex (13 men and 12 women). A subset of 25 Amerindians was also matched for age and sex with the BIW and PF populations. These matched populations had neither been hospitalized nor had taken antibiotics for at least 1 month before stool sampling. In all, 1,740 E. coli isolates were obtained after plating fresh fecal samples on Drigalski agar, with 5 or 10 randomly chosen E. coli isolates per individual.The...

The prevalence of Plasmodium falciparum malaria in Zanzibar has reached historic lows. Improving control requires quantifying malaria importation rates, identifying high-risk travelers, and assessing onwards transmission.Estimates of Zanzibar's importation rate were calculated through two independent methodologies. First, mobile phone usage data and ferry traffic between Zanzibar and mainland Tanzania were re-analyzed using a model of heterogeneous travel risk. Second, a dynamic mathematical model of importation and transmission rates was used.Zanzibar residents traveling to malaria endemic regions were estimated to contribute 1–15 times more imported cases than infected visitors. The malaria importation rate was estimated to be 1.6 incoming infections per 1,000 inhabitants per year. Local transmission was estimated too low to sustain transmission in most places.Malaria infections in Zanzibar largely result from imported malaria and subsequent transmission. Plasmodium falciparum malaria elimination appears feasible by implementing control measures based on detecting imported malaria cases and controlling onward transmission.

To identify forces shaping the Escherichia coli intraspecies ecological structure, we have characterized in terms of phylogenetic group (A, B1, D and B2) belonging, presence/absence of extraintestinal virulence genes (pap, sfa, hly and aer) and intra-host phylotype diversity a collection of 1898 commensal isolates originating from 387 animals (birds and mammals) sampled in the 1980s and the 2000s. These data have been compared with 760 human commensal isolates, sampled from 152 healthy subjects in the 2000s, and analysed with the same approach. The prevalence of the E. coli phylogenetic groups in birds, non-human mammals and humans is clearly different with a predominance of D/B1, A/B1 and A/B2 strains respectively. A major force shaping the ecological structure is the environment with a strong effect of domestication and the year of sampling followed by the climate. Host characteristics, as the diet and body mass, also influence the ecological structure. Human microbiota are characterized by a higher prevalence of virulence genes and a lower intra-host diversity than the non-human mammal ones. This work identifies for the first time a group of strains specific to the animals, the B1 phylogenetic group strains exhibiting the hly gene. In conclusion, a complex network of factors seems to shape the ecological structure of commensal E. coli, with anthropogenic factors playing a major role and perturbing natural niche equilibrium.

The Ross-Macdonald model has dominated theory for mosquito-borne pathogen transmission dynamics and control for over a century. The model, like many other basic population models, makes the mathematically convenient assumption that populations are well mixed; i.e., that each mosquito is equally likely to bite any vertebrate host. This assumption raises questions about the validity and utility of current theory because it is in conflict with preponderant empirical evidence that transmission is heterogeneous. Here, we propose a new dynamic framework that is realistic enough to describe biological causes of heterogeneous transmission of mosquito-borne pathogens of humans, yet tractable enough to provide a basis for developing and improving general theory. The framework is based on the ecological context of mosquito blood meals and the fine-scale movements of individual mosquitoes and human hosts that give rise to heterogeneous transmission. Using this framework, we describe pathogen dispersion in terms of individual-level analogues of two classical quantities: vectorial capacity and the basic reproductive number, . Importantly, this framework explicitly accounts for three key components of overall heterogeneity in transmission: heterogeneous exposure, poor mixing, and finite host numbers. Using these tools, we propose two ways of characterizing the spatial scales of transmission—pathogen dispersion kernels and the evenness of mixing across scales of aggregation—and demonstrate the consequences of a model's choice of spatial scale for epidemic dynamics and for estimation of , both by a priori model formulas and by inference of the force of infection from time-series data.

Background: Insecticide Treated Nets (ITNs) are an important tool for malaria control. ITNs are effective because they work on several parts of the mosquito feeding cycle, including both adult killing and repelling effects.

Mosquito-borne diseases pose some of the greatest challenges in public health, especially in tropical and sub-tropical regions of the world. Efforts to control these diseases have been underpinned by a theoretical framework developed for malaria by Ross and Macdonald, including models, metrics for measuring transmission, and theory of control that identifies key vulnerabilities in the transmission cycle. That framework, especially Macdonald's formula for R0 and its entomological derivative, vectorial capacity, are now used to study dynamics and design interventions for many mosquito-borne diseases. A systematic review of 388 models published between 1970 and 2010 found that the vast majority adopted the Ross–Macdonald assumption of homogeneous transmission in a well-mixed population. Studies comparing models and data question these assumptions and point to the capacity to model heterogeneous, focal transmission as the most important but relatively unexplored component in current theory. Fine-scale heterogeneity causes transmission dynamics to be nonlinear, and poses problems for modeling, epidemiology and measurement. Novel mathematical approaches show how heterogeneity arises from the biology and the landscape on which the processes of mosquito biting and pathogen transmission unfold. Emerging theory focuses attention on the ecological and social context for mosquito blood feeding, the movement of both hosts and mosquitoes, and the relevant spatial scales for measuring transmission and for modeling dynamics and control.

The study of integrons in 181 Escherichia coli isolates from three groups of healthy subjects who lived in communities and had not taken antibiotics for at least 1 month showed that the presence of integrons was associated with antibiotic resistance and phylogenetic grouping of the bacterial host and dependent on a subject's living environment.Integrons play an important role in antibiotic resistance of clinical Escherichia coli strains because they are able to capture, integrate, and express gene cassettes encoding antibiotic resistance (11). The prevalence of integrons ranges from 22 to 59% in clinical E. coli (20,26) and increases with the resistance of the isolates (17). Integrons are also present in resistant intestinal E. coli isolates from subjects living in a community (18). However, the subjects studied (18) were those admitted to a neurology ward and thus were, strictly speaking, not "perfectly healthy." Resistance in intestinal E. coli strains is promoted by recent exposure to antibiotics (23), diet (7), deficient hygiene, poor living conditions (28), and living in developing countries (16). E. coli populations are structured in four major phylogenetic groups, A, B1, B2, and D (13), and isolates from the B2 phylogenetic group appear to be the least resistant to antibiotics (14,24).We took advantage of collections of intestinal E. coli isolates from healthy adults free of recent direct exposure to antibiotics to investigate the epidemiology of integrons and the relationship between their prevalence and the isolates' phylogenetic grouping.We studied a collection of 181 E. coli isolates of known phylogenetic groups (9) and known antibiotic susceptibilities (2, 10), originating from three age-and sex-matched groups of healthy subjects living in communities (25 subjects/group, four to five isolates/subject): (i) Wayampi Amerindians living in isolation in southern French Guyana (WA), (ii) pig farmers (PF), and (iii) bank or insurance workers (BIW); the last two groups were from western mainland France. Subjects had not taken antibiotics for at least 1 month before the fecal specimen was obtained. When several isolates from the same subject displayed indistinguishable antibiotic susceptibility patterns and belonged to the same phylogenetic group, they were considered replicates and only one was selected at random. It was noted that the prevalence of group B2 in these isolates (27/181 [15%]) was lower than that in isolates from healthy women in Michigan (42/88 [48%]) (30), a difference that has been discussed elsewhere (9).DNA was extracted from each isolate, and plasmid DNA from E. coli K-12 DH1 containing plasmid PSU 2056 (21), PVC 2554 (6), or PSMB 731 (1) carrying, respectively, a class 1, 2, or 3 integron was used as a control. The intI1, intI2, and intI3 genes were detected by triplex real-time PCR on an ABI Prism 7000 sodium dodecyl sulfate thermocycler (Applera, Courtaboeuf, France) using specific primer pairs (Table 1). Dissociation temperatures were 85, 80, and 90°C for the amplification products, c...