Economic evaluation of physical activity mass media campaigns across the globe: a systematic review.

BACKGROUND: Physical activity mass media campaigns can deliver physical activity messages to many people, but it remains unclear whether they offer good value for money. We aimed to investigate the cost-effectiveness, cost-utility, and costs of physical activity mass media campaigns. METHODS: A search for economic evaluations (trial- or model-based) and costing studies of physical activity mass media campaigns was performed in six electronic databases (June/2021). The authors reviewed studies independently. A GRADE style rating was used to assess the overall certainty of each modelled economic evaluation. Results were summarised via narrative synthesis. RESULTS: Twenty-five studies (five model-based economic evaluations and 20 costing studies) were included, and all were conducted in high-income countries except for one costing study that was conducted in a middle-income country. The methods and assumptions used in the model-based analyses were highly heterogeneous and the results varied, ranging from the intervention being more effective and less costly (dominant) in two models to an incremental cost of US$130,740 (2020 base year) per QALY gained. The level of certainty of the models ranged from very low (n = 2) to low (n = 3). Overall, intervention costs were poorly reported. CONCLUSIONS: There are few economic evaluations of physical activity mass media campaigns available. The level of certainty of the models was judged to be very low to low, indicating that we have very little to little confidence that the results are reliable for decision making. Therefore, it remains unclear to what extent physical activity mass media campaigns offer good value for money. Future economic evaluations should consider selecting appropriate and comprehensive measures of campaign effectiveness, clearly report the assumptions of the models and fully explore the impact of assumptions in the results. REVIEW REGISTRATION: https://bit.ly/3tKSBZ3.

Dengue, Zika, and Chikungunya viral circulation and hospitalization rates in Brazil from 2014 to 2019: An ecological study.

BACKGROUND: In addition to their direct pathogenic effects, arthropod-borne (arboviruses) have been hypothesized to indirectly contribute to hospitalizations and death through decompensation of pre-existing comorbidities. Using nationwide data routinely collected from 1 January 2014 to 31 December 2019 in Brazil, we investigated whether local increases in arbovirus notifications were associated with excess hospitalization. METHODS: We estimated the relative risks for the association between municipality- and state-level increases in arboviral case notifications and age-standardized hospitalization rates (i.e., classified as direct or indirect based on ICD-10 codes) using Bayesian multilevel models with random effects accounting for temporal and geographic correlations. For municipality-level analyses, we excluded municipalities with <200 notifications of a given arbovirus and further adjusted the models for the local Gini Index, Human Development Index, and Family Healthcare Strategy (Estratégia de Saúde da Família) coverage. Models for dengue, Zika, and chikungunya were performed separately. RESULTS: From 2014 to 2019, Brazil registered 7,566,330 confirmed dengue cases, 159,029 confirmed ZIKV cases, and 433,887 confirmed CHIKV cases. Dengue notifications have an endemic and seasonal pattern, with cases present in 5334 of the 5570 (95.8%) Brazilian municipalities and most (69.5%) registered between February and May. Chikungunya notifications followed a similar seasonal pattern to DENV but with a smaller incidence and were restricted to 4390 (78.8%) municipalities. ZIKV was only notified in 2581 (46.3%) municipalities. Increases in dengue and chikungunya notifications were associated with small increases in age-standardized arbovirus-related hospitalizations, but no consistent association was found with all-cause or other specific indirect causes of hospitalization. Zika was associated to increases in hospitalizations by neurological diseases. CONCLUSIONS: Although we found no clear association between increased incidence of the three arboviruses and excess risks of all-cause or indirect hospitalizations at the municipality- and state-levels, follow-up investigations at the individual-level are warranted to define any potential role of acute arbovirus infection in exacerbating risks of hospitalization from underlying conditions.

Rainfall and other meteorological factors as drivers of urban transmission of leptospirosis.

BACKGROUND: Leptospirosis is an important public health problem affecting vulnerable urban slum populations in developing country settings. However, the complex interaction of meteorological factors driving the temporal trends of leptospirosis remain incompletely understood. METHODS AND FINDINGS: From March 1996-March 2010, we investigated the association between the weekly incidence of leptospirosis and meteorological anomalies in the city of Salvador, Brazil by using a dynamic generalized linear model that accounted for time lags, overall trend, and seasonal variation. Our model showed an increase of leptospirosis cases associated with higher than expected rainfall, lower than expected temperature and higher than expected humidity. There was a lag of one-to-two weeks between weekly values for significant meteorological variables and leptospirosis incidence. Independent of the season, a weekly cumulative rainfall anomaly of 20 mm increased the risk of leptospirosis by 12% compared to a week following the expected seasonal pattern. Finally, over the 14-year study period, the annual incidence of leptospirosis decreased significantly by a factor of 2.7 (8.3 versus 3.0 per 100,000 people), independently of variations in climate. CONCLUSIONS: Strategies to control leptospirosis should focus on avoiding contact with contaminated sources of Leptospira as well as on increasing awareness in the population and health professionals within the short time window after low-level or extreme high-level rainfall events. Increased leptospirosis incidence was restricted to one-to-two weeks after those events suggesting that infectious Leptospira survival may be limited to short time intervals.

Adoption of new therapies in the treatment of Hepatitis: a verification of the accuracy of budget impact analysis to guide investment decisions.

OBJECTIVES: While there are good Budget Impact Analysis (BIA) guidelines, studies still register potential bias. To do this, we compared the results between theoretical and real-world evidence (RWE) expenditures for medicines for Hepatitis C: boceprevir (BOC) and telaprevir (TVR). While both are not currently recommended in treatment guidelines following recent developments, this is an emblematic case because for 4 years these medicines consumed considerable resources. METHODS: Theoretical results and RWE expenditures were compared regarding the incorporation of BOC and TVR in 2013-2014 into the Brazilian Public Health System. Theoretical values were extracted from Commission for Technology Incorporation Report and RWE expenditures were extracted from the administrative data records using deterministic-probabilistic linkage. RESULTS: The estimated number of patients treated (BOC+TVR) was 13,012 versus 7,641 (real). The estimated purchase price for BOC was US$6.20 versus US$11.07 (real) and for TVR was US$42.21 versus US$84.09 (average/real). The estimated budget impact was US$285.16 million versus US$128.58 million (real). CONCLUSION: This study demonstrates appreciable divergence (US$156.58 million) between the theoretical budget impact and RWE expenditures due to underestimated purchase prices and overestimated populations. The greater the degree of accuracy the more reliable and usable BIAs become for decision-making.

Cost-effectiveness of screening for HIV in primary care: a health economics modelling analysis.

BACKGROUND: Early HIV diagnosis reduces morbidity, mortality, the probability of onward transmission, and their associated costs, but might increase cost because of earlier initiation of antiretroviral treatment (ART). We investigated this trade-off by estimating the cost-effectiveness of HIV screening in primary care. METHODS: We modelled the effect of the four-times higher diagnosis rate observed in the intervention arm of the RHIVA2 randomised controlled trial done in Hackney, London (UK), a borough with high HIV prevalence (≥0·2% adult prevalence). We constructed a dynamic, compartmental model representing incidence of infection and the effect of screening for HIV in general practices in Hackney. We assessed cost-effectiveness of the RHIVA2 trial by fitting model diagnosis rates to the trial data, parameterising with epidemiological and behavioural data from the literature when required, using trial testing costs and projecting future costs of treatment. FINDINGS: Over a 40 year time horizon, incremental cost-effectiveness ratios were £22 201 (95% credible interval 12 662-132 452) per quality-adjusted life-year (QALY) gained, £372 207 (268 162-1 903 385) per death averted, and £628 874 (434 902-4 740 724) per HIV transmission averted. Under this model scenario, with UK cost data, RHIVA2 would reach the upper National Institute for Health and Care Excellence cost-effectiveness threshold (about £30 000 per QALY gained) after 33 years. Scenarios using cost data from Canada (which indicate prolonged and even higher health-care costs for patients diagnosed late) suggest this threshold could be reached in as little as 13 years. INTERPRETATION: Screening for HIV in primary care has important public health benefits as well as clinical benefits. We predict it to be cost-effective in the UK in the medium term. However, this intervention might be cost-effective far sooner, and even cost-saving, in settings where long-term health-care costs of late-diagnosed patients in high-prevalence regions are much higher (≥60%) than those of patients diagnosed earlier. Screening for HIV in primary care is cost-effective and should be promoted. FUNDING: NHS City and Hackney, UK Department of Health, National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care.

Evidence of leptospiral exposure in neotropical primates rescued from illegal trade and a Zoo in Bahia, Brazil / Indícios de exposição a leptospiras em primatas neotropicais resgatados do comércio ilegal e de um Zoológico da Bahia

Few studies have compared the seroprevalence of antileptospiral agglutinins with the demonstration of urinary shedding of leptospires or evidence of active infection in the bloodstreams of non-human primates. The study population consists of 58 animals, including d 42 monkeys from the Zoological Park of Salvador (Parque Zoobotânico Getúlio Vargas), Bahia, Brazil. The study also evaluated 16 primates (Cebus sp.) rescued from illegal trade that were housed in the Wildlife Rehabilitation Center of Salvador (CETAS), Bahia, Brazil. The seroprevalence of antileptospiral antibodies was low (2%) in the animals from the Zoo. A higher rate (31%) was observed among the animals that were rescued from illegal trade in the state of Bahia. Even if all the blood and urine samples were negative for leptospiral DNA fragments, the high frequency of serological evidence of exposure suggests a potential risk of leptospirosis transmission when keeping these animals as pets.(AU)

Poucos estudos compararam a soroprevalência de aglutininas antileptospira com a demonstração de excreção urinária de leptospiras ou evidência de infecção ativa em primatas não humanos. A população estudada consistiu em 58 animais, sendo 42 primatas do Parque Zoobotânico Getúlio Vargas, Bahia, Brasil. O estudo avaliou ainda 16 primatas (Cebus sp.) resgatados do tráfico ilegal e abrigados no Centro de Triagem de Animais Silvestres Chico Mendes, Salvador, Bahia, Brasil. A soroprevalência de anticorpos antileptospira foi baixa (2%) nos animais do Zoológico. Uma taxa mais elevada (31%) foi observada nos animais resgatados do tráfico ilegal. Mesmo que todas as amostras de sangue e urina tenham sido negativas para DNA de leptospiras, a alta frequência de evidência de exposição nos animais de origem selvagem indicam o risco potencial da adoção de primatas como animais de estimação.(AU)

Constitutive expression of genes encoding notch receptors and ligands in developing lymphocytes, nTreg cells and dendritic cells in the human thymus.

The thymus is the site of T cell maturation. Notch receptors (Notch1-4) and ligands (DLL1-3 and Jagged1-2) constitute one of several pathways involved in this process. Our data revealed differential constitutive expression of Notch genes and ligands in T lymphocytes and thymic dendritic cells (tDCs), suggesting their participation in human thymocyte maturation. nTreg analyses indicated that the Notch components function in parallel to promote maturation in the thymus.

Taking stock: protocol for evaluating a family planning supply chain intervention in Senegal.

BACKGROUND: In Senegal, only 12% of women of reproductive age in union (WRAU) were using contraceptives and another 29% had an unmet need for contraceptives in 2010-11. One potential barrier to accessing contraceptives is the lack of stock availability in health facilities where women seek them. Multiple supply chain interventions have been piloted in low- and middle-income countries with the aim of improving contraceptive availability in health facilities. However, there is limited evidence on the effect of these interventions on contraceptive availability in facilities, and in turn on family planning use in the population. This evaluation protocol pertains to a supply chain intervention using performance-based contracting for contraceptive distribution that was introduced throughout Senegal between 2012 and 2015. METHODS: This multi-disciplinary research project will include quantitative, qualitative and economic evaluations. Trained researchers in the different disciplines will implement the studies separately but alongside each other, sharing findings throughout the project to inform each other's data collection. A non-randomised study with stepped-wedge design will be used to estimate the effect of the intervention on contraceptive stock availability in health facilities, and on the modern contraceptive prevalence rate among women in Senegal, compared to the current pull-based distribution model used for other commodities. Secondary data from annual Service Provision Assessments and Demographic and Health Surveys will be used for this study. Data on stock availability and monthly family planning consultations over a 4-year period will be collected from 200 health facilities in five regions to perform time series analyses. A process evaluation will be conducted to understand the extent to which the intervention was implemented as originally designed, the acceptability of third-party logisticians within the health system and potential unintended consequences. These will be assessed using monthly indicator data from the implementer and multiple ethnographic methods, including in-depth interviews with key informants and stakeholders at all levels of the distribution system, observations of third-party logisticians and clinic diaries. An economic evaluation will estimate the cost of the intervention, as well as its cost-effectiveness compared to the current supply chain model. DISCUSSION: Given the very limited evidence base, there is an important need for a comprehensive standardised approach to evaluating supply chain management, and distribution specifically. This evaluation will help address this evidence gap by providing rigorous evidence on whether private performance-based contracting for distribution of contraceptives can contribute to improving access to family planning in low- and middle-income countries.

Frequency of the morphological criteria of prostate adenocarcinoma in 387 consecutive prostate needle biopsies: emphasis on the location and number of nucleoli / Frequência de critérios morfológicos de adenocarcinoma da próstata em 387 biópsias de agulha da próstata consecutivas: com ênfase na localização e no número de nucléolos

ABSTRACT Introduction and objectives: We evaluated the sensitivity and specificity of morphological criteria for the diagnosis of prostate adenocarcinoma in consecutive, prostate needle biopsies specimens with emphasis on the location and number of nucleoli. Methods: The morphological features of 387 consecutive prostate needle biopsies specimens, in 2013, were systematically examined and stratified according to the final diagnosis of benign, suspicious and malignant lesions. We also tested how well each criterion predicted the final diagnosis after the immunohistochemical evaluation for expression of the basal cell markers (p63 and high molecular weight cytokeratin) and racemase. Results: A prominent nucleoli is the most common feature of carcinoma; however it is also relatively common in benign cases. The frequencies of prominent central nucleoli in malignant, suspicious and benign cases were 99%, 89% and 27%, respectively. Marginated nucleoli (85%, 60% and 7%), double nucleoli (86%, 53% and 10%), and multiple nucleoli (47%, 14% and 2%) were less common in benign cases, with significant difference among the groups. From the 36 cases initially diagnosed as suspicious, the presence of marginated nucleoli and mitoses were associated with the final diagnosis of malignancy. Prominent central nucleoli were more associated with cases which the final diagnosis after immunohistochemistry was benign. Conclusion: The location and number of nucleoli may be valuable morphological markers to identify suspicious lesions, since these features are more specific for malignancy than nucleolar prominence. The presence of prominent nucleoli commonly leads to the initial diagnosis of suspicious lesion that, subsequently, will be resulted in benignity confirmed by immunohistochemistry.

RESUMO Introdução e objetivos: Avaliamos a sensibilidade e a especificidade de critérios morfológicos para diagnóstico de adenocarcinoma da próstata em biópsias de agulha da próstata, consecutivas, com ênfase na localização e no número de nucléolos. Métodos: A morfologia de 387 biópsias de agulha consecutivas do ano de 2013 foi sistematicamente examinada e estratificada como diagnóstico de benigno, lesão suspeita ou maligno. Também testamos como cada critério previu o diagnóstico final após avaliação imuno-histoquímica para expressão de marcadores de células basais (p63 e citoqueratina de alto peso) e racemase. Resultados: Um nucléolo proeminente foi o achado mais comum do carcinoma, mas também foi relativamente comum em casos benignos. As frequências de um nucléolo proeminente central em lesões malignas, suspeitas e benignas foi de 99%, 89% e 27%, respectivamente. Nucléolo marginado (85%, 60% e 7%), nucléolos duplos (86%, 53% e 10%) e nucléolos múltiplos (47%, 14% e 2%) foram menos comuns em casos benignos, com diferenças significativas entre os grupos. Dos 36 casos com diagnóstico inicial de suspeito, a presença de nucléolo marginado e mitoses foi associada ao diagnóstico final de malignidade. Um nucléolo proeminente central foi mais associado a casos cujo diagnóstico final após imuno-histoquímica foi benigno. Conclusão: A localização e o número de nucléolos pode ser um marcador morfológico valioso para identificar lesões suspeitas, uma vez que esses achados são mais específicos para malignidade do que a proeminência nucleolar. A presença de nucléolo proeminente comumente leva ao diagnóstico inicial de lesão suspeita que, posteriormente, terá a conclusão de benignidade confirmada pela imuno-histoquímica.

Spatiotemporal Determinants of Urban Leptospirosis Transmission: Four-Year Prospective Cohort Study of Slum Residents in Brazil.

BACKGROUND: Rat-borne leptospirosis is an emerging zoonotic disease in urban slum settlements for which there are no adequate control measures. The challenge in elucidating risk factors and informing approaches for prevention is the complex and heterogeneous environment within slums, which vary at fine spatial scales and influence transmission of the bacterial agent. METHODOLOGY/PRINCIPAL FINDINGS: We performed a prospective study of 2,003 slum residents in the city of Salvador, Brazil during a four-year period (2003-2007) and used a spatiotemporal modelling approach to delineate the dynamics of leptospiral transmission. Household interviews and Geographical Information System surveys were performed annually to evaluate risk exposures and environmental transmission sources. We completed annual serosurveys to ascertain leptospiral infection based on serological evidence. Among the 1,730 (86%) individuals who completed at least one year of follow-up, the infection rate was 35.4 (95% CI, 30.7-40.6) per 1,000 annual follow-up events. Male gender, illiteracy, and age were independently associated with infection risk. Environmental risk factors included rat infestation (OR 1.46, 95% CI, 1.00-2.16), contact with mud (OR 1.57, 95% CI 1.17-2.17) and lower household elevation (OR 0.92 per 10m increase in elevation, 95% CI 0.82-1.04). The spatial distribution of infection risk was highly heterogeneous and varied across small scales. Fixed effects in the spatiotemporal model accounted for the majority of the spatial variation in risk, but there was a significant residual component that was best explained by the spatial random effect. Although infection risk varied between years, the spatial distribution of risk associated with fixed and random effects did not vary temporally. Specific "hot-spots" consistently had higher transmission risk during study years. CONCLUSIONS/SIGNIFICANCE: The risk for leptospiral infection in urban slums is determined in large part by structural features, both social and environmental. Our findings indicate that topographic factors such as household elevation and inadequate drainage increase risk by promoting contact with mud and suggest that the soil-water interface serves as the environmental reservoir for spillover transmission. The use of a spatiotemporal approach allowed the identification of geographic outliers with unexplained risk patterns. This approach, in addition to guiding targeted community-based interventions and identifying new hypotheses, may have general applicability towards addressing environmentally-transmitted diseases that have emerged in complex urban slum settings.

Constitutive expression of genes encoding notch receptors and ligandsin developing lymphocytes, nTreg cells and dendritic cells in the human thymus

The thymus is the site of T cell maturation. Notch receptors (Notch1-4) and ligands (DLL1-3 and Jagged1-2)constitute one of several pathways involved in this process. Our data revealed differential constitutive expression of Notch genes and ligands in T lymphocytes and thymic dendritic cells (tDCs), suggesting their participation in human thymocyte maturation. nTreg analyses indicated that the Notch components function in parallel to promote maturation in the thymus...

Promotion of rapid testing for HIV in primary care (RHIVA2): a cluster-randomised controlled trial.

BACKGROUND: Many people with HIV are undiagnosed. Early diagnosis saves lives and reduces onward transmission. We assessed whether an education programme promoting rapid HIV testing in general practice would lead to increased and earlier HIV diagnosis. METHODS: In this cluster randomised controlled trial in Hackney (London, UK), general practices were randomly assigned (1:1) to offer either opt-out rapid HIV testing to newly registering adults or continue usual care. All practices were invited to take part. Practices were randomised by an independent clinical trials unit statistician with a minimisation program, maintaining allocation concealment. Neither patients nor investigators were masked to treatment allocation. The primary outcome was CD4 count at diagnosis. Secondary outcomes were rate of diagnosis, proportion with CD4 count less than 350 cells per µL, and proportion with CD4 count less than 200 cells per µL. This study is registered with ClinicalTrials.gov, number ISRCTN63473710. FINDINGS: 40 of 45 (89%) general practices agreed to participate: 20 were assigned to the intervention group (44 971 newly registered adult patients) and 20 to the control group (38 464 newly registered adult patients), between April 19, 2010, and Aug 31, 2012. Intervention practices diagnosed 32 people with HIV versus 14 in control practices. Mean CD4 count at diagnosis was 356 cells per µL (SD 254) intervention practices versus 270 (SD 257) in control practices (adjusted difference of square root CD4 count 3·1, 95% CI -1·2 to 7·4; p=0·16);); in a pre-planned sensitivity analysis excluding patients diagnosed via antenatal care, the difference was 6·4 (95% CI, 1·2 to 11·6; p=0·017). Rate of HIV diagnosis was 0·30 (95% CI 0·11 to 0·85) per 10 000 patients per year in intervention practices versus 0·07 (0·02 to 0·20) in control practices (adjusted ratio of geometric means 4·51, 95% CI 1·27 to 16·05; p=0·021). 55% of patients in intervention practices versus 73% in control practices had CD4 count less than 350 cells per µL (risk ratio 0·75, 95% CI 0·53 to 1·07). 28% versus 46% had CD4 count less than 200 cells per µL (0·60, 0·32 to 1·13). All patients diagnosed by rapid testing were successfully transferred into specialist care. No adverse events occurred. INTERPRETATION: Promotion of opt-out rapid testing in general practice led to increased rate of diagnosis, and might increase early detection, of HIV. We therefore recommend implementation of HIV screening in general practices in areas with high HIV prevalence. FUNDING: UK Department of Health, NHS City and Hackney.

Influence of household rat infestation on leptospira transmission in the urban slum environment.

BACKGROUND: The Norway rat (Rattus norvegicus) is the principal reservoir for leptospirosis in many urban settings. Few studies have identified markers for rat infestation in slum environments while none have evaluated the association between household rat infestation and Leptospira infection in humans or the use of infestation markers as a predictive model to stratify risk for leptospirosis. METHODOLOGY/PRINCIPAL FINDINGS: We enrolled a cohort of 2,003 urban slum residents from Salvador, Brazil in 2004, and followed the cohort during four annual serosurveys to identify serologic evidence for Leptospira infection. In 2007, we performed rodent infestation and environmental surveys of 80 case households, in which resided at least one individual with Leptospira infection, and 109 control households. In the case-control study, signs of rodent infestation were identified in 78% and 42% of the households, respectively. Regression modeling identified the presence of R. norvegicus feces (OR, 4.95; 95% CI, 2.13-11.47), rodent burrows (2.80; 1.06-7.36), access to water (2.79; 1.28-6.09), and un-plastered walls (2.71; 1.21-6.04) as independent risk factors associated with Leptospira infection in a household. We developed a predictive model for infection, based on assigning scores to each of the rodent infestation risk factors. Receiver operating characteristic curve analysis found that the prediction score produced a good/excellent fit based on an area under the curve of 0.78 (0.71-0.84). CONCLUSIONS/SIGNIFICANCE: Our study found that a high proportion of slum households were infested with R. norvegicus and that rat infestation was significantly associated with the risk of Leptospira infection, indicating that high level transmission occurs among slum households. We developed an easily applicable prediction score based on rat infestation markers, which identified households with highest infection risk. The use of the prediction score in community-based screening may therefore be an effective risk stratification strategy for targeting control measures in slum settings of high leptospirosis transmission.

Prospective study of leptospirosis transmission in an urban slum community: role of poor environment in repeated exposures to the Leptospira agent.

BACKGROUND: Leptospirosis has emerged as an urban health problem as slum settlements have rapidly spread worldwide and created conditions for rat-borne transmission. Prospective studies have not been performed to determine the disease burden, identify risk factors for infection and provide information needed to guide interventions in these marginalized communities. METHODOLOGY/PRINCIPAL FINDINGS: We enrolled and followed a cohort of 2,003 residents from a slum community in the city of Salvador, Brazil. Baseline and one-year serosurveys were performed to identify primary and secondary Leptospira infections, defined as respectively, seroconversion and four-fold rise in microscopic agglutination titers. We used multinomial logistic regression models to evaluate risk exposures for acquiring primary and secondary infection. A total of 51 Leptospira infections were identified among 1,585 (79%) participants who completed the one-year follow-up protocol. The crude infection rate was 37.8 per 1,000 person-years. The secondary infection rate was 2.3 times higher than that of primary infection rate (71.7 and 31.1 infections per 1,000 person-years, respectively). Male gender (OR 2.88; 95% CI 1.40-5.91) and lower per capita household income (OR 0.54; 95% CI, 0.30-0.98 for an increase of $1 per person per day) were independent risk factors for primary infection. In contrast, the 15-34 year age group (OR 10.82, 95% CI 1.38-85.08), and proximity of residence to an open sewer (OR 0.95; 0.91-0.99 for an increase of 1 m distance) were significant risk factors for secondary infection. CONCLUSIONS/SIGNIFICANCE: This study found that slum residents had high risk (>3% per year) for acquiring a Leptospira infection. Re-infection is a frequent event and occurs in regions of slum settlements that are in proximity to open sewers. Effective prevention of leptospirosis will therefore require interventions that address the infrastructure deficiencies that contribute to repeated exposures among slum inhabitants.

Incremental costs of treating tetanus with intrathecal antitetanus immunoglobulin.

OBJECTIVE: To estimate the incremental cost of delivering intrathecal tetanus immunoglobulin compared to an intramuscular option. METHODS: To compare the two interventions, costs were estimated using standard cost methodology. Cost categories were personnel, overhead, consumables, antibiotics to treat infection, gases for respiratory assistance and immunoglobulin. Tetanus patients, aged 12 years or older, who were part of a randomised controlled clinical trial conducted in a referral hospital in Recife, Brazil, were allocated to two groups: a control group (58) and a study group (62). Patients allocated to the control group received 3000 international units (IU) of human immunoglobulin, with preservative, intramuscularly. The study group received the same quantity of immunoglobulin also intramuscularly plus an intrathecal dose of 1000 IU of a human immunoglobulin, free of preservatives, to prevent irritation of the meninges and avoid the need for corticosteroids. Thus, the difference between the two groups was the exclusive use of intrathecal immunoglobulin. The outcome measurements were clinical progression, hospital stay, respiratory assistance and respiratory infection. RESULTS: Delivering intrathecal immunoglobulin to patients saved a total of US$ 60 389, in a 10-day intensive care treatment, by preventing a worsening of their tetanus severity (e.g. from Grade I to Grades II, III, IV). Substantial cost saving was also observed in terms of hospital stay (US$ 173 104). CONCLUSIONS: Intrathecal treatment of tetanus is cost saving. This intervention deserves consideration by doctors and decision-makers as a mean of saving resources while maintaining high-quality health outcomes.

Cost and resource use of patients on antiretroviral therapy in the urban and semiurban public sectors of South Africa.

BACKGROUND: South Africa has the world's largest number of patients on antiretroviral treatment (ART). As coverage expands beyond urban environments, the cost of care is becoming increasingly important. METHODS: Health care cost data for the first year after initiation were analyzed for cohorts of patients in a semiurban and an urban public sector ART clinic in South Africa. We compared mean cost by CD4 cell count and time on ART between clinics. RESULTS: Patients in both clinics had comparable CD4 cell counts at initiation and under treatment. In the urban clinic, mean cost per patient-year on ART in 2011 USD was $1040 [95% confidence interval (CI): $800 to $1280], of which outpatient cost was $692 (67%) and inpatient cost was $348 (33%). Fourteen percent of urban patients required inpatient care at a mean length of stay of 9 days and mean cost per hospitalized patient of $1663 (95% CI: $1103 to $2041). In the semiurban clinic, mean cost per patient-year on ART was $1115 (95% CI: $776 to $1453), of which outpatient cost was $697 (63%) and inpatient cost $418 (37%). Seven percent of semiurban patients required inpatient care at a mean length of stay of 28 days and mean cost per hospitalized patient of $3824 (95% CI: $1143 to $6505). CONCLUSIONS: Outpatient ART provision in the semiurban setting cost the same as in the urban setting, but inpatient costs are higher in the semiurban clinic because of longer hospitalizations. Cost in both clinics was highest in the first 3 months on ART and at CD4 cell counts <50 cells/µL.

Effectiveness and cost-effectiveness of first BCG vaccination against tuberculosis in school-age children without previous tuberculin test (BCG-REVAC trial): a cluster-randomised trial.

BACKGROUND: Neonatal BCG vaccination is part of routine vaccination schedules in many developing countries; vaccination at school age has not been assessed in trials in low-income and middle-income countries. Catch-up BCG vaccination of school-age children who missed neonatal BCG vaccination could be indicated if it confers protection and is cost-effective. We did a cluster-randomised trial (BCG REVAC) to estimate the effectiveness (efficacy given in routine settings) of school-age vaccination. METHODS: We assessed the effectiveness of BCG vaccination in school-age children (aged 7-14 years) with unknown tuberculin status who did not receive neonatal BCG vaccination (subpopulation of the BCG REVAC cluster-randomised trial), between July, 1997, and June, 2006, in Salvador, Brazil, and between January, 1999, and December, 2007, in Manaus, Brazil. 763 schools were randomly assigned into BCG vaccination group or a not-vaccinated control group. Neither allocation nor intervention was concealed. Incidence of tuberculosis was the primary outcome. Cases were identified via the Brazilian Tuberculosis Control Programme. Study staff were masked to vaccination status when identified cases were linked to the study population. We estimated cost-effectiveness in Salvador by comparison of the cost for vaccination to prevent one case of tuberculosis (censored at 9 years) with the average cost of treating one case of tuberculosis. Analysis of all included children was by intention to treat. For calculation of the incidence rate we used generalised estimating equations and correlated observations over time. FINDINGS: We randomly assigned 20,622 children from 385 schools to the BCG vaccination group and 18,507 children from 365 schools to the control group. The crude incidence of tuberculosis was 54·9 (95% CI 45·3-66·7) per 100,000 person-years in the BCG vaccination group and 72·7 (62·8-86·8) per 100,000 person-years in the control group. The overall vaccine effectiveness of a first BCG vaccination at school age was 25% (3-43%). In Salvador, where vaccine effectiveness was 34% (8-53%), vaccination of 381 children would prevent one case of tuberculosis and was cheaper than treatment. The frequency of adverse events was very low with only one axillary lymphadenitis and one ulcer greater than 1 cm in 11,980 BCG vaccinations. INTERPRETATION: Vaccination of school-age children without previous tuberculin testing can reduce the incidence of tuberculosis and could reduce the costs of tuberculosis control. Restriction of BCG vaccination to the first year of life is not in the best interests of the public nor of programmes for tuberculosis control. FUNDING: UK Department for International Development, National Health Foundation.

Demand for sanitation in Salvador, Brazil: a hybrid choice approach.

Funds to promote access to water and sanitation in developing countries are scarce and most of the investments come from the national governments and households sources, not international resources. In many of these countries, mainly in middle income countries, households are paying direct taxes to access these services, and understanding what determines their choice and motivation is fundamental to promote access to them. It has been argued that is not enough to supply a wide range of alternatives unless the individuals can recognise their benefits and sustainability. The objective of this paper is to understand the choice of sanitation technology by residents in the city of Salvador, Brazil. We propose a unique hybrid choice model that incorporates a set of latent attitudinal variables and explains how the demographic factors within a household influence choice. The substantial difference of our hybrid choice model from descriptive frameworks is that it integrates choice and latent variables (such as attitudes and preferences) allowing us to model explicitly the cognitive process that influences sanitation adoption, draw conclusions from cognitive variables associated with individuals' socio-economic and demographic characteristics, and establishes a causal pathway among these variables. The results show that the attributes of health protection, accessibility, privacy, and house modernisation were what households cared about when opting for flush toilet and sewerage connection, rather than the high cost and consequent household socio-economic status associated with them. The hybrid model is statistically consistent with these findings, and seems to fill the gap between behavioural theory and discrete choice models applied to sanitation.

Incremental costs of introducing jet injection technology for delivery of routine childhood vaccinations: comparative analysis from Brazil, India, and South Africa.

BACKGROUND: Disposable-syringe jet injectors (DSJIs) have the potential to deliver vaccines safely and affordably to millions of children around the world. We estimated the incremental costs of transitioning from needles and syringes to delivering childhood vaccines with DSJIs in Brazil, India, and South Africa. METHODS: Two scenarios were assessed: (1) DSJI delivery of all vaccines at current dose and depth; (2) a change to intradermal (ID) delivery with DSJIs for hepatitis B and yellow fever vaccines, while the other vaccines are delivered by DSJIs at current dose and depth. The main advantage of ID delivery is that only a small fraction of the standard dose may be needed to obtain an immune response similar to that of subcutaneous or intramuscular injection. Cost categories included were vaccines, injection equipment, waste management, and vaccine transport. Some delivery cost items, such as training and personnel were excluded as were treatment cost savings caused by a reduction in diseases transmitted due to unsafe injections. RESULTS: In the standard dose and depth scenario, the incremental costs of introducing DSJIs per fully vaccinated child amount to US$ 0.57 in Brazil, US$ 0.65 in India and US$ 1.24 in South Africa. In the ID scenario, there are cost savings of US$ 0.11 per child in Brazil, and added costs of US$ 0.45 and US$ 0.76 per child in India and South Africa, respectively. The most important incremental cost item is jet injector disposable syringes. CONCLUSION: The incremental costs should be evaluated against other vaccine delivery technologies that can deliver the same benefits to patients, health care workers, and the community. DSJIs deserve consideration by global and national decision-makers as a means to expand access to ID delivery and to enhance safety at marginal additional cost.