Assessing the Residual Risk for Transfusion-Transmitted Infections in the Philippine Blood Supply

Due to a USAID-funded study on blood banks, a national policy was instituted in 1994 that set standards for Philippine blood services, promoted voluntary donation, and led to a ban on commercial blood banks. In this follow-up study, we assess the safety of the supply by determining the residual risk for transfusion-transmitted infections (syphilis, hepatitis B and C, HIV). We also identified unsafe facility practices and generated policy recommendations. A 1992 study found that transfusion-ready blood was not safe using the LQAS method (P > 0.05). We found that the 2012 residual risk became 0 to 0.9 percent attributable to the national policy. We noted poor to fair adherence to this policy. We identified unsafe practices such as use of rapid tests and lack of random blood retesting. Training and use of regional networks may improve safety. Despite improvement in safety, facilities complain of funding and logistical issues regarding compliance with the policy.     

Administrative issues related to infectious disease research in the age of bioterrorism

The recent unprecedented growth in infectious disease research funding and infrastructure has resulted in part from an outgrowth of concern about newly emerging and re-emerging diseases and the progressive development of antibiotic-resistant pathogens. However, the most compelling impetus is the suspected and demonstrated capability and will of unknown individuals, groups, or states to use biological agents and/or toxins as weapons. Although the actual number of known victims and fatalities from bioterrorism in the United States has been miniscule compared with many other daily hazards, biological agents have the potential to cause human mass casualties, severely damage segments of our economy or agricultural infrastructure, poison or compromise our food or water supply, and, perhaps most damaging, disrupt our society physically and psychologically. The significant institutional commitment necessary to participate in infectious disease research is described, with a focus on programs that involve research with pathogens thought to have potential for use by bioterrorists. Administrative considerations are described, and include obtaining necessary research funding to offset high operating costs; complying with "select agent" regulations, security screening of employees; building or renovating a biocontainment facility; finding skilled professional and technical manpower; providing adequate physical security in a threat environment; conducting targeted training; overcoming potential internal and external dissent; developing and/or providing sufficient occupational health and safety programs; achieving and maintaining compliance standards in a fluid regulatory environment; mitigating potentially hazardous working conditions; understanding personal and institutional liability; and reassuring and dealing with a concerned, skeptical, or even hostile public.     

Excluding blood donors at high risk of HIV infection in a west African city.

OBJECTIVE--To examine the potential impact of deferral of blood donors at high risk of HIV infection in a west African city where blood is screened for HIV antibodies but no other special measures are taken to protect the blood supply. DESIGN--Cross sectional study. SETTING--National Blood Transfusion Centre and Project RETRO-CI, an international collaborative AIDS research project, Abidjan, Côte d''Ivoire. SUBJECTS--1257 male first time blood donors. INTERVENTIONS--Blood donors were interviewed about demographic and behavioural characteristics and tested for HIV antibodies by enzyme immunoassay and, if positive, synthetic peptide based tests. MAIN OUTCOME MEASURES--HIV antibody status in relation to presence of behavioural risk factors; calculation of sensitivity, specificity, and predictive values of specific criteria for excluding HIV infected donors. RESULTS--The overall prevalence of HIV infection was 11.4%. The most important risk factors for HIV positivity were prostitute contact and being aged 30-39 years. For identifying seropositive donors individual criteria had sensitivity, specificity, and positive predictive values ranging from 15% to 98%, 38% to 91%, and 17% to 30% respectively. Prostitute contact in the past five years would have excluded 31% of all donors and 73% of HIV infected donors. 27% of those excluded would have been HIV positive. CONCLUSIONS--The widespread assumption that donor deferral is not feasible in sub-Saharan Africa needs reassessment. In Abidjan this approach was well accepted and potentially effective. Donor deferral requires evaluation as a strategy for improving blood safety in resource poor areas with high rates of HIV infection.     

Should we neglect or nurture replacement blood donors in sub-Saharan Africa?

Lack of blood is common in SSA but quantification of the overall shortfall is hampered by a lack of evidence-based targets for blood collection. Despite recommendations that all blood donors should be voluntary and non-remunerated, replacement donors are common throughout sub-Saharan Africa (SSA). Voluntary donors are generally recruited through centralised systems whereas replacement donors are recruited by families and donate through hospitals. Blood from a centralised service is more expensive than from a hospital-based service due to the higher costs of donor recruitment, quality assurance processes and the maintenance of distribution networks.Information about the contribution of replacement donors to the blood supply is scanty and inconsistent but it is likely that they currently provide over half of the blood in SSA. WHO's guidelines for transfusion services deal exclusively with voluntary donors and neglect the substantial contribution made by replacement donors. Examples of how the supply and quality of blood from the replacement donors can be improved have been published but need to be evaluated and disseminated. Political will and open-mindedness to innovative ways to improve supply and safety of blood from all types of donors are essential to promote more evidence-based approaches to blood transfusion practice in low-income countries.     

Estimating the Impact of State Budget Cuts and Redirection of Prevention Resources on the HIV Epidemic in 59 California Local Health Departments

Background

In the wake of a national economic downturn, the state of California, in 2009–2010, implemented budget cuts that eliminated state funding of HIV prevention and testing. To mitigate the effect of these cuts remaining federal funds were redirected. This analysis estimates the impact of these budget cuts and reallocation of resources on HIV transmission and associated HIV treatment costs.

Methods and Findings

We estimated the effect of the budget cuts and reallocation for California county health departments (excluding Los Angeles and San Francisco) on the number of individuals living with or at-risk for HIV who received HIV prevention services. We used a Bernoulli model to estimate the number of new infections that would occur each year as a result of the changes, and assigned lifetime treatment costs to those new infections. We explored the effect of redirecting federal funds to more cost-effective programs, as well as the potential effect of allocating funds proportionately by transmission category. We estimated that cutting HIV prevention resulted in 55 new infections that were associated with $20 million in lifetime treatment costs. The redirection of federal funds to more cost-effective programs averted 15 HIV infections. If HIV prevention funding were allocated proportionately to transmission categories, we estimated that HIV infections could be reduced below the number that occurred annually before the state budget cuts.

Conclusions

Reducing funding for HIV prevention may result in short-term savings at the expense of additional HIV infections and increased HIV treatment costs. Existing HIV prevention funds would likely have a greater impact on the epidemic if they were allocated to the more cost-effective programs and the populations most likely to acquire and transmit the infection.     

Theoretical models for coronary vascular biomechanics: progress & challenges

A key aim of the cardiac Physiome Project is to develop theoretical models to simulate the functional behaviour of the heart under physiological and pathophysiological conditions. Heart function is critically dependent on the delivery of an adequate blood supply to the myocardium via the coronary vasculature. Key to this critical function of the coronary vasculature is system dynamics that emerge via the interactions of the numerous constituent components at a range of spatial and temporal scales. Here, we focus on several components for which theoretical approaches can be applied, including vascular structure and mechanics, blood flow and mass transport, flow regulation, angiogenesis and vascular remodelling, and vascular cellular mechanics. For each component, we summarise the current state of the art in model development, and discuss areas requiring further research. We highlight the major challenges associated with integrating the component models to develop a computational tool that can ultimately be used to simulate the responses of the coronary vascular system to changing demands and to diseases and therapies.     

Donor issues in Indonesia: A developing country in South East Asia

In most developing countries in South East Asia blood services have not been treated properly as an important service to support health program. Indonesia as a large archipelago country in South East Asia has specific obstacles in managing a blood service. To position the country blood service profile especially in term of donor issues, we compared our blood service with that in other South East Asia countries.Indonesia has 17 thousand islands with 220 million inhabitants. Blood services have been mostly run by the Indonesian Red Cross as a government assignment since 1950. Donor recruitment programs have been directed toward 100% of Voluntary Non Remunerated Blood Donor (VNRD), which now have reached 81.3%. Dissemination of information on VNRD, donor recruiter's training and VNRD appreciation programs are strategies to increase and maintain the VNRD.Limited female donors and insufficient blood supply during the fasting month and holidays constitute major challenges. Low hemoglobin level, low body weight and fear are reasons for low number of female donors. Poor management of blood stock during fasting month, long holidays and also poor networking of blood supply are reasons for insufficient blood supply during the year.Considering the great size of Indonesia with different ethnic groups and cultures, worsened by lack of infrastructure, decisive and effective strategies in donor recruitment and retention programs are needed.     

Blood donation in Chile: Replacement and volunteer donors

In recent years, the Chilean Health Ministry has developed a strategy in order to improve the safety and opportunity of the blood supply through the creation of a nationally co-ordinated blood transfusion service, centralizing collection management, production and testing in three Blood Centers along the country and promoting voluntary, regular, blood donation.In 2007, a comprehensive study of the situation of Blood Transfusion Services in Chile concluded that several critical factors make it difficult to achieve a safe and adequate access to blood and blood components in the country. For example there is a low donation rate (14.3/1000 inhabitants), very low percentage of voluntary donors (10%), excessive amount of blood banks collecting, processing and testing blood revealing an atomized non-centralized system, lack of a national IT system and insufficient national standards. There are two regions in the country, Bio Bio and Valparaíso, where Regional Blood Centers are located, that have put in place several strategies in order to obtain better results.     

Labeling to manage marketing of GM foods

Biotechnology has the potential to introduce new food safety risks, liabilities and benefits, and although privately managed supply chains (involving proactive management of the production of branded products) are effective at providing, managing and communicating adequate information about products with well understood risks, products with uncertain risks pose a greater challenge. The demand for increased product information regarding genetically modified content, in particular, places new constraints on food supply chains, frequently resulting in communication failures. Here we assess and reject mandatory labeling as an appropriate response.     

HIV Programs for Sex Workers: Lessons and Challenges for Developing and Delivering Programs

There is evidence that HIV prevention programs for sex workers, especially female sex workers, are cost-effective in several contexts, including many western countries, Thailand, India, the Democratic Republic of Congo, Kenya, and Zimbabwe. The evidence that sex worker HIV prevention programs work must not inspire complacency but rather a renewed effort to expand, intensify, and maximize their impact. The PLOS Collection “Focus on Delivery and Scale: Achieving HIV Impact with Sex Workers” highlights major challenges to scaling-up sex worker HIV prevention programs, noting the following: sex worker HIV prevention programs are insufficiently guided by understanding of epidemic transmission dynamics, situation analyses, and programmatic mapping; sex worker HIV and sexually transmitted infection services receive limited domestic financing in many countries; many sex worker HIV prevention programs are inadequately codified to ensure consistency and quality; and many sex worker HIV prevention programs have not evolved adequately to address informal sex workers, male and transgender sex workers, and mobile- and internet-based sex workers. Based on the wider collection of papers, this article presents three major clusters of recommendations: (i) HIV programs focused on sex workers should be prioritized, developed, and implemented based on robust evidence; (ii) national political will and increased funding are needed to increase coverage of effective sex worker HIV prevention programs in low and middle income countries; and (iii) comprehensive, integrated, and rapidly evolving HIV programs are needed to ensure equitable access to health services for individuals involved in all forms of sex work.

Summary Points

• HIV prevention programs for sex workers, especially female sex workers, are cost-effective.
• There are opportunities to further increase the impact of HIV prevention programs for sex workers and to adapt interventions to a changing context.
• Many sex worker HIV prevention programs are insufficiently guided by understanding of epidemic transmission dynamics, situation analyses, and programmatic mapping; receive limited domestic financing in many countries; are inadequately codified to ensure consistency and quality; and have not evolved adequately to address informal sex workers, male and transgender sex workers, and mobile and internet-based sex workers.
• We recommend increasing our understanding of HIV epidemic transmission dynamics, improving situation analyses and programmatic mapping, increasing domestic financing for sex worker HIV prevention programs where feasible, delivering well-codified, comprehensive programs using “Science of Delivery” principles and developing more effective models to reach informal sex workers, male and transgender sex workers, and mobile and internet-based sex workers.
• Given their marginalization, concerted efforts must be made to ensure sex workers have equitable access to HIV prevention, care, and treatment services, as well as wider health services, particularly for STIs, mental health, and addictions.

     

Risk of HIV infection from blood transfusion in Montreal

OBJECTIVES: To determine the incidence (including associated donor characteristics and time trends) of HIV infection among repeat blood donors and to estimate the risk of HIV transmission from blood transfusion in Montreal and in Canada as a whole. DESIGN: Retrospective cohort analysis. SETTING: Montreal Centre Blood Transfusion Service. PARTICIPANTS: People who donated blood at least twice after Nov. 1, 1985, and at least once from Apr. 1, 1989, to Mar. 31, 1993. INTERVENTION: Blood was screened for HIV by enzyme-linked immunosorbent assay and results were confirmed by Western blot analysis. OUTCOME MEASURES: Incidence density (the incidence rate per person-time) of HIV infection among repeat blood donors by sex, age group and region of residence, and incidence density and risk among first-time donors and for Canada as whole. RESULTS: There were 200,196 eligible donors and 432,631 person-years (PY) of observation. From 1989 to 1993, there were 18 HIV seroconversions among repeat donors. The crude incidence density was 3.3 per 100,000 PY (95% confidence interval [CI] 1.8 to 5.4 per 100,000 PY); it was 4.9 per 100,000 PY among men and 0.61 per 100,000 PY among women. Age-specific incidence per 100,000 PY was 2.5 among those 12-29 years of age, 5.1 among those 30-49, 2.9 among those 40-49, and 1.4 among those 50 and older. Based on an estimated mean "window period" (from when a donor''s blood is capable of transmitting HIV until detectable antibody appears) of 25 days, the current risk of HIV infection from repeat donors in the window period is estimated at 1 in 440,000. Inclusion of blood units from first-time donors produces an overall risk of 1 in 390,000 (95% CI 1 in 250,000 to 655,000). The estimated risk per blood unit in Canada as a whole is 1 in 913000 (95% CI 1 in 507,000 to 2,050,000). CONCLUSIONS: This "sentinel" population of repeat blood donors is subject to important trends in HIV spread. Therefore, estimating the incidence density of HIV infection in repeat donors provides insight into the epidemiologic characteristics of HIV infection at minimal expense. As a result of measures to improve blood safety, including HIV testing, the incidence of HIV infection among blood donors in Canada is low and the risk of HIV transmission from transfusion is extremely small, although not zero.     

A policy to control the spread of HIV infection

Prevention of transmission of HIV infection is the most important public health concern of the AIDS epidemic. To date, unfortunately, we have failed to contain the epidemic. The increasingly rapid spread of HIV into the IV drug-abusing population and subsequent heterosexual transmission represent a further failure of the public health system. Current organization of the public health programs, especially the lack of independence and adequate financial and personnel support, is an extremely serious problem. More funding may not be the answer, unless there is better organization. Identification of infected individuals and a vigorous education program must be implemented. HIV antibody-positive individuals should be followed carefully in order to evaluate the risk factors for AIDS and efficacy of specific interventions.     

Self-sufficiency,free trade and safety

The relationship between free trade, self-sufficiency and safety of blood and blood components has been a perennial discussion topic in the blood service community. Traditionally, national self-sufficiency has been perceived as the ultimate goal that would also maximize safety. However, very few countries are, or can be, truly self-sufficient when self-sufficiency is understood correctly to encompass the whole value chain from the blood donor to the finished product. This is most striking when plasma derived medicines are considered. Free trade of blood products, or competition, as such can have a negative or positive effect on blood safety. Further, free trade of equipment and reagents and several plasma medicines is actually necessary to meet the domestic demand for blood and blood derivatives in most countries. Opposing free trade due to dogmatic reasons is not in the best interest of any country and will be especially harmful for the developing world. Competition between blood services in the USA has been present for decades. The more than threefold differences in blood product prices between European blood services indicate that competition is long overdue in Europe, too. This competition should be welcomed but carefully and proactively regulated to avoid putting safe and secure blood supply at risk.     

Neisseria gonorrhoeae effectively blocks HIV‐1 replication by eliciting a potent TLR9‐dependent interferon‐α response from plasmacytoid dendritic cells

Clinical and epidemiological research provides evidence for a positive correlation between Neisseria gonorrhoeae infection and HIV transmission; however, mechanistic studies examining this relationship have yielded conflicting results. To explore this interaction, we exposed ex vivo cultured peripheral blood cells from acute HIV⁺ individuals to N. gonorrhoeae. Unexpectedly, we observed a profound inhibition in HIV‐1 replication in the ex vivo cultures, and this was recapitulated when peripheral blood mononuclear cells (PBMCs) from healthy donors were co‐infected with HIV‐1 and N. gonorrhoeae. Next, we established that gonococcal‐infected PBMCs liberated a soluble factor that effectively blocked HIV‐1 replication. Cytokine analyses and antibody blocking experiments revealed that the type I interferon, interferon‐α (IFNα), was expressed upon exposure to N. gonorrhoeae and was responsible for the inhibition of HIV‐1. Intracellular staining, TLR9‐blocking and cell depletion‐based studies demonstrated that the IFNα was elicited by plasmacytoid dendritic cells (pDCs) in a TLR9‐dependent manner. The pDC response to N. gonorrhoeae was unexpected given pDCs more established role in innate defence against intracellular pathogens, suggesting this may be a bacterial immune evasion strategy. In the context of HIV, this overcomes the virus's otherwise effective avoidance of the interferon response and represents a previously unrecognized intersection between these two sexually transmitted pathogens.     

Randomized controlled trials of HIV/AIDS prevention and treatment in Africa: results from the Cochrane HIV/AIDS Specialized Register

Introduction

To effectively address HIV/AIDS in Africa, evidence on preventing new infections and providing effective treatment is needed. Ideally, decisions on which interventions are effective should be based on evidence from randomized controlled trials (RCTs). Our previous research described African RCTs of HIV/AIDS reported between 1987 and 2003. This study updates that analysis with RCTs published between 2004 and 2008.

Objectives

To describe RCTs of HIV/AIDS conducted in Africa and reported between 2004 and 2008.

Methods

We searched the Cochrane HIV/AIDS Specialized Register in September 2009. Two researchers independently evaluated studies for inclusion and extracted data using standardized forms. Details included location of trials, interventions, methodological quality, location of principal investigators and funders.

Results

Our search identified 834 RCTs, with 68 conducted in Africa. Forty-three assessed prevention-interventions and 25 treatment-interventions. Fifteen of the 43 prevention RCTs focused on preventing mother-to-child HIV transmission. Thirteen of the 25 treatment trials focused on opportunistic infections. Trials were conducted in 16 countries with most in South Africa (20), Zambia (12) and Zimbabwe (9). The median sample size was 628 (range 33-9645). Methods used for the generation of the allocation sequence and allocation concealment were adequate in 38 and 32 trials, respectively, and 58 reports included a CONSORT recommended flow diagram. Twenty-nine principal investigators resided in the United States of America (USA) and 18 were from African countries. Trials were co-funded by different agencies with most of the funding obtained from USA governmental and non-governmental agencies. Nineteen pharmaceutical companies provided partial funding to 15 RCTs and African agencies co-funded 17 RCTs. Ethical approval was reported in 65 trials and informed consent in 61 trials.

Conclusion

Prevention trials dominate the trial landscape in Africa. Of note, few principal investigators and funders are from Africa. These findings mirror our previous work and continue to indicate a need for strengthening trial research capacity in Africa.     

AIDS risk and prevention in transfusions

Transfusion of blood and blood products range from 2 to 8% of the cases of AIDS. The identification of HIV viral agent and the appearance of tests designed to detect antibodies associated with mechanisms of autologous transfusions and inactivation of virus of clotting factors concentrates have contributed to decrease this mean of transmission. Some aspects such as the difference of sensitivity in the tests, immunologic windows, and the appearance of new viruses such as the HIV 2 increase the complexity of the problem. Therefore, the services of hemotherapy all over the world must be aware of mechanisms of exclusion of potentially infected donors, in addition to education, and, mainly, the development of new techniques that can guarantee transfusion safety.     

Access to HIV Services at Non-Governmental and Community-Based Organizations among Men Who Have Sex with Men (MSM) in Cameroon: An Integrated Biological and Behavioral Surveillance Analysis

Background

Men who have sex with men (MSM) are more likely to be living with HIV than other adult men in low- and middle-income countries. MSM experience barriers to accessing HIV services including a lack of available specialized care, and community-level stigma and discrimination. This study aims to examine the uptake of HIV services at non-governmental and community-based organizations (NGOs/CBOs) to identify ways to improve coverage of HIV prevention and treatment among MSM.

Methods

An Integrated Biological and Behavioral Surveillance (IBBS) survey was conducted in Yaoundé and Douala, Cameroon in 2011 using the respondent driven sampling (RDS) method to recruit and interview 239 MSM in Yaoundé and 272 MSM in Douala.

Results

MSM in Yaoundé were statistically significantly more likely to have accessed NGO/CBO services or been reached by an outreach worker in the past 12 months if they had any STI symptoms (aOR 2.17 CI 1.02-4.59. p=0.04), or if they had a larger MSM social network (aOR 1.02 CI 1.01-1.04. p<0.01). MSM in Douala were more likely to have accessed NGO/CBO services or been reached by an outreach worker in the past 12 months if they were living with HIV (aOR 3.60 CI 1.35-9.60. p=0.01), or if they reported higher numbers of male sexual partners (aOR 1.17 CI 1.00-1.36. p=0.046). Compared to men in Douala, MSM in Yaoundé were significantly less likely to have accessed NGO/CBO services or been reached by an outreach worker in the past 12 months (aOR 0.22 CI 0 .14-0.34. p=<0.01).

Conclusions

With appropriate funding and resources, community-based organizations that provide care specifically for MSM can improve access to HIV prevention, treatment, and care services. Additionally, using social networks to reach MSM can connect greater numbers of the population to effective HIV interventions, which will improve health outcomes and decrease onward transmission of HIV.     

Funding policies for HIV and AIDS: time for change.

Funding for HIV and AIDS in England has been allocated to regions by a formula based on the number of cases of AIDS and HIV infection and on population size. Regions have distributed the resources directly to hospitals and community services. A survey of staff and managers in North East Thames region showed that funding arrangements have led to unsatisfactory development of services for HIV and AIDS. Firstly, because hospitals are funded according to current numbers of patients services are highly developed at the central London hospitals and underdeveloped in outer districts. Secondly, specialised community care teams have been established rather than integrating care for HIV and AIDS into generic primary care. Thirdly, the information on district of residence of infected patients is inaccurate, limiting allocation of funds according to population needs. Fourthly, prevention of infection has been given far less attention than treatment and care despite the lack of effective treatment. In future allocations for HIV and AIDS should be made to purchasers rather than directly to providers.