Population uptake and effectiveness of test-and-treat antiretroviral therapy guidelines for preventing the global spread of HIV: an ecological cross-national analysis.

OBJECTIVES: Although the benefits of adopting test-and-treat antiretroviral therapy (ART) guidelines that recommend initiation of ART regardless of CD4 cell counts have been demonstrated at the individual level, there is uncertainty about how this translates to the population level. Here, we explored whether adopting ART guidelines recommending earlier treatment initiation improves population ART access and viral suppression and reduces overall disease transmission. METHODS: Data on ART initiation guidelines and treatment coverage, viral suppression, and HIV incidence from 37 European and Central Asian countries were collected from the European Centre for Disease Prevention and Control and the Global HIV Policy Watch and HIV 90-90-90 Watch databases. We used multivariate linear regression models to quantify the association of ART initiation guidelines with population ART access, viral suppression, and HIV incidence, adjusting for potential confounding factors. RESULTS: Test-and-treat policies were associated with 15.2 percentage points (pp) [95% confidence interval (CI) 0.8-29.6 pp; P = 0.039] greater treatment coverage (proportion of HIV-positive people on ART) compared with countries with ART initiation at CD4 cell counts ≤ 350 cells/µL. The presence of test-and-treat policies was associated with 15.8 pp (95% CI 2.4-29.1 pp; P = 0.023) higher viral suppression rates (people on ART virally suppressed) compared with countries with treatment initiation at CD4 counts ≤ 350 cells/µL. ART initiation at CD4 counts ≤ 500 cells/µL did not significantly improve ART coverage compared to initiation at CD4 counts ≤ 350 cells/µL but achieved similar degrees of viral suppression as test-and-treat. CONCLUSIONS: Test-and-treat was found to be associated with substantial improvements in population-level access to ART and viral suppression, further strengthening evidence that rapid initiation of treatment will help curb the spread of HIV.

Exploring Campylobacter seasonality across Europe using The European Surveillance System (TESSy), 2008 to 2016.

BackgroundCampylobacteriosis is the most commonly reported food-borne infection in the European Union, with an annual number of cases estimated at around 9 million. In many countries, campylobacteriosis has a striking seasonal peak during early/mid-summer. In the early 2000s, several publications reported on campylobacteriosis seasonality across Europe and associations with temperature and precipitation. Subsequently, many European countries have introduced new measures against this food-borne disease.AimTo examine how the seasonality of campylobacteriosis varied across Europe from 2008-16, to explore associations with temperature and precipitation, and to compare these results with previous studies. We also sought to assess the utility of the European Surveillance System TESSy for cross-European seasonal analysis of campylobacteriosis.MethodsWard's Minimum Variance Clustering was used to group countries with similar seasonal patterns of campylobacteriosis. A two-stage multivariate meta-analysis methodology was used to explore associations with temperature and precipitation.ResultsNordic countries had a pronounced seasonal campylobacteriosis peak in mid- to late summer (weeks 29-32), while most other European countries had a less pronounced peak earlier in the year. The United Kingdom, Ireland, Hungary and Slovakia had a slightly earlier peak (week 24). Campylobacteriosis cases were positively associated with temperature and, to a lesser degree, precipitation.ConclusionAcross Europe, the strength and timing of campylobacteriosis peaks have remained similar to those observed previously. In addition, TESSy is a useful resource for cross-European seasonal analysis of infectious diseases such as campylobacteriosis, but its utility depends upon each country's reporting infrastructure.

Gender violence, poverty and HIV infection risk among persons engaged in the sex industry: cross-national analysis of the political economy of sex markets in 30 European and Central Asian countries.

OBJECTIVES: Persons engaged in the sex industry are at greater risk of HIV and other sexually transmitted infections than the general population. One major factor is exposure to higher levels of risky sexual activity. Expanding condom use is a critical prevention strategy, but this requires negotiation with those buying sex, which takes place in the context of cultural and economic constraints. Impoverished individuals who fear violence are more likely to forego condoms. METHODS: Here we tested the hypotheses that poverty and fear of violence are two structural drivers of HIV infection risk in the sex industry. Using data from the European Centre for Disease Prevention and Control and the World Bank for 30 countries, we evaluated poverty, measured using the average income per day per person in the bottom 40% of the income distribution, and gender violence, measured using homicide rates in women and the proportion of women exposed to violence in the last 12 months and/or since age 16 years. RESULTS: We found that HIV prevalence among those in the sex industry was higher in countries where there were greater female homicide rates (ß = 0.86; P = 0.018) and there was some evidence that self-reported exposure to violence was also associated with higher HIV prevalence (ß = 1.37; P = 0.043). Conversely, HIV prevalence was lower in countries where average incomes among the poorest were greater (ß = -1.05; P = 0.046). CONCLUSIONS: Our results are consistent with the theory that reducing poverty and exposure to violence may help reduce HIV infection risk among persons engaged in the sex industry.

Waterborne outbreaks in the Nordic countries, 1998 to 2012.

A total of 175 waterborne outbreaks affecting 85,995 individuals were notified to the national outbreak surveillance systems in Denmark, Finland and Norway from 1998 to 2012, and in Sweden from 1998 to 2011. Between 4 and 18 outbreaks were reported each year during this period. Outbreaks occurred throughout the countries in all seasons, but were most common (n = 75/169, 44%) between June and August. Viruses belonging to the Caliciviridae family and Campylobacter were the pathogens most frequently involved, comprising n = 51 (41%) and n = 36 (29%) of all 123 outbreaks with known aetiology respectively. Although only a few outbreaks were caused by parasites (Giardia and/or Cryptosporidium), they accounted for the largest outbreaks reported during the study period, affecting up to 53,000 persons. Most outbreaks, 124 (76%) of those with a known water source (n = 163) were linked to groundwater. A large proportion of the outbreaks (n = 130/170, 76%) affected a small number of people (less than 100 per outbreak) and were linked to single-household water supplies. However, in 11 (6%) of the outbreaks, more than 1,000 people became ill. Although outbreaks of this size are rare, they highlight the need for increased awareness, particularly of parasites, correct water treatment regimens, and vigilant management and maintenance of the water supply and distribution systems.

Mapping ongoing European research activities examining the infectious aetiology of chronic conditions.

Chronic conditions contribute to the majority of the mortality and morbidity burden in Europe. The extent to which infectious agents are responsible for the chronic disease burden remains elusive. The complex nature of the natural history of chronic conditions calls for an overview of ongoing research activities linking infectious agents with these conditions in order to guide research endeavours, direct research funding, steer prevention efforts, and point health policy towards promising interventions. A selection of websites hosted by institutions either financing or conducting research within the European Union was screened for ongoing research activities examining infectious aetiology of chronic conditions. The searches were conducted until September 2011, applying search strategies and inclusion criteria predefined in a study protocol. In total, 25 research activities met the inclusion criteria. Of those, ten activities were focused to investigate infectious aetiology of cancer, four focused on type 2 diabetes mellitus, and 11 focused on a wide spectrum of other chronic conditions. The identified research projects did not cover areas such as mental and behavioural disorders. Infectious agents analysed included enteroviruses, Epstein-Barr virus, human rhinoviruses, P. gingivalis, human papillomaviruses, cytomegalovirus, Helicobacter spp. and human parvovirus. Only three projects specifically addressed therapeutic interventions. Ultimately, linking infectious agents with chronic conditions may translate into prevention efforts with vaccinations or treatment strategies with antimicrobial agents, and could, thus, eventually reduce the heavy disease burden from chronic conditions. However, little translational research on therapeutic interventions was found in our search and should be fostered, particularly for more established infectious-chronic disease associations.

Strategies to intervene on social determinants of infectious diseases.

Systematic health inequalities exist in all European countries today. Individuals with lower socio-economic status suffer disproportionally from adverse health outcomes. While this is widely accepted for chronic diseases, a literature review covering the years 1999-2010 reveals that infectious diseases are also distributed unevenly throughout society, with vulnerable groups bearing a disproportionate burden. This burden is not restricted to a few 'signature infections of social determinants' such as tuberculosis or human immunodeficiency virus (HIV) infections, but also a wide array of other infectious diseases. Tremendous advances in public health over the last century have reduced the absolute magnitude of inequalities but relative differences remain. In order to explore the underlying reasons for such persistent inequalities in Europe, I examined interventions targeting social determinants of infectious diseases: interventions on social determinants tend to focus on chronic diseases rather than infectious diseases, and interventions for these mainly focus on HIV/AIDS or other sexually transmitted infections. Thus, there seems to be a need to intervene on inequalities in infectious diseases but ideally with a comprehensive public health approach. Three intervention strategies are discussed: population-at-risk, population, and vulnerable population approaches. Strengths and weaknesses of these options are illustrated.

Migrant tuberculosis screening in the EU/EEA: yield, coverage and limitations.

A systematic literature review was performed with the objective of assessing the effectiveness of tuberculosis (TB) screening methods and strategies in migrants in European Union/European Economic Area (including Switzerland) countries. Extracted data on yield and coverage were used as indicators of effectiveness. Reported yields varied considerably between studies and countries. Considering only the 14 studies representative of national screening programmes, a median yield of TB disease of 0.18% (interquartile range 0.10-0.35%) was reported. The data did not indicate differences in effectiveness between the three main strategies: 1) screening at port of entry; 2) screening just after arrival in reception/holding centres; and 3) screening in the community following arrival in European Union countries. The variation seen probably reflects variation in risk factors for TB, in particular the composition of the migrants entering the country. Recommendations include the need for improved data for guiding the optimal frequency and duration of screening; assessment and improvement of cost-effectiveness; access to healthcare for migrants, including illegal migrants; ensuring a continuum of care for those screened; and consideration of screening for latent TB infection with caution. Finally, screening should be a component of a wider approach, rather than a stand-alone intervention.

Cryptosporidiosis surveillance and water-borne outbreaks in Europe.

Cryptosporidium causes diarrhoeal disease that can be particularly severe in immuno-compromised individuals. Cryptosporidiosis is a notifiable disease at European Union level, and surveillance data are collected through the European Basic Surveillance Network. The disease distribution in Europe for 2005 showed 7,960 cryptosporidiosis cases reported from 16 countries. The crude incidence rate was 1.9 cases per 100,000, although there were considerable differences in the rates of cryptosporidiosis between countries. Infection was more commonly reported in young children. A pronounced seasonal peak was observed in the autumn of 2005, with 59% of the cases reported between August and November, although Ireland and Spain experienced a peak in spring and summer, respectively. Cryptosporidiosis outbreak investigations and analytic studies have associated the disease with drinking water supplies, animal contact, travel, and swimming pools. Contamination of the source water for drinking water supplies, as well as inadequate water treatment can be responsible for cryptosporidiosis outbreaks. Routine cryptosporidiosis surveillance from North West England over 17 years showed that the cases occurred predominantly in spring and autumn. British drinking water regulations and improvements in drinking water treatment have coincided with a decline in cryptosporidiosis incidence. Improvements in cryptosporidiosis surveillance such as detection, recording and reporting will help to recognise outbreaks and monitor interventions.

Gene-environment interactions in renal cell carcinoma.

The majority of renal cell carcinomas (RCCs) are sporadic, and increasing incidence rates suggest that such environmental risk factors as smoking play a role in the etiology of the disease. Cases with RCC were selected from the population-based cancer registry of Orange County, California, between 1994 and 1997; controls were recruited by telephone using random digit dialing. A total of 115 case and 259 control subjects were genotyped for N-acetyltransferase 2 (NAT2), which codes for a polymorphic enzyme involved in tobacco-carcinogen metabolism. Subjects with slow acetylator genotypes were found to be at twofold increased risk (odds ratio (OR) = 1.8; 95 percent confidence interval (CI): 1.1, 2.9) of RCC. Although cancer risk doubled among smokers (OR = 2.2; 95 percent CI: 1.3, 3.7), stratified analysis revealed gene-environment interaction among slow acetylators that smoked (OR = 3.2; 95 percent CI: 1.7, 6.1) compared with rapid acetylators that smoked (OR = 1.4; 95 percent CI: 0.7, 2.9). A dose response was found for pack-years among slow acetylators (p < 0.01) but not among rapid acetylators (p = 0.06). Although smoking is a well-established risk factor of RCC, our data suggest that the risk is pronounced among slow rather than rapid acetylators.

Excess hospital admissions during the July 1995 heat wave in Chicago.

INTRODUCTION: This study describes medical conditions treated in all 47 non-VA hospitals in Cook County, IL during the 1995 heat wave. We characterize the underlying diseases of the susceptible population, with the goal of tailoring prevention efforts. METHODS: Primary and secondary discharge diagnoses made during the heat wave and comparison periods were obtained from computerized inpatient hospital discharge data to determine reasons for hospitalization, and comorbid conditions, respectively. RESULTS: During the week of the heat wave, there were 1072 (11%) more hospital admissions than average for comparison weeks and 838 (35%) more than expected among patients aged 65 years and older. The majority of this excess (59%) were treatments for dehydration, heat stroke, and heat exhaustion; with the exception of acute renal failure no other primary discharge diagnoses were significantly elevated. In contrast, analysis of comorbid conditions revealed 23% (p = 0.019) excess admissions of underlying cardiovascular diseases, 30% (p = 0.033) of diabetes, 52% (p = 0.011) of renal diseases, and 20% (p = 0.027) of nervous system disorders. Patient admissions for emphysema (p = 0.007) and epilepsy (p = 0.009) were also significantly elevated during the heat wave week. CONCLUSIONS: The majority of excess hospital admissions were due to dehydration, heat stroke, and heat exhaustion, among people with underlying medical conditions. Short-term public health interventions to reduce heat-related morbidity should be directed toward these individuals to assure access to air conditioning and adequate fluid intake. Long-term prevention efforts should aim to improve the general health condition of people at risk through, among other things, regular physician-approved exercise.

Water distribution system and diarrheal disease transmission: a case study in Uzbekistan.

Deteriorating water treatment facilities and distribution systems pose a significant public health threat, particularly in republics of the former Soviet Union. Interventions to decrease the disease burden associated with these water systems range from upgrading distribution networks to installing reverse osmosis technology. To provide insight into this decision process, we conducted a randomized intervention study to provide epidemiologic data for water policy decisions in Nukus, Uzbekistan, where drinking water quality is suboptimal. We interviewed residents of 240 households, 120 with and 120 without access to municipal piped water. Residents of 62 households without piped water were trained to chlorinate their drinking water at home in a narrow-necked water container with a spout. All study subjects (1583 individuals) were monitored biweekly for self-reported diarrheal illness over a period of 9.5 weeks. The home chlorination intervention group had the lowest diarrheal rate (28.8/1,000 subjects/month) despite lack of access to piped water in their homes. Compared with the two groups that did not receive the intervention this rate was one-sixth that of the group with no piped water (179.2/1,000 subjects/month) and one-third that of the households with piped water (75.5/1,000 subjects/month). More than 30% of the households with piped water lacked detectable levels of chlorine residues in their drinking water, despite two-stage chlorination of the source water, and were at increased risk of diarrhea. Forty-two percent of these municipal users reported that water pressure had been intermittent within the previous two days. The dramatic reduction in diarrheal rates in the home-chlorination intervention group indicates that a large proportion of diarrheal diseases in Nukus are water-borne. The home-chlorination group had less diarrhea than the group with piped water, implicating the distribution system as a source of disease transmission. Taken together, these epidemiologic data would support the hypothesis that diarrhea in the piped water group could be attributed to cross-contamination between the municipal water supply and sewer, due to leaky pipes and lack of water pressure. Relatively inexpensive steps, including chlorination, maintaining water pressure, and properly maintaining the distribution system, rather than reverse osmosis technology, should reduce diarrheal rates.

Reproductive toxins and alligator abnormalities at Lake Apopka, Florida.

The alligator population at Lake Apopka in central Florida declined dramatically between 1980 and 1987. Endocrine-disrupting chemicals and specifically DDT metabolites have been implicated in the alligators' reproductive failure. The DDT metabolite hypothesis is based largely on the observation of elevated concentrations of p,p-DDE and p,p-DDD in alligator eggs obtained from Lake Apopka in 1984 and 1985. In the following commentary, we draw attention to two nematocides that are established reproductive toxins in humans, dibromochloropropane (DBCP) and ethylene dibromide (EDB), which could also have played a role in the reproductive failure observed in alligators from Lake Apopka in the early 1980s.

Molecular epidemiology in environmental health: the potential of tumor suppressor gene p53 as a biomarker.

One of the challenges in environmental health is to attribute a certain health effect to a specific environmental exposure and to establish a cause-effect relationship. Molecular epidemiology offers a new approach to addressing these challenges. Mutations in the tumor suppressor gene p53 can shed light on past environmental exposure, and carcinogenic agents and doses can be distinguished on the basis of mutational spectra and frequency. Mutations in p53 have successfully been used to establish links between dietary aflatoxin exposure and liver cancer, exposure to ultraviolet light and skin cancer, smoking and cancers of the lung and bladder, and vinyl chloride exposure and liver cancer. In lung cancer, carcinogens from tobacco smoke have been shown to form adducts with DNA. The location of these adducts correlates with those positions in the p53 gene that are mutated in lung cancer, confirming a direct etiologic link between exposure and disease. Recent investigations have also explored the use of p53 as a susceptibility marker for cancer. Furthermore, studies in genetic toxicology have taken advantage of animals transgenic for p53 to screen for carcinogens in vivo. In this review, we summarize recent developments in p53 biomarker research and illustrate applications to environmental health.

Tetrasomy 8 detected by interphase cytogenetics in a child with acute lymphocytic leukemia.

Tetrasomy 8 is a rare clonal anomaly in human acute leukemia. Here we present a case of a 7-year-old boy with acute lymphoblastic leukemia (ALL) displaying a tetrasomy 8 clone that could not be detected by conventional cytogenetics. In this study, bone marrow and peripheral blood cells were collected at five different diagnostic stages and analyzed by double targeted fluorescence in situ hybridization (FISH) with centromeric DNA probes for chromosomes 7, 8, 9, and 12. FISH analysis revealed a significant increase in tetrasomy 8 frequency, but not in other chromosomes examined. A smaller increase in trisomy 8 was also detected. At one stage over 60% of the cells were hyperdiploid with 40% being tetrasomic. The size of the tetrasomic clone changed during the course of the disease. The hyperdiploid frequencies of chromosome 8 detected by interphase FISH analysis in bone marrow and peripheral blood were similar. Our findings indicate the utility of FISH analysis in cytogenetic monitoring of leukemia patients and further show that tetrasomy 8 may play a specific role in a subtype of ALL.

Heat-related deaths during the July 1995 heat wave in Chicago.

BACKGROUND: During a record-setting heat wave in Chicago in July 1995, there were at least 700 excess deaths, most of which were classified as heat-related. We sought to determine who was at greatest risk for heat-related death. METHODS: We conducted a case-control study in Chicago to identify risk factors associated with heat-related death and death from cardiovascular causes from July 14 through July 17, 1995. Beginning on July 21, we interviewed 339 relatives, neighbors, or friends of those who died and 339 controls matched to the case subjects according to neighborhood and age. RESULTS: The risk of heat-related death was increased for people with known medical problems who were confined to bed (odds ratio as compared with those who were not confined to bed, 5.5) or who were unable to care for themselves (odds ratio, 4.1). Also at increased risk were those who did not leave home each day (odds ratio, 6.7), who lived alone (odds ratio, 2.3), or who lived on the top floor of a building (odds ratio, 4.7). Having social contacts such as group activities or friends in the area was protective. In a multivariate analysis, the strongest risk factors for heat-related death were being confined to bed (odds ratio, 8.2) and living alone (odds ratio, 2.3); the risk of death was reduced for people with working air conditioners (odds ratio, 0.3) and those with access to transportation (odds ratio, 0.3). Deaths classified as due to cardiovascular causes had risk factors similar to those for heat-related death. CONCLUSIONS: In this study of the 1995 Chicago heat wave, those at greatest risk of dying from the heat were people with medical illnesses who were socially isolated and did not have access to air conditioning. In future heat emergencies, interventions directed to such persons should reduce deaths related to the heat.

Changing the specificity of the sorting receptor for luminal endoplasmic reticulum proteins.

Luminal proteins of the endoplasmic reticulum (ER) share a common carboxy-terminal tetrapeptide which is necessary and sufficient for their retention in the ER. In animal cells this retention signal is usually KDEL, whereas the yeast Kluyveromyces lactis uses the closely related sequences HDEL and DDEL. The yeast ERD2 gene has been shown to determine the capacity and specificity of the retention system, implying that it encodes a sorting receptor. This receptor is thought to retrieve escaped ER proteins from the Golgi, where a human homologue of this protein has been located. This dual function of binding and retrieval requires a receptor with highly specific binding at a specific location in the cell (Golgi but not ER). Here, a region of the ERD2 protein responsible for the specificity of ligand recognition has been identified using three independent approaches. A single amino acid residue is shown to selectively affect HDEL retention: substitution of residue 51 of the K. lactis receptor is sufficient to abolish recognition of HDEL but not DDEL, generating a novel retention phenotype.