Availability and price of malaria rapid diagnostic tests in the public and private health sectors in 2011: results from 10 nationally representative cross-sectional retail surveys.

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 malaria medicine through private-sector subsidies in seven African countries.

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.

Communicating the AMFm message: exploring the effect of communication and training interventions on private for-profit provider awareness and knowledge related to a multi-country anti-malarial subsidy intervention.

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.

The impact of targeting all elderly persons in England and Wales for yearly influenza vaccination: excess mortality due to pneumonia or influenza and time trend study.

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.

Five years of malaria control in the continental region, Equatorial Guinea.

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.

Effect of the Affordable Medicines Facility--malaria (AMFm) on the availability, price, and market share of quality-assured artemisinin-based combination therapies in seven countries: a before-and-after analysis of outlet survey data.

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.

Impairment of kidney function and reduced quality-of-life in older people: a cross-sectional study.

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 <45 and the highest scores (defined as ≥median) of mobility (men: odds ratio (OR) 2.91, 95% confidence interval (CI) 1.56-5.41; women: OR 1.73, 95% CI 1.02-2.94), home management (men: OR 1.49, 95% CI 1.09-2.04; women: OR 3.50, 95% CI 1.18-10.35), social interaction (men: OR 3.34, 95% CI 1.73-6.45; women: 2.64, 95% CI 1.61-4.33) when compared with those with eGFR ≥60 and who reported no problems. Men with eGFR <45 had low morale (OR 2.45, 95% CI 1.02-5.87) but this was not found for women (OR 1.40, 95% CI 0.65-3.04), whereas women (but not men) with eGFR <45 reported problems with body care (women: OR 1.68; 95% CI 1.25-2.27: men: OR 0.89, 95% CI 0.55-1.46). CONCLUSIONS: an eGFR <45 is associated with poorer quality-of-life at older age. More research is needed to identify modifiable causes to improve quality-of-life in older people with such a degree of kidney function impairment.

Long-term interleukin-6 levels and subsequent risk of coronary heart disease: two new prospective studies and a systematic review.

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.

The association between drinking water turbidity and gastrointestinal illness: a systematic review.

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.