HIV and herpes simplex virus type 2 epidemiological synergy: Misguided observational evidence? A modelling study

Objectives To investigate whether observational studies of HIV and herpes simplex virus type 2 (HSV-2) infections have the capacity to assess the HIV/HSV-2 epidemiological synergy. Methods An individual-based Monte Carlo model was used to simulate HIV/HSV-2 epidemics in two scenarios: no HIV/HSV-2 biological interaction and HSV-2 seropositivity enhancing HIV acquisition. Cross-sectional observational studies were simulated by sampling individuals from the population to assess resulting crude and adjusted ORs of the HIV/HSV-2 association. Meta-analyses were conducted to estimate the pooled mean ORs. Impact of under-reporting of sexual behaviour and misc

Association between HCV infection and diabetes type 2 in Egypt: Is it time to split up?

Purpose: There is a conflicting evidence about the association between hepatitis C virus (HCV) infection and diabetes mellitus. The objective of this study was to assess this association in Egypt, the country with the highest HCV prevalence in the world. Methods: The source of data was from the Egypt Demographic and Health Survey conducted in 2008. Using multivariable logistic regression analyses to account for known confounders, the association was investigated at two levels']: (1) HCV exposure (HCV antibody status) and diabetes mellitus and (2) diabetes mellitus and chronic HCV infection (HCV RNA status) among HCV-exposed individuals. Results: We found no evidence for an association between HCV antibody status and diabetes (adjusted odds ratio [OR] = 0.87; 95% confidence interval [CI], 0.63-1.19). However, among HCV-exposed individuals, we found an evidence for an association between diabetes and active HCV infection (adjusted OR = 2.44, 95% CI, 1.30-4.57). Conclusions: Although it does not appear that HCV exposure and diabetes are linked, there might be an association between diabetes and chronic HCV infection. The HCV-diabetes relationship may be more complex than previously anticipated. Therefore, a call for an "amicable divorce" to the HCV-diabetes relationship could be premature

Evaluation of Syndromic Surveillance in the Netherlands: Its Added Value and Recommendations for Implementation

In the last decade, syndromic surveillance has increasingly been used worldwide for detecting increases or outbreaks of infectious diseases that might be missed by surveillance based on laboratory diagnoses and notifications by clinicians alone. There is, however, an ongoing debate about the feasibility of syndromic surveillance and its potential added value. Here we present our perspective on syndromic surveillance, based on the results of a retrospective analysis of syndromic data from six Dutch healthcare registries, covering 1999–2009 or part of this period. These registries had been designed for other purposes, but were evaluated for their potential use in signalling infectious disease dynamics and outbreaks. Our results show that syndromic surveillance clearly has added value in revealing the blind spots of traditional surveillance, in particular by detecting unusual, local outbreaks independently of diagnoses of specific pathogens, and by monitoring disease burden and virulence shifts of common pathogens. Therefore we recommend the use of syndromic surveillance for these applications

The Rise and Fall of HIV in High-Prevalence Countries: A Challenge for Mathematical Modeling

Several countries with generalized, high-prevalence HIV epidemics, mostly in sub-Saharan Africa, have experienced rapid declines in transmission. These HIV epidemics, often with rapid onsets, have generally been attributed to a combination of factors related to high-risk sexual behavior. The subsequent declines in these countries began prior to widespread therapy or implementation of any other major biomedical prevention. This change has been construed as evidence of behavior change, often on the basis of mathematical models, but direct evidence for behavior changes that would explain these declines is limited. Here, we look at the structure of current models and argue that the common "fixed risk per sexual contact" assumption favors the conclusion of substantial behavior changes. We argue that this assumption ignores reported non-linearities between exposure and risk. Taking this into account, we propose that some of the decline in HIV transmission may be part of the natural dynamics of the epidemic, and that several factors that have traditionally been ignored by modelers for lack of precise quantitative estimates may well hold the key to understanding epidemiologic trends

Mapping and characterising areas with high levels of HIV transmission in sub-Saharan Africa: A geospatial analysis of national survey data

BACKGROUND: In the generalised epidemics of sub-Saharan Africa (SSA), human immunodeficiency virus (HIV) prevalence shows patterns of clustered micro-epidemics. We mapped and characterised these high-prevalence areas for young adults (15-29 years of age), as a proxy for areas with high levels of transmission, for 7 countries in Eastern and Southern Africa: Kenya, Malawi, Mozambique, Tanzania, Uganda, Zambia, and Zimbabwe. METHODS AND FINDINGS: We used geolocated survey data from the most recent United States Agency for International Development (USAID) demographic and health surveys (DHSs) and AIDS indicator surveys (AISs) (collected between 2008-2009 and 2015-2016), which included about 113,000 adults-of which there were about 53,000 young adults (27,000 women, 28,000 men)-from over 3,500 sample locations. First, ordinary kriging was applied to predict HIV prevalence at unmeasured locations. Second, we explored to what extent behavioural, socioeconomic, and environmental factors explain HIV prevalence at the individual- and sample-location level, by developing a series of multilevel multivariable logistic regression models and geospatially visualising unexplained model heterogeneity. National-level HIV prevalence for young adults ranged from 2.2% in Tanzania to 7.7% in Mozambique. However, at the subnational level, we found areas with prevalence among young adults as high as 11% or 15% alternating with areas with prevalence between 0% and 2%, suggesting the existence of areas with high levels of transmission Overall, 15.6% of heterogeneity could be explained by an interplay of known behavioural, socioeconomic, and environmental factors. Maps of the interpolated random effect estimates show that environmental variables, representing indicators of economic activity, were most powerful in explaining high-prevalence areas. Main study limitations were the inability to infer causality due to the cross-sectional nature of the surveys and the likely under-sampling of key populations in the surveys. CONCLUSIONS: We found that, among young adults, micro-epidemics of relatively high HIV prevalence alternate with areas of very low prevalence, clearly illustrating the existence of areas with high levels of transmission. These areas are partially characterised by high economic activity, relatively high socioeconomic status, and risky sexual behaviour. Localised HIV prevention interventions specifically tailored to the populations at risk will be essential to curb transmission. More fine-scale geospatial mapping of key populations,-such as sex workers and migrant populations-could help us further understand the drivers of these areas with high levels of transmission and help us determine how they fuel the generalised epidemics in SSA

HIV-1 Clade D Is Associated with Increased Rates of CD4 Decline in a Kenyan Cohort

HIV-1 is grouped phylogenetically into clades, which may impact rates of HIV-1 disease progression. Clade D infection in particular has been shown to be more pathogenic. Here we confirm in a Nairobi-based prospective female sex worker cohort (1985-2004) that Clade D (n = 54) is associated with a more rapid CD4 decline than clade A1 (n = 150, 20.6% vs 13.4% decline per year, 1.53-fold increase, p = 0.015). This was independent of "protective" HLA and country of origin (p = 0.053), which in turn were also independent predictors of the rate of CD4 decline (p = 0.026 and 0.005, respectively). These data confirm that clade D is more pathogenic than clade A1. The precise reason for this difference is currently unclear, and requires further study. This is first study to demonstrate difference in HIV-1 disease progression between clades while controlling for protective HLA alleles

Concerted Efforts to Control or Eliminate Neglected Tropical Diseases

Background: The London Declaration (2012) was formulated to support and focus the control and elimination of ten neglected tropical diseases (NTDs), with targets for 2020 as formulated by the WHO Roadmap. Five NTDs (lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminths and trachoma) are to be controlled by preventive chemotherapy (PCT), and four (Chagas’ disease, human African trypanosomiasis, leprosy and visceral leishmaniasis) by innovative and intensified disease management (IDM). Guinea worm, virtually eradicated, is not considered here. We aim to estimate the global health impact of meeting these targets in terms of averted morbidity, mortality, and disability adjusted life years (DALYs). Methods: The Global Burden of Disease (GBD) 2010 study provides prevalence and burden estimates for all nine NTDs in 1990 and 2010, by country, age and sex, which were taken as the basis for our calculations. Estimates for other years were obtained by interpolating between 1990 (or the start-year of large-scale control efforts) and 2010, and further extrapolating until 2030, such that the 2020 targets were met. The NTD disease manifestations considered in the GBD study were analyzed as either reversible or irreversible. Health impacts were assessed by comparing the results of achieving the targets with the counterfactual, construed as the health burden had the 1990 (or 2010 if higher) situation continued unabated. Principle Findings/Conclusions: Our calculations show that meeting the targets will lead to about 600 million averted DALYs in the period 2011–2030, nearly equally distributed between PCT and IDM-NTDs, with the health gain amongst PCT-NTDs mostly (96%) due to averted disability and amongst IDM-NTDs largely (95%) from averted mortality. These health gains include about 150 million averted irreversible disease manifestations (e.g. blindness) and 5 million averted deaths. Control of soil-transmitted helminths accounts for one third of all averted DALYs. We conclude that the projected health impact of the London Declaration justifies the required efforts

Association between history of tuberculosis and vegetarianism from a nationally representative survey in India

A vegetarian diet has been implicated as a risk factor for tuberculosis (TB) among South Asians in the United Kingdom. To explore whether this is also the case in India, we analysed data from the nationally representative National Family Health Survey-3 (2006) which collected information on TB and diet, and tested for human immunodeficiency virus (HIV) 1. TB was reported by heads of households. Using logistic regression, we found that vegetarianism was not a risk factor for TB among HIV-1 negative married men and women aged 15 - 49 (women) or 15-54 (men) years (OR 0.66, 95%CI 0.49 - 0.89), while poverty and a history of blood transfusions were

The potential impact of RV144-like vaccines in rural South Africa: A study using the STDSIM microsimulation model

Background: The only successful HIV vaccine trial to date is the RV144 trial of the ALVAC/AIDSVAX vaccine in Thailand, which showed an overall incidence reduction of 31%. Most cases were prevented in the first year, suggesting a rapidly waning efficacy. Here, we predict the population level impact and cost-effectiveness of practical implementation of such a vaccine in a setting of a generalised epidemic with high HIV prevalence and incidence. Methods: We used STDSIM, an established individual-based microsimulation model, tailored to a rural South African area with a well-functioning HIV treatment and care programme. We estimated the impact of a single round of mass vaccination for everybody aged 15-49, as well as 5-year and 2-year re-vaccination strategies for young adults (aged 15-29). We calculated proportion of new infections prevented, cost-effectiveness indicators, and budget impact estimates of combined ART and vaccination programmes. Results: A single round of mass vaccination with a RV144-like vaccine will have a limited impact, preventing only 9% or 5% of new infections after 10 years at 60% and 30% coverage levels, respectively. Revaccination strategies are highly cost-effective if vaccine prices can be kept below 150 US/vaccine for 2-year revaccination strategies, and below 200 US/vaccine for 5-year revaccination strategies. Net cost-savings through reduced need for HIV treatment and care occur when vaccine prices are kept below 75 US/vaccine. These results are sensitive to alternative assumptions on the underlying sexual network, background prevention interventions, and individual's propensity and consistency to participate in the vaccination campaign. Discussion: A modestly effective vaccine can be a cost-effective intervention in highly endemic settings. To predict the impact of vaccination strategies in other endemic situations, sufficient knowledge of the underlying sexual network, prevention and treatment interventions, and individual propensity and consistency to participate, is key. These issues are all best addressed in an individual-based microsimulation model

Detection of excess influenza severity: Associating respiratory hospitalization and mortality data with reports of influenza-like illness by primary care physicians

Objectives. We explored whether excesses in influenza severity can be detected by combining respiratory syndromic hospital and mortality data with data on influenza-like illness (ILI) cases obtained from general practitioners. Methods. To identify excesses in the severity of influenza infections in the population of the Netherlands between 1999 and 2005, we looked for increases in influenza-associated hospitalizations and mortality that were disproportionate to the number of ILI cases reported by general practitioners. We used generalized estimating equation regression models to associate syndromic hospital and mortality data with ILI surveillance data obtained from general practitioners. Virus isolation and antigenic characterization data were used to interpret the results. Results. Disproportionate increases in hospitalizations and mortality (relative to ILI cases reported by general practitioners) were identified in 2003/04 during the A/Fujian/411/02(H3N2) drift variant epidemic. Conclusions. Combined surveillance of respiratory hospitalizations and mortality and ILI data obtained from general practitioners can capture increases in severe influenza-associated illness that are disproportionate to influenza incidence rates. Therefore, this novel approach should complement traditional seasonal and pandemic influenza surveillance in efforts to detect increases in influenza case fatality rates and percentages of patients hospitalized