Didier Guillemot and colleagues describe the evaluation of a nationwide programme in France aimed at decreasing unnecessary outpatient prescriptions for antibiotics. The campaign was successful, particularly in reducing prescriptions for children. Streptococcus pneumoniae than any other European country. In 2001, the government initiated “Keep Antibiotics Working”; the program's main component was a campaign entitled “Les antibiotiques c'est pas automatique” (“Antibiotics are not automatic”) launched in 2002. We report the evaluation of this campaign by analyzing the evolution of outpatient antibiotic use in France 2000–2007, according to therapeutic class and geographic and age-group patterns.Overuse of antibiotics is the main force driving the emergence and dissemination of bacterial resistance in the community. France consumes more antibiotics and has the highest rate of beta-lactam resistance in This evaluation is based on 2000–2007 data, including 453,407,458 individual reimbursement data records and incidence of flu-like syndromes (FLSs). Data were obtained from the computerized French National Health Insurance database and provided by the French Sentinel Network. As compared to the preintervention period (2000–2002), the total number of antibiotic prescriptions per 100 inhabitants, adjusted for FLS frequency during the winter season, changed by −26.5%  over 5 years. The decline occurred in all 22 regions of France and affected all antibiotic therapeutic classes except quinolones. The greatest decrease, −35.8% (95% CI −48.3% to −23.2%), was observed among young children aged 6–15 years. A significant change of −45% in the relationship between the incidence of flu-like syndromes and antibiotic prescriptions was observed.The French national campaign was associated with a marked reduction of unnecessary antibiotic prescriptions, particularly in children. This study provides a useful method for assessing public-health strategies designed to reduce antibiotic use. Streptococcus pneumoniae (multidrug-resistant pneumococci or MRP) is now very common. S. pneumoniae colonize the nose and throat (the upper respiratory tract) and can cause diseases that range from mild ear infections to life-threatening pneumonia, particularly in young children and elderly people.In 1928, Alexander Fleming discovered penicillin, the first antibiotic (a drug that kills bacteria). By the early 1940s, large amounts of penicillin could be made and, in the following decades, several other classes of powerful antibiotics were discovered. For a time, it looked like bacteria and the diseases that they cause had been defeated. But bacteria rapidly became resistant to these wonder drugs and nowadays, antibiotic resistance is a pressing public-health concern. Almost every type of disease-causing bacteria has developed resistance to one or more antibiotic in clinical use, and multidrug-resistant bacteria are causing outbreaks of potentially fatal diseases in hospitals and in the community. For example, multidrug-resistant S. pneumoniae antibiotic resistance in Europe occurs in France, which has one of the highest rates of antibiotic consumption in the world. In 2001 France initiated “le plan national pour préserver l'efficacité des antibiotiques” to reduce the inappropriate use of antibiotics, particularly for the treatment of VRIs among children. The main component of the program was the “Antibiotiques c'est pas automatique” (“Antibiotics are not automatic”) campaign, which ran from 2002 to 2007 during the winter months when VRIs mainly occur. The campaign included an educational campaign for health care workers, the promotion of rapid tests for diagnosis of streptococcal infections, and a public information campaign about VRIs and about antibiotic resistance. In this study, the researchers evaluate the campaign by analyzing outpatient antibiotic use throughout France from 2000 to 2007.For years, doctors have been prescribing (and patients have been demanding) antibiotics for viral respiratory infections (VRIs) such as colds and flu even though antibiotics do not cure viral infections. This overuse of antibiotics has been the main driving force in the spread of MRP. Thus, the highest rate of The researchers obtained information about antibiotic prescriptions and about the occurrence of flu-like illnesses during the study period from the French National Health Insurance database and national disease surveillance system, respectively. After adjusting for variations in the frequency of flu-like illnesses, compared to the preintervention period (2000–2002), the number of antibiotic prescriptions per 100 inhabitants decreased by a quarter over the five winters of the “Antibiotics are not automatic” campaign. The use of all major antibiotic classes except quinolones decreased in all 22 regions of France. Thus, whereas in 2000, more than 70 prescriptions per 100 inhabitants were issued during the winter in 15 regions, by 2006/7, no regions exceeded this prescription rate. The greatest decrease in prescription rate (a decrease of more than a third by 2006/7) was among children aged 6–15 years. Finally, although the rates of antibiotic prescriptions reflected the rates of flu-like illness throughout the campaign, by 2006/7 this relationship was much weaker, which suggests that fewer antibiotics were being prescribed for VRIs.S. pneumoniae vaccine during the study period, for example. However, an independent survey indicated that fewer members of the public expected an antibiotic prescription for a VRI at the end of the campaign than at the start, that more people knew that antibiotics only kill bacteria, and that doctors were more confident about not prescribing antibiotics for VRIs. Thus, campaigns like “Antibiotics are not automatic” may be a promising way to reduce the overuse of antibiotics and to slow the spread of antibiotic resistance until new classes of effective antibiotics are developed.These findings indicate that the “Antibiotics are not automatic” campaign was associated with a reduction in antibiotic prescriptions, particularly in children. Because the whole French population was exposed to the campaign, these findings do not prove that the campaign actually caused the reduction in antibiotic prescriptions. The observed decrease might have been caused by other initiatives in France or elsewhere or by the introduction of a http://dx.doi.org/10.1371/journal.pmed.1000084.Please access these Web sites via the online version of this summary at PLoS MedicinePerspective by Stephen Harbarth and Benedikt HuttnerThis study is further discussed in a Bugs and Drugs Web site from the UK National electronic Library of Infection provides information about antibiotic resistance and links to other resourcesThe antimicrobial drug resistance and on pneumococcal pneumoniaThe US National Institute of Allergy and Infectious Diseases provides information on US Centers for Disease Control and Prevention also have information on antibiotic resistance (in English and Spanish)The European Surveillance of Antimicrobial Consumption Web site provides information on antibiotic consumption in European countriesThe Les antibiotiques c'est pas automatique provides information about the “Antibiotics are not automatic” campaign (in French)Plan National pour Pérserver l'efficacité des antibiotiques is also available (in French)Information on the  The emergence and the dissemination of drug-resistant bacterial strains make treatment decisions challenging and may be associated with treatment failures. This phenomenon has become a major public health issue.Streptococcus pneumoniae is the most commonly identified bacterial cause of community-acquired invasive infections and pneumonia Very few new antimicrobial drugs are expected to become available in the near future, and several studies support the notion that antibiotic consumption is a key driving force in the rate  of beta-lactam–resistant pneumococci In the early 2000s, France, a country with nearly 62,000,000 inhabitants and nearly 54,000 general practitioners, faced growing problems with MRP, with >50% of strains showing decreased penicillin G susceptibility. France was also identified as the country with the highest antibiotic consumption in Europe In this article we evaluate the effectiveness of these campaigns by analyzing the evolution of outpatient antibiotic use in France from 2000 to 2007, for each therapeutic class, as well as by geographic and age-group patterns. We performed a time-series analysis and accounted for flu-like syndrome (FLS) variations.In 2002 the French National Health Insurance (NHI) launched a long-term nationwide campaign in the community. From its conception, the aim of the campaign was to decrease total antibiotic use in the community by 25%, targeting predominantly VRIs in young children. An extensive information dissemination campaign was developed with the central theme “Antibiotics are not automatic.” Each winter (October–March) it is relaunched, as higher levels of infections and prescriptions occur during this period. A description of the campaign is detailed in The NHI program covers all medical care provided by physicians in private practice, community clinics, and hospitals. Patients pay health service fees, which are refunded by the NHI. In France, everyone, even those with low or no income, are covered by the NHI program. We used anonymous computerized individual data from two main NHI agencies , which cover salaried workers and the self-employed (≥91% of the French population), to access all antibiotics prescribed, dispensed by outpatient pharmacies, and reimbursed by NHI from 2000 to 2007 . Each drug approved by the French Drug Agency is assigned a unique seven-digit code that enables identification of a particular product and its specific dosage, package size, formulation, and manufacturer. Each file contains this drug-related information, prescription date, patient's sex, year of birth, and region of residence.http://sentiweb.org/). According to the French Sentinel Network, FLS is defined as the combination of the following clinical symptoms: sudden onset fever ≥39°C, myalgia, and respiratory symptoms such as dyspnea and/or cough. Demographic data were obtained from the French National Institute for Statistics and Economic Studies .Weekly FLS incidence was provided by the French Sentinel Network We included the European part of France (henceforth referred to as France), which accounts for 83% of French territory and 96% of its population. For each of France's 22 administrative regions, reimbursement data were extrapolated to 100% of the regional population by dividing the number of prescriptions by the corresponding region's NHI coverage rate. The results are presented as the weekly rate of antibiotic prescriptions per 100 inhabitants.The study concerns antibiotics for systemic use  in the community. Antibiotics were divided into six categories according to the ATC classification: penicillins, cephalosporins, macrolides, quinolones, cyclines, and “other.”n and finishing at week 13 of year n+1. We conducted time-series analyses to quantitatively evaluate the impact of the successive, annual campaigns on antibiotic consumption. We used intervention models Our analysis describes the crude number of antibiotic prescriptions and FLS incidence over time, overall, and by region, antibiotic class, and age group . We focused on the period targeted by the public service campaign (October–March); more specifically, we examined the truncated series corresponding to a 26-wk period starting at week 40 of year The intervention models were built in two steps. For the first step, we chose the 2000–2002 period preceding the first campaign, i.e., starting at week 27 in 2000 and ending at week 40 in 2002, as the baseline and fitted a model to the series of antibiotic prescriptions accounting for seasonal variations and underlying autoregressive and moving average processes. As in other southern and eastern European countries For the second step, we assumed that observations before and after the campaign were drawn from the same ARMA model with changes only in the mean. Following this assumption, we removed the previously estimated periodic trigonometric function from the whole antibiotic prescription series (2000–2007) and added five dummy variables, one for each annual campaign, to the ARMA model identified in step 1 so that only the mean could change. We quantified the impact of each campaign as the average relative change for the period (from winter 2002–2003 to winter 2006–2007) compared with baseline (2000–2002); that is, the ratio of the observed change over the expected change predicted from the model had there been no campaign. The same procedure was repeated after dividing the population into three age categories  as well as considering data of the summer period (April–September) and data of the entire year (October–September).Finally, we further adjusted the intervention model for the whole population for FLS incidence. We tested the hypothesis of a different link between antibiotic consumption and FLS incidence before and after the start of the 2002 campaign by introducing an interaction term in the model.http://www.sas.com/). All statistical tests were two-tailed; a p-value of less than 0.05 was considered significant.Analyses were performed using SAS version 9.1 , we combined their data.Antibiotic prescriptions and FLS fluctuated seasonally, with higher incidence rates during winter months . MaximalThe mean number of prescriptions per 100 inhabitants for the general population was 72.4 for the 2000–2001 and 2001–2002 winters; this figure gradually decreased to 56.6 during the 2006–2007 season .Variations in antibiotic use were observed among France's 22 administrative regions. Antibiotic consumption declined in all regions between 2001–2002 and 2006–2007 . In 2000Penicillins, cephalosporins, and macrolides were the three most used antibiotic classes at baseline, with 27.0, 16.3, and 16.4 prescriptions per 100 inhabitants; their use also declined the most  among all antibiotic classes. Quinolones, which remain a less frequently prescribed antibiotic class (4.2 prescriptions per 100 inhabitants at baseline), was the only class whose use increased (+12.8%) .For children <6 y old, the average number of prescriptions per 100 children declined from 193.3 in 2001–2002 to 128.7 in 2006–2007. For 2- and 3-y-old children, this figure decreased from ∼250 to ∼150. A substantial reduction of antibiotic use was also observed for children 6–15 y old and young adults 26–35 y old .Three factors led us to consider 2 y of preintervention data as sufficient to correctly estimate modifications after 2002: (1) the stability of the estimated ARMA model parameters for the 2000–2007 period as compared with 2000–2002, (2) the assessment of Gaussian white noise residuals, and (3) the good fit of the one-step-ahead forecasts of the interrupted ARMA model with observed antibiotic prescriptions . Estimatp<0.0001). However, a significant decrease of 45% in the linear regression coefficient between FLS incidence and antibiotic prescriptions was observed after the first campaign . After controlling for the influence of the FLS incidence rate, we observed a −26.5% (95% CI −33.5% to −19.6%) change in winter antibiotic consumption for the total population, a decrease similar to that obtained without controlling for the FLS incidence rate. Including four dummy variables in the model for the April–September period did not show any clear change during summer. From 2003 to 2005, rate changes ranged between −3% to −5%, but were not significant. In 2006, an estimated decrease of −8.5% was marginally significant (p = 0.08).As expected, the FLS incidence rate was significantly associated with the weekly rate of antibiotic prescription  of winter antibiotic prescriptions in France; the reduction was consistent across all age groups and all 22 regions, as well as across the most frequently used therapeutic classes. The initial objective of the “Keep Antibiotics Working” program to reduce antibiotic use in the community by 25% was reached in 5 years.http://www.esac.ua.ac.be) program collects data on antimicrobial consumption in ambulatory care and hospital settings from 34 European countries' national surveillance systems and publishes a yearly report The impact of educational campaigns aimed at decreasing antibiotic prescriptions by preventing antibiotic misuse at the population level has rarely been evaluated. In Europe the European Surveillance of Antimicrobial Consumption . This change may be due to the use of rapid tests to diagnose group A streptococci tonsillitis, which was promoted by the campaign in this age group, which is at a higher risk of group A streptococci throat infections.Antibiotic consumption changed by −24.1% among young adults (26–35 y), who were initially the biggest antibiotic consumers among adults. Demographic characteristics of this population suggest that most parents of young children fall within this age category; as a result, it is likely that young adults have been specifically affected by the campaign. Finally, prescriptions in the 21–25 y age group remained stable from 2000 to 2007 (as compared to decreases observed in older and younger age groups). Two hypotheses may explain this observation. First, 21- to 25-y-old adults are less likely to live in or interact with collective institutions  or be in close contact with children than other age groups; as a result, they are less likely to be exposed to VRIs, which are typically spread by young children. Second, it may be difficult to further decrease antibiotic use in this age group, as they already represent the age group with the lowest antibiotic prescription rate before the campaign.While crude results did not differ markedly from those adjusted for FLS fluctuations, accounting for the latter was crucial to the interpretation of the changes recorded. Indeed, in many countries, VRIs account for a high share of unnecessary antibiotic prescriptions. Our intervention model highlighted a significant weakening of the association between FLS incidence rates and antibiotic prescriptions after the second yearly campaign. This observation suggests that the fraction of antibiotics prescribed for viral illnesses has significantly decreased, which is a highly encouraging result, as one of the campaign's main objectives was to reduce VRI-associated antibiotic overuse. However, the association between FLS and antibiotic prescriptions persists, at a low level, even after the campaign.Several limitations of this study should be noted. First, due to the quasiexperimental design  and limited preintervention data, a cause–effect relationship between the campaign “Antibiotics are not automatic” and decreased antibiotic use cannot be proved. For example, the influence of the antibiotic campaigns in other geographically proximate European countries such as Belgium cannot be excluded. Some southern European countries also conducted campaigns during the 2002–2007 period  and observed evolution of outpatient antibiotic use Second, we did not have access to information about the pathology for which antibiotics had been prescribed. In France, no information system exists that provides easy access to data linking drug use to a clinical condition.Third, we did not account for the introduction of the 7-PCV in our analysis. The 7-PCV initially received marketing authorization in France in 2002, specifically for children presenting specific risk factors. It became widely used only at the end of 2006, once it had been recommended for all children <2 y old (unpublished data). It is thus unlikely that its market introduction could explain much of the decreased antibiotic use observed over the 5-year investigation period.Fourth, FLS surveillance data do not account for other VRIs such as infections due to respiratory syncytial virus, which generally occur several weeks before a flu outbreak. It was not feasible to account for these viral infections, as surveillance data of these infections are not available in France. As a result, it is likely that we underestimated the association between community viral infection and antibiotic prescription.http://www.gepie.org/). The added value of such initiatives was not specifically investigated.Fifth, other local initiatives were promoted in France since 2000, such as the campaign “Antibiotics Only When Necessary” promoted in a county in southeastern France . Because our campaign did not target any specific therapeutic class, it may have prevented interclass switching. Nevertheless, a slight increase of quinolone prescriptions occurred. Although this was a moderate increase compared to large decreases recorded for all other classes, this trends points to the need for careful monitoring of quinolone-resistant bacteria in the community In France from 2001 to 2006, a decreasing trend was observed in the rate of pneumococci resistant to penicillin (47% to 32% of isolates) and the rate of pneumococci resistant to macrolides (49% to 36%) in France Click here for additional data file.


Infectious diseases remain a major health and socioeconomic problem in many low-income countries, particularly in sub-Saharan Africa. For many years, the three most devastating diseases, HIV/AIDS, malaria, and tuberculosis (TB) have received most of the world's attention. However, in rural and impoverished urban areas, a number of infectious diseases remain neglected and cause massive suffering. It has been calculated that a group of 13 neglected infectious diseases affects over one billion people, corresponding to a sixth of the world's population. These diseases include infections with different types of worms and parasites, cholera, and sleeping sickness, and can cause significant mortality and severe disabilities in low-income countries. For most of these diseases, vaccines are either not available, poorly effective, or too expensive. Moreover, these neglected diseases often occur in individuals who are also affected by HIV/AIDS, malaria, or TB, making the problem even more serious and indicating that co-infections are the rule rather than the exception in many geographical areas. To address the importance of combating co-infections, scientists from 14 different countries in Africa and Europe met in Addis Ababa, Ethiopia, on September 9–11, 2007. The message coming from these scientists is that the only possibility for winning the fight against infections in low-income countries is by studying, in the most global way possible, the complex interaction between different infections and conditions of malnourishment. The new scientific and technical tools of the post-genomic era can allow us to reach this goal. However, a concomitant effort in improving education and social conditions will be needed to make the scientific findings effective. Mycobacterium ulcerae), cholera (Vibrio cholerae), cysticercosis, dracunculiasis (Guinea worm), trematodal infections, hydatidosis, leishmaniasis, lymphatic filariasis (elephantiasis), onchocerciasis (river blindness), schistosomiasis, helminthiasis, trachoma (Chlamidia trachomatis), and trypanosomiasis , affect over one billion people (corresponding to a sixth of the world's population) Infectious diseases remain a major health and socioeconomic problem in many low-income countries, particularly in sub-Saharan Africa. Most of the public attention has so far been devoted to the three most devastating diseases, HIV/AIDS, malaria, and tuberculosis (TB). However, in rural and impoverished urban areas of low-income countries, a number of neglected infectious diseases (NIDs) cause massive suffering, although they receive little or no scientific or mass-media attention Amongst the numerous specific research programmes launched by several national and international organisations to understand and confront the burden of HIV/AIDS, malaria, and TB, little has been done to specifically address the complex issue of immunity during co-infections with the three major killers and NIDs. So far, it is mainly the European Commission (EC) that has recognised the need to pursue an active research policy for developing new or improved prophylactics and treatments for infectious diseases, including new vaccines and drugs for NIDs, keeping this research area alive in the face of declining national support. While the 6th Framework Programme (FP6) of the EC mainly addressed translational research for HIV/AIDS, malaria, and TB, the new 7th Framework Programme  will also include NIDs To address the increasing importance of co-infections, scientists from 14 different countries in Africa and Europe met in Addis Ababa, Ethiopia, on September 9–11, 2007, to identify and prioritise research gaps in this area. The meeting was convened by two ongoing EC-funded initiatives, namely the MUVAPRED integrated project and the BIOMALPAR network of excellence, and gathered high-level scientists, clinicians, and industrial expertise, as well as representatives from the EC and WHO/TDR. This report summarises the consensus of the expert group, which took the name of AFRIEND (African-European Partnership for Neglected Infectious Diseases). It is envisaged that this document could foster a debate in the scientific community and provide recommendations on future actions by the EC and WHO/TDR in the area of co-infections and NIDs.It is of key importance to focus future research on a detailed understanding of the mechanisms of immunity to pathogens during co-infections between HIV/AIDS, malaria, and TB, and NIDs. This information will be highly relevant for the development of new preventive and therapeutic interventions for use in impoverished areas of disease-endemic countries. Indeed, multiple infections, nutritional status, and level of exposure to microbial/parasitic compounds can alter the reactivity of the immune system in such a way that vaccines may need new/novel formulations. Research priorities should focus on immunological studies in humans, preceded and supported by experimentation on suitable animal models, and should include the following key areas.Identification of correlates of protection is of major importance for the development of new effective preventive/therapeutic strategies. Although some progress has been made to identify correlates of protection, much more intensive funding and research are needed to tackle this complex and central area of investigation. Indeed, to date, no convincing correlates of protection have been yet identified for HIV/AIDS, malaria, TB, or NIDs.+ and CD4+ T cells, antibody-producing B cells, neutralising antibodies). More recently, it has become clear that early triggering of innate immune mechanisms can also represent an important determinant of protective immunity. Assays to measure these immune responses are expensive and technically demanding. Therefore, in the search for reliable correlates of protection, priority should be given to the development of simplified, standardised, and low-cost assays.As a general assumption, the main correlates of protection in human infections are represented by the presence of pathogen-specific effector cells/molecules  2-type cytokine profile, upregulated regulatory T cell activity, and chronic immune activation. All of these are factors that may have adverse effects on the outcome of subsequent infections and vaccinations. In support of this, studies conducted in animals and humans living in worm-endemic areas have shown that helminths impair resistance against a number of infections, including HIV/AIDS, malaria, and TB Leishmania infection. However, the complexity of the issue is underlined by the notion that iron deficiency and malnourishment can protect children against severe malaria Infections in poor communities occur in a setting where the population is exposed to several environmental and social conditions that could influence the immune response to pathogens. These include chronic hunger, micronutrient deficiency, multiple pregnancies, etc. Although the relationship between nutrition and immunity is complex, it is clearly established that nutrient deficiencies can severely impair the immune response. Studies in animal models show an association between malnourishment and disseminated disease development after The role of genetic differences in the susceptibility of African populations to HIV/AIDS, malaria, TB, and NIDs has not yet been extensively studied. The significance of host genetic background in disease outcome can be exemplified by the well-known protective effect of the sickle cell trait against malaria in Africa. A number of reports have demonstrated the role of chemokine receptor variants in preventing, delaying, or accelerating progression of HIV infection to AIDS In view of the fact that reactivity of the immune system can be altered in circumstances of multiple infections, malnutrition, and other conditions, novel vaccine formulations able to stimulate protective immunity in states of altered responsiveness should be considered. The development of safe, potent vaccine adjuvants that enhance and direct vaccine-specific immunity is a crucial issue for all new vaccines for human use. Recent advances in immunological research, especially with regard to innate immunity, has resulted in a number of potent adjuvant candidates that can modulate immune responses in a more controlled and specific manner Additional research is necessary to understand the mechanisms of immune protection and memory during co-infection with HIV/AIDS, malaria, TB, and NIDs. The AFRIEND consensus meeting identified seven key areas with research gaps, where more attention is needed:Correlates of protectionMechanisms of infection and immunity at local sitesImmunological memoryImpact of co-infection on the outcome of HIV/AIDS, malaria, TB, and NIDsImpact of non-infectious agents on the outcome of HIV/AIDS, malaria, TB, and NIDsHost genetics and the outcome of HIV/AIDS, TB, malaria, and NIDsNovel adjuvants and their modes of action, and novel vaccine formulationsThis list is not in order of priority, as all of these issues should be tackled concomitantly, in order to obtain effective outcomes. Global coordination and harmonisation of efforts therefore are of key importance.To achieve these goals it will be essential to put in place a sustainable network between researchers in disease-endemic countries and researchers in the developed world, which together will implement an integrated immunological research effort across disciplines and diseases. This needs to include promotion of high-level training pathways for African researchers and sustaining their careers in African institutions. All of this will require consensus and support both at the political and social level in low-income countries.In fact, no scientific achievement, however relevant, could succeed in being applied without a proper context of social acceptability, feasibility, and affordability in low-income countries. Thus, research and development of vaccines and therapies for HIV/AIDS, malaria, TB, and NIDs must go together with capacity building, local empowerment, and social awareness.Alternative Language Abstract S1Translation of the Author Summary into Arabic by Marita Troye-Blomberg(0.04 MB DOC)Click here for additional data file.Alternative Language Abstract S2Translation of the Author Summary into Danish by T. Mark Doherty(0.03 MB DOC)Click here for additional data file.Alternative Language Abstract S3Translation of the Author Summary into French by Marita Troye-Blomberg(0.03 MB DOC)Click here for additional data file.Alternative Language Abstract S4Translation of the Author Summary into German by Andreas Thiel(0.03 MB DOC)Click here for additional data file.Alternative Language Abstract S5Translation of the Author Summary into Hungarian by Tamás Laskay(0.04 MB DOC)Click here for additional data file.Alternative Language Abstract S6Translation of the Author Summary into Italian by Diana Boraschi(0.03 MB DOC)Click here for additional data file.Alternative Language Abstract S7Translation of the Author Summary into Portuguese by Marita Troye-Blomberg(0.03 MB DOC)Click here for additional data file.Alternative Language Abstract S8Translation of the Author Summary into Spanish by Marita Troye-Blomberg(0.04 MB DOC)Click here for additional data file.Alternative Language Abstract S9Translation of the Author Summary into Swahili by Thomas Kariuki(0.03 MB DOC)Click here for additional data file.Alternative Language Abstract S10Translation of the Author Summary into Swedish by Marita Troye-Blomberg(0.04 MB DOC)Click here for additional data file.


A major deficit of all approaches to epidemic modelling to date has been the need to approximate or guess at human behaviour in disease-transmission-related contexts. Avatars are generally human-like figures in virtual computer worlds controlled by human individuals.We introduce the concept of a "havatar", which is a  pairing. Evidence is mounting that this pairing behaves in virtual contexts much like the human in the pairing might behave in analogous real-world contexts.We propose that studies of havatars, in a virtual world, may give a realistic approximation of human behaviour in real-world contexts. If the virtual world approximates the real world in relevant details , virtual epidemics in that world could accurately simulate real-world epidemics. Havatar modelling of epidemics therefore offers a complementary tool for tackling how best to halt epidemics, including perhaps HIV/AIDS, since sexual behaviour is a significant component of some virtual worlds, such as Second Life.Havatars place the control parameters of an epidemic in the hands of each individual. By providing tools that everyone can understand and use, we could democratise epidemiology. Ever since we discovered that mosquitoes transmit malaria, we have sought points of control, from eradication of mosquito larvae, to screening of windows and beds, to the development of vaccines, to more abstract points of control, such as keeping the reproductive rate of an epidemic, R below 1 . While f below 1 , "HIV-va below 1 , so thatEpidemiology modelling has generally followed two major approaches: the continuous and the discrete. In the continuous (deterministic) approach, we use differential or partial differential equations, characterised by lumped or aggregated variables and presumed constants relating them. We try to predict the variables, such as the number of susceptible or infected people, given constants, such as the rate of transmission ,6. In thStochastic process modelling  represenCertain control points, i.e., parameters that we think we can manipulate to alter the course of an epidemic, are evident with HIV/AIDS. For example, it has long been known that HIV/AIDS could be significantly controlled with condoms, if only we could get enough people to use them -21. ThaiTwo observations, however, make the multiple control point approach dubious . First iThe second doubt  about thIn a way, these efforts to refine different models make them approach one another. We discretise the continuous approach, by subdividing aggregated parameters, or smooth the discrete approach, by looking at the overall behaviour of networks, their so-called emergent features. But do they thereby better approximate the real world?While we try to empower people through education, stigma reduction, harm reduction, free condoms, needle exchange programs, etc., the role of the individual in halting the HIV/AIDS epidemic is basically passive with these approaches. We somehow hope that when they choose a mate, engage a sex worker, etc., individuals will modify their behaviour in a way that reduces or eliminates their contribution to the dynamics of the epidemic. When they fail to do as we hope, we attribute this to inadequate education or empowerment, or the heat of the moment. We expect that, somehow, our grand view of the epidemic, as professional epidemiologists or modellers, will influence individuals' behaviours and thus affect parameters such as the rate of transmission. Analogous to the continuum between the discrete and the continuous in our models, however, the socio-cultural "view" of the epidemic ranges from the local one of the individual in the epidemic, to that of the global view of scientists, mathematicians, health economists and epidemiologists who actually deal with a lumped or aggregated conceptualization of the epidemic. Even when they are successfully communicated, faith in different views of the epidemic is rarely shared between all concerned. People have different priorities and relate differently to the need for behavioural change - ultimately underpinned by differences in valuations of life and death itself. The consequences are not trivial. The success of science in understanding HIV/AIDS has relied heavily on the willing co-operation of individuals whose view of the epidemic cannot prevent them from interacting with it, such as sex workers and intravenous drug users.All epidemic modelling to date approximates and second-guesses human behaviour. We would like to propose an alternative way to model HIV/AIDS, that lets each individual person decide on the control parameters for their life, and which makes their actual behaviour part of the modelling. Our suggestion is an old approach, what used to be called "enlightened self-interest" . It assuWe start with the observation that, in certain virtual worlds, which appear to be those where the participants construct the rules of engagement with one another themselves, there seems to be a correlation between the personality of a person's avatar  and theiIn adult virtual worlds, as in the internet itself, a significant fraction of the interactions between havatars is sexual . HIV/AIDBeyond this, each individual has the opportunity of seeing the epidemic at any scale, through statistics gathered by the computer program running the virtual world, creation of maps, communication with and knowledge about other havatars, and by being allowed to run computer simulations of the epidemic themselves. For example, in Second Life, one can examine the profile of any havatar, which includes the names of the groups they belong to, and decide whether or not to become "friends" with them. Such textual, quantitative and visual tools can provide people with objective criteria that relate their own behaviour to an epidemic, and give them opportunities to change that behaviour to avoid being part of it.Havatars thus present the possibility of a bottom-up approach to epidemic control. They are already being used to plan for emergencies caused by epidemics ,43, so wHavatars could be used by epidemiological modellers in a variety of ways. The simplest would be to unleash simulated viruses that can infect avatars, are invisible, have no effects, but whose transmission from one havatar to another can be monitored. This has a large advantage over real-life networks in that the latter require tremendous amounts of fieldwork to uncover. Furthermore, such fieldwork might itself alter the social network. Details of where, when, what acts, and with whom have the general unreliability of self-reporting; fieldwork at best gives a snapshot of a dynamic system, while in a virtual world all this data could be made available on a continuous basis. Waivers that allow tracking of all transactions were signed by all 13 million Second Life participants  when theThe research on havatars that we propose raises questions of privacy, ethics and informed consent that are unresolved as of now, but it has been suggested that the general difficulty of a person knowing which other real life person corresponds to a given havatar may keep these problems at bay .The next level of havatar epidemiology research would be to create consequences of disease transmission. In virtual worlds, people react to parameters at many levels, and have the opportunity to grasp a situation as a whole . This isFor an HIV/AIDS simulation, we could envision more drastic consequences for havatars, with permission of their human components. For example, most people design their avatars to look good. Simulated HIV/AIDS might make them look ghastly, with weight loss, etc., cause them to interrupt their behaviour to take antiretroviral drugs, or even get too sick to do much and die. This might lead to stigma, formation of ALWA groups (Avatars Living With AIDS), etc. Analogous avatar effects have been simulated for neurological conditions . EconomiThe third level of epidemiological research would fully cross the virtual world/real-world boundary. This is already being done with computer-controlled sex toys that can be controlled by other havatars , and couWhether havatar sex will have an impact on HIV transmission between real humans is of course not yet known. When one havatar encounters another, they can examine each other's "profiles", which include, for example, listings of the groups they belong to. The record could show simulated HIV status as one of the consequences in the virtual world. Attempts to do anything similar in the real world are limited so far. Sex clubs and pornography actors have tried to restrict membership to HIV-free people, and a few cases of failure to divulge one's HIV status have hit the courts, but how this plays out in daily life is uncertain, and obviously of insufficient impact to halt the HIV/AIDS epidemic. Transferring codes of ethics developed in virtual worlds to real life is problematic, though even in the freewheeling atmosphere of Second Life, the reverse has already occurred in terms of gambling and banking . HoweverIt will be argued against this approach that the cost of Internet access is beyond the poor populations of the world where HIV/AIDS flourishes most, and that the havatar population is thus a biased sampling of the human population. However, if we consider the rate of adoption of cell phones  or progrhttp://www.mitacs.math.ca/ OptAIDS Workshop July 29, 2008 in Toronto. The goal, WHAM, the World Halting AIDS Model, [This paper is part of an effort to develop a worldwide model of the HIV/AIDS epidemic and how to control and stop it, beginning with the MITACS S Model, ,61 mightThe aim of epidemiological modelling has always been to gain control of epidemics. HIV/AIDS is an epidemic that is very much depends on the decisions made by individuals. Controlling them, telling people what to do for their own or the greater, common good, has proven to be a difficult and sometimes thankless task. Perhaps what we need to do is examine the relationship between the modeller and those modelled. Havatars give us an opportunity to reverse that relationship and place the control parameters in the hands of each individual. The modeller can enable this democratisation of epidemiology by providing tools for global and other perspectives that everyone can understand and use.The authors declare that they have no competing interests.RG wrote the first draft. All authors read and approved the final manuscript.


Staff shortages could harm the provision and quality of health care in Uganda, so staff retention and motivation are crucial. Understanding the impact of HIV/AIDS on staff contributes to designing appropriate retention and motivation strategies. This research aimed 'to identify the influence of HIV/AIDS on staff working in general hospitals at district level in rural areas and to explore support required and offered to deal with HIV/AIDS in the workplace'. Its results were to inform strategies to mitigate the impact of HIV/AIDS on hospital staff.A cross-sectional study with qualitative and quantitative components was implemented during two weeks in September 2005. Data were collected in two government and two faith-based private not-for-profit hospitals purposively selected in rural districts in Uganda's Central Region. Researchers interviewed 237 people using a structured questionnaire and held four focus group discussions and 44 in-depth interviews.HIV/AIDS places both physical and, to some extent, emotional demands on health workers. Eighty-six per cent of respondents reported an increased workload, with 48 per cent regularly working overtime, while 83 per cent feared infection at work, and 36 per cent reported suffering an injury in the previous year. HIV-positive staff remained in hiding, and most staff did not want to get tested as they feared stigmatization. Organizational responses were implemented haphazardly and were limited to providing protective materials and the HIV/AIDS-related services offered to patients. Although most staff felt motivated to work, not being motivated was associated with a lack of daily supervision, a lack of awareness on the availability of HIV/AIDS counselling, using antiretrovirals and working overtime. The specific hospital context influenced staff perceptions and experiences.HIV/AIDS is a crucially important contextual factor, impacting on working conditions in various ways. Therefore, organizational responses should be integrated into responses to other problematic working conditions and adapted to the local context. Opportunities already exist, such as better use of supervision, educational sessions and staff meetings. However, exchanges on interventions to improve staff motivation and address HIV/AIDS in the health sector are urgently required, including information on results and details of the context and implementation process. HIV/AIDS has an impact on health sector workers in various ways. It increases fear of infection at work, changes or increases tasks and workload, and increases the emotional burden and stress levels of health workers -3. HowevThe Ugandan health sector is the main provider of HIV/AIDS-related services for a population of about 29 million people. The HIV prevalence rate is 6.7 per cent among adults 15–49 years) and about 900,000 adults and 110,000 children (0–14 years) live with HIV [–49 yearsRetention of health workers is linked to job satisfaction, which is influenced by various factors such as physical working conditions, relationships with colleagues and managers, pay, promotion, job security, and responsibility, although priorities will differ in different contexts . Job satPublished studies about the impact of HIV/AIDS on the health sector and its workers in low-income countries focus mostly on occupational hazards ,11 and oStudies in Uganda -30 have At the time of the study Uganda had 56 districts, served by government, private for-profit and private not-for-profit (PNFP) health facilities. There were 10 regional referral hospitals and 45 district hospitals run by the government. PNFP facilities accounted for 43 per cent of the hospitals and 24 per cent of the lower health care facilities, mostly in rural areas. Many of the PNFP facilities provided health services and trained health workers, and 78 per cent of these facilities were faith based .This article describes the results of a study exploring the effects of HIV/AIDS on hospital staff and organizational responses to mitigate these effects in four different general hospitals in rural districts of the Central Region in Uganda. The study aimed 'to identify the influence of HIV/AIDS on staff working in general hospitals at district level in rural areas and to explore support required and offered to deal with HIV/AIDS at the workplace'.The study design was exploratory and cross-sectional and consisted of a quantitative and a qualitative component. It intended to answer the following research question:▪ What are the perceptions of hospital managers and staff regarding the effects of HIV/AIDS at their workplace?▪ What are the current overall working conditions in the selected hospitals?▪ What are the current support measures offered and required in the selected hospitals to assist staff in dealing with HIV/AIDS at work?▪ Are hospital staff motivated to work, and to what extent does HIV/AIDS influence staff motivation?No standard theoretical framework for the impact of HIV/AIDS on hospital staff exists in the literature, therefore the research team developed its own framework. Our main hypothesis was that staff would be discouraged from working because of low motivation and stress, which are influenced by HIV/AIDS and by general working conditions, and that this would contribute to low performance of health systems. According to Chen et al (2004), enhancing the performance of health systems requires, in addition to adequate financial and material resources, workforce objectives on coverage, competence and motivation . Staff mFour general hospitals in rural districts were selected purposively, as these were the facilities that provided most HIV/AIDS services close to the population. Purposive sampling is a sampling method used in qualitative research to select 'a limited number of informants strategically so that their in-depth information will give optimal insight into an issue about which little is known (: p.199).For the survey, the quantitative component of our study, quota sampling took place, recruiting an appropriate number (quota) in each category of health staff, maintaining a proportional representation of health staff in the sample. Quota sampling means that a quota is set for each attribute , and the quotas are set 'so that they represent together the known distribution of the control attributes across the known population (: p.37).'Respondents for the qualitative component were recruited purposively, using maximum variation sampling. In each hospital, four managers, six health workers from different departments and one or two support staff were selected. Health workers were selected for interviews from among those with experience in working with HIV/AIDS patients, with implementing HIV/AIDS-related tasks and general caring tasks. If a person was not available, either a new appointment was made or another person with similar tasks was selected. Support staff were interviewed according to their availability. In total, 44 respondents were interviewed, and 25 respondents participated in four focus group discussions.Quantitative data were collected by research assistants who had experience in conducting interviews and who were trained on the background of the study and the research questions. Data were collected through interviews, using a structured questionnaire. Questions were asked about infection control guidelines, availability and use of protective materials, treatment and disposals of sharps, perceived risk of HIV infection at work, occurrence of injuries, and support offered and used to prevent and deal with HIV infection. Additionally, questions were asked about working conditions, supportive supervision, training in HIV/AIDS tasks, and staff motivation. Data were collected during a period of two weeks in September 2005.Qualitative data were collected by experienced researchers through in-depth interviews and focus group discussions, using a topic guide. Open questions were asked about the impact of HIV/AIDS on work, dealing with HIV/AIDS at work, and support required and offered by the hospital. Questions were also asked about general working conditions and staff motivation.Quantitative data were analysed with Epi-info 6.1 and Stata 9.2, using non-parametric tests  for descriptive analyses. Assuming that the members of staff working in a particular hospital were not completely independent, Generalized Estimated Equation (GEE) models were used to determine independent factors associated with not being motivated. Motivation was dichotomized: 'not being motivated' included the categories: indifferent, discouraged and very discouraged, and 'motivated' included the categories motivated and very motivated to the question 'How motivated are you in your work?' Factors associated with not being motivated in univariate analysis (P < 0.10) were selected for multivariate analysis. The final model was created using stepwise backward selection of variables and was checked for confounding. Only the variables that showed a significant effect or acted as confounder were kept in the model. Key variables for analysis included fear of infection, injuries and actions taken, protective materials in place and used, support services to prevent and deal with HIV infection, and general working conditions. Qualitative data were analysed using a framework developed according to the research objectives, key issues and themes. Issues for analysis included the impact of HIV/AIDS at work, dealing with difficulties because of HIV/AIDS , support required and offered at work, general working conditions, and staff motivation.The quality of data was safeguarded by using experienced interviewers, assuring the confidentiality and privacy of respondents, and by asking informed consent and permission to tape interviews and focus group discussions. All research instruments were pre-tested. The research team members who conducted the in-depth interviews and focus group discussions were involved in the development of the research protocol and data collection instruments. They also participated in data analysis and report writing. Research assistants were trained to use the structured questionnaire and interviewed under supervision of an experienced researcher.The validity of data was assured by triangulation. Data were triangulated by:▪ asking the same questions during focus group discussions and in-depth interviews;▪ exploring the same topics among support staff, health workers and managers; and▪ comparing and contrasting information from the interviews and focus group discussions with information from the questionnaires and with the registers and reports from the hospitals.The protocol was approved by the Ethics Review Committee of Uganda Martyrs University.All the four hospitals provided services such as health education, voluntary counselling and testing (VCT), antiretroviral (ARV) distribution, treatment of sexually transmitted infections (STIs), treatment of opportunistic infections, and prevention of mother-to-child transmission (PMTCT). The characteristics of each hospital are described in Table The hospitals differed in number of beds and of clinical staff; public hospital B had the highest bed:staff ratio. The average length of stay for patients in the hospitals varied slightly and was between 4.3 and 5.75 days. There was a large variation in the number of registered ARV patients between the hospitals. Three hospitals had special activities related to HIV/AIDS.The study sample of the survey in each of the four hospitals was similar in sex and profession Table . In the The age range of the managers and the support staff in the study sample of the qualitative component was more or less equal between the different hospitals Table . The heaSix health workers participated in the focus group discussion in each hospital, except in hospital A where nine people took part. Participants were mostly women, most of whom were enrolled nurses/midwives (17 out of 25 participants). In total only three men participated.Overall, 86 per cent of the respondents reported that their workload had increased Table . This waShortages of qualified staff were mentioned in all hospitals, although records on staff departure demonstrated a low number of staff that had left among government staff: over the past five years in hospitals A and B, respectively, two and seven health workers had left. In the PNFP hospitals staff departure was a lot higher: in hospital D over the past five years 84 health workers had left, whereas the number of staff in hospitals A, B and D was similar Table  and, accAn average of 48 per cent of respondents reported working overtime regularly Table , which wSometimes they come for me when I am free. It is teamwork, when patients are many you come. If you refuse, they will not help you when you have a problem.' 'Significant differences were found between hospitals in the percentage of staff reporting to work overtime on a regular basis, which was highest in hospital A (61 per cent) and lowest in hospital C (34 per cent) (p = 0.02). In PNFP hospital C, 40 per cent of staff reported that they never worked overtime, corresponding with fewer staff reporting an increase in workload compared to the other hospitals Table . This coOverall, 83 per cent of the respondents reported being afraid of becoming infected at work. This did not differ significantly between the hospitals Table . Fear ofHealth workers fear getting infected with HIV while handling patients. Especially when there are less supplies of protectives in the hospital, this makes health workers so much afraid of contracting HIV. I believe that the staff have reduced their closeness to patients. Now those who are exposed to blood of people, they avoid examinations which will lead to contact with patients' blood.' 'Injuries were common in all hospitals: 36 per cent of the respondents reported an injury in the last year Table , and in I was pricked by a needle when I was putting an IV-line, I ran water on the finger to let the blood flow on it. I asked the patient to tell me about herself and she told me the husband had died. I just prayed to God'.'On very few occasions (11 per cent) the patient was tested, and only one person went for post-exposure prophylaxis (PEP), in hospital A.During the interviews most respondents said they accepted HIV/AIDS patients as people needing a lot of care and AIDS as 'any other disease'. Although staff did not lose morale, they were at times affected and felt frustrated, sad or depressed, especially when poor patients were left alone by their carers and when patients did not improve despite treatment. As one respondent stated:No, it doesn't affect me and for others, it is difficult to know because we haven't talked about it. I see colleagues being very concerned about the patients and giving their best. We have a doctor who gives patients money.' 'There were no major differences in answers between the hospitals. In most hospitals health workers and support staff also acknowledged being personally affected. Emotions related to providing care were difficult to discuss. This might be because staff did not think about emotional stress and saw HIV/AIDS as part of normal life, or because staff and management were not used to discussing feelings related to work.Discussing the status of colleagues or staff themselves was very difficult. Staff and management reported that hospital staff did not want to be tested and come out in the open due to fear of being stigmatized and, as a result, being isolated and talked about by their colleagues and by patients.The staff themselves fear stigma. The other staff are not so sympathetic. No. There was a midwife who died last year, she was being abused by another midwife. They were on duty and they got some quarrel over a patient and one of them told the other that "you know you are sick and tomorrow you are going to die" and I was there. And that is the thing that is making staff fear to test.' 'HIV-positive colleagues were mainly suspected through clinical signs, and they were suspected if they had lost their partner due to AIDS. Staff reported that HIV-positive colleagues were tested and treated elsewhere and not in the hospital where they work. AIDS-related deaths among staff occurred in all hospitals, although limited numbers were reported. In hospital A, B, C and D over the past five years, respectively four, six, seven and three staff were reported to have died from AIDS-related illness.Lack of qualified staff was a problem for all hospitals. In hospitals A, B and C most staff (63 to 70 per cent) were enrolled nurses and nursing assistants. In hospital D, only 40 per cent of staff were enrolled nurses and nursing assistants. It is likely that this hospital used students to do certain types of work. The problem of a limited number of qualified staff was addressed by having tasks conducted by less- or non-qualified staff, or qualified staff were asked to work overtime. According to respondents of the in-depth interviews, both ways of addressing the problem risked having a negative impact on quality of care, as illustrated by the following quote:Yes , counselling may not be perfect because they have to combine it with other work in the ward, which is also not perfected.' (Manager)'When working overtime, 81 per cent overall received no compensation Table . In hospAlthough the majority of respondents (60 per cent) reported feeling adequately protected 'Managers and staff reported that at times protective material was of poor quality, contributing to fear of infection.There were no significant differences in feeling adequately protected between hospitals, professional cadres, duration of service in hospital or having had a needle-stick injury in the previous year or not. Significantly more men than women felt adequately protected.Most staff (94 per cent) reported knowing how to protect themselves Table . OverallIn all hospitals, between 96 and 100 per cent of staff reported that they use disposable needles, and 97 to 100 per cent reported using safety boxes for disposal of these needles. In addition, 82 per cent of staff using needles reported that used needles were burned . An average of 50 per cent of the respondents reported being trained for all their HIV/AIDS tasks, ranging from 46 per cent in hospital B to 56 per cent in hospital D (data not shown). Tasks in which fewer than 20 per cent of respondents reported being trained were treatment of opportunistic infections, STI treatment, training and supervision of carers, and caring for HIV/AIDS patients on the wards. In the interviews, most staff and managers answered that especially training in testing and counselling was organized.Responses to feelings of frustration, depression and sadness were similar in the four hospitals: hospital staff reported 'doing their best' and accepting it when they were not able to help, either ignoring the feeling, dealing with it by themselves informally by praying, or talking to colleagues. At times they did consult seniors when problems occurred, as illustrated by this quote:My staff complain, they say: we have lost a patient and we did not want this patient to die. I tell them that is part of life, we have done our best and maybe it was God's plan.' (Manager of a ward)'In none of the four hospitals was a system in place to assist staff when they faced emotional difficulties, although opportunities existed. Three hospitals organized regular educational sessions, in which HIV/AIDS-related topics were discussed. In hospital B such sessions were less regular. However, these sessions might be considered too 'public' to deal with emotions. Supervision might offer another opportunity for those in charge to discuss difficulties in dealing with HIV/AIDS patients. Overall 57 per cent of respondents reported being supervised daily and 27 per cent at least monthly. Daily supervision was lowest in hospital B (39 per cent) and highest in hospital A (68 per cent) (p = 0.02). Supervision was considered by most respondents in the hospitals sufficient to cope with work . The PNFP hospitals offered spiritual guidance: hospital C had early-morning devotion times, in which problems were sometimes discussed, and hospital D offered a minister for talking and praying. In the in-depth interviews there were no clear differences in answers between staff in the different hospitals, which indicates that the spiritual guidance provided did not make it noticeably easier to cope with HIV/AIDS patients.Staff could make use of the available HIV/AIDS services, although respondents reported differently with respect to their availability Table . There wNone of the hospitals in the survey had a written policy to deal with HIV-positive staff. Respondents in all hospitals reported that HIV-positive staff continued working until they were too ill, and that they did not come out in the open. Staff known by management to be HIV-positive received free treatment: ARVs when meeting the requirements, treatment of opportunistic infections, and counselling. In addition, respondents reported that hospital staff could be given lighter duties and private rooms in the hospital for admission. Staff and management in the public hospitals reported that salaries were paid until death of a sick staff member. In the PNFP hospitals salaries were reported as being paid up to three months, although most staff were not sure about this. Only in hospital C did staff report that financial support was received. Support to HIV-positive staff proposed by respondents in all hospitals was food, financial support to staff and relatives, lighter duties, and private rooms.When asked about motivation in general, most staff (71 per cent) in the four hospitals reported feeling motivated Table . MotivatIf you have a problem, there is someone to talk to – there is good communication.' 'Results of the multivariate analysis showed that not being motivated was associated with having a high or medium level of education, being male, working overtime, not being aware of counselling or believing it is not offered, using ARVs, and not receiving immediate supervision on a daily basis Table .In this study staff and managers reported that HIV/AIDS has an impact on workload, leads to changes in tasks and affects emotions, although the latter was less pronounced in this study. Injuries were reported to be common, and most staff feared infection at work. Respondents knew colleagues who were HIV-positive, although HIV-positive staff remained in hiding, and staff did not want to get tested due to fear of being stigmatized. No HIV-positive staff talked openly about their HIV status. The reported impact of HIV/AIDS demonstrated in these Ugandan hospitals corroborates published studies elsewhere: frequent occurrence of injuries, reported by 36 per cent of respondents in our study, is reported by 57 per cent of respondents at the central hospital in Uganda , and ranIn the Ugandan hospitals, organizational responses to the impact of HIV/AIDS were implemented haphazardly. None of the hospitals had written policies to prevent and mitigate the impact of HIV/AIDS and to support HIV-positive staff. Organizational responses were reported to consist of informing staff about infection control, making protective materials and existing HIV/AIDS-related services available, although in none of the hospitals respondents reported that these services were clearly communicated to staff. Areas that were not explicitly addressed in any of the hospitals were stigma, HIV counselling and testing among staff, supporting HIV-positive staff, availability and use of PEP, and emotional support. Lack of organizational support is also shown in studies in Zambia ,26. The We explored the relationship between the perceived impact of HIV/AIDS and staff motivation. Motivation appeared to be determined, among others, by working conditions, such as overtime, frequency of supervision, provision of HIV counselling, and use of ARVs by staff. These factors are greatly influenced by HIV/AIDS. It might be that because of a lack of strategies to support HIV-positive staff, staff using ARVs do not feel motivated. This could not be explored, as no HIV-positive staff came forward during our study.Staff with a higher level of education in particular were less often motivated than other staff, which might be linked to the reported lack of qualified staff and, therefore, having more responsibilities. Men are less often motivated than women in the survey, but it is not clear why, and answers from the interviews did not confirm this.The most important reported reason for staff motivation was 'liking the work', and salaries and financial benefits appeared less important. This is corroborated elsewhere, and various studies -47 show As low motivation of health workers contributes to poor health worker performance and thus affects quality of care, Human Resources Management (HRM) activities to improve staff motivation need to be implemented. Managers should be aware that there is a complicated relationship between motivation and performance. According to expectancy theory, motivation to perform is a combination of feeling able to successfully perform a task when putting effort into it, obtaining a positive outcome (reward) upon completion, and valuing this outcome. This means that health facility managers need to implement HRM activities and use leadership skills to:▪ assure that the expected level of performance is discussed and agreed upon by staff and management;▪ support staff in such a way that they feel able to achieve the expected level of performance;▪ assure that expected positive outcomes of performance  outweigh expected negative outcomes (e.g. being tired and overworked); and▪ assure that expected rewards are provided when performance is achieved .A combination of interventions in all these areas is likely to lead to motivation for performance.Our study identified that staff and managers considered HIV/AIDS to be constraining their work, as it either led to a perceived negative outcome (such as fear of getting infected while delivering care) or had an impact on their perceived ability to provide quality care . Integrating activities to prevent and mitigate the impact of HIV/AIDS into existing HRM activities, instead of developing a 'vertical' HIV/AIDS workplace programme, can improve these perceptions. Examples of this type of activity are the integration of discussions on infection control, stigma and difficulties with HIV/AIDS patients into staff meetings and daily supervision; including HIV/AIDS-related topics in educational sessions to improve staff knowledge and skills; and including support to HIV-positive staff in workplace policies for chronically ill staff. Workload issues can be addressed by improving teamwork, rotating tasks, and taking measures aimed at staff attraction and retention. Our study identified motivating and discouraging factors among staff, but ranking these factors is required to assist managers to prioritize and align incentives for performance with valued positive outcomes of staff performance.Caution has to be taken to replicate strategies without adapting these to the prevailing context. Although the type of hospital (public or PNFP) did not influence the reported impact of HIV/AIDS or organizational responses, the specific hospital context did seem to influence the perceptions and experiences of hospital staff, although differences were not always statistically significant. Two examples to illustrate this Table  and 6:In hospital B, staff were generally less motivated. The reported working conditions were less positive than in the other hospitals: hospital B had the highest bed:staff ratio, the lowest availability of five types of protective materials, the lowest number of staff that received daily supervision, irregularly organized educational sessions and the highest number of staff reporting not receiving compensation for overtime. In addition, it was one of the two hospitals with the highest number of injuries, and respondents of hospital B had the lowest knowledge of PEP and its availability in the hospital. Lastly, although pay was higher in hospital B than in hospitals C and D, staff motivation in hospital B was lower than hospitals C and D. A focus for interventions would be to analyse leadership and management and to improve upon available activities such as supervision and educational sessions.On the other hand, in hospital A many respondents were motivated despite the fact that the most overtime was reported in this hospital and a low number of staff received compensation. Hospital A had a high number of respondents being aware of guidelines, knowing about and using HIV/AIDS-related services for staff and being aware of PEP offered in the hospital. In this hospital a high number of respondents reported being supervised daily. However, in hospital A staff complained about a heavy workload due to extra tasks related to HIV/AIDS. This is in contradiction to the bed:staff ratio and the reported number of new patients in the outpatient department and might be linked to reported extra tasks related to HIV/AIDS such as RCT. The focus for intervention might be on evaluating staff experiences with RCT so as to better adapt these to staff capabilities.It is important to know that although general measures should be designed to mitigate the impact of HIV/AIDS and to motivate staff, these examples demonstrate that each hospital management team needs to have a different focus in strategies. They show that differences occur in leadership and management, availability of resources and organization of services between hospitals working in similar conditions. Management needs skills and support to analyse the working conditions in their facilities and to adapt generic guidelines to their own specific situation.Informing policymakers which interventions are successful under which circumstances and for which staff groups is important, as it allows the formulation and implementation of evidence-based approaches . VariousWe were not able to measure stress, as no validated instrument for Uganda exists. Therefore, the influence of HIV/AIDS on stress could not be identified. Additionally, for some members of the research team it was difficult to probe on sensitive topics such as personal experiences with HIV/AIDS, HIV status of respondents and colleagues, and emotional feelings, which might have influenced data collection. The survey was based on the availability of staff, which could have caused a selection bias and which we were not able to check as data on absence and sick leave were not available in the hospitals. However, management assured us that absence and sick leave were not major problems faced in any of the hospitals and that staff were systematically scheduled to work in different shifts, without differences in profile. In addition, our own impression during the study was that absence due to stress, burnout or low motivation was not an issue in any of the hospitals. The questionnaire and the interview guide could have better addressed motivation by including questions in line with expectancy theory. Lastly, the results reflect staff opinion on their knowledge, skills and practice. Confirming if reported knowledge, skills and practice correspond with actual knowledge, skills and practice was not possible, due to time and budget constraints.The study demonstrates that HIV/AIDS is a crucially important contextual factor, impacting on working conditions and staff motivation in various ways, and that staff perceptions and experiences with HIV/AIDS are influenced by individual hospital settings.Given the fact that HIV/AIDS is a contextual factor, exacerbating working conditions that are already difficult, organizational responses to address the impact of HIV/AIDS need to be integrated with responses to address other problematic working conditions. Opportunities are present such as supervision, educational sessions, staff meetings and clearly providing counsellors to hospital staff. However, this can only be achieved if HIV/AIDS workplace policy and programmes are systematically developed and implemented, and when they are adapted to the local context. More information exchange on successes and failures of interventions to improve staff motivation and address HIV/AIDS in the health sector is urgently required to assure appropriate resource allocation. This requires additional data collection methods to the commonly applied randomized trials, which often exclude the context and process of implementation.The author(s) declare that they have no competing interests.MD and VB were principal investigators of the study and were responsible for protocol development, study implementation, data analysis, and report writing. MD drafted the manuscript. EM, GN and OJ were members of the research team and contributed to protocol development, study implementation, data analysis, and report writing. VB, EM, GN and OJ commented on the first manuscript. MB analysed data of the quantitative study component, contributed to report writing and commented on the draft manuscripts. GvdW discussed the conceptual framework for the study and substantially commented on the draft manuscripts. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here: