Comparing Cutaneous Research Funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases with 2010 Global Burden of Disease Results

Importance

Disease burden data helps guide research prioritization.

Objective

To determine the extent to which grants issued by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) reflect disease burden, measured by disability-adjusted life years (DALYs) from Global Burden of Disease (GBD) 2010 project.

Design

Two investigators independently assessed 15 skin conditions studied by GBD 2010 in the NIAMS database for grants issued in 2013. The 15 skin diseases were matched to their respective DALYs from GBD 2010.

Setting

The United States NIAMS database and GBD 2010 skin condition disability data.

Main Outcome(s) and Measure(s)

Relationship of NIAMS grant database topic funding with percent total GBD 2010 DALY and DALY rank for 15 skin conditions.

Results

During fiscal year 2013, 1,443 NIAMS grants were issued at a total value of $424 million. Of these grants, 17.7% covered skin topics. Of the total skin disease funding, 82% (91 grants) were categorized as “general cutaneous research.” Psoriasis, leprosy, and “other skin and subcutaneous diseases” (ie; immunobullous disorders, vitiligo, and hidradenitis suppurativa) were over-represented when funding was compared with disability. Conversely, cellulitis, decubitus ulcer, urticaria, acne vulgaris, viral skin diseases, fungal skin diseases, scabies, and melanoma were under-represented. Conditions for which disability and funding appeared well-matched were dermatitis, squamous and basal cell carcinoma, pruritus, bacterial skin diseases, and alopecia areata.

Conclusions and Relevance

Degree of representation in NIAMS is partly correlated with DALY metrics. Grant funding was well-matched with disability metrics for five of the 15 studied skin diseases, while two skin diseases were over-represented and seven were under-represented. Global burden estimates provide increasingly transparent and important information for investigating and prioritizing national research funding allocations.     

Incorporating Scale Dependence in Disease Burden Estimates: The Case of Human African Trypanosomiasis in Uganda

Background

The WHO has established the disability-adjusted life year (DALY) as a metric for measuring the burden of human disease and injury globally. However, most DALY estimates have been calculated as national totals. We mapped spatial variation in the burden of human African trypanosomiasis (HAT) in Uganda for the years 2000–2009. This represents the first geographically delimited estimation of HAT disease burden at the sub-country scale.

Methodology/Principal Findings

Disability-adjusted life-year (DALY) totals for HAT were estimated based on modelled age and mortality distributions, mapped using Geographic Information Systems (GIS) software, and summarised by parish and district. While the national total burden of HAT is low relative to other conditions, high-impact districts in Uganda had DALY rates comparable to the national burden rates for major infectious diseases. The calculated average national DALY rate for 2000–2009 was 486.3 DALYs/100 000 persons/year, whereas three districts afflicted by rhodesiense HAT in southeastern Uganda had burden rates above 5000 DALYs/100 000 persons/year, comparable to national GBD 2004 average burden rates for malaria and HIV/AIDS.

Conclusions/Significance

These results provide updated and improved estimates of HAT burden across Uganda, taking into account sensitivity to under-reporting. Our results highlight the critical importance of spatial scale in disease burden analyses. National aggregations of disease burden have resulted in an implied bias against highly focal diseases for which geographically targeted interventions may be feasible and cost-effective. This has significant implications for the use of DALY estimates to prioritize disease interventions and inform cost-benefit analyses.     

Occult hepatitis B demonstrated by anti-HBc and HBV DNA in HIV-positive patients

Background:

In patients who are hepatitis B virus (HBV) DNA-positive, but HBV surface antigen (HBsAg) -negative, the infection is referred to as occult hepatitis B infection (OBI). Occult HBV infection is harmful when other liver diseases are present, and can aggravate liver damage in in patients with chronic liver diseases. In human immunodeficiency virus (HIV) infection the suppression of viral replication by the immune system might be inactivated, and classical HBV infection in OBI patients may occur. Health care professionals should be aware of OBI in HIV patients. The routine test for HBV infection in Iran is the enzyme-linked immunosorbent assay for the HBV surface antigen (ELISA HBsAg); therefore, the aim of this study was to evaluate the prevalence of OBI in Iranian HIV patients.

Methods:

This cross-sectional study was conducted in 2012 on sera from all the known and accessible HIV patients in Jahrom and Fassa, two cities in southern Iran. All samples were tested for the HBsAg, HBV core antibody (HBcAb). All the results were analyzed using SPSS.

Results:

Of the 91 patients, seven (7.7%) were HBsAg-positive and forty-five (49.5%) were HBcAb-positive. In patients with negative HBsAg (84 patients), 39 (46.4%) were HBcAb positive and 53 (63%) were positive for HBV DNA.

Conclusion:

The prevalence of HBV infection is relatively high in HIV patients, and more accurate tests than those presently in use should be used for diagnosis.Key Words: Hepatitis B, HIV infection, Occult hepatitis     

Effectiveness of School-based Education on HIV/AIDS Knowledge, Attitude, and Behavior among Secondary School Students in Wuhan, China

Background

Human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) are among the most complex health problems in the world. Young people are at high risk of HIV and AIDS infections and are, therefore, in need of targeted prevention. School-based HIV/AIDS health education may be an effective way to prevent the spread of AIDS among adolescents.

Methods

The study was a school-based intervention conducted in three middle schools and two high schools in Wuhan, China, which included 702 boys and 766 girls, with ages from 11 to 18 years old. The intervention was a one-class education program about HIV/AIDS for participants. HIV/AIDS knowledge, attitude, and high-risk behaviors were investigated using an anonymous self-administered questionnaire before and after the education intervention. Chi-square test was used to compare differences before and after the intervention. Non-conditional logistic regression analysis was used to identify the factors that affect HIV/AIDS knowledge.

Results

Misconceptions about basic medical knowledge and non-transmission modes of HIV/AIDS among all the students prevail. Approximately 10% to 40% of students had negative attitudes about HIV/AIDS before the intervention. After the intervention, all of the students had significant improvements in knowledge and attitude about HIV/AIDS (P<.05), indicating that educational intervention increased the students’ knowledge significantly and changed their attitudes positively. Logistic regression analyses indicated that before the intervention the students’ level of knowledge about HIV/AIDS was significantly associated with grade, economic status of the family, and attitudes toward participation in HIV/AIDS health information campaigns.

Conclusions

HIV/AIDS education programs were welcomed by secondary students and positively influenced HIV/AIDS-related knowledge and attitudes. A systematic and long-term intervention among secondary school students must be conducted for the prevention of HIV.     

Expanding ART for treatment and prevention of HIV in South Africa: estimated cost and cost-effectiveness 2011-2050

Background

Antiretroviral Treatment (ART) significantly reduces HIV transmission. We conducted a cost-effectiveness analysis of the impact of expanded ART in South Africa.

Methods

We model a best case scenario of 90% annual HIV testing coverage in adults 15–49 years old and four ART eligibility scenarios: CD4 count <200 cells/mm³ (current practice), CD4 count <350, CD4 count <500, all CD4 levels. 2011–2050 outcomes include deaths, disability adjusted life years (DALYs), HIV infections, cost, and cost per DALY averted. Service and ART costs reflect South African data and international generic prices. ART reduces transmission by 92%. We conducted sensitivity analyses.

Results

Expanding ART to CD4 count <350 cells/mm³ prevents an estimated 265,000 (17%) and 1.3 million (15%) new HIV infections over 5 and 40 years, respectively. Cumulative deaths decline 15%, from 12.5 to 10.6 million; DALYs by 14% from 109 to 93 million over 40 years. Costs drop $504 million over 5 years and $3.9 billion over 40 years with breakeven by 2013. Compared with the current scenario, expanding to <500 prevents an additional 585,000 and 3 million new HIV infections over 5 and 40 years, respectively. Expanding to all CD4 levels decreases HIV infections by 3.3 million (45%) and costs by $10 billion over 40 years, with breakeven by 2023. By 2050, using higher ART and monitoring costs, all CD4 levels saves $0.6 billion versus current; other ART scenarios cost $9–194 per DALY averted. If ART reduces transmission by 99%, savings from all CD4 levels reach $17.5 billion. Sensitivity analyses suggest that poor retention and predominant acute phase transmission reduce DALYs averted by 26% and savings by 7%.

Conclusion

Increasing the provision of ART to <350 cells/mm3 may significantly reduce costs while reducing the HIV burden. Feasibility including HIV testing and ART uptake, retention, and adherence should be evaluated.     

Total HIV/AIDS Expenditures in Dehong Prefecture,Yunnan Province in 2010: The First Systematic Evaluation of Both Health and Non-Health Related HIV/AIDS Expenditures in China

Objective

We assessed HIV/AIDS expenditures in Dehong Prefecture, Yunnan Province, one of the highest prevalence regions in China, and describe funding sources and spending for different categories of HIV-related interventions and at-risk populations.

Methods

2010 HIV/AIDS expenditures in Dehong Prefecture were evaluated based on UNAIDS’ National AIDS Spending Assessment methodology.

Results

Nearly 93% of total expenditures for HIV/AIDS was contributed by public sources. Of total expenditures, 52.7% was allocated to treatment and care, 24.5% to program management and administration and 19.8% to prevention. Spending on treatment and care was primarily allocated to the treatment of opportunistic infections. Most (40.4%) prevention spending was concentrated on most-at-risk populations, injection drug users (IDUs), sex workers, and men who have sex with men (MSM), with 5.5% allocated to voluntary counseling and testing. Prevention funding allocated for MSM, partners of people living with HIV and prisoners and other confined populations was low compared to the disproportionate burden of HIV/AIDS in these populations. Overall, people living with HIV accounted for 57.57% of total expenditures, while most-at-risk populations accounted for only 7.99%.

Conclusions

Our study demonstrated the applicability of NASA for tracking and assessing HIV expenditure in the context of China, it proved to be a useful tool in understanding national HIV/AIDS response from financial aspect, and to assess the extent to which HIV expenditure matches epidemic patterns. Limited funding for primary prevention and prevention for MSM, prisoners and partners of people living with HIV, signal that resource allocation to these key areas must be strengthened. Comprehensive analyses of regional and national funding strategies are needed to inform more equitable, effective and cost-effective HIV/AIDS resource allocation.     

Late Diagnosis and Entry to Care after Diagnosis of Human Immunodeficiency Virus Infection: A Country Comparison

Background

Testing for HIV infection and entry to care are the first steps in the continuum of care that benefit individual health and may reduce onward transmission of HIV. We determined the percentage of people with HIV who were diagnosed late and the percentage linked into care overall and by demographic and risk characteristics by country.

Methods

Data were analyzed from national HIV surveillance systems. Six countries, where available, provided data on two late diagnosis indicators (AIDS diagnosis within 3 months of HIV diagnosis, and AIDS diagnosis within 12 months before HIV diagnosis) and linkage to care (≥1 CD4 or viral load test result within 3 months of HIV diagnosis) for people diagnosed with HIV in 2009 or 2010 (most recent year data were available).

Principal Findings

The percentage of people presenting with late stage disease at HIV diagnosis varied by country, overall with a range from 28.7% (United States) to 8.8% (Canada), and by transmission categories. The percentage of people diagnosed with AIDS who had their initial HIV diagnosis within 12 months before AIDS diagnosis varied little among countries, except the percentages were somewhat lower in Spain and the United States. Overall, the majority of people diagnosed with HIV were linked to HIV care within 3 months of diagnosis (more than 70%), but varied by age and transmission category.

Conclusions

Differences in patterns of late presentation at HIV diagnosis among countries may reflect differences in screening practices by providers, public health agencies, and people with HIV. The percentage of people who received assessments of immune status and viral load within 3 months of diagnosis was generally high.     

Determinants of Clinician Knowledge on Aging and HIV/AIDS: A Survey of Practitioners and Policy Makers in Kampala District,Uganda

Objective

The HIV/AIDS epidemic has evolved with an increasing burden in older adults. We assessed for knowledge about aging and HIV/AIDS, among clinicians in Kampala district, Uganda.

Methods

A cross-sectional survey of 301 clinicians complemented by 9 key-informant interviews between May and October 2011. Data was analyzed by multivariable logistic regression for potential determinants of clinician knowledge about HIV/AIDS in older adults, estimating their adjusted Odds Ratios (aOR) and 95% confidence intervals (95% CI) using Stata 11.2 software.

Results

Two-hundred and sixty-two questionnaires (87.7%) were returned. Respondents had a median age of 30 years (IQR 27–34) and 57.8% were general medical doctors. The mean knowledge score was 49% (range 8.8%–79.4%). Questions related to co-morbidities in HIV/AIDS (non-AIDS related cancers and systemic diseases) and chronic antiretroviral treatment toxicities (metabolic disorders) accounted for significantly lower scores (mean, 41.7%, 95% CI: 39.3%–44%) compared to HIV/AIDS epidemiology and prevention (mean, 65.7%, 95% CI: 63.7%–67.7%). Determinants of clinician knowledge in the multivariable analysis included (category, aOR, 95% CI): clinician age (30–39 years; 3.28∶1.65–9.75), number of persons with HIV/AIDS seen in the past year (less than 50; 0.34∶0.14–0.86) and clinical profession (clinical nurse practitioner; 0.31∶0.11–0.83). Having diploma level education had a marginal association with lower knowledge about HIV and aging (p = 0.09).

Conclusion

Our study identified gaps and determinants of knowledge about HIV/AIDS in older adults among clinicians in Kampala district, Uganda. Clinicians in low and middle income countries could benefit from targeted training in chronic care for older adults with HIV/AIDS and long-term complications of antiretroviral treatment.     

Costs and Impacts of Scaling up Voluntary Medical Male Circumcision in Tanzania

Background

Given the proven effectiveness of voluntary medical male circumcision (VMMC) in preventing the spread of HIV, Tanzania is scaling up VMMC as an HIV prevention strategy. This study will inform policymakers about the potential costs and benefits of scaling up VMMC services in Tanzania.

Methodology

The analysis first assessed the unit costs of delivering VMMC at the facility level in three regions—Iringa, Kagera, and Mbeya—via three currently used VMMC service delivery models (routine, campaign, and mobile/island outreach). Subsequently, using these unit cost data estimates, the study used the Decision Makers'' Program Planning Tool (DMPPT) to estimate the costs and impact of a scaled-up VMMC program.

Results

Increasing VMMC could substantially reduce HIV infection. Scaling up adult VMMC to reach 87.9% coverage by 2015 would avert nearly 23,000 new adult HIV infections through 2015 and an additional 167,500 from 2016 through 2025—at an additional cost of US$253.7 million through 2015 and US$302.3 million from 2016 through 2025. Average cost per HIV infection averted would be US$11,300 during 2010–2015 and US$3,200 during 2010–2025. Scaling up VMMC in Tanzania will yield significant net benefits (benefits of treatment costs averted minus the cost of performing circumcisions) in the long run—around US$4,200 in net benefits for each infection averted.

Conclusion

VMMC could have an immediate impact on HIV transmission, but the full impact on prevalence and deaths will only be apparent in the longer term because VMMC averts infections some years into the future among people who have been circumcised. Given the health and economic benefits of investing in VMMC, the scale-up of services should continue to be a central component of the national HIV prevention strategy in Tanzania.     

Subtype Classification of Iranian HIV-1 Sequences Registered in the HIV Databases, 2006-2013

Background

The rate of human immunodeficiency virus type 1 (HIV-1) infection in Iran has increased dramatically in the past few years. While the earliest cases were among hemophiliacs, injection drug users (IDUs) fuel the current epidemic. Previous molecular epidemiological analysis found that subtype A was most common among IDUs but more recent studies suggest CRF_35AD may be more prevalent now. To gain a better understanding of the molecular epidemiology of HIV-1 infection in Iran, we analyzed all Iranian HIV sequence data from the Los Alamos National Laboratory.

Methods

All Iranian HIV sequences from subtyping studies with pol, gag, env and full-length HIV-1 genome sequences registered in the HIV databases (www.hiv.lanl.gov) between 2006 and 2013 were downloaded. Phylogenetic trees of each region were constructed using Neighbor-Joining (NJ) and Maximum Parsimony methods.

Results

A total of 475 HIV sequences were analyzed. Overall, 78% of sequences were CRF_35AD. By gene region, CRF_35AD comprised 83% of HIV-1 pol, 62% of env, 78% of gag, and 90% of full-length genome sequences analyzed. There were 240 sequences re-categorized as CRF_AD. The proportion of CRF_35AD sequences categorized by the present study is nearly double the proportion of what had been reported.

Conclusions

Phylogenetic analysis indicates HIV-1 subtype CRF_35AD is the predominant circulating strain in Iran. This result differed from previous studies that reported subtype A as most prevalent in HIV- infected patients but confirmed other studies which reported CRF_35AD as predominant among IDUs. The observed epidemiological connection between HIV strains circulating in Iran and Afghanistan may be due to drug trafficking and/or immigration between the two countries. This finding suggests the possible origins and transmission dynamics of HIV/AIDS within Iran and provides useful information for designing control and intervention strategies.     

Voluntary medical male circumcision: modeling the impact and cost of expanding male circumcision for HIV prevention in eastern and southern Africa

Background

There is strong evidence showing that voluntary medical male circumcision (VMMC) reduces HIV incidence in men. To inform the VMMC policies and goals of 13 priority countries in eastern and southern Africa, we estimate the impact and cost of scaling up adult VMMC using updated, country-specific data.

Methods and Findings

We use the Decision Makers'' Program Planning Tool (DMPPT) to model the impact and cost of scaling up adult VMMC in Botswana, Lesotho, Malawi, Mozambique, Namibia, Rwanda, South Africa, Swaziland, Tanzania, Uganda, Zambia, Zimbabwe, and Nyanza Province in Kenya. We use epidemiologic and demographic data from recent household surveys for each country. The cost of VMMC ranges from US$65.85 to US$95.15 per VMMC performed, based on a cost assessment of VMMC services aligned with the World Health Organization''s considerations of models for optimizing volume and efficiencies. Results from the DMPPT models suggest that scaling up adult VMMC to reach 80% coverage in the 13 countries by 2015 would entail performing 20.34 million circumcisions between 2011 and 2015 and an additional 8.42 million between 2016 and 2025 (to maintain the 80% coverage). Such a scale-up would result in averting 3.36 million new HIV infections through 2025. In addition, while the model shows that this scale-up would cost a total of US$2 billion between 2011 and 2025, it would result in net savings (due to averted treatment and care costs) amounting to US$16.51 billion.

Conclusions

This study suggests that rapid scale-up of VMMC in eastern and southern Africa is warranted based on the likely impact on the region''s HIV epidemics and net savings. Scaling up of safe VMMC in eastern and southern Africa will lead to a substantial reduction in HIV infections in the countries and lower health system costs through averted HIV care costs. Please see later in the article for the Editors'' Summary.     

Associations between HIV and human pathways revealed by protein-protein interactions and correlated gene expression profiles

Background

AIDS is one of the most devastating diseases in human history. Decades of studies have revealed host factors required for HIV infection, indicating that HIV exploits host processes for its own purposes. HIV infection leads to AIDS as well as various comorbidities. The associations between HIV and human pathways and diseases may reveal non-obvious relationships between HIV and non-HIV-defining diseases.

Principal Findings

Human biological pathways were evaluated and statistically compared against the presence of HIV host factor related genes. All of the obtained scores comparing HIV targeted genes and biological pathways were ranked. Different rank results based on overlapping genes, recovered virus-host interactions, co-expressed genes, and common interactions in human protein-protein interaction networks were obtained. Correlations between rankings suggested that these measures yielded diverse rankings. Rank combination of these ranks led to a final ranking of HIV-associated pathways, which revealed that HIV is associated with immune cell-related pathways and several cancer-related pathways. The proposed method is also applicable to the evaluation of associations between other pathogens and human pathways and diseases.

Conclusions

Our results suggest that HIV infection shares common molecular mechanisms with certain signaling pathways and cancers. Interference in apoptosis pathways and the long-term suppression of immune system functions by HIV infection might contribute to tumorigenesis. Relationships between HIV infection and human pathways of disease may aid in the identification of common drug targets for viral infections and other diseases.     

Projected Demographic Profile of People Living with HIV in Australia: Planning for an Older Generation

Background

Advances in HIV antiretroviral therapy (ART) has reduced mortality in people living with HIV (PLHIV), resulting in an ageing population of PLHIV. Knowledge of demographic details such as age, geographical location and sex, will aid in the planning of training and resource allocation to effectively care for the future complex health needs of PLHIV.

Methods

An agent-based, stochastic, geographical model was developed to determine the current and future demographic of PLHIV in Australia. Data and parameters were sourced from Australia''s National HIV Registry and peer reviewed literature. Processes that were simulated include progression to AIDS, mortality and internal migration.

Findings

The model estimates the mean age of PLHIV in Australia is increasing at a rate of 0.49 years each year. The expected proportion of PLHIV in over 55 years is estimated to increase from 25.3% in 2010 to 44.2% in 2020. Median age is lower in inner-city areas of the capital cities than in rural areas. The areas with the highest prevalence of HIV will continue to be capital cities; however, other areas will have greater percentage growth from 2010 to 2020.

Conclusions

The age of the population of people living with HIV is expected to increase considerably in the future. As the population of PLHIV ages, specialist clinical training and resource provision in the aged care sector will also need to be addressed.     

Food Access and Diet Quality Are Associated with Quality of Life Outcomes among HIV-Infected Individuals in Uganda

Background

Food insecurity is associated with poor nutritional and clinical outcomes among people living with HIV/AIDS. Few studies investigate the link between food insecurity, dietary diversity and health-related quality of life among people living with HIV/AIDS.

Objective

We investigated whether household food access and individual dietary diversity are associated with health-related quality of life among people living with HIV/AIDS in Uganda.

Methods

We surveyed 902 people living with HIV/AIDS and their households from two clinics in Northern Uganda. Health-related quality of life outcomes were assessed using the Medical Outcomes Study (MOS)-HIV Survey. We performed multivariate regressions to investigate the relationship between health-related quality of life, household food insecurity and individual dietary diversity.

Results

People living with HIV/AIDS from severe food insecurity households have mean mental health status scores that are 1.7 points lower (p<.001) and physical health status scores that are 1.5 points lower (p<.01). Individuals with high dietary diversity have mean mental health status scores that were 3.6 points higher (p<.001) and physical health status scores that were 2.8 points higher (p<.05).

Conclusions

Food access and diet quality are associated with health-related quality of life and may be considered as part of comprehensive interventions designed to mitigate psychosocial consequences of HIV.     

Routine HIV Testing among Hospitalized Patients in Argentina. Is It Time for a Policy Change?

Introduction

The Argentinean AIDS Program estimates that 110,000 persons are living with HIV/AIDS in Argentina. Of those, approximately 40% are unaware of their status, and 30% are diagnosed in advanced stages of immunosuppression. Though studies show that universal HIV screening is cost-effective in settings with HIV prevalence greater than 0.1%, in Argentina, with the exception of antenatal care, HIV testing is always client-initiated.

Objective

We performed a pilot study to assess the acceptability of a universal HIV screening program among inpatients of an urban public hospital in Buenos Aires.

Methods

Over a six-month period, all eligible adult patients admitted to the internal medicine ward were offered HIV testing. Demographics, uptake rates, reasons for refusal and new HIV diagnoses were analyzed.

Results

Of the 350 admissions during this period, 249 were eligible and subsequently enrolled. The enrolled population was relatively old compared to the general population, was balanced on gender, and did not report traditional high risk factors for HIV infection. Only 88 (39%) reported prior HIV testing. One hundred and ninety (76%) patients accepted HIV testing. In multivariable analysis only younger age (OR 1.02; 95%CI 1.003-1.05) was independently associated with test uptake. Three new HIV diagnoses were made (undiagnosed HIV prevalence: 1.58%); none belonged to a most-at-risk population.

Conclusions

Our findings suggest that universal HIV screening in this setting is acceptable and potentially effective in identifying undiagnosed HIV-infected individuals. If confirmed in a larger study, our findings may inform changes in the Argentinean HIV testing policy.     

The Burden of Parasitic Zoonoses in Nepal: A Systematic Review

Background

Parasitic zoonoses (PZs) pose a significant but often neglected threat to public health, especially in developing countries. In order to obtain a better understanding of their health impact, summary measures of population health may be calculated, such as the Disability-Adjusted Life Year (DALY). However, the data required to calculate such measures are often not readily available for these diseases, which may lead to a vicious circle of under-recognition and under-funding.

Methodology

We examined the burden of PZs in Nepal through a systematic review of online and offline data sources. PZs were classified qualitatively according to endemicity, and where possible a quantitative burden assessment was conducted in terms of the annual number of incident cases, deaths and DALYs.

Principal Findings

Between 2000 and 2012, the highest annual burden was imposed by neurocysticercosis and congenital toxoplasmosis (14,268 DALYs [95% Credibility Interval (CrI): 5450–27,694] and 9255 DALYs [95% CrI: 6135–13,292], respectively), followed by cystic echinococcosis (251 DALYs [95% CrI: 105–458]). Nepal is probably endemic for trichinellosis, toxocarosis, diphyllobothriosis, foodborne trematodosis, taeniosis, and zoonotic intestinal helminthic and protozoal infections, but insufficient data were available to quantify their health impact. Sporadic cases of alveolar echinococcosis, angiostrongylosis, capillariosis, dirofilariosis, gnathostomosis, sparganosis and cutaneous leishmaniosis may occur.

Conclusions/Significance

In settings with limited surveillance capacity, it is possible to quantify the health impact of PZs and other neglected diseases, thereby interrupting the vicious circle of neglect. In Nepal, we found that several PZs are endemic and are imposing a significant burden to public health, higher than that of malaria, and comparable to that of HIV/AIDS. However, several critical data gaps remain. Enhanced surveillance for the endemic PZs identified in this study would enable additional burden estimates, and a more complete picture of the impact of these diseases.     

Risk of Melanoma in People with HIV/AIDS in the Pre- and Post-HAART Eras: A Systematic Review and Meta-Analysis of Cohort Studies

Objective

Following the introduction of highly active antiretroviral therapy (HAART) the risk of AIDS-defining cancers decreased but incidence of many non-AIDS-defining cancers has reportedly increased in those with HIV/AIDS. Whether melanoma risk has also changed in HIV/AIDS patients post-HAART is unknown and therefore we evaluated this in comparison with the risk before HAART.

Design

Systematic review and meta-analysis.

Methods

We searched Medline, Embase and ISI science citation index databases to April 2013. All cohort studies of patients diagnosed with HIV/AIDS that permitted quantitative assessment of the association with melanoma were eligible. Detailed quality assessment of eligible studies was conducted, focussing particularly on adjustment for ethnicity, a priori considered essential for an unbiased assessment of melanoma risk. Data were pooled using a random effects model.

Results

From 288 articles, we identified 21 that met the inclusion criteria, 13 presenting data for the post-HAART era and 8 for the pre-HAART era. Post-HAART the pooled relative risk (pRR) for the association between HIV/AIDS and melanoma was 1.26 (95% CI, 0.97–1.64) and 1.50 (95% CI 1.12–2.01) among studies that accounted for ethnicity, with evidence of significant heterogeneity (P = 0.004, I² = 55.5). Pre-HAART pRRs were 1.26 (95% CI 1.11–1.43; P_het = 0.82) and 1.28 (95% CI 1.10–1.49) among studies adjusted for ethnicity.

Conclusions

People with HIV/AIDS remain at a significantly increased risk of developing melanoma in the post-HAART era. White skinned people with HIV/AIDS should be screened regularly and counselled against excessive sun exposure.     

Representation of Women and Pregnant Women in HIV Research: A Limited Systematic Review

Background

HIV-related outcomes may be affected by biological sex and by pregnancy. Including women in general and pregnant women in particular in HIV-related research is important for generalizability of findings.

Objective

To characterize representation of pregnant and non-pregnant women in HIV-related research conducted in general populations.

Data Sources

All HIV-related articles published in fifteen journals from January to March of 2011. We selected the top five journals by 2010 impact factor, in internal medicine, infectious diseases, and HIV/AIDS.

Study Eligibility Criteria

HIV-related studies reporting original research on questions applicable to both men and women of reproductive age were considered; studies were excluded if they did not include individual-level patient data.

Study appraisal and synthesis methods.

Articles were doubly reviewed and abstracted; discrepancies were resolved through consensus. We recorded proportion of female study participants, whether pregnant women were included or excluded, and other key factors.

Results

In total, 2014 articles were published during this period. After screening, 259 articles were included as original HIV-related research reporting individual-level data; of these, 226 were determined to be articles relevant to both men and women of reproductive age. In these articles, women were adequately represented within geographic region. The vast majority of published articles, 183/226 (81%), did not mention pregnancy (or related issues); still fewer included pregnant women (n=33), reported numbers of pregnant women (n=19), or analyzed using pregnancy status (n=9).

Limitations

Data were missing for some key variables, including pregnancy. The time period over which published works were evaluated was relatively short.

Conclusions and implications of key findings.

The under-reporting and inattention to pregnancy in the HIV literature may reduce policy-makers’ ability to set evidence-based policy around HIV/AIDS care for pregnant women and women of child-bearing age.     

The Innate Immune Response in HIV/AIDS Septic Shock Patients: A Comparative Study

Introduction

In recent years, the incidence of sepsis has increased in critically ill HIV/AIDS patients, and the presence of severe sepsis emerged as a major determinant of outcomes in this population. The inflammatory response and deregulated cytokine production play key roles in the pathophysiology of sepsis; however, these mechanisms have not been fully characterized in HIV/AIDS septic patients.

Methods

We conducted a prospective cohort study that included HIV/AIDS and non-HIV patients with septic shock. We measured clinical parameters and biomarkers (C-reactive protein and cytokine levels) on the first day of septic shock and compared these parameters between HIV/AIDS and non-HIV patients.

Results

We included 30 HIV/AIDS septic shock patients and 30 non-HIV septic shock patients. The HIV/AIDS patients presented low CD4 cell counts (72 [7-268] cells/mm³), and 17 (57%) patients were on HAART before hospital admission. Both groups were similar according to the acute severity scores and hospital mortality. The IL-6, IL-10 and G-CSF levels were associated with hospital mortality in the HIV/AIDS septic group; however, the CRP levels and the surrogates of innate immune activation (cytokines) were similar among HIV/AIDS and non-HIV septic patients. Age (odds ratio 1.05, CI 95% 1.02-1.09, p=0.002) and the IL-6 levels (odds ratio 1.00, CI 95% 1.00-1.01, p=0.05) were independent risk factors for hospital mortality.

Conclusions

IL-6, IL-10 and G-CSF are biomarkers that can be used to predict prognosis and outcomes in HIV/AIDS septic patients. Although HIV/AIDS patients are immunocompromised, an innate immune response can be activated in these patients, which is similar to that in the non-HIV septic population. In addition, age and the IL-6 levels are independent risk factors for hospital mortality irrespective of HIV/AIDS disease.