The HIV/AIDS pandemic threatens economic, social, and environmental sustainability throughout sub-Saharan Africa. This paper reports on a qualitative study exploring interrelationships between HIV/AIDS, labor availability, agricultural productivity, household resources, food consumption, and health status in rural southeastern Uganda. Respondents reported an increase in widow-and-orphan-headed households; labor shortages due to illness and caretaking; degradation of household resources from health-related expenses; loss of land tenure and assets following deaths, especially for widows and orphans; and changes in agricultural practices and productivity. Our study highlights a potential downward spiral of livelihood degradation for vulnerable households and suggests targeted interventions to improve sustainability. Approximately 63% of people globally living with the virus reside in the region  and the Like many other diseases prevalent in sub-Saharan Africa, such as malaria and tuberculosis, HIV/AIDS is not only a burden to infected individuals, households, communities, and institutions, but also creates a severe obstacle to social and economic development and sustainability in many developing countries ,8, as thFrom a more positive viewpoint, addressing HIV/AIDS and its associated socioeconomic problems can reverse the downward spiral of livelihood degradation, propel affected households toward higher incomes, and contribute to sustainable development in affected communities . To achiWhile the hope and expectation is that medical advances will ultimately eliminate the threat of HIV/AIDS in these communities, the HIV/AIDS pandemic can be seen as one example of how a shock to these rural communities can threaten their sustainability, especially when the communities are home to socially and economically vulnerable populations. Therefore, the lessons learned from this investigation can be generalized to the design of policies that support communities facing related shocks, whether from other chronic diseases, ecological shocks such as crop failure and drought, or economic volatilities such as commodity and energy price fluctuations.Although Uganda is considered to be an HIV “success story” because the prevalence of infection has decreased from an estimated 15% or higher in the early 1990s, one of the highest rates in the world at the time, to about 6.7% today, there are still nearly 1 million Ugandans who are HIV-infected . Most HIThis paper reports on the results of a series of in-depth semi-structured interviews and focus group discussions conducted in Kampala city and the Mayuge district in southeastern Uganda with government officials, health experts, and local community leaders in 2006. The interviews were designed to gather information regarding participants’ perspectives on the effects of HIV/AIDS infection on household composition, labor allocation, land transactions, health expenditures, and agricultural practices in farming households and communities in Uganda. These interviews are part of a larger, multi-stage research project designed to explore relationships between sustainable agriculture, household food security, and health status in the study area ,24. The This paper is structured as follows. First, we provide a brief review of the literature on this subject. We then describe our methodology and results. We conclude with a discussion of our observations and how they fit into the larger work that is being conducted on the impacts of the HIV/AIDS pandemic on rural households in Africa.2.Starting from the top of There is a growing literature that explores the relationships shown in Household composition and structure. Most research on HIV/AIDS has focused either on the household head or on the PWLA as the unit of analysis, but for studies of agricultural production, the household is generally considered to be the relevant unit of analysis. In sub-Saharan Africa, households account for the majority of agricultural production, agricultural production is the main source of self-employment, and the majority of households rely on household labor for agricultural production . With help of advice they are boosted and get energy. Some of them work normally but they are also advised not to overwork. Some work from 7 to 9am but they do not return in the afternoon. In that case they can do other house activities.The reported work hours of PLWA, especially those in stage A and even stage B, seem very low, especially given that many households in the area where this study was conducted are engaged in subsistence agriculture and are food insecure even when all family members are contributing labor to the household. These reported work reductions likely reflect a perceived “ideal” work schedule rather than reality. Interviewees reported that HIV/AIDS counselors and health care officials in the community advise people with HIV infection to limit their work hours and to not overexert themselves, even if they are feeling healthy. Respondents shared the belief that if possible a person with HIV/AIDS should “rest more” and “conserve energy” in order to promote a longer life. For example, a local community representative commented:The PLWA usually does now work but it depends. If he is the head of the house he is forced to work. Mostly in a week the person can work for 5 days otherwise if he/she works too much the disease will bring him/her down.Respondents also noted that few households can actually afford to observe these guidelines, and indicated that they knew of few people who had actually been able to cut back on work when not seriously ill. An agricultural community coordinator commented:However, even if the labor reductions are not as severe as reported, respondents expressed concern that care giving requirements have significantly impacted the economic security of most HIV-affected households.Follow-up questions about work involvement in particular activities revealed slightly less drastic reductions in labor availability, but also raised concerns about the time required for seeking medical care. PLWA were estimated to work on the farm or in the garden a little less than half of the hours worked by healthy family members and to contribute only a few hours a day to completion of household chores. PLWA were also estimated to contribute less to “heavy” labor activities. Some of these work hours were replaced by the considerable amounts of time estimated to be spent traveling to clinics for medical care. The time required for clinic visits was estimated at 5 hours a day one day per week during stage A and two to three days per week during stage B. During stage C, the burden of time seeking medical care shifted to a family member, who was required to pick up medications once the PLWA became bedridden.Land transfers. Land transfers following the death of a parent or husband are a major concern in Uganda, where clans control most land and individuals have limited rights. Participants indicated that the majority of men distribute their land to their adult male children before they die. When male children marry, they bring their wives into the household. Therefore, rules that ensure that male children will inherit land serve to keep the land holdings of a particular clan concentrated geographically. However, these inheritance practices can leave widows without land resources and livelihoods, unless a widow with minor children is allowed to remain on the land until a son comes of age. Children who are orphaned might have the land transferred to an uncle or other male relative at least until the oldest male child comes of age; however, some widows and orphans are left without any land after the death of the male head of household. Respondents emphasized their concerns in comments like these from NGO representatives:It is obvious that the male progeny takes responsibility as heir. The land is kept in the family; a brother takes over if there are no sons. Women are viewed as property and part of the package. So in this case daughters are not regarded as part of the family or clan. Only sons are seen as heirs and so socio-culture does play a role in land transfer following death of a man in the family.The land is normally passed on to the boys and their families while the girls mostly get nothing. This has to do with socio-culture because girls are not recognized. For widows, they are not recognized either, and this is a problem. In the land tribunals these are the most frequent cases. If the widow doesn’t have children, there are no discussions; she has to pack her belongings and go.obutaka” who help to settle clan disputes and help widows to protect their land rights.The rules are changing to some extent in an attempt to protect the inheritance rights of women. For example, there are now community members called “Family structure. Participants raised special concerns about the fate of children as the number of orphans overwhelms the number of available caregivers. In traditional African culture, children are members of an extensive network of relatives beyond their biological parents. Community leaders expressed fear that the traditional extended family of Basonga culture is being lost as the demand for orphan care increases. In the past, the death of both mother and father was a relatively rare event, and the extended family could afford to take in a few orphans. The AIDS epidemic has greatly increased the need for orphan care, and has also caused economic hardships that prevent extended families from taking on the responsibility of raising additional children. Also, community leaders noted that a greater emphasis is being placed on independent nuclear families, and that is contributing to the breakdown of traditional support networks. Thus, even though relatives are often willing to provide some support for children in their extended families, perhaps by providing some financial support for child-headed households, responsibility for support of orphans now often falls beyond the extended family. Although many non-governmental organizations are now operating in this community, support is minimal and need is growing.Social status and social networks. Participants indicated that the perception of PLWAs in their communities is changing. More women are joining support groups and doing alternative income generating activities. Furthermore, individual respondents and focus group participants indicated that new community-based groups are involving both non-affected and affected people as a way to empower the whole community. Several organizations and events have been initiated specifically to fight stigma and discrimination against the PLWAs in the community. The AIDS Support Organization (TASO), an NGO that provides a range of supportive activities for members, encourages the formation of drama groups as a tool for AIDS awareness in the community (counseling and testing for HIV are required in order to become a member of TASO). However, the potential for stigma and evidence of its effects still exist. This is indicated by the fact that many men hide their status from their wives. In some cases men will go to different counseling agents or will buy drugs far from their villages, where they think their records will remain confidential from their spouses and other community members.Health expenditures. It is difficult to obtain estimates for the actual costs of medical care for PLWAs because of the long duration of illness. Survey participants were unable to give exact estimates for these expenses, but emphasized the great variety of costs incurred by PLWAs and their families, including transportation to clinics, laboratory tests, clinician and hospital fees, medications, and funeral costs, as well as the purchase of special nutritious foods recommended by TASO. Although medications are supposed to be available at no cost at government hospitals, supplies are often low, which requires PLWAs to purchase subsidized medication from non-governmental organizations at a cost of about 100 Ugandan shillings per day (roughly 5 U.S. cents at the time of the interviews). Additional expenses are incurred by visiting traditional healers, transporting the body for burial, and paying for food for relatives who travel to visit the PLWA and those who attend funeral services and stay for several days or weeks after the burial. Costs for funerals are managed to some extent through community organizations that provide a form of funeral insurance. Most participants indicated that there are a growing number of households that are unable to meet the expenses of the illness and death of a family member, and that a growing number of PLWA can only afford panadol (acetaminophen) or aspirin for pain management rather than drugs specifically for HIV/AIDS. Medication increases expenditure during illness. People divert the little funds they have to buy medicine. Sometimes we do meet young people and on many occasions they mention that they are orphans and had sold land to take care of the sick. In some situations people sell their houses and forgo their savings, but I don’t have concrete figures.When the people come to see the sick, the family members have to prepare for the visitors. They hardly come with food. The visitors just come to greet the sick person; they do not help with agriculture activities. This feeding means using the little they have. By the time a person is sick for a year or two, the family is left with nothing.The bills of medication go beyond death. Sometimes these are higher than the income of the family. People have died in hospitals and have associated costs including the funeral rites. During the funeral, in order to feed the crowds, they encroach on the property and land and animals are sold off to meet the expenses.These illness-related expenses are clearly eroding household livelihoods, especially of poorer and more vulnerable households, as summarized by the following comments from community leaders and NGO representatives:TASO works with the Ministry of Health to provide resources to families that are affected with HIV/AIDS, including supplementary non-perishable food. This contribution offsets the expenses listed in Changes in agriculture. Respondents consistently reported that agricultural production has gone down in all affected households over the past five years. Reasons reported included the time demands of caretaking and the limited ability of the PLWAs to perform agricultural activities such as digging, planting, weeding, and timely harvest. There was, however, general agreement that plant diseases such as banana and cassava mosaic and extreme weather events might have contributed to the low production in addition to the HIV epidemic. Households with multiple wives (a common practice among the Basonga people) and many children usually maintain their usual farming practices, and households with greater financial resources may hire additional laborers so that they can grow their preferred crops. However, even in light of general population growth—and a resulting increase in the number of individuals seeking to cultivate the same land area—respondents noted that affected households may leave some land fallow because they do not have time and labor to devote to agriculture.Study participants noted several changes in agricultural practices that have occurred in households affected by HIV/AIDS. While changes to crops with lower labor requirements were reported, in many cases, intensified production of market crops  was also reported. Adoption of many of these crops was supported by the National Agricultural Advisory Services (NAADS) and the outreach programs of local community support organizations through programs designed to help rebuild the livelihoods of small scale subsistence farmers and other vulnerable households that lacked adequate household labor for production of other market crops. This more intensive production allowed households to gain higher yields for lower levels of labor input and cultivated land. Production of poultry, vanilla, and kitchen gardens can occur close to the home, minimizing travel for caretakers and PLWAs. Adoption of labor-saving and output-enhancing production techniques such as use of manure to improve fertility and use of grass around contour bands to reduce erosion have increased for households able to make these innovations. However, some shifts from cash crops to subsistence crops were also reported. Another concern is that diseases like banana and cassava mosaic and extreme weather events can lead to low production, and any reduction in output can push vulnerable households into hunger.Agricultural market participation. When asked about their ability to sell their goods in remote markets, participants reported that due to high time-cost of illness, affected households may be less able to transport their goods to far-away markets, such as those near the Kenya-Uganda border, where they might obtain higher prices for their products. They may, therefore, sell their produce to middlemen who come to buy produce cheaply in villages and sell them in town at higher prices. Participants believe that these farmers are being offered unfairly low prices by these middlemen, who are exploiting the vulnerability of affected households. This problem has inhibited the success of the backyard vanilla production program in particular. A potential solution to this problem is the formation of marketing cooperatives that may allow farmers to obtain higher prices and to avoid the middlemen. A village leader’s comments reflect this perspective:The market is a problem to the farmer. The farmer is being exploited by the middleman. We don’t need middlemen and perhaps through organizations like Uganda Farmers Association we can have a stronger voice.5.Household composition. Although we did not find evidence of higher female mortality, our general results are quite similar to other studies, with a reported increase in female, elder, and child headed households. This often results in new higher-responsibility roles for more vulnerable family members , who were often reported to leave school and/or enter the labor market, and even migrate to ensure their own survival and that of the household. It is also clear that a crisis of orphan care is occurring.Labor allocation. As widely reported elsewhere, our results indicate that caretaking responsibilities fall most heavily on women and girls, and our quantitative estimates indicate that these responsibilities can absorb the majority of the caretaker’s time as the illness progresses, representing a substantial loss of labor for the household. Our work-hour estimates demonstrate that women consistently work a higher number of hours than men, regardless of the type of work activity. Consistent with other studies, household and agricultural labor is also lost due to the PLWA’s lowered ability to work. We found that in some cases these labor reductions are based on advice of medical professionals, and are an attempt to preserve health status. We also found that these voluntary work reductions may not be possible for poorer households, potentially contributing to a downward spiral of deterioration of health along with increased poverty.Land transfers. Consistent with many other studies, we found that women and girls are highly vulnerable to loss of not only land, but also household capital, and in some cases even the loss of their home within a given community. As shown in Social status and social connections. Relative to other studies, we find a somewhat more optimistic picture regarding social stigma and loss of social connections because of HIV/AIDS. In Uganda’s case this may be related to government policies and information campaigns, such as the “Zero Grazing” policy implemented in the 1990s that evolved into the current “ABC” policy , that have helped Uganda maintain a relatively low HIV prevalence compared to other countries in sub-Saharan Africa and have encouraged open discussion about the disease [ disease ,67,68. WHousehold consumption and health expenditures. However, consistent with other studies, we find that expenses from HIV have a severe negative effect on household welfare. These effects seem most pronounced in poorer households, which lack resources even before having an HIV-infected household member. These effects are seen both during illness, when households cannot afford drugs, other medical care, and appropriate foods, and also after a death, when they incur funeral expenses that remain constant regardless of household resources. In contrast to other studies, we found that the importance of consumption of highly nutritious foods was highly emphasized, and purchase of these foods often seems to take priority only over the purchase of ARVs. Both governmental and nongovernmental organizations were reported to be providing both food and medical support, but access to both seemed uneven and somewhat unreliable. Our results provided more qualitative detail regarding potential in-kind contributions from relatives. We found a mixed picture, with assistance being uncertain and potentially declining over time. Again, as in the descriptions of increasing burdens of care for orphans and the resulting increase in the number of independent nuclear households, we see evidence of a support network stretched to its limits, and of households needing to put a high priority on meeting their own needs rather than supporting more distant relatives.Agriculture. As reported elsewhere in sub-Saharan Africa, declines in agricultural production were also reported in our study area. Our study finds a mixed picture in terms of cropping patterns. Consistent with other studies, shifts to crops with lower labor requirements are reported [reported ,40,52. Hreported . In factParticipation in markets. We did not find other studies that discuss the effects of HIV/AIDS on land rental and sales, other than the indication that women may not have rights to sell land, and may be afraid to rent land for fear of losing title. Our specific questions regarding land transfers led us to identify two important potential effects. First, a PLWA who is a household head may try to acquire additional land to provide an inheritance for his children. Second, consistent with other studies, we found that households will sell land only as a very last resort, since in this land-scarce region it is a highly valuable asset.Although we did not investigate labor market interactions to a great extent, our survey provided evidence that those able to hire outside labor were more likely to be able to maintain their previous production strategies. Rather than finding that household members who previously participated in external labor markets returned to the household to supplement household agricultural labor, we found the opposite, with women and children sometimes forced to leave agriculture and seek external wage employment. Our findings related to crop marketing and the effects of illness on participation in remote markets are very consistent with other studies. The greatest marketing concern raised was a vulnerability to exploitation by middlemen that is being solved in part through the development of community-based institutions (marketing cooperatives).6.Our qualitative findings have shown how detailed qualitative research can bring insights into complex issues surrounding HIV/AIDS in the rural communities of Uganda. They have provided insights into the social and economic burden posed by a household member infected with HIV through the progression from early infection to AIDS to death, and they have provided some preliminary insights into the strategies through which some households cope with the challenges faced. Results from this study were used to guide the development of a follow-up quantitative survey. In particular, these fieldwork results helped to identify significant new issues  that resulted in development of an important set of quantitative follow-up questions. The research therefore also illustrates the complementarity between qualitative and quantitative research methods. At the same time, these interviews highlighted the many other development issues facing these communities. For example, productivity declines in agriculture were said to occur both due to the effects of HIV and to shocks to the agricultural system. The semi-structured interview format helped to reveal additional potential threats to household livelihoods, thus potentially avoiding incorrect conclusions or recommendations based on a more narrow understanding of the issues faced by these communities. At the same time, the research reveals that particular policy interventions, such as helping households develop a more resilient portfolio of agricultural activities, may help protect vulnerable households against multiple shocks.As shown in other studies, there are significant obstacles to sustainable development in communities that are highly affected by AIDS as the resources in these communities are being diminished . HousehoWe believe local communities should be involved in identifying and designing appropriate and effective programs to address local challenges. These communities should work not in isolation but hand in hand with NGOs and the government to address these concerns. Such multi-scale, multi-actor policy approaches can increase the prospects for a longer-term sustainable environment for these vulnerable groups. While information such as that provided by our in-depth interviews can in and of itself contribute to improved policy design, the quantitative simulation models developed through the larger project of which these interviews are a part should also contribute to participatory opportunities for exploration of alternative outcomes and policy design by stakeholders at multiple levels.


Antibiotic resistance is a major public health problem affecting both current and future generations. The influence of environmental factors on antibiotic use and resistance development in bacteria is largely unknown. This study explored the perceptions of healthcare providers on antibiotic use and resistance development in relation to environmental factors i.e. physical, natural, social and behavioural factors.A qualitative interview study was conducted using face-to-face, semi-structured interviews among registered allopathic doctors, veterinarians and drug dispensers in Orissa, India. The interview transcripts were analyzed using latent content analysis.The main findings of this study relate to two themes: 'Interrelationship between antibiotic use, resistance development and environment' and 'Antibiotic management contributing to the development and spread of resistance'. The interviewees viewed the following as possible contributors to antibiotic use/misuse and resistance development: changes in the natural and physical environment i.e. climate variability, pollution, physiography and population growth; the socioeconomic environment affecting health-seeking behaviour and noncompliance with medication; a lack of healthcare facilities and poor professional attitudes; and ineffective law enforcement regarding medicine dispensing and disposal.Generally, the interviewees perceived that although behavioural and social environmental factors are major contributors to resistance development, changes in the physical and natural environment also influence development of antibiotic resistance. The respondents also perceived that there is a lack of information about, and poor awareness of, what constitutes prudent use of antibiotics. They suggested a need for information, education, dissemination and proper implementation and enforcement of legislation at all levels of the drug delivery and disposal system in order to improve antibiotic use and prevent pharmaceutical contamination of the environment. The environment is an omnipresent factor governing all human and animal activities and behaviours and also the micro-organisms that cause diseases in them. According to Smith et al. the environment consists of four major components-physical, natural, social and behavioural . The phyAll over the world, development of resistance to antibiotics is on the increase amongst pathogenic bacteria ,4. HowevIn general in India, and also in Orissa, there is a high incidence of infectious diseases, increasing use of antibiotics by a wide range of health care providers and increasing resistance, associated with commonly occurring indiscriminate use of antibiotics in humans as well as in animals ,6,7. In It is possible that environmental factors have a role to play in the way antibiotics are used in a population and the consequent development of resistance. To explore this issue, a qualitative study is needed to understand the way people perceive the issue and the meaning they attach to it, which can be further addressed quantitatively.We therefore, conducted a qualitative study among healthcare providers in the eastern Indian state of Orissa, taking it as an example, to explore their opinions about antibiotic use and antibiotic resistance development in relation to environmental factors.Out of the 30 districts of Orissa, four were purposely selected for the study. These districts were selected based on the geography, population density, urbanization, ethnicity, literacy rate and availability of healthcare facilities. The intention was to incorporate a variety of behavioural, social, natural and physical environmental factors. The districts of Cuttack and Khurda, were selected as representing an urban environment, proximity to sea, high population density (about 640 people per square kilometre), and high literacy rate (about 80%) . The disOnly allopathic providers were selected as they were most likely to handle antibiotics. To maintain a balanced distribution among the various types of healthcare providers i.e. registered allopathic doctors, veterinarians and drug dispensers included in the study, two participants from each district and from each healthcare provider category  were selected. Thirty-six potential participants had to be contacted to reach the desired distribution among the participants, as 12  did not agree to participate due to their busy schedule. All the participants were contacted in person or by telephone by the first author (KCS) before the interviews. All the participants participated voluntarily; no payment was offered nor given. Detailed information about the interviewees is presented in Table Data was collected by face-to-face interviews using open-ended questions (Appendix 1). All interviews were conducted in a mix of local language (Oriya) and English and lasted for an average of 29 (range 20-40) minutes for registered allopathic doctors, 24 (range 15-40) minutes for veterinarians and 17 (range 13-20) minutes for drug dispensers. All the interviews were conducted by the first author who is a native of the study area and has an educational background in biological and environmental sciences as well as experience in social services. The co-investigators have different backgrounds: agriculture, environmental medicine, pharmacy, nursing and qualitative research, all with a public health perspective.The tape-recorded interviews were transcribed verbatim and the transcripts were translated into English and analyzed using latent content analysis .Latent content analysis deals with the identification of the underlying meaning of the text. The selection of the unit of analysis is the first step in the content analysis. Meaning units i.e. parts of the original transcript text that are related to the aim of the study are selected from the interview transcript. The meaning units are condensed and coded. Similar codes are clustered together and collapsed into subcategories and categories. A category is a group of related codes. The theme is then identified and illustrates the underlying meaning of the text.Such a procedure was followed to analyse the contents of the interviews. During the conduct of this procedure, the tape-recorded versions and the Oriya and English transcripts were consulted repeatedly during the coding procedure to understand the full meaning of the text.The study was approved by the ethical committee of the Kalinga Institute of Medical Sciences, Orissa, India. Before the interview, information was given about the purpose of the study to the interviewees and they were told that they could withdraw from the study at any time. Written consent was obtained from each interviewee. All the interviews were carried out in complete privacy at the place chosen by the interviewee  and the names of the interviewees were kept confidential.Two major themes 'Interrelationship between antibiotic use, resistance development and environment' Table  and 'AntThis theme evolved from two categories (i) Influence of ecological factors on antibiotic prescription and (ii) Influence of presence of antibiotics in the natural environment leading to resistance development.Under this category two main subcategories were identified (i) Abiotic factors (ii) Biotic factorsThe abiotic factors are the non-living factors of the environment e.g. chemical-minerals, water; physical-temperature, sunlight. Two main abiotic factors, climate and physiography, were identified in this subcategory. Interviewees perceived that climatic factors such as precipitation, temperature and humidity had significant impact on antibiotic prescription. Interviewees felt that seasons influenced the occurrence of infectious diseases and hence changed the antibiotic prescription patterns. According to them, each season had its own types of diseases. In high temperature conditions in the summer, stress-related diseases in animals were more common. Diarrhoea was more common in humans in the rainy season. Both complaints led to high antibiotic prescription. High temperatures in the summer and high humidity in the rainy season resulted in more skin infections in humans and in the winter, although people were normally healthier, respiratory tract infections, including the common cold, led to misuse of antibiotics."When the monsoons start, at that time bacterial disease is more common and it is common in animals. There is less infection in winter. In summer, protozoan diseases are more common, due to summer stress; all Indian animals carry most of the diseases. Protozoan diseases are particularly common in forest areas. In coastal areas, a higher antibiotics prescription rate is more common. The environment is slowly changing, the temperature is rising." "In most of the cases, high doses of antibiotics are prescribed from the beginning, probably due to the change in climate." The interviewees' perception was that antibiotic use varied in different geographical areas, for example - in coastal and non-coastal areas. According to prescribers, higher antibiotics were used in coastal areas to control infectious diseases whereas in hilly areas most of the patients took traditional herbal treatment and lower antibiotics. They viewed that geographical variation in antibiotic consumption and resistance may be associated with factors such as regional climate, socioeconomic conditions, local population density and behaviours of a particular community towards antibiotic prescribing or consuming."In my view rampant use of antibiotics for minor infections is one cause of resistance in coastal areas; they are prescribing higher antibiotics unnecessarily." The interviewees also felt that pollution had a significant impact on antibiotic prescription. They perceived that in polluted areas, both infections and resistant bacteria spread more quickly."In polluted areas resistance is high, where pollution  is more, infections spread quickly. Now higher antibiotics are used due to pollution. In polluted areas, antibiotics are used for many days. We have to change two or three antibiotics." According to the interviewees, the health of humans is influenced by their habitat i.e. the area where they live and its components like plants, animals, micro-organisms and other human beings. The interviewees further perceived that large numbers of people making use of fewer health care facilities, leading to a high patient load in hospitals, caused improper diagnosis and inappropriate use of antibiotic treatment. The participants reported that overcrowding created unhygienic conditions which also caused infectious diseases to spread more rapidly, leading to increased irrational antibiotic prescription."In crowded areas, due to the unhygienic environment; infectious diseases are more common, if population density is high, then there are more diseases and more antibiotic prescriptions." Two main subcategories were identified under this category (i) Antibiotics in the natural environment and (ii) Effect of presence of antibiotics in the natural environment.Interviewees put forward a viewpoint that, due to the widespread improper disposal of pharmaceuticals, antibiotics are contaminating the aquatic as well as the terrestrial environment. According to them, hospital waste, out-of-date medicines from shops and unwanted household pharmaceuticals were not disposed properly and this was polluting water, grasslands and air. They believed that properly implemented and enforced environmental law or policy was essential for the safe disposal of pharmaceutical waste."Out-of-date medicine, if thrown outside, will impact the environment. What we throw away, it will mix with water, again when we drink that water, that water again enter into the blood and obviously it will have an impact. Environmental law is essential." According to the interviewees, the improper disposal of antibiotics was affecting aquatic organisms, grazing animals and also human beings, who were using river or pond water for drinking and cooking."If pharmaceutical wastes are disposed improperly, it will affect. Expired medicine loose its efficacy, but not toxicity.... If we throw these wastes outsides that will mix up with pond or river water; if that water is taken by human or animal it may create problem; what happened recently at Cuttack, some cattle died by eating expired medicine including some antibiotics which were thrown improperly at the river beach. Some aquatic organisms also died. Every drug is in proper dose medicine and improper dose poison." Interviewees also assumed that antibiotics in the environment had a significant impact on micro-organisms. One interviewee pointed out that waterborne bacteria might develop resistance if they were exposed to low doses of antibiotics in water."If waterborne diseases causing bacteria are exposed to low doses of antibiotic every day, they gradually become tolerant to that particular drug and resistance will develop." Some of the interviewees were of the opinion that there was not much research on the environmental aspects of antibiotic resistance and they suggested further research in this area in order to find out the exact problems and their proper solutions."Antibiotic resistance in relation to the environment is a research question, further study is essential in this field." This theme emerged from the categories (i) Antibiotic use and factors influencing prescribing and (ii) Health systems and policy factors influencing resistanceUnder this category, two subcategories were identified (i) Humans and (ii) AnimalsThe interviewees used the term 'higher antibiotics' in varying meanings including new generation, broad spectrum, high dose or high-price antibiotics. Their view was that the prescribing of any type of 'higher antibiotics' in the first encounter was one of the reasons for bacterial non-response to 'old' antibiotics. Most of them viewed that the indiscriminate use of antibiotics has lead to the resistance problem. In their opinion, high patient load, prior prescription by unqualified prescribers and high prices of antibiotics are major reasons for inappropriate prescribing of antibiotics. The interviewed doctors said that a single doctor prescribes to approximately 50-90 patients per day in both rural and urban hospitals. This high patient load can cause improper diagnosis, leading to inappropriate treatment and improper use of antibiotics. All the interviewed doctors mentioned that before visiting an authorized medical practitioner, many patients take earlier treatment from 'quacks', i.e. untrained people, who act as physicians and give medical advice and treatment. Furthermore, patients may also have bought medicines directly from the drug store on the advice of drug dispensers or based on their own diminutive knowledge. The interviewees said that quacks are prescribing incomplete courses and doses of antibiotics and some of them suggested that the quacks should receive training."Doctors are not available, quacks are helping the patients...... in my view we have to give training to them and license them, something that has recently been done in Kolkota [a city in India], and we have to train them as paramedical practitioners." Drug dispensers said that sometimes prescribers are influenced by a particular company and prefer to prescribe that company's medical products. They thought that these factors influence antibiotic prescriptions. On probing, some of the drug dispensers admitted recommending antibiotics themselves even for the common cold."If the patients say that they have a sore throat, we prescribe five tablets of roxithromycin. We force them to take [buy] the full course, but they often just take for one day or one to two tablets. The common cold is very common here and people usually take anticold tablets with antibiotics. We prescribe lower antibiotics like cefadroxil for colds. If they aren't cured, we prescribe higher antibiotics like cefixime." According to the interviewed veterinary surgeons, penicillin, amoxicillin, cloxacillin, ciprofloxacin and tetracycline are the most commonly used antibiotics on dairy and poultry farms and for household pets for therapeutic purposes. These are also commonly prescribed antibiotics in humans. In their opinion, prior prescription by unqualified prescribers was influencing antibiotic prescriptions for animals although pharmaceutical companies do not exert the same influence in veterinary practice as in human medicine. Prescribers perceived that if antibiotics were used on dairy farms during lactation, it would get into the milk. In their perception, this might be one of the reasons behind the resistance development as people use a lot of milk in food preparation. All the veterinarians said that in the case of poultry, antibiotics were used both for prophylactic purposes and as growth promoters in feeds. They disliked the use of antibiotics as growth promoters and some of them suggested the use of probiotics for this purpose instead."In poultry, antibiotics are generally used as growth promoters in feeds, e.g. tetracycline and lincomycin. Nonhuman use of antibiotics definitely creates resistance problems in humans." Three major factors influencing resistance were recognized under this category: (i) Patients (ii) Health systems and professionals and (iii) Policy and regulatory issues.Interviewees felt that patients' noncompliance with prescribers' instructions, self-medication, poverty, ignorance about antibiotic use and lack of awareness about resistance were all possible contributors to resistance development. According to them, poverty in rural areas and self-medication in urban areas were the major reasons for patients taking incomplete courses of antibiotics. The interviewees felt that the cost of the drugs varied from company to company and believed that many patients were under the impression that more expensive drugs were more effective and were therefore purchasing high-priced antibiotics but not completing the entire course of treatment due to the high expense involved. Interviewees were of the opinion that a lack of public awareness about the consequences of improper use of antibiotics was a cause of irrational antibiotic use, which led to resistance development."If patients have taken incorrect medicine, it will develop resistance and due to resistance to previously prescribed antibiotics, the doctor will prescribe new, more expensive antibiotics. Because of the high price involved, the patient is unable to buy the full course, which will once again create resistance to the new antibiotics, so public awareness is essential." A majority of the prescribers interviewed considered that a lack of infrastructure, improper diagnosis of diseases, inadequate prescription by some prescribers and irrational use of antibiotics by some patients were the major health system and professional factors responsible for improper use of antibiotics. For them, inadequate prescription meant insufficient dose or too short a course of antibiotics and irrational use involved indiscriminate and improper treatment of diseases. They said that sometimes antibiotics were used for a disease condition that might not need antibiotic treatment and this was the result of improper diagnosis."The common cold is a viral disease but we are prescribing antibiotics for this, possibly to prevent a suspect secondary infection, not for the original viral infection." According to the interviewees, there was a lack of good laboratories for culturing and sensitivity testing, which caused improper diagnosis and hence irrational antibiotic prescribing in humans. Veterinarians reported that the lack of good laboratories and staff was the major factor responsible for improper use of antibiotics in veterinary practice. All interviewees considered that this erroneous way of antibiotic treatment was one of the causes of resistance development.Many interviewees said that weak implementation of prevailing legislation governing the health care system was one of the possible contributors to resistance development. Due to weak drug policy, fake and low-quality antibiotics are available in the market and prescription-only drugs are also available without a doctor's prescription. Some interviewed doctors suggested that the selling of antibiotics without a prescription from an authorized medical prescriber should be banned and that a strong drug policy was needed to promote rational use of drugs. The participants informed that antibiotics are also commonly prescribed by some of the homeopathic and ayurivedic healthcare providers although they are not supposed to do so. Most of the doctors suggested that antibiotics used in humans should not be used in animals."Now fake medicines are available in India, I do not know how it is possible." "Unauthorized medical practice should be banned, either they are quacks or homeopathic or ayurivedic doctors, they should prescribe their own medicine, the majority of them are prescribing antibiotics, they don't have enough knowledge about dosage, course......half of the drugs which are banned in developed country end up and are prescribed here." To the best of our knowledge, this is the first qualitative study exploring perceptions about the interrelationships between antibiotic use, resistance development and environmental factors, i.e. physical, natural, social and behavioural factors. The views put forward here suggest that the possible contributors to antibiotics use/misuse and resistance development are - changes in the natural and physical environment, i.e. climate variability, pollution, physiography and population growth; socioeconomic environmental factors affecting health-seeking behaviour and noncompliance with medication; a lack of healthcare facilities and poor professional attitudes; and ineffective law enforcement in relation to drug dispensing, manufacture and disposal.According to Brown , there iThere is a general lack of studies on whether changes in weather conditions modify levels of antibiotic resistance. However, some studies from Europe and the United States have reported on geographical variation in antibiotic consumption and resistance, taking into account the influence of social and climatological factors -17, whicPrevious studies have shown that outdoor environmental air pollution from various sources, such as motor vehicles, industry, and neighbourhood-level solid waste burning, is associated with increased morbidity and mortality from respiratory infections in children and adults ,19. IncrThe impact of antibiotic use on the environment was also perceived by healthcare providers. One participant suggested that antibiotic contamination of the aquatic environment may be one of the reasons for the resistance found in waterborne bacteria, due to exposure to below-threshold concentrations in water. Studies have shown that antibiotics and antibiotic resistant bacteria are found in the aquatic environment ,21, howeParticipants in this study perceived that socioeconomic and behavioural factors, i.e. poverty; self-medication and non-compliance result in inappropriate use of antibiotics. This finding is consistent with the results of other studies from low- and middle-income countries ,24. The According to previous studies from India by Basu et. al.  and PateThe participants also offered a view that monitoring resistance patterns at the local level and making available this data to local prescribers may help appropriate empirical therapy. They also felt that information about and awareness of what constitutes prudent use of antibiotics given to practitioners routinely, might help reduce unnecessary antibiotic use and hence prevent resistance development. Our participants, especially the drug dispensers perceived that supplier incentives to the prescribers, is one of the factors responsible for higher antibiotic prescription rate. A study in China , in addiStudies have documented the presence of antibiotics in milk from dairy animals ,34. The In India, state governments have adopted central government guidelines on policies and programmes for healthcare development, and the state of Orissa adopted a policy on rational drug use in 1997 . PreviouAfter the United Nations Conference on the Human Environment in Stockholm in 1972, India passed the Environmental (Protection) Act in 1986. It provides for "the protection and improvement of environment and the prevention of hazards to human beings, other living creatures, plants and property". There is need for effective enforcement of this law to protect our environment from pharmaceutical waste.- in this case the relationship between antibiotic use, resistance development and the environment. In order to improve the trustworthiness of our study, we used data triangulation during the analysis. Data was collected from different healthcare professionals including allopathic doctors, veterinarians and drug dispensers. The informants were from different geographical areas and socioeconomic environments, in this case proximity to sea/inland areas and urban/rural environments. During the coding procedure, both Oriya and English versions of the transcripts, and in some complex cases, tape recorded data, were used simultaneously in order to avoid misinterpretation of the full meaning. The authors of this study were from different educational backgrounds and countries, and each one brought a unique perspective to the study, enhancing its conformability. In the analyses, this factor served to broaden the interpretation and the final result is a negotiated outcome.A qualitative approach is the preferred method to explore an emerging concept Generally, the interviewees perceived that although behavioural and social environmental factors are major contributors to resistance development, changes in the physical and natural environment also influence development of antibiotic resistance through the occurrence of infectious diseases and consequent use of antibiotics. The authors feel that quantitative studies are needed to verify the perceptions of our interviewees regarding the interrelationships between environmental factors and antibiotic use and development of resistance. The authors have therefore initiated studies towards this end. The respondents also perceived that there is a lack of information about, and poor awareness of, what constitutes prudent use of antibiotics. They suggested a need for information, education, dissemination and proper implementation and enforcement of legislation at all levels of the drug delivery and disposal system in order to improve antibiotic use and prevent pharmaceutical contamination of the environment.The authors declare that they have no competing interests.KCS, AJT and CSL designed the study. KCS interviewed, transcribed and translated the interview transcripts from Oriya to English and made preliminary analysis. All authors contributed to the final analysis of the interviews. All authors have read and approved the final manuscript.1. What are the common indications of antibiotic prescribing/dispensing and factors influencing these? Probe: Common infectious diseases, antibiotics prescription and prior treatments2. What is your view on antibiotic resistance? Probe: Possible causes, drug quality, human and nonhuman use of antibiotics and their impact3. What is your view on environmental issues in relation to antibiotics? Probe: Antibiotic use and resistance development in relation to the environment, disposal of pharmaceutical waste and its impactThe pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/10/629/prepub


Of course, in the 19th century, Darwin was making inferences simply based on observations of morphological variation. Yet, if he were alive today, he would be struck by how prescient his statement was, even as applied to questions about the long co-evolution of primates and viral pathogens, including lentiviruses PLoS Genetics, Degenhardt and colleagues provide a link between CNV and disease susceptibility in non-human primates The human genome was originally thought to be structurally stable, but it turns out to be quite dynamic, with many genomic regions duplicated or deleted among individuals to the extent that they exist in variable copy numbers. Within these copy number variations (CNVs), genes that encode proteins involved in immune responses are over-represented Asian macaques—including rhesus, pigtail, and cynomolgus—are commonly used as animal models to study the determinants of AIDS pathogenesis and evaluate HIV-1 vaccine candidates. After being challenged with Simian Immunodeficiency Virus (SIV)—the simian counterpart of HIV—some macaques rapidly develop features similar to AIDS, whereas others do so more slowly. A similar clinical conundrum exists in humans, as many people who are HIV-1–positive progress rapidly to AIDS, whereas others resist disease progression, despite not receiving antiretroviral therapy. Both viral and host factors contribute to the variability in AIDS progression rates in humans CCR5 abolishes CCR5 expression and confers near-absolute protection against acquiring HIV CCL3L genes were shown to be subject to CNV in humans and chimpanzee CCL3L1-containing segmental duplication was found to be associated with reduced CCL3/CCL3L1 chemokine levels, reduced chemotaxis of CCR5-expressing cells, and reduced proportions of HIV target cells that express CCR5 CCL3L1 copy number might be a basis for variable HIV-AIDS susceptibility. A low copy number of the CCL3L1-containing segmental duplication was shown to be associated with or correlate with an increased risk of acquiring HIV infection Among host factors that may contribute to variable HIV-AIDS susceptibility, significant attention has focused on the role of variations in genes that influence HIV transmission, such as the genes that encode CC chemokine receptor 5 (CCR5), the major HIV co-receptor required for cell entry of virus, and CCR5 chemokine ligands such as CC ligand 3 (CCL3) and its paralog CCL3L1 PLoS Genetics, Degenhardt and colleagues tested whether a low CCL3L copy number was associated with a faster rate of progression to AIDS in macaques challenged experimentally with SIV CCL3L genes experience a significantly more rapid rate of progression to experimental AIDS, with the CCL3L CNV accounting for ∼18% of the variability in experimental AIDS progression rates.In this issue of CCL3L copy number in Indian rhesus macaques may underlie the more rapid progression to AIDS in Indian versus Chinese macaques. Thus, in addition to serving as a determinant of interindividual differences in the outcome of experimental AIDS, CCL3L gene dose may account for some of the observed interpopulation differences in simian AIDS progression rates.Indian rhesus macaques progress more quickly to experimental AIDS than do Chinese macaques CCL3L CNV was a better predictor of outcome than population affiliation. While other genes may also influence progression to simian AIDS in experimentally infected rhesus macaques CCL3L CNV has strong effects on progression to simian AIDS. These results have practical implications for efforts to develop an effective HIV vaccine. To distinguish more clearly between vaccine efficacy and intrinsic variation in host response, it may be important to stratify rhesus macaques by CCL3L CNV.Previous studies have shown that there is a clear genetic distinction between rhesus macaques that originate from India versus China CCL3L  and CCL4L  genes, which are found on chromosome 17q12; a similar diversity might exist in nonhuman primates  may modify the association between CCL3L1 copy number and risk of acquiring HIV infection Understanding the role of chemokine CNVs in primate disease is made more complicated by several observations. At least in humans, there are multiple primates . However to vary . For exanscripts , and a hCCL3L genes CCL3L copy numbers in nonhuman primates are much higher than those found in human populations CCL3L genes (CCL3L copies per diploid genome Using real-time PCR-based approaches, Degenhardt et al. confirmed an earlier report that chimpanzees have variable copy numbers of 3L genes . These rCCL3L copy number in primates may reflect that the variability represents an ancient host defense mechanism. While this hypothesis needs to be tested with additional empirical data, it is consistent with the observation that there is a parallel to primate chemokine CNV in viruses: many viral pathogens have hijacked DNA sequences found in primates and adapted them to encode chemokine receptors and chemokines that specifically target and, in some cases, neutralize the primate chemokine system One possible reason for the extensive variability in Darwin, an astute observer of nature, might ask, “Why does there appear to be so much structural variation for genes encoding chemokines?” The ancient and dynamic battle between mammalian hosts and pathogens has exerted unrelenting selection pressure on the host genome, promoting the development of a complex and adaptable immune system. Conversely, the successful replication and persistence of latent viruses within the mammalian host implies that they have evolved the means to evade or manipulate host immune defenses. In the case of viruses, it is clear that they have targeted the immune responses mediated by chemokines


The epidemic of HIV/AIDS and treatments that have emerged to alleviate, have brought about a shift in the burden of disease from death to quality of life/disability. The aim was to determine which factors are associated with improvements in the level of health of male and female patients with HIV/AIDS in Andalusia, in terms of disability-adjusted life years.Descriptive study based on a sample group of 8800 people on the Andalusian AIDS register between 1983 and 2004. Dependent variables: Life lost due to premature mortality (YLL), years lost due to disability (YLD) and disability-adjusted life years (DALY). Independent variables: vital state, sex, age at the time of diagnosis, age at the time of death, transmission category, province of residence, AIDS-indicator disease and the period of diagnosis. A bivariate analysis was carried out to find out if the health level variables changed in accordance with the independent variables. Using the independent variables which had a statistically significant link with the level of health variables, a multivariate linear regression model, disaggregated by gender, was constructed.Amongst the women, we found a model which explained the level of health of 64.9%: a link was found between a higher level of health (lower DALYs) and not intravenous drug use, the province of residence, being diagnosed during the HAART era and older age at the time of diagnosis. Amongst the men, we found a model which explained the level of health of 64.4%: a link was found between a higher level of health (lower DALYs) and intravenous drug use, the province of residence, being diagnosed during the HAART era and older age at the time of diagnosis.A higher level of health (lower DALY) amongst both men and women was found to be linked to not be intravenous drug user, the province of residence, being diagnosed during the HAART era and older age at the time of diagnosis. The human immunodeficiency virus (HIV) and acquired autoimmune deficiency syndrome (AIDS) epidemic constitutes a large-scale worldwide public health problem, with important demographic, social and economic repercussions. HIV/AIDS has resulted in the deaths of more than 25 million people since it was first identified in 1981. This means that it is one of the most destructive epidemics in living history [HIV/AIDS has been classified as a chronic disease . The WHOIn terms of AIDS incidence and mortality rates, previous studies have shown that there are differences between men and women, although these differences are not always the same in all cases. In Spain, incidence and mortality rates are different, in accordance with these trends .The most common transmission method in Spain has been through the use of intravenous drugs. Many different studies have shown the differences in the advance of the disease amongst intravenous drug users in comparison with patients who contracted the disease in other ways. Patients who use drugs tend to have a poorer prognosis. Although these differences also vary between regions ,5.With regard to differences between regions, there is great variation in less developed countries such as Brazil. Brito  examinedIn terms of levels of education and socioeconomic levels, studies have shown that, in a number of different settings, patients with a higher level of education have a better prognosis ,10-12 anSpecialist studies have shown that physical quality of life decreases as HIV progresses, as a result of symptoms and antiretroviral treatment . As suchThe aim of this study is to determine which factors are associated with improvements to the level of health of male and female patients with HIV/AIDS in Andalusia, in terms of disability-adjusted life years.Descriptive study. 9699 people included on the Andalusia AIDS Register between 1983 and 2004 were considered for the study. 246 were excluded because there was no date of death, 482 because there was no date of diagnosis and a further 171 because their place of residence was outside Andalusia. The final population taken into account for this study was 8800 people.The data used for this study were extracted from the Andalusian Register of AIDS cases, which forms part of the national system of epidemiological monitoring in which all 17 of the Spanish Autonomous Communities participate.Disability-adjusted life years can be calculated using the following equation:YLL = Years of life lost due to premature mortalityYLD = Years lost due to disabilityThe YLL is an estimated figure reflecting the number of years lost as a result of premature death based on a predetermined life expectancy. The YLL is calculated based on the life expectancy at the age of death obtained via a standard life table with a low mortality .YLD = N* DThe YLD is an estimate of the number of years that a patient has lived with a disability . YLD = Ni = Duration of (years lived) with the illness for the patient i.ND = Value reflecting disability between 0 = maximum health and 1 = death.For the purposes of this study, we have used the results of research carried out by  with thest of May 2005. There are two possible categories: alive or dead.This is the information collected regarding the vital state of HIV/AIDS patients on the 31Two possible categories: male or female.A continuous variable calculated based on the patient's date of diagnosis and date of birth.A continuous variable calculated based on the patient's date of death and date of birth.This variable reflects the reason why the illness was transmitted, taking into account whether or not the individual belongs to a risk group of some sort. This variable has four categories: homosexual, heterosexual, intravenous drug user and other.• The "homosexuals" category refers to homosexual individuals who engage in sexual relations entailing risk, i.e. without using a condom.• The "heterosexuals" category refers to heterosexual individuals who engage in sexual relations entailing risk, i.e. without using a condom.• The "other" category includes categories with few cases, such as recipients of blood products, children of at-risk mothers, patients infected by blood transfusions, and unknown cause.Province of residence of the patient at the time of diagnosis.Three diagnosis periods have been used based on the level of implementation of HAART in Spain: pre-HAART (before 1996), limited use of HAART (1997 and 1998) and HAART (after 1998).A bivariate analysis was carried out to find out if the health level variables changed in accordance with the independent variables . The inclusion of these variables is justified according to previous studies detailed in the literature. The Student's t-test and ANOVA table were used to examine the qualitative variables with variance homogeneity and normal distribution, and the other variables were analysed using the Mann-Whitney U-test and the Kruskall Wallis H-test. The continuous independent variables were examined using linear regression analysis. All of the analyses were carried out independently for the men and women in the sample group.Using the independent variables which proved to have a statistically significant link with the DALY variable, we constructed two multivariate linear regression models – one for the men and one for the women.Health leveli is the dependent variable of the (DALY) level for a person with HIV/AIDS iwhere Ri: Route of infectionDi: Place of residenceIi: Period of diagnosisAi Age at the time of diagnosisTodos los análisis fueron efectuados con el software SPSS for Windows 14.0.The research commission of the institution granted ethical approval for the study.Table With regard to the province of origin of patients with HIV/AIDS, the province with the least cases in Andalusia was Jaen (444), followed by Huelva and Almeria, with 511 and 600 cases respectively. The provinces with the most cases were Cadiz (1541), Seville (1713) and Malaga (1511).The average age for AIDS diagnosis was 33.7 years of age. The average age at the time of diagnosis was 31.3 years for women (SD 10.5) and 34.1 for men (SD 9.0). The average survival time for those infected with HIV/AIDS was 49.6 months (SD 50.4) and the average age at time of death was 36.3 for women (SD 10.5) and 38.6 for men (SD 9.3) Table .In terms of the level of health, the average DALY for patients with HIV/AIDS in Andalusia was 33.01 (SD 21.98) – 31.15 for the women (SD 24.78) and 33.37 for the men (SD 21.38). The average number of Years of Life Lost due to HIV/AIDS was 29.06 (SD 24.36) – 26.82 for the women (SD 27.09) and 29.49 for the men (23.77). The average value of Years Lived with Disability due to HIV/AIDS was 3.95 (SD 4.06) – 4.33 for the women (SD 4.16) and 3.88 for the men (4.04).In the bivariate analysis, female intravenous drug users had lower levels of health, i.e. they had higher YLLs, YLDs and DALYs due to HIV/AIDS  than those who did not use intravenous drugs   and higher DALYs (p = 0.039). Likewise, a link was found between living in Malaga and having a lower YLD.In addition, a link was found between living in Granada at the time of diagnosis and lower YLLs (p < 0.001), higher YLDs (p = 0.020) and lower DALYs (p < 0.001).A link was found between older age at the time of diagnosis and lower Years of Life Lost due to the illness (Coefficient = -0.446), lower Years of Life with Disability (Coefficient = -0.087) and lower Disability-Adjusted Life Years (Coefficient = -0.533).In the multivariate analysis with linear regression a model was found which explained 24.5% (Coefficient of determination = 0.245) of the level of health (DALY)  than those who did not use intravenous drugs   and Cadiz (p = 0.003) was found to be linked to higher YLLs and higher DALYs (p = 0.039), living in Almeria (p = 0.030) and Malaga (p = 0.010) was to be linked to higher YLDs, and living in Huelva (p = 0.039) and Cadiz (p = 0.001) was found to be linked to higher DALYs. In addition, a link was found between living in Granada at the time of diagnosis and lower DALYs (p = 0.001).Older age at the time of diagnosis was found to be linked to lower Years of Life Lost due to the illness (Coefficient = -20.437), lower Years of Life with Disability (Coefficient = -20.17) and lower Disability-Adjusted Life Years (Coefficient = -16.411).In the multivariate analysis with linear regression a model was found which explained 64.4% (Coefficient of determination = 0.644) of the level of health (DALY). A higher level of health (lower DALY) was found to be linked to intravenous drug use, the province of residence, being diagnosed during the HAART era and older age at the time of diagnosis  and a higher level of health amongst patients with HIV/AIDS. This reflects the effectiveness of the treatment. Most studies have shown that HAART is more effective than the technologies used before its introduction -24.The differences in levels of health according to the province of residence at the time of diagnosis may be a result of different clinical practices in the different healthcare centres. It is also possible that different cultural factors influence patients' access to healthcare services. Other studies must be carried out in order to evaluate these differences.An older age at time of diagnosis linked to lower DALY, it could be related to shorter life expectancy. This result could be used as an argument in the debate about whether it is appropriate to assign age-related weightings in the calculation of DALYs. However, some researchers believe that if age is taken into account, other factors such as social roles (occupation or productivity), or income, would also have to be considered . The maiThe factors linked to the level of health were the same for both sexes. However, the coefficient of determination was different, and was higher amongst the men in the sample group than amongst the women. This suggests that there are other variables at play which are not specified in the model (not available in the database), and which lead to differences and asymmetry between the two groups. The data merely allow us to make speculative suggestions about what these other variables may be, and they could include access to the healthcare system, social support and even therapeutic bias.One limiting factor of this study is the fact that it did not include clinical factors, such as CD4 levels, the viral load or severity of the illness, number of years as an HIV carrier, adherence to treatment or coinfection, and as such the mortality rate was not adjusted to take these parameters into account. We would recommend that these data are included in future research so that the results of this study can be confirmed.Advances in HIV/AIDS treatment have led to greater survival rates and limited quality of life amongst patients, with a considerable burden of disease. Healthcare services must meet the challenge of offering the care required for HIV/AIDS patients, providing them with the treatment available and facilitating access to the whole population. In this way, factors which are extrinsic to the patient's clinical situation, such as the province of residence at the time of diagnosis or intravenous drug use, will cease to be related to the burden of disease. However, other socio-economic attributes could have played important role independent of treatment and care, more so when injecting drug users constituted the bulk of the study populations. Improvement of HIV care would certainly improve DALY but not completely because HIV is not simply a medical disease.A higher level of health (lower DALY) amongst both men and women was found to be linked to intravenous drug use, the province of residence, being diagnosed during the HAART era and older age at the time of diagnosis.HIV/AIDS: The human immunodeficiency virus (HIV) and acquired autoimmune deficiency syndrome (AIDS); YLL: Life lost due to premature mortality; YLD: Years lost due to disability; DALY: Disability-adjusted life years.The authors declare that they have no competing interests.CBT and AOLL drafted the manuscript. CBT participated in the design of the study and performed the statistical analysis. JJMM and IRP conceived of the study, participated in its design and coordination and helped to draft the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


Factors associated with the survival of truth of clinical conclusions in the medical literature are unknown. We hypothesized that publications with a first author having a higher Hirsch' index value (h-I), which quantifies and predicts an individual's scientific research output, should have a longer half-life.474 original articles concerning cirrhosis or hepatitis published from 1945 to 1999 were selected. The survivals of the main conclusions were updated in 2009. The truth survival was assessed by time-dependent methods (Kaplan Meier method and Cox). A conclusion was considered to be true, obsolete or false when three or more observers out of the six stated it to be so. 284 out of 474 conclusions (60%) were still considered true, 90 (19%) were considered obsolete and 100 (21%) false. The median of the h-I was = 24 (range 1–85). Authors with true conclusions had significantly higher h-I (median = 28) than those with obsolete  or false conclusions . The factors associated (P<0.0001) with h-I were: scientific life (h-I = 33 for>30 years vs. 16 for<30 years), -methodological quality score (h-I = 36 for high vs. 20 for low scores), and -positive predictive value combining power, ratio of true to not-true relationships and bias . In multivariate analysis, the risk ratio of h-I was 1.003 , and was not significant (P = 0.56). In a subgroup restricted to 111 articles with a negative conclusion, we observed a significant independent prognostic value of h-I . Using an extrapolation of h-I at the time of article publication there was a significant and independent prognostic value of baseline h-I .The present study failed to clearly demonstrate that the h-index of authors was a prognostic factor for truth survival. However the h-index was associated with true conclusions, methodological quality of trials and positive predictive values. Science progresses via a series of paradigms that are held to be true until they are replaced by a better approximation of reality In the previous study, we did not analyze any author's related factor We used 474 previously assessed articles non-randomized studies, randomized trials and meta-analyses. In each five year period we selected 20 non-randomized articles from two journals, 10 published in Lancet and 10 in Gastroenterology. In each period we tried to select 20 randomized trials on cirrhosis or hepatitis, 10 from Lancet and 10 from Gastroenterology. We chose these two journals because they have published clinical studies in hepatitis and cirrhosis since at least 1945, because they are peer- reviewed with a high level of selection and have a high impact factors greater than 10. A hand search was utilized to select articles from 1945 to 1985. As a true randomization was very difficult to organize we used a selection by order of publication inside each 5 year period. The first article of the period concerning cirrhosis or hepatitis was chosen, then the last of the period, then the second, and then the one before the last and so on up to 20 articles. From 1985 to 1999 we used PUBMED electronic search specifying the following “limits”: cirrhosis or hepatitis, human, Lancet or Gastroenterology. Abstracts were randomly downloaded using a similar selection method, stratified by five year periods. We selected the first abstract listed on the first electronic page, then the first on the last electronic page, then the last on the second electronic page, then the last on the page before the last and so on up to 20 articles.We identified original articles concerning cirrhosis or hepatitis in adults from 1945 to 1999 in 11 five year periods. The articles selection was stratified into 3 categories: In each period we tried to select 20 randomized trials on cirrhosis or hepatitis, 10 from Lancet and 10 from Gastroenterology. This was possible from 1970 to 1999. In the periods from 1945 to 1969 we selected all identified randomized trials whatever the journal, with a range from four (1945-1950) to 20 trials (1965-1969). From 1945 to 1982 we used the_ manual method the hand searching method as previously described The one conclusion from each abstract that seemed to best summarize the findings was copied to a database. Editing of these sentences was restricted to the rephrasing of outdated terminology and the elimination of redundant words.Six hepatologists, called the observers, assessed the form which contained the selected conclusions in a random order. The observers were fulltime hepatologists from different subspecialties but working in a hospital and aged from 31 to 65 years. Observers were blind to the period, the journal, the authors, the method , and the methodological quality from which each conclusion was derived. They classified each conclusion into one of three categories: 1) still true in 2000 (updated in 2009), 2) obsolete but not false, 3) false.The following seven factors were analyzed; 1) the design ; 2) the quality assessment of randomized trials and meta-analyses had been made independent of this study by one of us (TP) by means of scoring methods A conclusion was considered to be true, obsolete or false when three or more observers out of the six stated it to be so. When there was a split decision 3 to 3 regarding conclusions being true-not true the final conclusion was considered to be true; these splits concerned 9 out of 474 (1.9%) articles. When there was a split decision 3 to 3 regarding conclusions being obsolete-non obsolete the final conclusion was obsolete; these splits concerned 26 articles out of 474 (5.5%). When the article was not classified as either true or obsolete it was considered as false. The half-life was calculated according to the Kaplan Meier method using the censored time as the duration between the year of publication to the year 2000 (updated in 2009). The censored time is the time at risk of being refuted or found to be obsolete. We analyzed the truth survival: if the conclusion was assessed to be still true the case was censored at the end of follow-up. If the conclusion was assessed to be false or obsolete it was considered as a failure. The comparison between factors used the two-sided logrank test and the multivariate analysis proportional hazard regression analysis.The h-I of first authors was the main prognostic factor assessed in the present study. The h-I were assessed in the first 6 months of 2010. The h-I was originally computed using Google Scholar  for first authors. Because Google Scholar is not a perfect Gold Standard of estimating h-I, other methods were used. The commonness of last names can introduce a false estimate of the h-I The date of the publication as well as the scientific age of the author (time between first and last publications) are mathematically associated with the h-I, which is cumulative, and increases over time The seven characteristics of studies No change was made for the selection of articles, and methodological quality assessment. Observer conclusions were updated in 2009, that is with 10 years more of follow-up. One previous observer had retired, two had moved and two new ones agreed to participate . The observers were asked to modify their previous conclusions if necessary. A conclusion was changed when at least three observers out of the five stated it to be so. Five changes occurred, one previously false conclusion and one previously obsolete became true, two previously true became false and one became obsolete.The main a priori endpoint was the prognostic value of the h-I  in the multivariate analysis including previously identified prognostic factors. The other “significant” P values were detailed when < = 0.10 and were described as NS if >0.10.Statistical descriptions and analyses used non-parametric methods. Median was expressed with a 95% confidence interval. Multiple comparisons used the Kruskal Wallis variance analysis with Dunn s' multiple comparison test. In comparison with the previous analysis the same time-dependent analyses were used. 2010), for an author with a mean speed (h-speed) of 2.53, it was possible to extrapolate that for one article of the present database published in 1995 (h-Ibaseline) the h-I was at this baseline date: h-Ibaseline = h-I2010- (h-speed × (2010-1995))  = 81-2.53x(15) = 43. This baseline h-I was also assessed in the prognostic analysis.It was not possible to assess directly the h-I of the author at the time of publication (baseline h-I) for each article included in the present survey. However it was possible to estimate the baseline h-I using backwards the progression rate of the given h-I. For example a Scholar h-I = 81 in 2010  were still considered true, 90 were considered obsolete (19%) and 100 (21%) false. The half-life of truth was 45 years. The survival rate of conclusions was 85% (95%CI 83-89%) at 20 years and -52%  at 40 years.The first author Scholar h-I  was 24 (20-27), with a range from 1 to 85, and an increase of 0.87 (0.82-0.93) h-I per year of scientific life. There was a skewed distribution, not normal, with 33 articles published by 21 authors with h-I values -of 60 or higher. For authors publishing after 1994, the h-I, estimated using Scopus, was 17 (15-20) with an increase of 1.13 (1.00-1.40) per year. For the period after 1980, the h-I estimated using ISI, was 21 (17-25) with an increase of 0.72 (0.63-0.88) per year. The median baseline h-I was 0 (0-0) before 1965 and 6 (5-8) after 1980.As expected the h-I was highly associated with duration of scientific life and recent publications . AuthorsArticles with true conclusions had significantly higher h-I  than those with obsolete  or false conclusions  . The samUsing univariate and not time-dependent analysis, the h-I was also associated with methodological quality either using scores  or positThere was no significant association between the h-I and truth survival using time-dependent analysis both in uni- and multivariate analyses . CompariFor the main endpoint the risk ratio of the h-I was 1.003 (0.994-1.011) and was not significant (P = 0.56). There was a significant difference of the 50 years survival of conclusions according to the negative or positive finding, 72±12% (negative finding) and 40±3% (positive finding), respectively (P<0.0001) .In a subgroup analysis restricted to 111 articles with negative conclusions we observed a significant independent predictive value of the h-I in multivariate analysis . Negative conclusions of authors with an h-I >24 had an 82%±6% 50 years survival vs. 65%±9% for those < = 24 (NS). The observed difference was even greater among the Lancet's studies: 74%±16% vs. 47%±18% (NS).The 50 year survival of the 30 higher h-I “outstanding category” conclusions was 48% (95% CI 29-73%) vs. 35%  among the others. Using Scholar h-I and ISI h-I the 25 year survival of the 30 higher vs others were 67% (44-90%) vs 60%  and 71% (51-90%) vs 59% .Concordance between the h-I estimated using Google scholar on the overall scientific life of authors and the h-I estimated using Scopus and ISI for the scientific life after 1994, was assessed for the 217 authors of articles published after 1994 and applicable ISI (1à not applicable out of 227). There was a highly significant concordance between the 3 h-I estimates. The Spearman's rank correlation between Scholar and Scopus was 0.72, between Scholar and ISI 0.81 (P<0.0001) and between Scopus and ISI 0.82 . The median h-I Scholar value was 31  with a median of 29 years (95%CI 28-32) of scientific life; the median h-I Scopus value was 17  with a median of 15 years  of scientific life; the median h-I ISI value was 21 . The rate of h-I per year was 1.08  according to Scholar 1.13  according to Scopus and 0.73 (95%CI 0.63-0.88). The classification of authors that ranked above/under the h-I median by Scholar (>31), by Scopus (>17) or by ISI (>21) had a high kappa concordance rate of  =  Scholar/Scopus 0.61 , Scholar/ISI 0.69  and Scopus/ISI 0.85 . For h-I rate above/below 1 per year, the kappa were Scholar/Scopus 0.45 , Scholar/ISI 0.59  and Scopus/ISI 0.31 . In comparison with h-I estimated using Google Scholar, the h-I estimated using Scopus or ISI had similar variability according to characteristics of included first author  and origFor baseline H-I the prognostic value was opposite between uni and multivariate analyses. Using univariate comparison , articleWe observed that the h-I at the end of the study was associated with true conclusions, but its prognostic value did not survive with time-dependent analysis as previously observed for methodological quality. On the contrary baseline h-I (when the paper was written), was significantly and independently associated with truth survival, when adjusted on other covariables. Negative conclusions remained a robust and independent predictor of truth survival We confirmed in the present study the intriguing prognostic value of negative conclusions , which persisted after other factors had been taken into account. This prognostic value was not due to obsolete conclusions as among negative conclusions, as only 2% of negative conclusions had been rated as obsolete compared to 25% of positive conclusions. We found few negative studies which had been published in order to reveal previous false positive conclusions (Proteus phenomenon) Subgroup analyses are hazardous, but in a multivariate analysis restricted to 111 articles with negative conclusions we observed a significant independent predictive value of the h-I. This retrospective observation without a priori hypothesis must be confirmed by another study. We previously observed in the present cohort that the prognostic value of negative versus positive conclusions was mainly due to high differences among the randomized trials' conclusions: 68±13% for 52 negative conclusions compared with 14±4% (P<0.001) for 118 positive conclusions Our study has significant limitations. The study is retrospective between 1945 and 2000 and only prospective for the last 10 years of follow-up (updated in 2009). The inclusion criteria selected authors who may not have been representative of the overall biomedical community. They had published articles on liver diseases with high methodological levels  in two competitive journals (mainly Lancet and Gastroenterology) with high impact factors in 2008, 28.4 and 12.6, respectively. We also used methods to assess methodological quality which are not the most recent and valid ones.This selection should explain the high observed h-I . The h-I cannot be compared between different scientific fields or between different periods of publications There is no gold standard for scientific truth definition. We used a definition that was decided by the majority vote of a panel of 5 experts, 10 to 65 years after the findings' publication. The main advantage was the duration of follow-up with subsequent progresses in the field of knowledge. The main weakness was the arbitrary choice of experts. To limit the risk of bias, the experts were chosen from different domains of Hepatology and had different ages The h-I estimates had limitations and we cannot rule out that these limitations might be able to explain the absence of clear and independent prognostic values Finally the extrapolation of baseline h-I at the year when the paper was written suggest a clear and independent prognostic value of h-I. The main limitation of this index in comparison with the 2010 h-I estimates, is its indirect assessment. This extrapolation rely on the normality and linearity of the h-I progression rate. We used median to reduce the risk of variability but a real prospective validation of the h-I prognostic value is needed.The h-I is simple, probably more accurate than other citation indexes for estimating authors' scientific outputs, and it is accepted when its limitations are understood For living hepatologists, at least, our conclusions were balanced. The present study failed to clearly demonstrate that the h-index of authors was a prognostic factor for truth survival. However the h-I was partly validated as associated with true conclusions, the methodological quality of trials and with positive predictive values combining power, ratio of true to not-true relationships and bias.Furthermore an indirect (extrapolated) estimate of baseline h-I clearly observed a high and independent prognostic value for articles published after 1980. Prospective study in the next decades should be initiated to confirm this observation.Table S1(0.07 MB DOCX)Click here for additional data file.Table S2(0.09 MB DOCX)Click here for additional data file.