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Background Since 2003 Tanzania has upgraded its approximately 7000 drug stores to Accredited Drug Dispensing Outlets (ADDOs), involving dispenser training, introduction of record keeping and enhanced regulation. Prior to accreditation, drug stores could officially stock over-the-counter medicines only, though many stocked prescription-only antimalarials. ADDOs are permitted to stock 49 prescription-only medicines, including artemisinin combination therapies and one form of quinine injectable. Oral artemisinin monotherapies and other injectables were not permitted at any time. By late 2011 conversion was complete in 14 of 21 regions. We explored variation in malaria-related knowledge and practices of drug retailers in ADDO and non-ADDO regions. Methods Data were collected as part of the Independent Evaluation of the Affordable Medicines Facility - malaria (AMFm), involving a nationally representative survey of antimalarial retailers in October-December 2011. We randomly selected 49 wards and interviewed all drug stores stocking antimalarials. We compare ADDO and non-ADDO regions, excluding the largest city, Dar es Salaam, due to the unique characteristics of its market. Results Interviews were conducted in 133 drug stores in ADDO regions and 119 in non-ADDO regions. Staff qualifications were very similar in both areas. There was no significant difference in the availability of the first line antimalarial (68.9% in ADDO regions and 65.2% in non-ADDO regions); both areas had over 98% availability of non-artemisinin therapies and below 3.0% of artemisinin monotherapies. Staff in ADDO regions had better knowledge of the first line antimalarial than non-ADDO regions (99.5% and 91.5%, p = 0.001). There was weak evidence of a lower price and higher market share of the first line antimalarial in ADDO regions. Drug stores in ADDO regions were more likely to stock ADDO-certified injectables than those in non-ADDO regions (23.0% and 3.9%, p = 0.005). Conclusions ADDO conversion is frequently cited as a model for improving retail sector drug provision. Drug stores in ADDO regions performed better on some indicators, possibly indicating some small benefits from ADDO conversion, but also weaknesses in ADDO regulation and high staff turnover. More evidence is needed on the value-added and value for money of the ADDO roll out to inform retail policy in Tanzania and elsewhere.

Conjugate vaccines against Haemophilus influenzae type b (Hib) are widely used. The full implications of Hib vaccination schedule for vaccine effectiveness (VE) are unclear.We searched the literature for observational studies reporting the effectiveness of conjugate Hib vaccines administered according to different schedules. We summarized dose-specific VE estimates, where appropriate, using random effects meta-analysis.Thirty-one eligible articles (reporting 30 studies conducted in 17 countries) were identified. Meta-analysis of case-control studies using community controls produced VE estimates against Hib meningitis of 55% (95% confidence interval: 2-80%, based on 3 studies), 96% (86-99%, 3 studies) and 96% (86-99%, 4 studies) after 1, 2 and 3 doses of vaccines other than the polyribosyl ribitol phosphate outer membrane protein vaccine. Estimates were similar using hospital controls. VE against invasive Hib disease in case-control studies was estimated as 59% (30-76%, 3 studies) and 97% (87-99%, 3 studies) for 1 and 3 doses (insufficient data were identified to estimate 2-dose VE). Point estimates from 2 studies suggested VE90% after 1 dose of the polyribosyl ribitol phosphate outer membrane protein vaccine, but meta-analysis was not possible. Using data from 4 cohort studies, 3-dose VE was estimated as 94% (88-97%). There was some evidence that Hib vaccine was less effective when administered with acellular (rather than whole cell) pertussis vaccine. Weak evidence from 2 studies suggested that a booster confers some additional protection following full primary vaccination and may compensate for an incomplete primary series.Observational data suggest that ≥2 doses of Hib vaccine are required for high effectiveness, but do not strongly favor any particular schedule.

OBJECTIVE: to assess the association of kidney function with quality-of-life in community-dwelling older adults aged 75 years or more in the UK. DESIGN: cross-sectional study. SETTING: primary care; 12 UK general practices participating in a cluster trial of health screening. SUBJECTS: estimated glomerular filtration rate (eGFR, ml/min/1.73 m(2)) using the four-variable modified diet in renal disease equation was derived in 1,195 men and 1,772 women with available bloods, these were 92% of 3,211 study participants who consented to interviews and 73% of those invited into the original cluster trial of health screening. MAIN OUTCOME MEASURES: interviews by trained fieldworker using the Sickness Impact Profile (home management, mobility, self-care, social interaction), and the Philadelphia Geriatric Morale Scale. Higher scores imply worse quality-of-life in a given domain. RESULTS: in age- and co-morbidity-adjusted analyses there was an association of eGFR

SUMMARYMatching individuals reported to a sentinel surveillance scheme for hepatitis C between 2000 and 2005 to individuals with a hospital episode for hepatitis C-related liver disease in the same hospitals, we estimated that the number of cases of hepatitis C-related end-stage liver disease in these English hospitals was 42% (597/419) higher than Hospital Episode Statistics (HES) would indicate. Further, matching records of hepatitis C-related deaths in HES to death certificates, we estimated that, between 2000 and 2005, the true number of deaths from hepatitis C-related end-stage liver disease was between 185% (353/124) and 257% (378/106) higher than the number recorded in routine mortality statistics. We provide estimates of under-recording that can be used to modify existing models of disease burden due to hepatitis C and provide a simple approach to improve the monitoring of trends in severe hepatitis C-related morbidity over time.

Background: To assess the availability, price and market share of quality-assured artemisinin-based combination therapy (QAACT) in remote areas (RAs) compared with non-remote areas (nRAs) in Kenya and Ghana at end-line of the Affordable Medicines Facility-malaria (AMFm) intervention. Methods: Areas were classified by remoteness using a composite index computed from estimated travel times to three levels of service centres. The index was used to five categories of remoteness, which were then grouped into two categories of remote and non-remote areas. The number of public or private outlets with the potential to sell or distribute anti-malarial medicines, screened in nRAs and RAs, respectively, was 501 and 194 in Ghana and 9980 and 2353 in Kenya. The analysis compares RAs with nRAs in terms of availability, price and market share of QAACT in each country. Results: QAACT were similarly available in RAs as nRAs in Ghana and Kenya. In both countries, there was no statistical difference in availability of QAACT with AMFm logo between RAs and nRAs in public health facilities (PHFs), while private-for-profit (PFP) outlets had lower availability in RA than in nRAs (Ghana: 66.0 vs 82.2 %, p < 0.0001; Kenya: 44.9 vs 63.5 %, p =, Malaria Journal, 14, 398; 2015

OBJECTIVES: To describe the state of the public and private malaria diagnostics market shortly after WHO updated its guidelines for testing all suspected malaria cases prior to treatment. METHODS: Ten nationally representative cross-sectional cluster surveys were conducted in 2011 among public and private health facilities, community health workers and retail outlets (pharmacies and drug shops) in nine countries (Tanzania mainland and Zanzibar surveyed separately). Eligible outlets had antimalarials in stock on the day of interview or had stocked antimalarials in the past 3 months. RESULTS: Three thousand four hundred and thirty-nine rapid diagnostic test (RDT) products from 39 manufacturers were audited among 12,197 outlets interviewed. Availability was typically highest in public health facilities, although availability in these facilities varied greatly across countries, from 15% in Nigeria to >90% in Madagascar and Cambodia. Private for-profit sector availability was 46% in Cambodia, 20% in Zambia, but low in other countries. Median retail prices for RDTs in the private for-profit sector ranged from $0.00 in Madagascar to $3.13 in Zambia. The reported number of RDTs used in the 7 days before the survey in public health facilities ranged from 3 (Benin) to 50 (Zambia). CONCLUSIONS: Eighteen months after WHO updated its case management guidelines, RDT availability remained poor in the private sector in sub-Saharan Africa. Given the ongoing importance of the private sector as a source of fever treatment, the goal of universal diagnosis will not be achievable under current circumstances. These results constitute national baselines against which progress in scaling-up diagnostic tests can be assessed.

Improving access to quality-assured artemisinin combination therapies (ACTs) is an important component of malaria control in low- and middle-income countries. In 2010 the Global Fund to Fight AIDS, Tuberculosis, and Malaria launched the Affordable Medicines Facility--malaria (AMFm) program in seven African countries. The goal of the program was to decrease malaria morbidity and delay drug resistance by increasing the use of ACTs, primarily through subsidies intended to reduce costs. We collected data on price and retail markups on antimalarial medicines from 19,625 private for-profit retail outlets before and 6-15 months after the program's implementation. We found that in six of the AMFm pilot programs, prices for quality-assured ACTs decreased by US$1.28-$4.34, and absolute retail markups on these therapies decreased by US$0.31-$1.03. Prices and markups on other classes of antimalarials also changed during the evaluation period, but not to the same extent. In all but two of the pilot programs, we found evidence that prices could fall further without suppliers' losing money. Thus, concerns may be warranted that wholesalers and retailers are capturing subsidies instead of passing them on to consumers. These findings demonstrate that supranational subsidies can dramatically reduce retail prices of health commodities and that recommended retail prices communicated to a wide audience may be an effective mechanism for controlling the market power of private-sector antimalarial retailers and wholesalers.

BackgroundThe Affordable Medicines Facility-malaria (AMFm) is primarily an artemisinin combination therapy (ACT) subsidy, aimed at increasing availability, affordability, market share and use of quality-assured ACTs (QAACTs). Mainland Tanzania was one of eight national scale programmes where AMFm was introduced in 2010. Here we present findings from outlet and household surveys before and after AMFm implementation to evaluate its impact from both the supply and demand side.MethodsOutlet surveys were conducted in 49 randomly selected wards throughout mainland Tanzania in 2010 and 2011, and data on outlet characteristics and stocking patterns were collected from outlets stocking antimalarials. Household surveys were conducted in 240 randomly selected enumeration areas in three regions in 2010 and 2012. Questions about treatment seeking for fever and drugs obtained were asked of individuals reporting fever in the previous two weeks.ResultsThe availability of QAACTs increased from 25.5% to 69.5% among all outlet types, with the greatest increase among pharmacies and drug stores, together termed specialised drug sellers (SDSs), where the median QAACT price fell from $5.63 to $0.94. The market share of QAACTs increased from 26.2% to 42.2%, again with the greatest increase in SDSs. Household survey results showed a shift in treatment seeking away from the public sector towards SDSs. Overall, there was no change in the proportion of people with fever obtaining an antimalarial or ACT from baseline to endline. However, when broken down by treatment source, ACT use increased significantly among clients visiting SDSs.DiscussionUnchanged ACT use overall, despite increases in QAACT availability, affordability and market share in the private sector, reflected a shift in treatment seeking towards private providers. The reasons for this shift are unclear, but likely reflect both persistent stockouts in public facilities, and the increased availability of subsidised ACTs in the private sector.

Background: The Affordable Medicines Facility - malaria (AMFm), implemented at national scale in eight African countries or territories, subsidized quality-assured artemisinin combination therapy (ACT) and included communication campaigns to support implementation and promote appropriate anti-malarial use. This paper reports private for-profit provider awareness of key features of the AMFm programme, and changes in provider knowledge of appropriate malaria treatment. Methods: This study had a non-experimental design based on nationally representative surveys of outlets stocking anti-malarials before (2009/10) and after (2011) the AMFm roll-out. Results: Based on data from over 19,500 outlets, results show that in four of eight settings, where communication campaigns were implemented for 5–9 months, 76%-94% awareness of the AMFm ‘green leaf’ logo, 57%-74% awareness of the ACT subsidy programme, and 52%-80% awareness of the correct recommended retail price (RRP) of subsidized ACT were recorded. However, in the remaining four settings where communication campaigns were implemented for three months or less, levels were substantially lower. In six of eight settings, increases of at least 10 percentage points in private for-profit providers’ knowledge of the correct first-line treatment for uncomplicated malaria were seen; and in three of these the levels of knowledge achieved at endline were over 80%. Conclusions: The results support the interpretation that, in addition to the availability of subsidized ACT, the intensity of communication campaigns may have contributed to the reported levels of AMFm-related awareness and knowledge among private for-profit providers. Future subsidy programmes for anti-malarials or other treatments should similarly include communication activities.

Objective To investigate the impact on mortality due to pneumonia or influenza of the change from risk-based to age group-based targeting of the elderly for yearly influenza vaccination in England and Wales. Design Excess mortality estimated using time series of deaths registered to pneumonia or influenza, accounting for seasonality, trend and artefacts. Non-excess mortality plotted as proxy for long-term trend in mortality. Setting England and Wales. Participants Persons aged 65–74 and 75+ years whose deaths were registered to underlying pneumonia or influenza between 1975/1976 and 2004/2005. Outcome measures Multiplicative effect on average excess pneumonia and influenza deaths each winter in the 4–6 winters since age group-based targeting of vaccination was introduced (in persons aged 75+ years from 1998/1999; in persons aged 65+ years from 2000/2001), estimated using multivariable regression adjusted for temperature, antigenic drift and vaccine mismatch, and stratified by dominant circulating influenza subtype. Trend in baseline weekly pneumonia and influenza death rates. Results There is a suggestion of lower average excess mortality in the six winters after age group-based targeting began compared to before, but the CI for the 65–74 years age group includes no difference. Trend in baseline pneumonia and influenza mortality shows an apparent downward turning point around 2000 for the 65–74 years age group and from the mid-1990s in the 75+ years age group. Conclusions There is weakly supportive evidence that the marked increases in vaccine coverage accompanying the switch from risk-based to age group-based targeting of the elderly for yearly influenza vaccination in England and Wales were associated with lower levels of pneumonia and influenza mortality in older people in the first 6 years after age group-based targeting began. The possible impact of these policy changes is observed as weak evidence for lower average excess mortality as well as a turning point in baseline mortality coincident with the changes.

Background A successful malaria control programme began in 2004 on Bioko Island, Equatorial Guinea. From 2007, the same multiple malaria interventions, though reduced in scope for funding reasons, were introduced to the four mainland provinces of Equatorial Guinea (the continental region) aiming to recreate Bioko’s success. Two provinces received long-lasting insecticidal nets (LLINs) and two provinces received biannual indoor residual spraying (IRS). Enhanced case management and communications were introduced throughout. Methods Estimates of intervention coverage and indicators of malaria transmission for 2007 to 2011 were derived from annual malaria indicator surveys (MIS). Results were complemented by health information system (HIS) and entomological data. The personal protection offered by LLINs and IRS against Plasmodium falciparum infection was estimated with logistic regression. Results The estimated proportion of children aged 1–4 using either an LLIN the previous night or living in a house sprayed in the last six months was 23% in 2007 and 42% in 2011. The estimated prevalence of P. falciparum in children aged 1–4 was 68% (N=1,770; 95% confidence interval [CI]: 58-76%) in 2007 and 52% (N=1,602; 95% CI: 44-61%) in 2011. Children 1–4 years had lower prevalence if they used an LLIN the previous night (N=1,124, 56%; adjusted odds ratio [aOR] 0.64, 95% CI: 0.55-0.74) or if they lived in a sprayed house (N=1,150, 57%; aOR 0.80, 95% CI: 0.62-1.03) compared to children with neither intervention (N=4,131, 66%, reference group). The minority of children who both used an LLIN and lived in a sprayed house had the lowest prevalence of infection (N=171, 45%; aOR 0.52, 95% CI: 0.35-0.78). High site-level intervention coverage did not always correlate with lower site-level P. falciparum prevalence. The malaria season peaked in either June or July, not necessarily coinciding with MIS data collection. Conclusions Though moderate impact was achieved after five years of vector control, case management, and communications, prevalence remained high due to an inability to sufficiently scale-up coverage with either IRS or LLINs. Both LLINs and IRS provided individual protection, but greater protection was afforded to children who benefitted from both.

Summary Background Malaria is one of the greatest causes of mortality worldwide. Use of the most effective treatments for malaria remains inadequate for those in need, and there is concern over the emergence of resistance to these treatments. In 2010, the Global Fund launched the Affordable Medicines Facility—malaria (AMFm), a series of national-scale pilot programmes designed to increase the access and use of quality-assured artemisinin based combination therapies (QAACTs) and reduce that of artemisinin monotherapies for treatment of malaria. AMFm involves manufacturer price negotiations, subsidies on the manufacturer price of each treatment purchased, and supporting interventions such as communications campaigns. We present findings on the effect of AMFm on QAACT price, availability, and market share, 6–15 months after the delivery of subsidised ACTs in Ghana, Kenya, Madagascar, Niger, Nigeria, Uganda, and Tanzania (including Zanzibar). Methods We did nationally representative baseline and endpoint surveys of public and private sector outlets that stock antimalarial treatments. QAACTs were identified on the basis of the Global Fund's quality assurance policy. Changes in availability, price, and market share were assessed against specified success benchmarks for 1 year of AMFm implementation. Key informant interviews and document reviews recorded contextual factors and the implementation process. Findings In all pilots except Niger and Madagascar, there were large increases in QAACT availability (25·8–51·9 percentage points), and market share (15·9–40·3 percentage points), driven mainly by changes in the private for-profit sector. Large falls in median price for QAACTs per adult equivalent dose were seen in the private for-profit sector in six pilots, ranging from US$1·28 to $4·82. The market share of oral artemisinin monotherapies decreased in Nigeria and Zanzibar, the two pilots where it was more than 5% at baseline. Interpretation Subsidies combined with supporting interventions can be effective in rapidly improving availability, price, and market share of QAACTs, particularly in the private for-profit sector. Decisions about the future of AMFm should also consider the effect on use in vulnerable populations, access to malaria diagnostics, and cost-effectiveness. Funding The Global Fund to Fight AIDS, Tuberculosis and Malaria, and the Bill & Melinda Gates Foundation.

Background The relevance to coronary heart disease (CHD) of cytokines that govern inflammatory cascades, such as interleukin-6 (IL-6), may be underestimated because such mediators are short acting and prone to fluctuations. We evaluated associations of long-term circulating IL-6 levels with CHD risk (defined as nonfatal myocardial infarction [MI] or fatal CHD) in two population-based cohorts, involving serial measurements to enable correction for within-person variability. We updated a systematic review to put the new findings in context. Methods and Findings Measurements were made in samples obtained at baseline from 2,138 patients who had a first-ever nonfatal MI or died of CHD during follow-up, and from 4,267 controls in two cohorts comprising 24,230 participants. Correction for within-person variability was made using data from repeat measurements taken several years apart in several hundred participants. The year-to-year variability of IL-6 values within individuals was relatively high (regression dilution ratios of 0.41, 95% confidence interval [CI] 0.28–0.53, over 4 y, and 0.35, 95% CI 0.23–0.48, over 12 y). Ignoring this variability, we found an odds ratio for CHD, adjusted for several established risk factors, of 1.46 (95% CI 1.29–1.65) per 2 standard deviation (SD) increase of baseline IL-6 values, similar to that for baseline C-reactive protein. After correction for within-person variability, the odds ratio for CHD was 2.14 (95% CI 1.45–3.15) with long-term average (“usual”) IL-6, similar to those for some established risk factors. Increasing IL-6 levels were associated with progressively increasing CHD risk. An updated systematic review of electronic databases and other sources identified 15 relevant previous population-based prospective studies of IL-6 and clinical coronary outcomes (i.e., MI or coronary death). Including the two current studies, the 17 available prospective studies gave a combined odds ratio of 1.61 (95% CI 1.42–1.83) per 2 SD increase in baseline IL-6 (corresponding to an odds ratio of 3.34 [95% CI 2.45–4.56] per 2 SD increase in usual [long-term average] IL-6 levels). Conclusions Long-term IL-6 levels are associated with CHD risk about as strongly as are some major established risk factors, but causality remains uncertain. These findings highlight the potential relevance of IL-6–mediated pathways to CHD., John Danesh and colleagues show that long-term IL-6 levels are associated with coronary heart disease risk, thus highlighting the potential relevance of IL-6−mediated pathways to coronary heart disease., Editors' Summary Background. Coronary heart disease (CHD), the leading cause of death among adults in developed countries, kills one person in the US every minute. With age, “atherosclerotic plaques”—deposits of fats, calcium, and various cellular waste products—coat the walls of arteries, causing them to narrow and harden, interrupting blood flow through the body. When this occurs in the coronary arteries, which nourish the heart muscle, the end result is CHD. If a plaque breaks off the artery wall, it can get trapped in the arteries and completely stop the blood flow, causing death of the heart muscle. The technical term for this is “myocardial infarction” (MI), although it is more commonly known as a heart attack. Smoking, high blood pressure, high blood levels of cholesterol (a type of fat), being overweight, and being physically inactive all increase the risk of developing CHD, as do some inherited factors. Treatments for CHD include lifestyle changes (for example, losing weight and exercising regularly) and medications that lower blood pressure and blood cholesterol. In the worst cases, the narrowed artery can be widened using a device called a stent or surgically bypassed. Why Was This Study Done? Atherosclerosis might, at least partly, be an inflammatory condition. Inflammation—an immune response to injury characterized by swelling and redness—involves the production of proteins called “cytokines,” which attract cells of the immune system to the site of injury. In atherosclerosis, damage to the artery walls seems to trigger inflammation, which helps the atherosclerotic plaques grow. Because of the potential involvement of inflammation in atherosclerosis, increased levels of circulating cytokines might be associated with an increased risk of CHD. If they are, cytokines might provide a new therapeutic target for the treatment of CHD. In this study, the researchers have asked whether prolonged moderate increases in the cytokine interleukin-6 (IL-6) in the bloodstream are associated with CHD risk. IL-6, which is produced very early in inflammation, survives only briefly in the human body and its levels fluctuate within individuals. Consequently, its relevance to CHD has been unclear in previous studies. What Did the Researchers Do and Find? Between 1967 and 1991, nearly 25,000 healthy, mainly middle-aged people were enrolled into two studies—the Reykjavik Study and the British Regional Heart Study—and followed for about 20 years, during which time 2,138 people had a first-ever nonfatal heart attack or died of CHD. The researchers measured baseline IL-6 blood levels in these participants and in 4,267 similar participants who had not had a CHD event. They also measured IL-6 levels in 558 healthy participants several years into the study to determine a “regression dilution ratio” for IL-6. This ratio gives an idea of the year-to-year consistency of IL-6 levels. When the researchers used this ratio to estimate the impact of prolonged increases in IL-6 levels on CHD, they found that increased long-term IL-6 levels more than doubled the risk for CHD in their study populations. The researchers then combined these new results with those of 15 previous relevant studies. This combined analysis indicated very similar findings to those in the new data. What Do These Findings Mean? These findings indicate prolonged moderate increases in IL-6 levels are associated with risk of CHD as strongly as several major established risk factors, including blood pressure and blood cholesterol levels, but whether there is a cause-and-effect relationship remains unknown. More studies are needed to find out whether this result is generalisable to other populations, but the broad agreement between the Icelandic and British studies suggests that they should be. This study renews interest in IL-6–mediated inflammatory pathways and CHD. Additional Information. Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050078. Read a related PLoS Medicine Perspective article The MedlinePlus encyclopedia has pages on coronary heart disease and atherosclerosis (in English and Spanish) Information is available from the US National Heart Lung and Blood Institute on coronary heart disease and atherosclerosis Information for patients and caregivers is provided by the American Heart Association on all aspects of heart disease, including inflammation and heart disease Information is available from the British Heart Foundation on heart disease and on keeping the heart healthy Further details are available about the Reykjavik Study and the British Regional Heart Study Wikipedia has pages on inflammation and on interleukin-6 (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)

The aim of the study was to investigate the differing epidemiology of hepatitis C-related end-stage liver disease in ethnic minorities in England. We used Hospital Episode Statistics from 1997/98 to 2004/05 to directly age-standardize numbers of episodes and deaths from hepatitis C-related end-stage liver disease in ethnic groups using the white English population as standard and the age-structured population by ethnic group from the 2001 Census. We estimated the odds of having a diagnosis of end-stage liver disease amongst hepatitis C-infected individuals in each ethnic group compared with whites using logistic regression. The main outcome measures were age-standardized morbidity and mortality ratios and morbidity and mortality odds ratios. Standardized ratios (95% confidence interval) for hepatitis C-related end-stage liver disease ranged from 73 (38-140) in Chinese people to 1063 (952-1186) for those from an 'Other' ethnic group. Amongst individuals with a diagnosis of hepatitis C infection, the odds ratios (95% CI) of severe liver disease were 1.42 (1.13-1.79), 1.57 (1.36-1.81), 2.44 (1.85-3.22), 1.73 (1.36-2.19) and 1.83 (1.08-3.10) comparing individuals of Black African, Pakistani, Bangladeshi, Indian and Chinese origin with whites, respectively. Ethnic minority populations in England are more likely than whites to experience an admission or to die from severe liver disease as a result of hepatitis C infection. Ethnic minority populations may have a higher prevalence of hepatitis C or they may experience a poorer prognosis because of differential access to health services, longer duration of infection or the prevalence of co-morbidities.

In England, a large number of individuals are infected with the hepatitis C virus (HCV) and may develop future liver complications, such as decompensated cirrhosis and hepatocellular carcinoma (HCC). Estimates of the magnitude of this future burden are required to plan healthcare resources. We have estimated past incidence of HCV infection in England and predict future burden of end-stage liver disease in the HCV-infected population. A model of the natural history of HCV as a series of disease stages was constructed. A back-calculation approach was performed, using the natural history model and data on annual HCC deaths in England from 1996 to 2004 with mention of HCV and hospital episode statistics for end-stage liver disease with HCV. The number of HCV-infected people living with compensated cirrhosis is predicted to rise from 3705 [95% credible interval (CrI): 2820-4975] in 2005 to 7550 (95% CrI: 5120-11,640) in 2015. The number of decompensated cirrhosis and/or HCC cases is also predicted to rise, to 2540 (95% CrI: 2035-3310) by 2015. HCV incidence increased during the 1980s, with an annual incidence of 12 650 (95% CrI: 6150-26,450) by 1989. HCV-related cirrhosis and deaths from HCC in England are likely to increase dramatically within the next decade. If patients are left undiagnosed and untreated, the future burden of the disease on healthcare resources will be substantial.

Background Studies suggest that routine variations in public drinking water turbidity may be associated with endemic gastrointestinal illness. We systematically reviewed the literature on this topic. Methods We searched databases and websites for relevant studies in industrialized countries. Studies investigating the association between temporal variations in drinking water turbidity and incidence of acute gastrointestinal illness were assessed for quality. We reviewed good quality studies for evidence of an association between increased turbidity and gastrointestinal illness. Results We found six relevant good quality studies. Of five studies investigating effluent water turbidity, two found no association. Two studies from Philadelphia reported increased paediatric and elderly hospital use on specific days after increased turbidity. A fifth study reported more telephone health service calls on specific days after peak turbidity. There were differences between studies affecting their comparability, including baseline turbidity and adjustment for seasonal confounders. Conclusion It is likely that an association between turbidity and GI illness exists in some settings or over a certain range of turbidity. A pooled analysis of available data using standard methods would facilitate interpretation.