Source of previous treatment for re-treatment TB cases registered under the National TB control Programme, India, 2010

Background

In 2009, nearly half (289,756) of global re-treatment TB notifications are from India; no nationally-representative data on the source of previous treatment was available to inform strategies for improvement of initial TB treatment outcome.

Objectives

To assess the source of previous treatment for re-treatment TB patients registered under India''s Revised National TB control Programme (RNTCP).

Methodology

A nationally-representative cross sectional study was conducted in a sample of 36 randomly-selected districts. All consecutively registered retreatment TB patients during a defined 15-day period in these 36 districts were contacted and the information on the source of previous treatment sought.

Results

Data was collected from all 1712 retreatment TB patients registered in the identified districts during the study period. The data includes information on 595 ‘relapse’ cases, 105 ‘failure’ cases, 437 ‘treatment after default (TAD)’ cases and 575 ‘re-treatment others’ cases. The source of most recent previous anti-tuberculosis therapy for 754 [44% (95% CI, 38.2%–49.9%)] of the re-treatment TB patients was from providers outside the TB control programme. A higher proportion of patients registered as TAD (64%) and ‘retreatment others’ (59%) were likely to be treated outside the National Programme, when compared to the proportion among ‘relapse’ (22%) or ‘failure’ (6%). Extrapolated to national registration, of the 292,972 re-treatment registrations in 2010, 128,907 patients would have been most recently treated outside the national programme.

Conclusions

Nearly half of the re-treatment cases registered with the national programme were most recently treated outside the programme setting. Enhanced efforts towards extending treatment support and supervision to patients treated by private sector treatment providers are urgently required to improve the quality of treatment and reduce the numbers of patients with recurrent disease. In addition, reasons for the large number of recurrent TB cases from those already treated by the national programme require urgent detailed investigation.     

The Consequences of High Cigarette Excise Taxes for Low-Income Smokers

Background

To illustrate the burden of high cigarette excise taxes on low-income smokers.

Methodology/Principal Findings

Using data from the New York and national Adult Tobacco Surveys from 2010–2011, we estimated how smoking prevalence, daily cigarette consumption, and share of annual income spent on cigarettes vary by annual income (less than $30,000; $30,000–$59,999; and more than $60,000). The 2010–2011 sample includes 7,536 adults and 1,294 smokers from New York and 3,777 adults and 748 smokers nationally. Overall, smoking prevalence is lower in New York (16.1%) than nationally (22.2%) and is strongly associated with income in New York and nationally (P<.001). Smoking prevalence ranges from 12.2% to 33.7% nationally and from 10.1% to 24.3% from the highest to lowest income group. In 2010–2011, the lowest income group spent 23.6% of annual household income on cigarettes in New York (up from 11.6% in 2003–2004) and 14.2% nationally. Daily cigarette consumption is not related to income.

Conclusions/Significance

Although high cigarette taxes are an effective method for reducing cigarette smoking, they can impose a significant financial burden on low-income smokers.     

An Integrated Tiered Service Delivery Model (ITSDM) Based on Local CD4 Testing Demands Can Improve Turn-Around Times and Save Costs whilst Ensuring Accessible and Scalable CD4 Services across a National Programme

Background

The South African National Health Laboratory Service (NHLS) responded to HIV treatment initiatives with two-tiered CD4 laboratory services in 2004. Increasing programmatic burden, as more patients access anti-retroviral therapy (ART), has demanded extending CD4 services to meet increasing clinical needs. The aim of this study was to review existing services and develop a service-model that integrated laboratory-based and point-of-care testing (POCT), to extend national coverage, improve local turn-around/(TAT) and contain programmatic costs.

Methods

NHLS Corporate Data Warehouse CD4 data, from 60–70 laboratories and 4756 referring health facilities was reviewed for referral laboratory workload, respective referring facility volumes and related TAT, from 2009–2012.

Results

An integrated tiered service delivery model (ITSDM) is proposed. Tier-1/POCT delivers CD4 testing at single health-clinics providing ART in hard-to-reach areas (<5 samples/day). Laboratory-based testing is extended with Tier-2/POC-Hubs (processing ≤30–40 CD4 samples/day), consolidating POCT across 8–10 health-clinics with other HIV-related testing and Tier-3/‘community’ laboratories, serving ≤40 health-clinics, processing ≤150 samples/day. Existing Tier-4/‘regional’ laboratories serve ≤100 facilities and process <350 samples/day; Tier-5 are high-volume ‘metro’/centralized laboratories (>350–1500 tests/day, serving ≥200 health-clinics). Tier-6 provides national support for standardisation, harmonization and quality across the organization.

Conclusion

The ITSDM offers improved local TAT by extending CD4 services into rural/remote areas with new Tier-3 or Tier-2/POC-Hub services installed in existing community laboratories, most with developed infrastructure. The advantage of lower laboratory CD4 costs and use of existing infrastructure enables subsidization of delivery of more expensive POC services, into hard-to-reach districts without reasonable access to a local CD4 laboratory. Full ITSDM implementation across 5 service tiers (as opposed to widespread implementation of POC testing to extend service) can facilitate sustainable ‘full service coverage’ across South Africa, and save>than R125 million in HIV/AIDS programmatic costs. ITSDM hierarchical parental-support also assures laboratory/POC management, equipment maintenance, quality control and on-going training between tiers.     

Understanding Private Sector Antimalarial Distribution Chains: A Cross-Sectional Mixed Methods Study in Six Malaria-Endemic Countries

Background

Private for-profit outlets are important treatment sources for malaria in most endemic countries. However, these outlets constitute only the last link in a chain of businesses that includes manufacturers, importers and wholesalers, all of which influence the availability, price and quality of antimalarials patients can access. We present evidence on the composition, characteristics and operation of these distribution chains and of the businesses that comprise them in six endemic countries (Benin, Cambodia, Democratic Republic of Congo, Nigeria, Uganda and Zambia).

Methods and Findings

We conducted nationally representative surveys of antimalarial wholesalers during 2009–2010 using an innovative sampling approach that captured registered and unregistered distribution channels, complemented by in-depth interviews with a range of stakeholders. Antimalarial distribution chains were pyramidal in shape, with antimalarials passing through a maximum of 4–6 steps between manufacturer and retailer; however, most likely pass through 2–3 steps. Less efficacious non-artemisinin therapies (e.g. chloroquine) dominated weekly sales volumes among African wholesalers, while volumes for more efficacious artemisinin-based combination therapies (ACTs) were many times smaller. ACT sales predominated only in Cambodia. In all countries, consumer demand was the principal consideration when selecting products to stock. Selling prices and reputation were key considerations regarding supplier choice. Business practices varied across countries, with large differences in the proportions of wholesalers offering credit and delivery services to customers, and the types of distribution models adopted by businesses. Regulatory compliance also varied across countries, particularly with respect to licensing. The proportion of wholesalers possessing any up-to-date licence from national regulators was lowest in Benin and Nigeria, where vendors in traditional markets are important antimalarial supply sources.

Conclusions

The structure and characteristics of antimalarial distribution chains vary across countries; therefore, understanding the wholesalers that comprise them should inform efforts aiming to improve access to quality treatment through the private sector.     

Age-Related Incidence and Family History in Frontotemporal Dementia: Data from the Swedish Dementia Registry

Objectives

Frontotemporal dementia (FTD) is considered to be a mainly early-onset neurodegenerative disorder with a strong hereditary component. The aim of the study was to investigate age-related incidence and family history in FTD compared to other dementia disorders, especially Alzheimer''s disease (AD).

Methods

The Swedish Dementia Registry (SveDem) registers all new cases of dementia diagnosed by the participating centres, including data on demographics, diagnosis, and investigations used. Data for the period 2008–2011 were extracted and compared with age-related population data on a regional and national level.

Results

There were 20 305 patients registered in SveDem during 2008–2011, whereof 352 received a diagnosis of FTD. Mean age at diagnosis for FTD was 69.6 years and almost 70% of FTD cases were 65 years or older at the time of diagnosis. Both FTD and AD showed an increased incidence with age, which reached a maximum in the age group 80–84 years at 6.04 and 202 cases per 100 000 person-years, respectively. The proportion of cases with a positive family history was significantly lower in FTD than in AD.

Conclusions

Contrary to general opinion within the field, data from SveDem show that the incidence of FTD increases with age, and that the majority of cases are diagnosed after the age of 65 years. In addition, data from SveDem might suggest that the importance of hereditary factors in general is similar in FTD and AD. The recognition of these findings has important consequences for the diagnosis, treatment and care of patients with FTD.     

Effective Coverage for Antiretroviral Therapy in a Ugandan District with a Decentralized Model of Care

Introduction

While increasing access to antiretroviral therapy (ART) is reported from many African countries, data on effective coverage particular from settings without external support or research remains scarce. We examined and report effective coverage data from a public ART program in rural Uganda.

Methods

We conducted a retrospective cohort study at all ART-providing governmental health facilities in Iganga District, Eastern Uganda. Based on all HIV patients registered between April 2004 and September 2009 (n = 4775), we assessed indicators of program performance and determined rates of retention and Cox proportional hazards for attrition. Effective ART coverage was calculated using projections (SPECTRUM software) adapted to the district demographic structure and number of people receiving ART.

Results

By September 2009, district public sector effective ART coverage was 10.3% for adults and 1.9% for children. After a median follow-up of 26.9 months, overall ART retention was 54.7%. The probability of retention was 0.72 (95% confidence interval (CI) 0.69–0.75) at 12 and 0.58 (CI 0.54–0.62) at 36 months after ART initiation. Individual health facilities differed considerably regarding performance indicators and retention. Overall, 198 (16.9%) individual files of 1171 registered ART patients were lost. Young adult age (15–24 years) had a higher risk of attrition (HR 2.1, CI 1.4–3.2) as well as WHO stage I (HR 4.8, CI 1.9–11.8) and WHO stage IV (HR 2.5, CI 1.3–4.7). An interval ≥6 weeks between HIV testing and ART initiation was associated with a reduced risk (HR 0.6, CI 0.47–0.78).

Conclusion

Compared to reported national data effective ART coverage in Iganga District was low. Intensified efforts to improve access, retention in care, and quality of documentation are urgently needed. Children and young adults require special attention in the program.     

The dynamics of condom use with regular and casual partners: analysis of the 2006 national sexual behavior survey of Thailand

Objective

This study aims to determine factors associated with levels of condom use among heterosexual Thai males in sex with regular partners and in sex with casual partners.

Methods

The data used in this study are from the national probability sample of the 2006 National Sexual Behavior Study, the third nationally representative cross-sectional survey in Thailand. A subtotal of 2,281 men were analyzed in the study, including young (18–24) and older (25–59) adults who were residents of rural areas of Thailand, non-Bangkok urban areas, and Bangkok. Two outcomes of interest for this analysis are reported condom use in the past 12 months by males in relationships with the most recent regular and casual partners who were not sex workers. Chi-square statistics, bivariate regressions and the proportional odds regression models are used in the analysis.

Results

Condom use for men with their regular partner is revealed to be positively related to education, knowledge of condom effectiveness, and pro-condom strategy, and negatively related to non-professional employment, status of registered marriage, and short relationship duration. Condom use with casual partner is positively determined by education, condom knowledge, non-professional occupation, short relationship duration, and lack of history of paid sex.

Conclusion

The national survey emphasized the importance of risk perceptions and condom motivations variables in explaining condom use among men in Thailand. These factors include not only education and knowledge of condom effectiveness and pro-condom strategy but also types of partners and their relationship context and characteristics. Program intervention to promote condom use in Thailand in this new era of predominant casual sex rather than sex with sex workers has to take into account more dynamic partner-based strategies than in the past history of the epidemics in Thailand.     

The Prevalence and Determinants of Undiagnosed and Diagnosed Type 2 Diabetes in Middle-Aged Irish Adults

Background

The prevalence of type 2 diabetes within the Republic of Ireland is poorly defined, although a recent report suggested 135,000 cases in adults aged 45+, with approximately one-third of these undiagnosed. This study aims to assess the prevalence of undiagnosed and diagnosed diabetes in middle-aged adults, and compare features related to either condition, in order to investigate why certain individuals remain undetected.

Methods

This was a cross-sectional study involving a sample of 2,047 men and women, aged between 50–69 years, randomly selected from a large primary care centre. Univariate logistic regression was used to explore socio-economic, metabolic and other health related variable associations with undiagnosed or diagnosed diabetes. A final multivariate analysis was used to determine odds ratios and 95% confidence intervals for having undiagnosed compared to diagnosed diabetes, adjusted for gender, age and significant covariates determined from univariate models.

Principle Findings

The total prevalence of diabetes was 8.5% (95% CI: 7.4%–8.8%); 72 subjects (3.5%) had undiagnosed diabetes (95% CI: 2.8%–4.4%) and 102 subjects (5.0%) had diagnosed diabetes (95% CI: 4.1%–6.0%). Obesity, dyslipidaemia, and family history of diabetes were positively associated with both undiagnosed and diagnosed type 2 diabetes. Compared with diagnosed subjects, study participants with undiagnosed diabetes were significantly more likely to have low levels of physical activity and were less likely to be on treatment for diabetes-related conditions or to have private medical insurance.

Conclusions

The prevalence of diabetes within the Cork and Kerry Diabetes and Heart Disease Study is comparable to recent estimates from the Slán National Health and Lifestyle Survey, a study which was nationally representative of the general population. A considerable proportion of diabetes cases were undiagnosed (41%), emphasising the need for more effective detection strategies and equitable access to primary healthcare.     

Progress in Reversing the HIV Epidemic through Intensified Access to Antiretroviral Therapy: Results from a Nationally Representative Population-Based Survey in Kenya, 2012

Background

In 2014, the Joint United Nations Programme on HIV/AIDS (UNAIDS) called for 90% of persons living with HIV (PLHIV) to know their status, 90% of these to be on antiretroviral therapy (ART), and 90% of these to be virally suppressed by 2020 (90-90-90). It is not clear whether planned ART scale-up in countries whose eligibility criteria for ART initiation are based on recommendations from the 2013 World Health Organization treatment guidelines will be sufficient to meet UNAIDS'' new global targets.

Materials and Methods

Using data from a nationally representative population-based household survey of persons in Kenya we compared coverage and unmet need associated with HIV diagnosis, ART, and viral suppression among PLHIV aged 15–64 years in 2012 based on criteria outlined in the 2014 national ART guidelines and UNAIDS’ 90-90-90 goals. Estimates were weighted to account for sampling probability and nonresponse.

Results

Eight in ten PLHIV aged 15–64 years needed ART based on treatment eligibility. Need for treatment based on the national treatment policy was 97.4% of treatment need based on UNAIDS’ 90-90-90 goals, requiring an excess of 24,000 PLHIV to access treatment beyond those eligible for ART to achieve UNAIDS’ 90-90-90 treatment target. The gap in treatment coverage was high, ranging from 43.1% nationally to 52.3% in Nyanza among treatment-eligible PLHIV and 44.6% nationally to 52.4% in Nyanza among all PLHIV.

Conclusion

Maintaining the current pace of ART scale-up in Kenya will result in thousands of PLHIV unreached, many with high viral load and at-risk of transmitting infection to others. Careful strategies for reaching 90-90-90 will be instrumental in determining whether intensified access to treatment can be achieved to reach all who require ART.     

Pregnant women's access to PMTCT and ART services in South Africa and implications for universal antiretroviral treatment

Objectives

We describe pregnant womens'' access to PMTCT and HAART services and associated birth outcomes in South Africa.

Methods

Women recuperating in postnatal wards of a referral hospital participated in an evaluation during February–May 2010 during which their maternity records were examined to describe their access to VCT, CD4 Counts, dual ART or HAART during pregnancy.

Results

Of the 1609 women who participated in this evaluation, 39% (95%CI36.7–41.5%) tested HIV-positive during their pregnancy. Of the HIV-positive women 2.9% did not have a CD4 count done and an additional 31.3% did not receive their CD4 results. The majority (96.8%) of the HIV-positive women commenced dual ART at their first antenatal visit independent of their CD4 result. During February–May 2010, 48.0% of the women who had a CD4 result were eligible for HAART (CD4<200 cells/mm³) and 29.1% of these initiated HAART during pregnancy. Under the current South African PMTCT guidelines 71.1% (95%CI66.4–75.4%) of HIV positive pregnant women could be eligible for HAART (CD4<350 cells/mm³). There were significantly more preterm births among HIV-positive women (p = 0.01) and women who received HAART were no more at risk of preterm deliveries (AOR 0.73;95%CI0.39–1.36;p = 0.2) as compared to women who received dual ART. Nine (2.4%; 95%CI1.1–4.5%) HIV exposed infants were confirmed HIV infected at birth. The in-utero transmission rate was highest among women who required HAART but did not initiate treatment (8.5%) compared to 2.7% and 0.4% among women who received HAART and women who were not eligible for HAART and received PMTCT prophylaxis respectively.

Conclusion

In this urban South African community the antenatal HIV prevalence remains high (39%) and timeous access to CD4 results during pregnancy is limited. Under the current South African guidelines, and assuming that access to CD4 results has improved, more than 70% of HIV-positive pregnant women in this community would be requiring HAART.     

From Where Are Tuberculosis Patients Accessing Treatment in India? Results from a Cross-Sectional Community Based Survey of 30 Districts

Background

Tuberculosis (TB) notification in India by the Revised National TB Control Programme (RNTCP) provides information on TB patients registered for treatment from the programme. There is limited information about the proportion of patients treated for TB outside RNTCP and where these patients access their treatment.

Objectives

To estimate the proportion of patients accessing TB treatment outside the RNTCP and to identify their basic demographic characteristics.

Methods

A cross sectional community-based survey in 30 districts. Patients were identified through a door-to-door survey and interviewed using a semi-structured questionnaire.

Results

Of the estimated 75,000 households enumerated, 73,249 households (97.6%) were visited. Of the 371,174 household members, 761 TB patients were identified (∼205 cases per 100,000 populations). Data were collected from 609 (80%) TB patients of which 331 [54% (95% CI: 42–66%)] were determined to be taking treatment ‘under DOTS/RNTCP’. The remaining 278 [46% (95% CI: 34–57%)] were on treatment from ‘outside DOTS/RNTCP’ sources and hence were unlikely to be part of the TB notification system. Patients who were accessing treatment from ‘outside DOTS/RNTCP’ were more likely to be patients from rural areas [adjusted Odds Ratio (aOR) 2.5, 95% CI (1.2–5.3)] and whose TB was diagnosed in a non-government health facility (aOR 14.0, 95% CI 7.9–24.9).

Conclusions

This community-based survey found that nearly half of self-reported TB patients were missed by TB notification system in these districts. The study highlights the need for 1) Reviewing and revising the scope of the TB notification system, 2) Strengthening and monitoring health care delivery systems with periodic assessment of the reach and utilisation of the RNTCP services especially among rural communities, 3) Advocacy, communication and social mobilisation activities focused at rural communities with low household incomes and 4) Inclusive involvement of all health-care providers, especially providers of poor rural communities.     

Outcomes of Antiretroviral Therapy in Vietnam: Results from a National Evaluation

Objectives

Vietnam has significantly scaled up its national antiretroviral therapy (ART) program since 2005. With the aim of improving Vietnam’s national ART program, we conducted an outcome evaluation of the first five years of the program in this concentrated HIV epidemic where the majority of persons enrolled in HIV care and treatment services are people who inject drugs (PWID). The results of this evaluation may have relevance for other national ART programs with significant PWID populations.

Design

Retrospective cohort analysis of patients at 30 clinics randomly selected with probability proportional to size among 120 clinics with at least 50 patients on ART.

Methods

Charts of patients whose ART initiation was at least 6 months prior to the study date were abstracted. Depending on clinic size, either all charts or a random sample of 300 charts were selected. Analyses were limited to treatment-naïve patients. Multiple imputations were used for missing data.

Results

Of 7,587 patient charts sampled, 6,875 were those of treatment-naïve patients (74.4% male, 95% confidence interval [CI]: 72.4–76.5, median age 30, interquartile range [IQR]: 26–34, 62.0% reported a history of intravenous drug use, CI: 58.6–65.3). Median baseline CD4 cell count was 78 cells/mm³ (IQR: 30–162) and 30.4% (CI: 25.8–35.1) of patients were at WHO stage IV. The majority of patients started d4T/3TC/NVP (74.3%) or d4T/3TC/EFV (18.6%). Retention rates after 6, 12, 24, and 36 months were 88.4% (CI: 86.8–89.9), 84.0% (CI: 81.8–86.0), 78.8% (CI: 75.7–81.6), and 74.6% (CI: 69.6–79.0). Median CD4 cell count gains after 6, 12, 24, and 36 months were 94 (IQR: 45–153), 142 (IQR: 78–217), 213 (IQR: 120–329), and 254 (IQR: 135–391) cells/mm³. Patients who were PWID showed significantly poorer retention.

Conclusions

The study showed good retention and immunological response to ART among a predominantly PWID group of patients despite advanced HIV infections at baseline.     

Geographic Access to High Capability Severe Acute Respiratory Failure Centers in the United States

Objective

Optimal care of adults with severe acute respiratory failure requires specific resources and expertise. We sought to measure geographic access to these centers in the United States.

Design

Cross-sectional analysis of geographic access to high capability severe acute respiratory failure centers in the United States. We defined high capability centers using two criteria: (1) provision of adult extracorporeal membrane oxygenation (ECMO), based on either 2008–2013 Extracorporeal Life Support Organization reporting or provision of ECMO to 2010 Medicare beneficiaries; or (2) high annual hospital mechanical ventilation volume, based 2010 Medicare claims.

Setting

Nonfederal acute care hospitals in the United States.

Measurements and Main Results

We defined geographic access as the percentage of the state, region and national population with either direct or hospital-transferred access within one or two hours by air or ground transport. Of 4,822 acute care hospitals, 148 hospitals met our ECMO criteria and 447 hospitals met our mechanical ventilation criteria. Geographic access varied substantially across states and regions in the United States, depending on center criteria. Without interhospital transfer, an estimated 58.5% of the national adult population had geographic access to hospitals performing ECMO and 79.0% had geographic access to hospitals performing a high annual volume of mechanical ventilation. With interhospital transfer and under ideal circumstances, an estimated 96.4% of the national adult population had geographic access to hospitals performing ECMO and 98.6% had geographic access to hospitals performing a high annual volume of mechanical ventilation. However, this degree of geographic access required substantial interhospital transfer of patients, including up to two hours by air.

Conclusions

Geographic access to high capability severe acute respiratory failure centers varies widely across states and regions in the United States. Adequate referral center access in the case of disasters and pandemics will depend highly on local and regional care coordination across political boundaries.     

Maternal Mortality in India: Causes and Healthcare Service Use Based on a Nationally Representative Survey

Background

Data on cause-specific mortality, skilled birth attendance, and emergency obstetric care access are essential to plan maternity services. We present the distribution of India''s 2001–2003 maternal mortality by cause and uptake of emergency obstetric care, in poorer and richer states.

Methods and Findings

The Registrar General of India surveyed all deaths occurring in 2001–2003 in 1.1 million nationally representative homes. Field staff interviewed household members about events that preceded the death. Two physicians independently assigned a cause of death. Narratives for all maternal deaths were coded for variables on healthcare uptake. Distribution of number of maternal deaths, cause-specific mortality and uptake of healthcare indicators were compared for poorer and richer states. There were 10 041 all-cause deaths in women age 15–49 years, of which 1096 (11.1%) were maternal deaths. Based on 2004–2006 SRS national MMR estimates of 254 deaths per 100 000 live births, we estimated rural areas of poorer states had the highest MMR (397, 95%CI 385–410) compared to the lowest MMR in urban areas of richer states (115, 95%CI 85–146). We estimated 69 400 maternal deaths in India in 2005. Three-quarters of maternal deaths were clustered in rural areas of poorer states, although these regions have only half the estimated live births in India. Most maternal deaths were attributed to direct obstetric causes (82%). There was no difference in the major causes of maternal deaths between poorer and richer states. Two-thirds of women died seeking some form of healthcare, most seeking care in a critical medical condition. Rural areas of poorer states had proportionately lower access and utilization to healthcare services than the urban areas; however this rural-urban difference was not seen in richer states.

Conclusions

Maternal mortality and poor access to healthcare is disproportionately higher in rural populations of the poorer states of India.     

Tuberculosis in HIV-negative and HIV-infected patients in a low-incidence country: clinical characteristics and treatment outcomes

Background

In Switzerland and other developed countries, the number of tuberculosis (TB) cases has been decreasing for decades, but HIV-infected patients and migrants remain risk groups. The aim of this study was to compare characteristics of TB in HIV-negative and HIV-infected patients diagnosed in Switzerland, and between coinfected patients enrolled and not enrolled in the national Swiss HIV Cohort Study (SHCS).

Methods and Findings

All patients diagnosed with culture-confirmed TB in the SHCS and a random sample of culture-confirmed cases reported to the national TB registry 2000–2008 were included. Outcomes were assessed in HIV-infected patients and considered successful in case of cure or treatment completion. Ninety-three SHCS patients and 288 patients selected randomly from 4221 registered patients were analyzed. The registry sample included 10 (3.5%) coinfected patients not enrolled in the SHCS: the estimated number of HIV-infected patients not enrolled in the SHCS but reported to the registry 2000–2008 was 146 (95% CI 122–173). Coinfected patients were more likely to be from sub-Saharan Africa (51.5% versus 15.8%, P<0.0001) and to present disseminated disease (23.9% vs. 3.4%, P<0.0001) than HIV-negative patients. Coinfected patients not enrolled in the SHCS were asylum seekers or migrant workers, with lower CD4 cell counts at TB diagnosis (median CD4 count 79 cells/µL compared to 149 cells/µL among SHCS patients, P = 0.07). There were 6 patients (60.0%) with successful outcomes compared to 82 (88.2%) patients in the SHCS (P = 0.023).

Conclusions

The clinical presentation of coinfected patients differed from HIV-negative TB patients. The number of HIV-infected patients diagnosed with TB outside the SHCS is similar to the number diagnosed within the cohort but outcomes are poorer in patients not followed up in the national cohort. Special efforts are required to address the needs of this vulnerable population.     

Early Outcomes of MDR-TB Treatment in a High HIV-Prevalence Setting in Southern Africa

Background

Little is known about treatment of multidrug-resistant tuberculosis (MDR-TB) in high HIV-prevalence settings such as sub-Saharan Africa.

Methodology/Principal Findings

We did a retrospective analysis of early outcomes of the first cohort of patients registered in the Lesotho national MDR-TB program between July 21, 2007 and April 21, 2008. Seventy-six patients were included for analysis. Patient follow-up ended when an outcome was recorded, or on October 21, 2008 for those still on treatment. Fifty-six patients (74%) were infected with HIV; the median CD4 cell count was 184 cells/μl (range 5–824 cells/μl). By the end of the follow-up period, study patients had been followed for a median of 252 days (range 12–451 days). Twenty-two patients (29%) had died, and 52 patients (68%) were alive and in treatment. In patients who did not die, culture conversion was documented in 52/54 patients (96%). One patient had defaulted, and one patient had transferred out. Death occurred after a median of 66 days in treatment (range 12–374 days).

Conclusions/Significance

In a region where clinicians and program managers are increasingly confronted by drug-resistant tuberculosis, this report provides sobering evidence of the difficulty of MDR-TB treatment in high HIV-prevalence settings. In Lesotho, an innovative community-based treatment model that involved social and nutritional support, twice-daily directly observed treatment and early empiric use of second-line TB drugs was successful in reducing mortality of MDR-TB patients. Further research is urgently needed to improve MDR-TB treatment outcomes in high HIV-prevalence settings.     

The macroeconomic consequences of renouncing to universal access to antiretroviral treatment for HIV in Africa: a micro-simulation model

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/mm³ 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.     

Mesenchymal-to-Endothelial Transition in Kaposi Sarcoma: A Histogenetic Hypothesis Based on a Case Series and Literature Review

Objectives

Although several studies have been conducted regarding Kaposi sarcoma (KS), its histogenesis still remains to be elucidated. The aim of our study was to analyze the immunophenotype of Kaposi sarcoma and to present a hypothesis about the histogenesis of this tumor, based on a case series and a review of relevant literature.

Methods

In 15 cases of KSs diagnosed during 2000–2011, the clinicopathological features were correlated with the immunoexpression of c-Kit, SMA, CD34, CD31, vascular endothelial growth factor (VEGF), COX-2, c-KIT, smooth muscle antigen (SMA), and stem cell surface marker CD105.

Results

Both CD105 and c-KIT rate of the spindle-shaped tumor cell positivity increased in parallel to the pathological stage. All cases displayed CD105 and weak c-KIT positivity in the endothelial cells. SMA, VEGF, and COX-2 were focally expressed in all cases. CD34 marked both endothelium and spindle-shaped tumor cells. No c-KIT expression was noticed in KS of the internal organs.

Conclusions

KS seems to be a variant of myofibroblastic tumors that originates from the viral modified pluripotent mesenchymal cells of the connective tissue transformed in spindle-shaped KS cells, followed by a mesenchymal-endothelial transition and a myofibroblastic-like differentiation. This paper mailnly showed that KS cannot be considered a pure vascular tumor.     

Health services for Buruli ulcer control: lessons from a field study in Ghana

Background

Buruli ulcer (BU), caused by Mycobacterium ulcerans infection, is a debilitating disease of the skin and underlying tissue. The first phase of a BU prevention and treatment programme (BUPaT) was initiated from 2005–2008, in the Ga-West and Ga-South municipalities in Ghana to increase access to BU treatment and to improve early case detection and case management. This paper assesses achievements of the BUPaT programme and lessons learnt. It also considers the impact of the programme on broader interests of the health system.

Methods

A mixed-methods approach included patients'' records review, review of programme reports, a stakeholder forum, key informant interviews, focus group discussions, clinic visits and observations.

Principal Findings

Extensive collaboration existed across all levels, (national, municipality, and community), thus strengthening the health system. The programme enhanced capacities of all stakeholders in various aspects of health services delivery and demonstrated the importance of health education and community-based surveillance to create awareness and encourage early treatment. A patient database was also created using recommended World Health Organisation (WHO) forms which showed that 297 patients were treated from 2005–2008. The proportion of patients requiring only antibiotic treatment, introduced in the course of the programme, was highest in the last year (35.4% in the first, 23.5% in the second and 42.5% in the third year). Early antibiotic treatment prevented recurrences which was consistent with programme aims.

Conclusions

To improve early case management of BU, strengthening existing clinics to increase access to antibiotic therapy is critical. Intensifying health education and surveillance would ultimately increase early reporting and treatment for all cases. Further research is needed to explain the role of environmental factors for BU contagion. Programme strategies reported in our study: collaboration among stakeholders, health education, community surveillance and regular antibiotic treatment can be adopted for any BU-endemic area in Ghana.