Search

Summary: Background: Encephalitis is a worldwide public health issue, with a substantially high burden among children in southeast Asia. We aimed to determine the causes of encephalitis in children admitted to hospitals across the Greater Mekong region by implementing a comprehensive state-of-the-art diagnostic procedure harmonised across all centres, and identifying clinical characteristics related to patients’ conditions. Methods: In this multicentre, observational, prospective study of childhood encephalitis, four referral hospitals in Cambodia, Vietnam, Laos, and Myanmar recruited children (aged 28 days to 16 years) who presented with altered mental status lasting more than 24 h and two of the following minor criteria: fever (within the 72 h before or after presentation), one or more generalised or partial seizures (excluding febrile seizures), a new-onset focal neurological deficit, cerebrospinal fluid (CSF) white blood cell count of 5 per mL or higher, or brain imaging (CT or MRI) suggestive of lesions of encephalitis. Comprehensive diagnostic procedures were harmonised across all centres, with first-line testing was done on samples taken at inclusion and results delivered within 24 h of inclusion for main treatable causes of disease and second-line testing was done thereafter for mostly non-treatable causes. An independent expert medical panel reviewed the charts and attribution of causes of all the included children. Using multivariate analyses, we assessed risk factors associated with unfavourable outcomes (ie, severe neurological sequelae and death) at discharge using data from baseline and day 2 after inclusion. This study is registered with ClinicalTrials.gov, NCT04089436, and is now complete. Findings: Between July 28, 2014, and Dec 31, 2017, 664 children with encephalitis were enrolled. Median age was 4·3 years (1·8–8·8), 295 (44%) children were female, and 369 (56%) were male. A confirmed or probable cause of encephalitis was identified in 425 (64%) patients: 216 (33%) of 664 cases were due to Japanese encephalitis virus, 27 (4%) were due to dengue virus, 26 (4%) were due to influenza virus, 24 (4%) were due to herpes simplex virus 1, 18 (3%) were due to Mycobacterium tuberculosis, 17 (3%) were due to Streptococcus pneumoniae, 17 (3%) were due to enterovirus A71, 74 (9%) were due to other pathogens, and six (1%) were due to autoimmune encephalitis. Diagnosis was made within 24 h of admission to hospital for 83 (13%) of 664 children. 119 (18%) children had treatable conditions and 276 (42%) had conditions that could have been preventable by vaccination. At time of discharge, 153 (23%) of 664 children had severe neurological sequelae and 83 (13%) had died. In multivariate analyses, risk factors for unfavourable outcome were diagnosis of M tuberculosis infection upon admission (odds ratio 3·23 [95% CI 1·04–10·03]), coma on day 2 (2·90 [1·78–4·72]), supplementary oxygen requirement (1·89 [1·25–2·86]), and more than 1 week duration between symptom onset and admission to hospital (3·03 [1·68–5·48]). At 1 year after inclusion, of 432 children who were discharged alive from hospital with follow-up data, 24 (5%) had died, 129 (30%) had neurological sequelae, and 279 (65%) had completely recovered. Interpretation: In southeast Asia, most causes of childhood encephalitis are either preventable or treatable, with Japanese encephalitis virus being the most common cause. We provide crucial information that could guide public health policy to improve diagnostic, vaccination, and early therapeutic guidelines on childhood encephalitis in the Greater Mekong region. Funding: Institut Pasteur, Institut Pasteur International Network, Fondation Merieux, Aviesan Sud, INSERM, Wellcome Trust, Institut de Recherche pour le Développement (IRD), and Fondation Total.

BackgroundSocioeconomic disadvantage is a risk factor for dementia, but longitudinal studies suggest that it does not affect the rate of cognitive decline. Our objective is to understand the manner in which socioeconomic disadvantage shapes dementia risk by examining its associations with midlife cognitive performance and cognitive decline from midlife to old age, including cognitive decline trajectories in those with dementia.Methods and findingsData are drawn from the Whitehall II study (N = 10,308 at study recruitment in 1985), with cognitive function assessed at 4 waves (1997, 2002, 2007, and 2012). Sociodemographic, behavioural, and cardiometabolic risk factors from 1985 and chronic conditions until the end of follow-up in 2015 (N dementia/total = 320/9,938) allowed the use of inverse probability weighting to take into account data missing because of loss to follow-up between the study recruitment in 1985 and the introduction of cognitive tests to the study in 1997. Generalized estimating equations and Cox regression were used to assess associations of socioeconomic markers (height, education, and midlife occupation categorized as low, intermediate, and high to represent hierarchy in the socioeconomic marker) with cognitive performance, cognitive decline, and dementia (N dementia/total = 195/7,499). In those with dementia, we examined whether retrospective trajectories of cognitive decline (backward timescale) over 18 years prior to diagnosis differed as a function of socioeconomic markers. Socioeconomic disadvantage was associated with poorer cognitive performance (all p < 0.001). Using point estimates for the effect of age, the differences between the high and low socioeconomic groups corresponded to an age effect of 4, 15, and 26 years, for height, education, and midlife occupation, respectively. There was no evidence of faster cognitive decline in socioeconomically disadvantaged groups. Low occupation, but not height or education, was associated with risk of dementia (hazard ratio [HR] = 2.03 [95% confidence interval (CI) 1.23-3.36]) in an analysis adjusted for sociodemographic factors; the excess risk was unchanged after adjustment for cognitive decline but was completely attenuated after adjustment for cognitive performance. In further analyses restricted to those with dementia, retrospective cognitive trajectories over 18 years prior to dementia diagnosis showed faster cognitive decline in the high education (p = 0.006) and occupation (p = 0.001) groups such that large differences in cognitive performance in midlife were attenuated at dementia diagnosis. A major limitation of our study is the use of electronic health records rather than comprehensive dementia ascertainment.ConclusionsOur results support the passive or threshold cognitive reserve hypothesis, in that high cognitive reserve is associated with lower risk for dementia because of its association with cognitive performance, which provides a buffer against clinical expression of dementia.

OBJECTIVE: To assess the extent to which user fees for antiretroviral therapy (ART) represent a financial barrier to access to ART among HIV-positive patients in Yaoundé, Cameroon. METHODS: Sociodemographic, economic and clinical data were collected from a random sample of 707 HIV-positive patients followed up in six public hospitals of the capital city (Yaoundé) and its surroundings through face-to-face interviews carried out by trained interviewers independently from medical staff and medical questionnaires filled out by prescribing physicians. Logistic regression models were used to identify factors associated with self-reported financial difficulties in purchasing ART during the previous 3 months. FINDINGS: Of the 532 patients treated with ART at the time of the survey, 20% reported financial difficulty in purchasing their antiretroviral drugs during the previous 3 months. After adjustment for socioeconomic and clinical factors, reports of financial difficulties were significantly associated with lower adherence to ART (odds ratio, OR: 0.24; 95% confidence interval, CI: 0.15-0.40; P < 0.0001) and with lower CD4+ lymphocyte (CD4) counts after 6 months of treatment (OR: 2.14; 95% CI: 1.15-3.96 for CD4 counts < 200 cells/µl; P = 0.04). CONCLUSION: Removing a financial barrier to treatment with ART by eliminating user fees at the point of care delivery, as recommended by WHO, could lead to increased adherence to ART and to improved clinical results. New health financing mechanisms based on the public resources of national governments and international donors are needed to attain universal access to drugs and treatment for HIV infection.

This work aimed to analyze the rate of disclosure to relatives and friends over time and to identify factors affecting disclosure among seropositive adults initiating antiretroviral therapy (ART) in rural district hospitals in the context of decentralized, integrated HIV care and task-shifting to nurses in Cameroon. Stratall was a 24-month, randomized, open-label trial comparing the effectiveness of clinical monitoring alone with laboratory plus clinical monitoring on treatment outcomes. It enrolled 459 HIV-infected ART-naive adults in 9 rural district hospitals in Cameroon. Participants in both groups were sometimes visited by nurses instead of physicians. Patients with complete data both at enrolment (M0) and at least at one follow-up visit were included in the present analysis. A mixed Poisson regression was used to estimate predictors of the evolution of disclosure index over 24 months (M24).The study population included 385 patients, accounting for 1733 face-to-face interviews at follow-up visits from M0 to M24. The median [IQR] number of categories of relatives and friends to whom patients had disclosed was 2 [1]-[3] and 3 [2]-[5] at M0 and M24 (p-trend

OBJECTIVES: Using cohort data nested in a randomized trial conducted in Cameroon, this study aimed to investigate time trends and predictors of the susceptibility to transmitting HIV during the first 24 months of treatment. METHODS: The outcome, susceptibility to transmitting HIV, was defined as reporting inconsistent condom use and experiencing incomplete virological suppression. Mixed logistic regressions were performed to identify predictors of this outcome among 250 patients reporting to have had sexual relationships either with HIV-negative or unknown HIV status partner(s). RESULTS: Despite an initial decrease from 76% at M0 to 50% at M6, the rate of inconsistent condom use significantly increased from M12 (59%) to M24 (66%) (p = 0.017). However, the proportion of patients susceptible to transmitting HIV significantly decreased over follow-up from 76% at M0, to 50% at M6, 31% at M12 and 27% at M24 (p

AIM: Previous economic literature on the cost-effectiveness of antiretroviral treatment (ART) programs has been mainly focused on the microeconomic consequences of alternative use of resources devoted to the fight against the HIV pandemic. We rather aim at forecasting the consequences of alternative scenarios for the macroeconomic performance of countries. METHODS: We used a micro-simulation model based on individuals aged 15-49 selected from nationally representative surveys (DHS for Cameroon, Tanzania and Swaziland) to compare alternative scenarios : 1-freezing of ART programs to current levels of access, 2- universal access (scaling up to 100% coverage by 2015, with two variants defining ART eligibility according to previous or current WHO guidelines). We introduced an "artificial" ageing process by programming methods. Individuals could evolve through different health states: HIV negative, HIV positive (with different stages of the syndrome). Scenarios of ART procurement determine this dynamics. The macroeconomic impact is obtained using sample weights that take into account the resulting age-structure of the population in each scenario and modeling of the consequences on total growth of the economy. RESULTS: Increased levels of ART coverage result in decreasing HIV incidence and related mortality. Universal access to ART has a positive impact on workers' productivity; the evaluations performed for Swaziland and Cameroon show that universal access would imply net cost-savings at the scale of the society, when the full macroeconomic consequences are introduced in the calculations. In Tanzania, ART access programs imply a net cost for the economy, but 70% of costs are covered by GDP gains at the 2034 horizon, even in the extended coverage option promoted by WHO guidelines initiating ART at levels of 350 cc/mm(3) CD4 cell counts. CONCLUSION: Universal Access ART scaling-up strategies, which are more costly in the short term, remain the best economic choice in the long term. Renouncing or significantly delaying the achievement of this goal, due to "legitimate" short term budgetary constraints would be a misguided choice.

BACKGROUND: In July, 2009, French health authorities, like those in many other countries, decided to embark on a mass vaccination campaign against the pandemic A(H1N1) influenza. Private general practitioners (GPs) were not involved in this campaign. We studied GPs' pandemic vaccine (pvaccine) uptake, quantified the relative contribution of its potential explanatory factors and studied whether their own vaccination choice was correlated with their recommendations to patients about pvaccination. METHODOLOGY/PRINCIPAL FINDINGS: In this cross-sectional telephone survey, professional investigators interviewed an existing panel of randomly selected private GPs (N = 1431; response rate at inclusion in the panel: 36.8%; participation rate in the survey: 100%). The main outcome variable was GPs' own pvaccine uptake. We used an averaging multi-model approach to quantify the relative contribution of factors associated with their vaccination. The pvaccine uptake rate was 61% (95%CI = 58.3-63.3). Four independent factors contributed the most to this rate (partial Nagelkerke's R(2)): history of previous vaccination against seasonal influenza (14.5%), perception of risks and efficacy of the pvaccine (10.8%), opinions regarding the organization of the vaccination campaign (7.1%), and perception of the pandemic's severity (5.2%). Overall, 71.3% (95%CI = 69.0-73.6) of the participants recommended pvaccination to young adults at risk and 40.1% (95%CI = 37.6-42.7) to other young adults. GPs' own pvaccination was strongly predictive of their recommendation to both young adults at risk (OR = 9.6; 95%CI = 7.2-12.6) and those not at risk (OR = 8.5; 95%CI = 6.4-11.4). CONCLUSIONS/SIGNIFICANCE: These results suggest that around 60% of French private GPs followed French authorities' recommendations about vaccination of health care professionals against the A(H1N1) influenza. They pinpoint priority levers for improving preparedness for future influenza pandemics. Besides encouraging GPs' own uptake of regular vaccination against seasonal influenza, providing GPs with clear information about the risks and efficacy of any new pvaccine and involving them in the organization of any future vaccine campaign may improve their pvaccine uptake.

This study aims to investigate the time pattern of inconsistence condom use (ICU) during the first year of antiretroviral therapy (ART) and its relationship with treatment adherence in naïve HIV-infected adult patients.Data collection was nested within a longitudinal trial on HIV treatment. ICU was defined as reporting to have "never", "sometimes" or "nearly always" used condoms with one's main or casual partner(s)--either HIV-negative or of unknown HIV status in the three previous months. Adherence was defined as taking 100% of their ART prescribed doses in the 4 days before the visit and "not having interrupted treatment", even once, for more than two consecutive days during the 4 previous weeks. Mixed logistic regression was used to study the relationship between adherence and ICU.Among the 459 patients enrolled, 212 (46%) during 334 visits reported to have had sexual intercourse at least once with their partner(s)--either HIV-negative or of unknown HIV status--during the first 12 months of ART. The proportion of ICU was 76%, 50% and 59% at month 0 (M0), month 6 (M6) and month 12 (M12), while 60% and 66% of patients were ART-adherent at M6 and M12, respectively. After adjustment for the frequency of sexual activity, type of sexual partner(s), perceived social class and desire for a child, patients adherent to ART were less likely to report ICU when compared with baseline (AOR [95% CI]: 0.38 [0.19-0.76]; P = 0.006).Adherence to ART is associated with a lower risk of ICU but this result needs to be interpreted carefully. As adherence behaviors are not only determined by problems with the healthcare systems but also by social barriers encountered by patients in their daily life, counseling should not only be ART adherence-centered but also patient-centered, including sexual risk minimization and psychosocial support.

BACKGROUND: Brazil became the first developing country to guarantee free and universal access to HIV/AIDS treatment, with antiretroviral drugs (ARVs) being delivered to nearly 190,000 patients. The analysis of ARV price evolution and market dynamics in Brazil can help anticipate issues soon to afflict other developing countries, as the 2010 revision of the World Health Organization guidelines shifts demand towards more expensive treatments, and, at the same time, current evolution of international legislation and trade agreements on intellectual property rights may reduce availability of generic drugs for HIV care. METHODS AND FINDINGS: Our analyses are based on effective prices paid for ARV procurement in Brazil between 1996 and 2009. Data panel structure was exploited to gather ex-ante and ex-post information and address various sources of statistical bias. In-difference estimation offered in-depth information on ARV market characteristics which significantly influence prices. Although overall ARV prices follow a declining trend, changing characteristics in the generic segment help explain recent increase in generic ARV prices. Our results show that generic suppliers are more likely to respond to factors influencing demand size and market competition, while originator suppliers tend to set prices strategically to offset compulsory licensing threats and generic competition. SIGNIFICANCE: In order to guarantee the long term sustainability of access to antiretroviral treatment, our findings highlight the importance of preserving and stimulating generic market dynamics to sustain developing countries' bargaining power in price negotiations undertaken with originator companies.

BACKGROUND: In July 2009, French public health authorities embarked in a mass vaccination campaign against A/H1N1 2009 pandemic-influenza. We explored the attitudes and behaviors of the general population toward pandemic vaccination. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a cross-sectional online survey among 2,253 French representative adults aged 18 to 64 from November 17 to 25, 2009 (completion rate: 93.8%). The main outcome was the acceptability of A/H1N1 vaccination as defined by previous receipt or intention to get vaccinated ("Yes, certainly", "Yes, probably"). Overall 17.0% (CI 95%, 15.5% to 18.7%) of respondents accepted A/H1N1 vaccination. Independent factors associated with acceptability included: male sex (p = .0001); older age (p = .002); highest or lowest level of education (p = .016); non-clerical occupation (p = .011); having only one child (p = .008); and having received seasonal flu vaccination in prior 3 years (p

BACKGROUND: Many people living with HIV/AIDS (PLWHA) suffer from stigma and discrimination. There is an ongoing debate, however, about whether stigma, fear and discrimination actually fuel the persisting spread of HIV, or slow it down by reducing contacts between the whole population and high-risk minorities. To contribute to this debate, we analysed the relationship between perceived discrimination and unsafe sex in a large sample of French PLWHAs. METHODOLOGY/PRINCIPAL FINDINGS: In 2003, we conducted a national cross-sectional survey among a random sample of HIV-infected patients. The analysis was restricted to sexually active respondents (N = 2,136). Unsafe sex was defined as sexual intercourse without a condom with a seronegative/unknown serostatus partner during the prior 12 months. Separate analyses were performed for each transmission group (injecting drug use (IDU), homosexual contact, heterosexual contact). Overall, 24% of respondents reported experiences of discrimination in their close social environment (relatives, friends and colleagues) and 18% reported unsafe sex during the previous 12 months. Both prevalences were higher in the IDU group (32% for perceived discrimination, 23% for unsafe sex). In multivariate analyses, experience of discrimination in the close social environment was associated with an increase in unsafe sex for both PLWHAs infected through IDU and heterosexual contact (OR = 1.65 and 1.80 respectively). CONCLUSIONS: Our study clearly confirms a relationship between discrimination and unsafe sex among PLWHAs infected through either IDU or heterosexual contact. This relationship was especially strong in the heterosexual group that has become the main vector of HIV transmission in France, and who is the more likely of sexual mixing with the general population. These results seriously question the hypothesis that HIV-stigma has no effect or could even reduce the infection spread of HIV.