Epidemiological models for sexually transmitted diseases

The classical models for sexually transmitted infections assume homogeneous mixing either between all males and females or between certain subgroups of males and females with heterogeneous contact rates. This implies that everybody is all the time at risk of acquiring an infection. These models ignore the fact that the formation of a pair of two susceptibles renders them in a sense temporarily immune to infection as long as the partners do not separate and have no contacts with other partners. The present paper takes into account the phenomenon of pair formation by introducing explicitly a pairing rate and a separation rate. The infection transmission dynamics depends on the contact rate within a pair and the duration of a partnership. It turns out that endemic equilibria can only exist if the separation rate is sufficiently large in order to ensure the necessary number of sexual partners. The classical models are recovered if one lets the separation rate tend to infinity.This work has been supported by Deutsche Forschungsgemeinschaft     

Association of sexually transmitted infections and human papillomavirus co-infection with abnormal cervical cytology among women in Saudi Arabia

Human papillomavirus (HPV) is a causative agent of cervical and other cancers. Sexually transmitted Infections (STIs) may play a crucial role in HPV persistence, leading to serious complications, including cervical cancer. This study investigated the association of HPV/STI co-infection in cervical samples with cervical dysplasia among women in Saudi Arabia. HPV-positive cervical samples (n = 142) were obtained from previous studies and newly collected samples (n = 209) were obtained from women aged 19–83 years. For HPV detection and genotyping, PCR and Genoflow HPV assay kits were used. STIs were detected using a Genoflow STD array kit. Of 351 samples, 94 (27%) were positive for STIs. Among HPV-positive samples, 36 (25%) were positive for STIs; the most common pathogens were Ureaplasma urealyticum/Ureaplasma parvu (13%) and Mycoplasma hominis (6%). A global significant correlation was detected between HPV and STIs with progression of abnormal cervical cytology (χ² = 176, P < 0.0001). Associations between cervical cytology diagnosis and HPV status, STI types (opportunistic and pathogenic), and the presence of Ureaplasma spp., and Mycoplasma hominis were significant (P < 0.05). Our results suggest that additional study in a larger population is warranted to determine the association between HPV/STI co-infection and cervical neoplasia in Saudi women.     

Sexual networks: implications for the transmission of sexually transmitted infections

The structures of sexual networks are essential for understanding the dynamics of sexually transmitted infections. Standard epidemiological models largely disregard the complex patterns of intimate contacts. Social network analysis offers important insight into how to conceptualize and model social interaction and has the potential to greatly enhance the understanding of disease epidemics.     

Comparability of results from pair and classical model formulations for different sexually transmitted infections

The "classical model" for sexually transmitted infections treats partnerships as instantaneous events summarized by partner change rates, while individual-based and pair models explicitly account for time within partnerships and gaps between partnerships. We compared predictions from the classical and pair models over a range of partnership and gap combinations. While the former predicted similar or marginally higher prevalence at the shortest partnership lengths, the latter predicted self-sustaining transmission for gonorrhoea (GC) and Chlamydia (CT) over much broader partnership and gap combinations. Predictions on the critical level of condom use (C(c)) required to prevent transmission also differed substantially when using the same parameters. When calibrated to give the same disease prevalence as the pair model by adjusting the infectious duration for GC and CT, and by adjusting transmission probabilities for HIV, the classical model then predicted much higher C(c) values for GC and CT, while C(c) predictions for HIV were fairly close. In conclusion, the two approaches give different predictions over potentially important combinations of partnership and gap lengths. Assuming that it is more correct to explicitly model partnerships and gaps, then pair or individual-based models may be needed for GC and CT since model calibration does not resolve the differences.     

Expression of structural proteins in human female and male genital epithelia and implications for sexually transmitted infections

Men and women differ in their susceptibility to sexually transmittable infections (STIs) such as human immunodeficiency virus (HIV). However, a paucity of published information regarding the tissue structure of the human genital tract has limited our understanding of these gender differences. We collected cervical, vaginal, and penile tissues from human adult donors. Tissues were prepared with hematoxylin and eosin stains or immunofluorescence labeling of epithelial cell proteins and were analyzed for structural characteristics. Rhesus macaque genital tissues were evaluated to assess the use of this model for HIV/simian immunodeficiency virus transmission events. We found the stratified squamous epithelia of the male and female genital tract shared many similarities and important distinctions. Expression of E-cadherins, desmogleins 1/2, and involucrin was seen in all squamous epithelia, though expression patterns were heterogeneous. Filaggrin and a true cornified layer were markedly absent in female tissues but were clearly seen in all male epithelia. Desmogleins 1/2 were more consistent in the outermost strata of female squamous genital epithelia. Macaque tissues were similar to their respective human tissues. These initial observations highlight how male and female genital epithelia resemble and differ from one another. Further information regarding tissue structural characteristics will help to understand how STIs traverse these barriers to cause infection. This knowledge will be essential in future HIV pathogenesis, transmission, and prevention studies.     

Cytology and clinical spectrum of sexually transmitted infections in Lebanese women as revealed by Pap smear: a cross-sectional study from 2002-2006

To study the cytology profile of cervical smears and the respective prevalence and incidence of certain cervico-vaginal infections detectable by routine Pap smear cytology in Lebanese women from 2002 to 2006. Pap smear cytology results were compiled from the archives of the Institut National de Pathologie for the period extending from 2002 until 2006. This study covered 118,230 cervical specimens obtained from Lebanese women attending clinics and hospitals in all the five districts of Lebanon; prevalence and incidence rates for infections detectable by routine Pap smear examination were determined. A rise in prevalence of these infections by 2.1 percent (2,555) from 2002 to 2006 was revealed. A doubling of Pap smears showing HPV-associated changes was detected (1.4 percent in 2002 to 2.9 percent in 2006), and a simultaneous almost 7-fold increase of Atypical Squamous Cells of Undetermined Significance (ASCUS) cytology was detected during this period; the rise in ASCUS cytology was age-dependent. Moreover, a 60 percent increase in prevalence of bacterial vaginosis (2.3 percent in 2002 to 3.7 percent in 2006) and a more than 3-fold decline in Trichomonas vaginalis infection (1 percent in 2002 to 0.3 percent in 2006) were also noted in this population during this period. An increase in the prevalence and incidence of cervico-vaginal infections detectable by Pap smear cytology in Lebanese women was revealed from 2002 to 2006. Such changes could point to recent modifications of sexual and health behaviours in the Lebanese community.     

Neurofibrillary tangles mediated human neuronal tauopathies: insights from fly models

Tauopathies represent a group of neurodegenerative disorder which are characterized by the presence of tau positive specialized argyrophilic and insoluble intraneuronal and glial fibrillar lesions known as neurofibrillary tangles (NFTs). Tau is a neuron specific microtubule binding protein which is required for the integrity and functioning of neuronal cells, and hyperphosphorylation of tau and its subsequent aggregation and paired helical filaments (PHFs) and NFTs has emerged as one of the major pathogenic mechanisms of tauopathies in human and mammalian model systems. Modeling of human tauopathies in Drosophila results in manifestation of associated phenotypes, and a recent study has demonstrated that similar to human and mammalian models, accumulation of insoluble tau aggregates in the form of typical neurotoxic NFTs triggers the pathogenesis of tauopathies in fly models. In view of the availability of remarkable genetic tools, Drosophila tau models could be extremely useful for in-depth analysis of the role of NFTs in neurodegeneration and tau aetiology, and also for the screening of novel gene(s) and molecule(s) which suppress the toxicity of tau aggregates.     

On the solution of mathematical models of herd immunity in human helminth infections

The general solution of the mathematical model of herd immunity to human helminth infections recently proposed by Anderson and May [3] is obtained. The numerical solution of a more accurate biological model is indistinguishable from the corresponding exact solution of a more tractable mathematical model. Computer simulations of some particular cases of this model support the notion that both ecological and immunological factors determine the observed convex patterns of age-prevalence and age-intensity curves of human helminth infections.This work was made thanks to the advise and support of Dr. Robert M. May while the author was Postdoctoral Fellow at Princeton University     

A cognitive behavioural intervention to reduce sexually transmitted infections among gay men: randomised trial

ObjectiveTo determine the effectiveness of a brief cognitive behavioural intervention in reducing the incidence of sexually transmitted infections among gay men.DesignRandomised controlled trial with 12 months'' follow up.SettingSexual health clinic in London.Participants343 gay men with an acute sexually transmitted infection or who reported having had unprotected anal intercourse in the past year.Results72% (361/499) of men invited to enter the study did so. 90% (308/343) of participants returned at least one follow up questionnaire or re-attended the clinic and requested a check up for sexually transmitted infections during follow up. At baseline, 37% (63/172) of the intervention group and 30% (50/166) of the control group reported having had unprotected anal intercourse in the past month. At 12 months, the proportions were 27% (31/114) and 32% ( 39/124) respectively (P=0.56). However, 31% (38/123) of the intervention group and 21% (35/168) of controls had had at least one new infection diagnosed at the clinic (adjusted odds ratio 1.66, 95% confidence interval 1.00 to 2.74). Considering only men who requested a check up for sexually transmitted infections, the proportion diagnosed with a new infection was 58% (53/91) for men in the intervention group and 43% (35/81) for men in the control group (adjusted odds ratio 1.84, 0.99 to 3.40). Using a regional database that includes information from 23 sexual health clinics in London, we determined that few participants had attended other sexual health clinics.ConclusionsThis behavioural intervention was acceptable and feasible to deliver, but it did not reduce the risk of acquiring a new sexually transmitted infection among these gay men at high risk. Even carefully designed interventions should not be assumed to bring benefit. It is important to evaluate their effects in randomised trials with objective clinical end points.

What is already known on this topic

The need for effective HIV prevention strategies based on reducing sexual risk behaviour remains importantFew interventions to reduce sexual risk behaviour have been rigorously evaluated using randomised controlled trials

What this study adds

This is the first randomised controlled trial of an intervention addressing sexual behaviour in homosexual men that uses sexually transmitted infections and self reported behaviour as end pointsThe intervention was brief and feasible to use in a busy clinic, but it did not reduce the risk of participants acquiring new infectionsThe potential for behavioural interventions to do more harm than good needs to be taken seriously     

Axons as computing devices: basic insights gained from models.

Detailed models of single neurons are typically focused on the dendritic tree and ignore the axonal tree, assuming that the axon is a simple transmission line. In the last 40 years, however, several theoretical and experimental studies have suggested that axons could implement information processing tasks by exploiting: 1) the time delay in action potential (AP) propagation along the axon; 2) the differential filtering of APs into the axonal subtrees; and 3) their activity-dependent excitability. Models for axonal trees have attempted to examine the feasibility of these ideas. However, because the physiological and anatomical data on axons are seriously limited, realistic models of axons have not been developed. The present paper summarizes the main insights that were gained from simplified models of axons; it also highlights the stochastic nature of axons, a topic that was largely neglected in classical models of axons. The advance of new experimental techniques makes it now possible to pay a very close experimental visit to axons. Theoretical tools and fast computers enable to go beyond the simplified models and to construct realistic models of axons. When tightly linked, experiments and theory will help to unravel how axons share the information processing tasks that single neurons implement.     

Helminth parasite proteomics: from experimental models to human infections

Schistosomiasis is a major human helminth infection endemic in developing countries. Urogenital schistosomiasis, caused by S. haematobium, is the most prevalent human schistosome disease in sub-Saharan Africa. Currently control of schistosome infection is by treatment of infected people with the anthelmintic drug praziquantel, but there are calls for continued efforts to develop a vaccine against the parasites. In order for successful vaccine development, it is necessary to understand the biology and molecular characteristics of the parasite. Ultimately, there is need to understand the nature and dynamics of the relationship between the parasite and the natural host. Thus, my studies have focused on molecular characterization of different parasite stages and integrating this information with quantitative approaches to investigate the nature and development of protective immunity against schistosomes in humans. Proteomics has proved a powerful tool in these studies allowing the proteins expressed by the parasite to be characterized at a molecular and immunological level. In this review, the application of proteomic approaches to understanding the human-schistosome relationship as well as testing specific hypotheses on the nature and development of schistosome-specific immune responses is discussed. The contribution of these approaches to informing schistosome vaccine development is highlighted.     

A new design of stochastic partnership models for epidemics of sexually transmitted diseases with stages

A problem of importance in modelling epidemics of sexually transmitted diseases is the development of mathematical structures accommodating sexual and other contacts among members of a population. Because these models may be complex, it is often necessary to use computer intensive methods in their analysis, which raises questions on the design of computer models. In this paper a new approach to designing models sexual contacts is presented within the context of a stochastic model accommodating the formation and dissolution of partnerships in heterosexual populations. Emphasis will be placed on the development of algorithms with a view towards developing software to implement computer intensive methods. Unlike previous formulations, rather than using rejection methods in Monte Carlo simulations to impose necessary constraints on random functions describing partnership formation, in the new formulation all constraints are satisfied with probability one.     

Genetically-modified-animal models for human infections: the Listeria paradigm

Several human pathogens exhibit a restricted host-tropism, relying on the species-specific interaction of microbial ligand(s) with host receptor(s). This specificity accounts for some of the difficulties in modeling human infections in animals. The discovery of L. monocytogenes host-specificity and elucidation of the underlying mechanism has led to the generation of transgenic mice expressing one of its human receptors, E-cadherin. This model is presented here as a paradigm of a genetically-modified-animal model for studying a human infectious disease.     

Immune anticipation of mating in Drosophila: Turandot M promotes immunity against sexually transmitted fungal infections

Although it is well known that mating increases the risk of infection, we do not know how females mitigate the fitness costs of sexually transmitted infections (STIs). It has recently been shown that female fruitflies, Drosophila melanogaster, specifically upregulate two members of the Turandot family of immune and stress response genes, Turandot M and Turandot C (TotM and TotC), when they hear male courtship song. Here, we use the Gal4/UAS RNAi gene knockdown system to test whether the expression of these genes provides fitness benefits for females infected with the entomopathogenic fungus, Metarhizium robertsii under sexual transmission. As a control, we also examined the immunity conferred by Dorsal-related immunity factor (Dif), a central component of the Toll signalling pathway thought to provide immunity against fungal infections. We show that TotM, but not TotC or Dif, provides survival benefits to females following STIs, but not after direct topical infections. We also show that though the expression of TotM provides fecundity benefits for healthy females, it comes at a cost to their survival, which helps to explain why TotM is not constitutively expressed. Together, these results show that the anticipatory expression of TotM promotes specific immunity against fungal STIs and suggest that immune anticipation is more common than currently appreciated.