Science funding in low- and middle-income countries: the example of vaccine research.

There has been a recent increase in funding sources and overall commitment to tackle global health issues and reduce morbidity and mortality. The Wellcome Trust, the UK's largest charity, has a long track record of funding research in global health and has developed a new research strategy to tackle these issues. Here, we describe the Wellcome Trust's approach to funding researchers in low- and middle-income countries with a focus on how our funding portfolio supports vaccine delivery and development, with specific reference to mucosal immunity.

Human immunodeficiency virus (HIV) in developing countries.

The human immunodeficiency virus (HIV) is causing the most destructive epidemic of recent times, having been responsible for the deaths of more than 25 million people since it was first recognised in 1981. This global epidemic remains out of control, with reported figures for 2005 of 40 million people infected with HIV. During 2005 there were 4.9 million new infections, showing that transmission is not being prevented, and there were 3.1 million deaths from the acquired immunodeficiency syndrome (AIDS), reflecting the lack of a definitive cure and the limited access to suppressive antiretroviral treatment in the developing countries that are most severely affected. The current state of the epidemic and the response to date are here reviewed. Present and future opportunities for prevention, treatment and surveillance are discussed, with particular reference to progress towards an HIV vaccine, the expansion of the provision of highly active antiretroviral therapy, and the need to focus control programmes on HIV as an infectious disease, rather than as a development issue.

Understanding sexual behaviour change in rural southwest Uganda: a multi-method study.

Studies report substantial sexual behaviour change in Africa in response to HIV/AIDS. Generally there seems to be an increase in condom use and a reduction in partners, with men reporting more change than women. However, it is not only important to know whether people are changing their sexual behaviour but also their reasons for changing and the consistency and extent of change. Between 1996 and 2000 a study involving 196 respondents was carried out in rural southwest Uganda to investigate the exact nature of behaviour change and the reasons for change or lack of change since people became aware of HIV/AIDS. Data were collected from three rounds of questionnaire surveys, four rounds of open in-depth interviews, six rounds of semi-structured interviews and from informal conversations and participant observation. In order to obtain a comprehensive assessment of behaviour change the data for each participant from all sources were compared and discrepancies were then followed up by re-interviewing participants. After triangulation between all sources of data, 48% of respondents had ever used a condom. Condom use in 76% of all cases was at least partly AIDS related, while 19% was exclusively for protection against HIV. Condom use tended to be sporadic: only 13% of condom users currently used a condom regularly and most of this use was for family planning. After triangulation, 45% had reduced the number of sexual partners. Of all partner reductions, 93% was at least partly AIDS related; 29% was exclusively to avoid HIV. Half of those who had reduced the number of partners either stuck to one partner or abstained. Men reported more change than women. Of those who reported no partner reduction, 89% could not reduce the number of partners because they already had only few or a single partner or abstained; most of these were women. Most of those who could change their sexual behaviour had already changed, though the degree of change (particularly condom use) was often minimal. Not only behaviour change, but also the maintenance of safe behaviour is important. Also, understanding reasons for change and extent and consistency of change are important when planning and evaluating interventions.

Aetiology of sexually transmitted infections and response to syndromic treatment in southwest Uganda.

OBJECTIVE: To determine the aetiology of genital ulcers and discharges in rural south western Uganda and to assess response to syndromic treatment. METHOD: A longitudinal, prospective study using laboratory testing and questionnaires to evaluate 561 adult men and women presenting with clinically verified genital ulcers, urethral, or vaginal discharge at a general outpatient clinic and two health centres between December 1999 and July 2001. RESULTS: One third of patients had genital ulcers and two thirds discharges. There was good response to treatment in 461/508 patients (90.7%). Herpes simplex virus type 2 was found in 95/217 (43.8%) genital ulcers. In 24.1% of ulcer cases there was also a genital discharge. HIV seropositivity was high in ulcer cases (63.2%), with significantly more HSV2 and secondary bacterial infection than in seronegative cases. Neisseria gonorrhoeae was found in 135/204 (66.2%) male genital discharges. Female genital discharges were mostly associated with bacterial vaginosis (36.1%), Trichomonas vaginalis (18.9%), and candidiasis (18.6%). CONCLUSIONS: The aetiological pattern of STI syndromes reported will help inform revision of national STI guidelines. The importance of herpes simplex virus type 2, the variation in causes of genital ulcers according to HIV serostatus, the high frequency of multiple infections and secondary bacterial contamination of genital ulcers are notable. These results help explain the lack of effect of an STI intervention on HIV incidence in a recent trial in this area.

The effect of tuberculin skin testing on viral load and anti-mycobacterial immune responses in HIV-1-infected Ugandan adults.

OBJECTIVE: To determine whether tuberculin skin testing (TST) is associated with an increase in human immunodeficiency virus (HIV) viral load, and to examine the effect of TST on anti-mycobacterial immune responses. DESIGN: A nested cohort study of HIV-1-infected adults. METHOD: Forty-two participants (21 TST-positive and 21 TST-negative) from a larger cohort were recruited to the study. Blood was collected for CD4+ T-cell count, whole blood was cultured, and plasma saved for viral load. These measurements were taken before, 3 days after, 3 months after, and 3 months plus 3 days after TST. Cytokine responses to culture filtrate proteins (CFP) of Mycobacterium tuberculosis and phytohaemagglutinin (PHA) were examined in the whole blood assay. RESULTS: Twenty-nine participants attended all four visits. No statistically significant change in viral load, CD4+ T-cell count, or cytokine response to PHA was observed at any visit. However, TST was associated with a transient increase in the interferon-gamma response to CFP and a lasting increase in the interleukin-5 response to CFP. CONCLUSION: There appeared to be a systemic effect of TST on the anti-tuberculosis immune response.

Community sex education among adolescents in rural Uganda: utilizing indigenous institutions.

Although adolescent girls in Uganda are particularly vulnerable to HIV infection, providing relevant sexual health education to them is problematic. The senga (father's sister), is the traditional channel for socializing adolescent girls into sex and marriage among many ethnic groups in Uganda. This paper discusses the implementation and community acceptability of 'modern' sengas who were trained to provide HIV-related counselling to adolescent girls. Fourteen sengas were trained in two villages and, in the course of the 1-year study, 247 individuals made a total of 403 visits to them. By including both traditional services (such as advice on and assistance with labial elongation) and modern health and sex education, the sengas provided a 'middle road' between tradition and modernity. As a result, despite initial suspicion by the community, their activities were supported by the community generally and effective as intervention.

Incidence of visual loss in rural southwest Uganda.

BACKGROUND: Surveys have been conducted to measure prevalence of eye disease in Africa, but not of incidence, which is needed to forecast trends. The incidence of visual loss is reported in southwest Uganda. METHODS: A rural population residing in 15 neighbouring villages was followed between 1994-5 (R1) and 1997-8 (R2). Survey staff screened adult residents (13 years or older) for visual acuity using laminated Snellen's E optotype cards at each survey. Those who failed (VA >6/18) were evaluated by an ophthalmic clinical officer and an ophthalmologist. Incidence of visual loss (per 1000 person years (PY)) was calculated among those who had normal vision at R1. RESULTS: 2124 people were studied at both survey rounds (60.9% of those screened at R1); 48% were male. Participants in R1 were older (34.7 versus 31.5 years at R2, p<0.001). Visual loss in R2 occurred in 56 (2.8%) of 1997, yielding a crude incidence rate of 9.9, and an age standardised incidence rate of 13.2, per 1000 PY. Incidence of visual loss increased with age from 1.21 per 1000 PY among people aged 13-34 to 64.2 per 1000 PY in those aged 65 years or older (p for trend >0.001). The six commonest causes of visual loss were: cataract, refractive error, macular degeneration, chorioretinitis, glaucoma, and corneal opacity. If similar rates are assumed for the whole of Uganda, it is estimated that 30 348 people would develop bilateral blindness or bilateral visual impairment, per year. CONCLUSIONS: Cataract and refractive error were the major causes of incident visual loss in south west Uganda. These data are valuable for forecasting and planning eye services.

Social marketing of pre-packaged treatment for men with urethral discharge (Clear Seven) in Uganda.

We implemented social marketing of pre-packaged treatment for men with urethral discharge (Clear Seven) in Uganda, and studied its feasibility, acceptability and effectiveness as a possible means to treat STDs and thereby prevent HIV. Clear Seven was distributed at private health care outlets in three rural districts and two divisions of the capital. Comparisons were made with a pre-intervention period in the same sites plus one additional rural district. There were almost universally positive attitudes to Clear Seven. Cure rate (84% versus 47%), treatment compliance (93% versus 87%), and condom use during treatment (36% versus 18%) were significantly higher among Clear Seven users (n=422) than controls (n=405). Partner referral was similar but fewer Clear Seven partners were symptomatic when seeking treatment. Distribution of socially marketed pre-packaged treatment for male urethritis should be expanded in sub-Saharan Africa. Consideration should be given to developing similar kits for women.

HIV-1 epidemic trends in rural south-west Uganda over a 10-year period.

The objective of this study was to examine the epidemic trends of HIV-1 infection in a rural population cohort in Uganda followed for 10 years. The methods used were to assess incidence and prevalence trends in adults in this longitudinal cohort study. The results showed that incidence of infection has fallen significantly in all adults, and separately in males, females, young adults and older adults over the course of the study period. There was also a reduction in prevalence, especially in young men and women. There was some evidence of a cohort effect in women. The conclusions are that this study provides the first evidence of a falling incidence in a rural general population in Africa. This was an observational cohort exposed to national health education messages, giving hope that similar campaigns elsewhere in Africa could be used effectively in efforts to control the HIV epidemic.

Generalizability of population-based studies on AIDS: a comparison of newly and continuously surveyed villages in rural southwest Uganda.

BACKGROUND: Population-based studies are thought to provide generalizable epidemiological data on the human immunodeficiency virus type 1 (HIV-1) epidemic. However, longitudinal studies are susceptible to bias from added attention caused by study activities. We compare HIV-1 prevalence in previously and newly surveyed villages in rural southwest Uganda. METHODS: The study population resided in 25 neighbouring villages, of which 15 have been surveyed for 10 years. Respondents (>/=13 years) provided socio-demographic and sexual behaviour data and a blood sample for HIV-1 serology in private after informed consent. We tested the independent effect of residency: (1) original versus new villages; (2) proximity to main road; and (3) proximity to trading centre on HIV-1 serostatus of respondents using multivariate logistic regression. RESULTS: There were 8,990 adults censused, 68.3% were from the original villages, 48.2% were males and 6111 (68.0%) were interviewed and had definite HIV-1 serostatus. The HIV-1 prevalence was 6.1% overall, 5.7% in the new, and 6.4% in the original villages (P = 0.25). Residency in the new or original villages did not independently predict HIV-1 serostatus of respondents (P = 0.46). Independent predictors of HIV-1 serostatus were education (primary or higher, odds ratio [OR] = 1.7 and 1.4, respectively), being separated or widowed OR = 4.2, reported previous use of a condom OR = 1.8, or reported genital ulceration OR = 3.3, and age group 25-34 and 35-44 years OR = 5.8 and OR = 4.8 (all P

Evaluation of E-optotypes as a screening test and the prevalence and causes of visual loss in a rural population in SW Uganda.

BACKGROUND: Few population-based eye surveys have been conducted in sub-Saharan Africa, limiting the quality of epidemiological information on visual loss from Africa. In the present paper, we describe the prevalence of visual loss in rural Uganda and the screening accuracy of E-optotypes when used by non-medical staff. METHODS: Residents of 15 neighbouring villages were screened for visual loss (<6/18 in either eye) using Snellen's E-optotypes. Individuals who failed were initially referred to an ophthalmic clinical officer (OCO), who retested visual acuity and subsequently referred to an ophthalmologist to determine the cause of visual loss. Subjects from two villages (248 individuals) who passed visual acuity screening were re-examined by the OCO to estimate the accuracy of the screening procedure. RESULTS: Of the 4076 adults (aged 13 years and over, 69.3% of the censused population) who participated, 191 (4.7%) failed the vision screening criteria and 648 (15.9%) had non-vision impairing conditions. The prevalence of visual loss was at least 3.9%: 0.4% had bilateral blindness, 1.6% had bilateral visual impairment, 0.7% had unilateral blindness and 1.2% unilateral visual impairment. Cataract was the leading cause for all categories of visual loss except bilateral blindness, for which suspected glaucoma was most frequent. Refractive errors were the second leading cause of bilateral and unilateral visual impairment. Based on one subject (0.4%) in the validation sample who was found to have low vision, we estimated the sensitivity and specificity of E-optotypes for detecting visual loss to be 93% and 99%, respectively. CONCLUSIONS: Cataract and refractive errors were responsible for most of the visual loss in rural Uganda. Snellen's E-optotypes provide a suitable cost-saving tool for conducting population-based eye surveys in sub-Saharan Africa.

Declining HIV-1 incidence and associated prevalence over 10 years in a rural population in south-west Uganda: a cohort study.

BACKGROUND: In Uganda, there have been encouraging reports of reductions in HIV-1 prevalence but not in incidence, which is the most reliable measure of epidemic trends. We describe HIV-1 incidence and prevalence trends in a rural population-based cohort between 1989 and 1999. METHODS: We surveyed the adult population of 15 neighbouring villages for HIV-1 infection using annual censuses, questionnaires, and serological surveys. We report crude annual incidence rates by calendar year and prevalence by survey round. FINDINGS: 6566 HIV-1 seronegative adults were bled two or more times between January, 1990, and December, 1999, contributing 31984 person years at risk (PYAR) and 190 seroconversions. HIV-1 incidence fell from 8.0 to 5.2 per 1000 PYAR between 1990 and 1999 (p=0.002, chi(2) for trend). Significant sex-specific and age-group-specific reductions in incidence were evident. Incidence was 37% lower for 1995-99 than for 1990-94 (p=0.002, t-test). On average, 4642 adult residents had a definite HIV-1 serostatus at each yearly survey round. HIV-1 prevalence fell significantly between the first and tenth annual survey rounds (p=0.03, chi(2) for trend), especially among men aged 20-24 years (6.5% to 2.2%) and 25-29 years (15.2% to 10.9%) and women aged 13-19 years (2.8% to 0.9%) and 20-24 years (19.3% to 10.1%) (all p<0.001, chi(2) for trend). INTERPRETATION: Our findings of a significant drop in adult HIV-1 incidence in rural Ugandans give hope to AIDS control programmes elsewhere in sub-Saharan Africa where rates of HIV-1 infection remain high.