The specific objectives and recent results of the current projects can be summarized as follows:

• Tuberculosis: Drug resistance surveillance

The general aim of this project is to document the prevalence of drug resistant TB in various continents and regions, both to provide useful information for treatment regimens and to evaluate TB control programmes. Our studies made clear that two approaches could be applied for this purpose: representative sample surveys that can be repeated every 5 years, and follow-up of drug resistance in relapse and failure cases. The focus lies on first-line drugs, but if possible and if appropriate in the settings, second-line drugs are included as well. Furthermore, this project aims to evaluate various factors influencing the outcome of treatment regimens, such as the use of intermittent DOT regimens versus non-DOT daily regimens in the Philippines, and to evaluate different MDRTB regimens in Bangladesh. Besides resistance surveillance, operational research is included to improve direct microscopy, optimize specimen transport for culture, and optimize cheap, rapid and easy alternatives for the classical drug-susceptibility tests.

The general aim of this project is to gain a better understanding of the creation and amplification of resistance to the first-line drugs by TB bacilli in the course of treatment. Secondly, we want to estimate to what extent reinfection and initial multiple infection with various M. tuberculosis strains play a role in cases of apparent failure or relapse after treatment. Important types of resistance are always man-made, due to therapeutic errors, and are especially frequent where serious economic and management problems occur. Original short-course treatment regimens were based on daily dosing, and rifampicin use exclusively in a quadruple combination in the intensive phase. The replacement of daily by intermittent, twice or thrice-weekly dosing, and the use of R in combination with Isoniazide in the second phase, are two recent trends meant to make directly observed therapy (DOT) more feasible. In strictly controlled trials this yields equally good results as daily dosing, but it is far from clear to what extent these regimens may also cause resistance under field conditions. To achieve these objectives drug-susceptibility testing (including estimation of minimal inhibitory concentrations) and DNA-fingerprinting techniques will be applied on serial isolates from patients under various treatment regimens, as well as on duplicate pretreatment isolates.

• Tuberculosis: Search for mixed infections in patients from the penitentiary hospital in Tbilissi, Georgia

As the prevalence of MDRTB was found to be high (9% of isolates) in previous investigations, it was decided to treat all patients in the hospital with the standardized re-treatment regimen (Category 2) from the WHO, regardless of patients’ treatment histories. The three main objectives of this study are: Firstly, to determine the rate of re-infection with an MDRTB strain in this high-risk population. Secondly, to determine the risk of the ‘amplifier effect’, i.e., the creation of additional resistance during a standardized treatment in this setting with a high level of initial resistance. And thirdly, to determine the rate of mixed infections, i.e., the simultaneous infection with different M. tuberculosis isolates, and the extent to which treatment outcome is influenced by this phenomenon. Therefore, a cohort follow-up study including at least 300 smear-positive TB patients will be organized. Preliminary results showed the presence of possible mixed infections in about 8% of pulmonary TB patients in this setting. Furthermore, this study will allow us to determine the prevalence of resistance to second-line drugs in this setting with a relatively high MDRTB rate.

Most importantly, the envisaged study will take the researchers deep into the unknown world of TB patients and the daunting challenge of achieving cure through a protracted treatment schedule closely impacted on by health service policy and organization, and within a context of scarce resources. The study is to follow the broad path of the TB ‘career’ from diagnosis through the intensive and follow-up phases up to the variable outcomes of a treatment process in South Africa provided almost exclusively by the government-run primary health care (PHC) services. The study is to be comprehensive in its scope covering, in addition to the social and psychological experience, patterns of adherence to treatment among patients, costs to TB patients and their households, and a diverse range of health system factors. Parallel microbiological analyses will document the findings. All these will be investigated in the light of the South African government’s policy and programme to strengthen PHC and devolve resources and decision-making to district and local level. Although the research has not run its full course, some weak points and strengths of the local TB programmes have already been identified, leading to the first practical interventions. The decision was taken to (re-) train all clinic TB coordinators in the National Tuberculosis Control Programme, and to (re-) train 90% of all staff at clinics. Furthermore, stocktaking of the positive elements in TB control in this province of South Africa provided useful information for other provinces.

Tuberculosis (TB), which had been considered a disease of the past, has re-emerged as a serious problem in Europe as well as in the developing world. Even more alarming is the appearance of drug resistance. There are foci in Eastern Europe where one in four cases are caused by multi-drug resistant TB (MDR-TB) strains. A strategic obstacle for the improvement of TB control is the lack of inexpensive and simple techniques that can replace the slow and laborious conventional methods for diagnosing TB and detecting drug resistance. However, there are newer, more appropriate methodologies that warrant further evaluation. This Concerted Action will develop, adapt and evaluate some of these promising new tools. It will build upon collaborations that have developed between a network of European researchers and their Latin American colleagues. Preliminary studies by this group have begun to address some of the objectives in this project, and the work outlined will expand these collaborations to develop useful and appropriate methodologies and test them in prospective clinical trials in high TB prevalence areas. It will also gather information on the epidemiology of MDR-TB in Latin America.

The first general meeting in Antwerp (July 2002) was a general success, and launched the project.

• Development of new methods for the identification of the reservoir of Mycobacterium ulcerans and for a better understanding of the mode of infection of Buruli ulcer

One approach to improving our understanding of the ecology of Mycobacterium ulcerans has been to study the molecular epidemiology of M. ulcerans, for which several methods have been used: IS2404-RFLP, analysis of 16S rRNA, AFLP and DR analysis (spoligotyping). The discriminatory power of these fingerprinting analyses was limited, since isolates from different continents showed different patterns but it was not possible to differentiate isolates from the same country.

However fingerprinting methods have been successfully used to clarify the phylogenetical position of M. ulcerans towards its closely related species e.g. M. marinum. This study has been achieved and concluded the presence of intermediary forms between M. marinum and M. ulcerans and this is confirming Stinear et al. hypothesis in which M. ulcerans is a progenitor of M. marinum by acquiring DNA elements from the environment.

The general aim of this project is to better control Buruli ulcer (BU) in Benin by using a multidisciplinary approach. Trends in BU patients, as seen in a rural hospital of southern Benin, were evaluated on 1700 cases of Mycobacterium ulcerans disease cases (Buruli ulcer) treated at the "Centre Sanitaire et Nutritionnel Gbemonten", in Zagnanado (Benin). The patients lived in the 4 Regions of Southern Benin: Atlantique, Mono, Oueme and Zou, with the largest number coming from the Zou Region where the center is located. In this Region, the 1999 detection rate of Buruli ulcer (21.5/100 000 pop.) exceeded that of leprosy (13.4/100 000 pop.) and tuberculosis (20.2/100 000 pop.).

The median age of patients is 15 years (q1=7, q3=30). There is a significant difference in the age and sex composition, with more males in the under 20-year-old group while females are more frequent in the over 20-year-olds.

More than 13% of the patients have osteomyelitis. This form of the disease is related to the period of delay in presentation to the hospital. The median hospitalization time was reduced from 267 days in 1989 to 32 days in 2002. It was shown that effective BCG vaccination at birth protected BU patients against the development of severe forms of this disease such as osteomyelitis.

The influence of HIV infection on BU was also studied. It was confirmed the HIV infection plays an important role in the development and extent of dissemination of BU.

A multidisciplinary approach (e.g. education, training and treatment) is required for optimal management of M. ulcerans disease to decrease morbidity and socioeconomic impact of Buruli ulcer on rural populations in Benin.

• Development of diagnostic tools and medical prophylaxis to control bovine paratuberculosis

This collaboration aims to improve direct and indirect diagnostic tests for bovine paratuberculosis, a disease caused by Mycobacterium avium subsp paratuberculosis. Direct detection of these bacilli in stools will be emphasized by the development of an immunocapture assay to detect specific antigens and the optimization of a PCR assay. Improvement of indirect diagnostic tests to estimate the TH2 and TH0 cellular responses by quantifying IL-5 and IL-10 or GM-CSF, respectively, will allow us to determine the type of response and to see if this can help in predicting the evaluation of infection. Furthermore, the immunological capacity and efficiency of plasmid vaccines based on genes encoding for antigens A85A and A85B will be evaluated in existing mouse models and newly developed models in small ruminants. Finally, a newly developed DNA-fingerprinting method based on the insertion sequence IS900 (Flanking Sequence Polymorphism, FSP) will be optimized and evaluated on a panel of well-documented M. paratuberculosis isolates originating from wild and captive animals.

• As National Reference Laboratory for the identification and AST for M. tuberculosis and NTM, an external qualtiy control for AST for M. tuberculosis in perypheral laboratories in Belgium, was performed in collaboration with the Pasteur Institute of Brussels.

• As Supranational Reference Laboratory (SRL) for the Surveillance of Resistant Tuberculosis, recognized by the WHO, we participated in an external quality control for AST for M. tuberculosis. About 500 analyses were performed for laboratories in the former Soviet-Union.

• As International Reference Laboratory for the Control of Buruli Ulcer, recognized by the WHO, the Unit performed bacteriological analysis for the diagnosis of BU in West-African patients.

In Abidjan, Côte d’Ivoire, 32% of female sex workers (FSWs) and 13% of their male clients are infected with HIV. HIV-negative female sex workers are frequently exposed to the virus based on reported numbers of clients per day, consistency in using condoms and duration of sex work, and are estimated to have on average 57 unprotected sexual exposures to HIV per year. FSWs with a duration of sex work of more than 3 years are unlikely have remained HIV-negative by chance alone and possibly display an HIV-protective phenotype by one or several endogenous factors. In this population of HIV-exposed seronegative sex workers, immunological factors associated with protection against HIV infection are studied. Potential protective factors include both innate and adaptive immune responses. Expression levels of the HIV-1 coreceptor CXCR4, but not CCR5, were decreased among sex workers compared to controls. CXCR4 down-regulation was associated with a prolonged duration of sex work. However, an HIV protective role for the decreased CXCR4 expression remains unclear since HIV strains that are sexually transmitted predominantly use CCR5 as a coreceptor. Neither the CCR5 binding b -chemokines nor Th1 and Th2 cytokines were found to differ among the sex workers, but they were found to have slightly increased T cell activation levels compared to controls. Low-level HIV-specific T helper responses were detected in a minority of sex workers. Levels of HIV-specific T cells were directly associated with the frequency of HIV exposure among the sex workers. Exposed seronegative sex workers also had increased alloantigen-reactive humoral responses together decreased cellular responses compared to controls.

Genetic variability is a hallmark of the Human Immunodeficiency Viruses. Like any other RNA-virus, HIV exists as a quasispecies, i.e. a large set of distinct but related genomes. The error-prone nature of HIV’s reverse transcriptase enzyme is to blame for the rapid adaptation of the virus to immune pressure or antiretroviral treatment. In the last few years, the interest in viral fitness has increased. Fitness is a parameter that describes the replicative adaptation of a virus to its environment. Previously, we have shown together with our American colleagues that relative viral fitness can be related to HIV pathogenesis. Now, we are focussing on possible differences in viral fitness among HIV types, groups and subtypes. More specifically, we performed head-by-head dual infections/competitions with HIV-1 subtypes A, B, C, D and A/E, a selection of group O viruses and a variety of HIV-2 strains. The results are currently being analysed and written down in a paper. Furthermore, we are looking at the possible fitness-differences between syncytium-inducing and non syncytium-inducing viral clones and the fitness of circulating recombinant forms (more specifically CRF02_AG).

As the problem of drug resistance in HIV pathogenesis is reaching new heights, we also plan to study the evolution of viral fitness in multi-drug resistant patients.

• Development of a two-chamber system of epithelial cells and dendritic – T cell cocultures

We developed a co-culture system of dendritic cells (generated from monocytes with GM-CSF and IL-4) and autologous T cells to model early targets during sexual HIV transmission. This model seems suited to test antiviral compounds like nucleoside and non-nucleoside reverse transcriptase inhibitors (NRTI and NNRTI, respectively), acting between penetration of HIV into the target cell and integration into the host DNA. Other drugs, especially fusion and binding inhibitors, should instead act on the level of the epithelial cells of the vagina, cervix or rectum. To mimic this situation in our in vitro model, addition of epithelial cells to our present system is an important issue. A two-chamber model will be evaluated, consisting of a lower chamber with dendritic cells and T cells and an upper chamber with epithelial cells. Preliminary experiments indicated a confluent monolayer of endocervical or endometrial epithelial cells was a very potent barrier for HIV transmission, since even after 24 hours, no virus could be detected in the lower chamber. This probably reflects the in vivo situation, in which the risk for sexual HIV transmission is rather low (less then 0.1%). However, in vivo, the vaginal epithelium is also often damaged through inflammation and infection with other pathogens, e.g., herpes simplex viruses, resulting in a higher transmission of HIV. To evaluate this situation, we will "damage" the in vitro epithelial layer by infecting it with a herpes simplex virus (HSV-2), followed by an infection with HIV. Transmission of HIV and subsequent infection of target cells (dendritic cells and T cells) will be evaluated, together with the impact of the dual infection on the viral replication in these target cells and the influence on their immune function. Once we establishment this new model, several antiviral compounds can be evaluated for their potency in preventing or blocking infection.

There is an urgent need for HIV prevention, mainly in resource-poor settings. Condoms are not always acceptable and therefore vaginal microbicidal drugs may be an acceptable alternative.

We used an in vitro model, based on monocyte (MO)-derived dendritic cells (DC) and CD4 T cells, to evaluate the potency of several antiviral drugs as microbicides. The MO-DC constitute a model of mucosal DC, early targets during sexual transmission, having a crucial role in transfer of HIV to T cells, but also in the induction of a beneficial immune response against HIV.

In preliminary studies, we showed polyanionic binding-inhibitors, fusion inhibitors (T-20) and co-receptor blockers could suppress viral growth at concentrations of 10-100 µg/ml. However, these products were unable to really prevent HIV infection, unless they were used in concentrations that produced immune-suppression. By contrast, the NNRTI UC-781 and TMC-120 apparently could prevent infection at nanomolar concentrations, whereas immune suppression was only present in the micromolar range. Therefore, we further explored the use of several other, new NN-RTIs, discovered at the Centre for Molecular Design of Janssen Pharmaceutics. The results of these experiments were very promising and showed these new drugs were amongst the most potent ones we have tested so far. Complete suppression of viral replication was possible at concentrations of 10-100 nanomolar whereas immune suppression only occurs at concentrations of 1-10 micromolar. A selection of these compounds was evaluated for their potency to prevent infection if treatment was limited to 24 hours. In these experiments, prevention of infection was possible at drug concentrations of 10-100 nanomolar. These results indicate a short treatment, at the time of incubation of target cells with virus, can prevent infection of these target cells.

• Biological follow-up of HIV/AIDS patients in Senegal

The general aims of this project are to strengthen the capacity the laboratory of Virology and Bacteriology of the Faculty of Medicine and Pharmacy of the University "Cheikh Anta Diop" of Dakar, to train scientific and technical personnel and to evaluate new and mobile methods for the immunological follow-up of HIV/AIDS patients. The introduction of anti-retroviral treatment for HIV in Africa requires affordable virological and immunological follow-up. This kind of follow-up is currently difficult, in particular in remote reference centres. Simplified techniques are not always reliable and are often labour intensive. Sophisticated methods such as flow cytometry to perform CD4 counts are too expensive and require expensive reagents. In this project we evaluated a new, affordable and mobile cytometer to measure CD4 counts. The results of the evaluation are encouraging and show that follow-up can indeed be affordable although well-trained personnel are required to assure good quality.

The main objectives of this project are to identify and optimise laboratory test for the demonstration of protective immune responses (virus neutralization) and cellular immune responses; to adapt these methods for use in developing countries; and to train personnel from developing countries for laboratory monitoring after anti-retroviral therapy.

ITM has done a lot of research on the diversity of HIV in developing countries, which has contributed to our knowledge essential for vaccine development. Current laboratory test are unsuitable or insufficiently adapted to evaluate the protective capacity of anti-HIV vaccines under field conditions.

With the financial support of this project we were able to support the salary costs of the scientific department staff, to renew the "state-of-the-art" laboratory equipment of the laboratories, and to further develop laboratory tests to measure virus neutralization and cellular immune responses. With regard to laboratory testing, special attention was also paid to the evaluation of screening tests to monitor the recovery of the immune system after anti-retroviral therapy. In this regard the HIV p24 antigen test was assessed as a surrogate marker of HIV mRNA viral. Alternative tests for CD4 counting were evaluated. Laboratory training was provided to 6 technicians and 2 scientists from DRC, Ivory Coast, Senegal and Rwanda.

Within the existing Institutional collaboration between the Institutes of Tropical Medicine of Lima (IMTAVH) and IMT Antwerp, the following additional objectives were pursued through the Aids Impulse Programme: facilitating and up-scaling clinical studies to improve the management and treatment of AIDS-patients in Lima and Peru; linking these activities to the prevention of HIV transmission and to social action in Lima, with adolescents and pregnant women as special target groups, and establishment of an immunological laboratory at IMTVAH for the diagnostic follow-up of HIV-infection, AIDS-treatment, and related research on HIV and infectious diseases. The laboratory was fully equipped in 2002 (Facscalibur, incubators, laminar flow) and Guido Vanham spent two months (October-November 2002) at the Institute to train scientific personnel in laboratory immunology and immunological follow-up of HIV/AIDS patients under anti-retroviral treatment.

• The Unit of Immunology performs routine CD4 T cell determinations for the outpatient clinic of ITM in the context of laboratory follow-up of patients living with HIV/AIDS. The laboratory is also involved as a technical expert in the organization and follow-up of National Quality Control Program on lymphocyte immunophenotyping coordinated by Scientific Institute of Public Health (Wetenschappelijk instituut Volksgezondheid) of the Federal Government of Belgium. The laboratory is also advisor in the WHO steering committee, which provides recommendations for CD4 counting in resource poor settings, and participates in the organization of international workshops on the same subject.

• The laboratory provides technical support and training (CD4 counting) to scientists and technicians from developing countries. Now that the antiretroviral treatment (ART) of HIV is being introduced in developing countries, the need and demand for sound laboratory training e.g., for CD4 T-cell counts, has increased sharply.

• The laboratory evaluates new and affordable technologies for laboratory follow-up of patients under ART for in collaboration with international organizations such as Medicines Without Frontiers, WHO etc.

• Members of the scientific staff act as referees for international scientific Journals (AIDS, J. Acquired. Immune Deficiency Syndrome, Vaccine, Clinical and experimental Immunology, Tropical Medicine & International Health, The Lancet, J. Inf. diseases, J. Clin. Inf. Diseases and many others).

THEME 1: HIV VACCINE DEVELOPMENT
Subproject 1: Vaccine induced protective cross-neutralization of HIV-1
Aims:		To develop immunogens that induce humoral immunity to HIV-1
Sponsors:		Bill & Melinda Gates Foundation
Responsible staff:		Wouter Janssens
Subproject 2: Antigen indentification
Aims:		Identification of human Immunodeficiency Virus vaccine antigens and human broad neutralizing monoclonal antibodies
Sponsors:		IWT
Responsible staff:		Wouter Janssens
Subproject 3: Human HIV neutralizing antibodies of African origin
Aims:		Isolation and identification of neutralizing antibodies from recombinant phage display libraries generated from an African patient infected with HIV clade A virus through mother-child transmission.
Sponsors:		Institutional Funding (Aids Mecenaat)
Responsible staff:		Helen Donners
Subproject 4: NEUTNET
Aims:		Standardization of HIV neutralisation assays to be used in vaccine research and clinical trials, composed of 13 European international partners
Sponsors:		Part of European Sixth framework programme, without specific funding
Responsible staff:		Helen Donners and Leo Heyndrickx
Subproject 5: PBL-SCID model
Aims:		Study of the human humoral immune respons towards envelope proteins of HIV in an intrasplenic human PBL-SCID model
Sponsors:		FWO
Responsible staff:		Helen Donners and Leo Heyndrickx
THEME 2: HIV MICROBICIDES AND TRANSMISSION
Subproject 1: Modeling
Aims:		Development of in vitro models using primary cells to study heterosexual HIV transmission
Sponsors:		FWO and IWT
Responsible staff:		Yven Van Herrewege
Subproject 2: Pseudoviruses
Aims:		Development of pseudoviruses as screening tools in drug research
Sponsors:		Tibotec
Responsible staff:		Leo Heyndrickx
Subproject 3: Testing of candidate-microbicides
Aims:		Testing of novel concepts and pharmacological compounds for female-controlled prevention in various in vitro models
Sponsors:		EMPRO, Tibotec, ANRS
Responsible staff:		Yven Van Herrewege
THEME 3: HIV IMMUNOTHERAPY
Aims:		Development of a novel strategy to induce protective T cell responses in patients under HAART by using autologous viral sequences and autologous dendritic cells
Sponsors:		GOA; FWO; IWT and ANRS
Responsible staff:		Guido Vanham
THEME 4: HIV-2 RESISTANCE MONITORING
Aims:		Development of specific assays for screening and monitoring HIV-2 infected individuals starting antiretroviral therapy
Sponsors:		DGOS
Responsible staff:		Wouter Janssens
THEME 5: PROTEOMICS
Aims:		Analysis of interactions between viral and interferon-induced proteins by functional proteomics
Sponsors:		FWO
Responsible staff:		Wouter Janssens
THEME 6: HTLV-1 IN PERU
Aims:		An integrated cohort study on clinical, virological, immunological and human genetic aspects of Human T Lymphotropic Virus type 1 at the Instituto de Medicina Tropical of Lima, Peru
Sponsors:		DGOS and VLIR
Responsible staff:		Guido Vanham
THEME 7: DIAGNOSTICS
Aims:		Alternatives in diagnosis and follow-up in resource poor settings
Sponsors:		UNC/DGOS
Responsible staff:		Katrien Fransen/Amber Litzroth
Aims:		WHO Collaborating Centre for HIV/AIDS Diagnostic and Laboratory Support 2004-2008
Sponsors:		WHO
Responsible staff:		Katrien Fransen/Greet Beelaert
Abbreviations
ANRS	Agence Nationale de Recherche sur le SIDA – France
DGOS	Directoraal Generaal Ontwikkelings Samenwerking – Directorate General Aid in Development
EMPRO	European Commission
FWO	Fonds voor Wetenschappelijk Onderzoek Vlaanderen – The National Fund for Scientific Research
GOA	Gemeenschappelijk Onderzoeksfonds Antwerpen – Joint Research Fund Antwerp University
IWT	Instituut voor Wetenschaps Technologie – The Institute for the promotion of Innovation by Science and Technology in Flanders
UNC	University of North Carolina
VLIR	Vlaamse Interuniversitaire Raad – Flemish Inter-university Council
WHO	World Health Organization

The research activities have contributed to the development of strategies for STD/HIV control. There is strong cross-fertilisation between research on the one hand and technical assistance and teaching on the other hand.

This project is a follow up on The multicentre Study on Factors determining the Differential Spread of HIV in four African Cities which left several questions unanswered. The aim of this project is to gain better insights in the sexual behaviour of young people and in networking between commercial sex workers and their clients in four cities in sub-Saharan Africa. While the multicentre study employed a standardised questionnaire with closed questions this study employed qualitative methods. In each town, in-depth interviews on adolescent sexuality were conducted with 75 young men and 75 women (aged 15 to 20) using purposive, quota sampling, with age, educational and socio-economic variables. These interviews were transcribed verbatim and processed for analysis with qualitative analysis software (Atlas.ti). Open-ended questions treated current and past sexual experiences and contextual risk factors. Alongside, interviews were also done with 75 men (aged 20 to 49) in the general population and 50-100 clients of sex workers; though data from these interviews does not focus directly on adolescent behaviour, they may contain important information on men’s contacts with young adolescents or their own experiences as adolescents. 8 focus group discussions on perceptions of adolescent sexuality were also conducted in each town, as well as informal and formal observations of situations related to adolescent sexuality (such as youth attendance in video halls, dance parties, funerals, bars,).

Data analysis is nearly completed for two sites (Kisumu in Kenya and Ndola in Zambia) and is ongoing for the other two sites (Cotonou in Benin and Yaoundé in Cameroon). In December 2002 results of the study in Kisumu have been presented to stakeholders, including the provincial medical authorities, NGO’s and youth themselves through a number of workshops.

In 2001 the STD/HIV Research and Intervention Unit conducted a youth needs assessment in Nyanza Province, Western Kenya which is the region in Kenya worst affected by the HIV/AIDS epidemic (among adults in the capital Kisumu the prevalence of HIV infection is 25%). This assessment highlighted the inadequate responses of government and community to youth’s most pressing needs. Based on the proposals that young people themselves brought up and on the current knowledge of what works, a multi-component programme was designed. It aims to provide appropriate sexuality and reproductive health education, training in life skills, personal counseling and tailored health services to young people aged 10 to 20 years in two districts in Nyanza Province. It will also offer opportunities in vocational training and livelihood skills, and support income generating activities. A network of youth peer educators will conduct outreach activities in the communities and refer young people to the youth centre and the youth friendly clinic. The main objectives of the youth programme is to reduce the spread of HIV infection through a decrease in unsafe sexual behaviour. The effects of the programme will be assessed by a comparison between a baseline survey among youth in the general population and a follow-up survey.

The project has started in August 2002 and the first youth centre is expected to open in March 2003. The baseline survey is planned for March-April 2003.

This project consists of three parts:

1. A literature review is conducted to explore published studies related to very young adolescents. The review will focuses on interrelated issues and domains surrounding first sexual experience including: age and circumstances of first sex, relationship characteristics, sexual networking patterns and partner selection, age differences between sexual partners, use of health services, substance use, and other contextual factors that strengthen protective behaviours or enhance risky behaviours.

2. Through the "Study on Adolescents’ sexual behaviour and on contacts with sex workers in four African cities with different levels of HIV infection" qualitative research was conducted on sexual interactions of groups at high risk of HIV infection in four urban populations in Africa to reach a better understanding of their role in the dynamics of HIV infection and to identify prevention strategies (see above). The qualitative interviews with 150 youth aged 15-19 in each of the 4 cities are analysed to retrospectively check sexuality-related experiences which occurred when these youth were 10-to-14 years old, and to describe contextual factors that strengthen protective behaviour or enhance risky behaviours during this period and later in adolescence.

3. During site visits to Kisumu and Ndola, results from the qualitative study of youth sexuality are discussed with stakeholders and community members. During the site visits also an assessment will be made of interventions that are already being carried out to address the specific conditions of 10-to-14 year olds and/or explore which kinds of interventions local organisations/institutions can implement with and among the very young adolescents in order to delay first sex, reduce sexual partners, promote faithfulness and monogamous relationships, and promote condom use.

The objective of this study was to make an assessment of the utilisation of antiretroviral drugs (ART) in the private sector in Kinshasa, the drugs not yet being available in the public sector and in NGO projects. Interviews were taken from physicians, patients coming the reference laboratory of the Programme National de Lutte contre le SIDA for a CD4 count and clients of NGO’s that take care of HIV infected patients. The physicians that were interviewed had altogether more than 300 patients on ART. Most prescriptions were adequate but there was a big problem for patients to access the drugs. Twenty-eight samples of patients from Kinshasa on ART were tested for resistance. Testing of samples from patients in Pointe-Noire is still ongoing.

Based on data from the Centre de Traitement Ambulatoire of Pointe-Noire, which is supported by the French Red Cross, and a spreadsheet model estimates were made – under different assumptions – of the costs of caring for HIV infected patients at the CTA in Kinshasa which is being set up by Médecins sans Frontières Belgium.

Preliminary data from these studies as well as the spreadsheet model have been presented in Kinshasa at a workshop on care of HIV infected patients.

In the 1980’s up to 1991 the department of microbiology was a partner in Projet SIDA. One of the responsibilities of the department was the running of a dedicated clinic for sex workers in Matonge, the "hot area" of Kinshasa. Following the political turmoil of 1991, the running of the clinic of Matonge was taken over by MSF. This organisation also opened an STD clinic on the Place de la Victoire in the same neighbourhood. The clinic of Matonge is attended by sex workers, while the Centre Victoire is open to men and women with STI related complaints. The objectives of the present study was to assess the prevalence of HIV infection in sex workers, 10 years after the last study had been conducted, and to measure the prevalence of other STI’s in sex workers and in men and women with STD related complaints. Preliminary data suggest that the prevalence of HIV infection among sex workers remains relatively low in Kinshasa.

At the end of 2002 the above project was approved by the European Commission. Project activities are due to start in February 2003. The Project aims to provide the National Health Authorities in Cambodia and Thailand with improved understanding of high-risk situations among vulnerable women, and of reproductive health needs, in order to help them develop appropriate policies and strategies.

The project consists of three inter-related studies:

1. Validation of the management protocol of vaginal discharge in Cambodia.

2. Assessment of circumstances of sex work and mobility among female sex workers in Cambodia.

3. Assessment of circumstances of mobility and of reproductive health needs among vulnerable women in Thailand.

The latter two studies will employ qualitative research methods as well as classical epidemiological methods.

In early 1997 the unit was contracted by the European Commission to implement a 4-year project, "Care and Prevention of Sexually Transmitted Diseases in Cambodia" in close collaboration with the National Centre for HIV/AIDS, Dermatology and STD (the National HIV/AIDS Control Programme in Cambodia). This project ended in January 2001 and activities that had started under the EC project were maintained in Phnom Penh and in Sihanoukville, thanks to funding from the Institute of Tropical Medicine through an agreement between the Institute and the Ministry of Cooperation and Development. The project consists of the provision of technical assistance in matters of STD control, logistical support and capacity building, as well as support with supplies. In 2001 the project has benefited from extra financial inputs through the AIDS Impulse Programme.

Since 1998 the unit has a collaboration with the Institut National de Santé Publique (INSP) in Abidjan, Ivory Coast. This collaboration is funded by DGIC and in 2001 an additional budget was freed within the AIDS Impulse Programme. This additional funding allowed for the further strengthening of the infrastructure at the INSP (library and computer network). In addition the collaboration consists of training of staff of the INSP (in computer skills and project management), the organisation of regional courses in epidemiology (in collaboration with Projet Retro-CI of the Centers for Disease Control and Prevention) and joint research projects. The research activities which the unit carries out in collaboration with the INSP and Projet retro-CI are concentrated around the Clinique de Confiance, a dedicated clinic for sex workers in Abidjan. The clinic conducts HIV surveillance among sex workers and in 2002 initiated a study on the acceptability of the diaphragm by sex workers.

Research activities however had to be put on hold in the last quarter of 2002 because of political instability.

The activities of this project used to be concentrated on Antwerp and Ghent. However in 2002 an agreement was made with the Province of Vlaams-Brabant to start up activities in Leuven as well. The objectives of the programme are to improve knowledge about STIs and HIV and to create networks that can provide culturally adapted STI/HIV prevention and care services. These networks also enable contact with hard to reach groups of migrants and ensure the sustainability of the activities. Prevention activities include meetings with African migrants and training of peer educators. The self-help group Muungano targets HIV infected migrants. The members of the group meet on a monthly basis to discuss subjects such as therapy adherence and to strengthen solidarity within the group.

On World AIDS Day (1^st December) a meeting was organised where religious leaders of different denominations, from the African community were invited to talk about AIDS. The opening speech of the meeting was held by Mrs M Vogels, Flemish Minister of Health and Social Affairs. The meeting was very well attended and drew our attention to another potentially important stake holder in HIV prevention, the religious leaders. In 2003 the possibility will be explored to have more frequent meeting with these community leaders and to involve them more in HIV prevention in Belgium but also in the countries they come from.

Thérèse Delvaux is responsible for policy research on integration of reproductive health services in primary health care services. With new developments in the area of prevention of mother to child transmission of HIV she spent most of her time on this topic. In collaboration with Carine Ronsmans of the London School of Hygiene and Tropical Medicine, the INSP in Abidjan and Projet Retro-CI, she worked on a study of the effects of the introduction of a programme of prevention if mother to child transmission on the quality of obstetric services in San Pedro, a coastal town in Ivory Coast. The baseline assessment has been done but the introduction of the intervention is now delayed because of the political problems in Ivory Coast.

Hedwig Maex, who has extensive experience with DGIC and VVOB, was contracted to write a document on main streaming of HIV/AIDS in Belgian co-operation programmes. The document has been discussed with staff of DGIC. Hedwig went to present the need for an integrated approach to AIDS and for mainstreaming to a meeting of attachés in Ouagadougou (Burkina Faso). Her presentation was very favourably received.

Since May 1998 the unit has been subcontracted by FHI (Family Health International) to provide technical assistance to STI control projects in several African countries. In 2002 a new agreement has been signed. FHI has asked the unit to extend its scope of work. Technical assistance will be provided in the areas of HIV care with antiretrovirals and in STI control. Two staff members of the unit work part-time for FHI. Bart Ostyn has done a first evaluation mission to Rwanda where FHI is intended to start a programme of access to ART.

François Crabbé who is based is Cambodia has also been asked by FHI to provide technical assistance for a survey on sexually transmitted infections in East-Timor. He made a first visit to East-Timor and has written a protocol for the survey.

In the past year the STI laboratory of the unit has provided laboratory support (training, quality control, evaluation) to several projects on microbicides, including a WHO study on cellulose sulphate in Uganda, India and Nigeria and a CONRAD study in India. The unit has made an agreement with CONRAD, a US based NGO, for further collaboration. The unit will provide technical assistance to STI laboratories in developing countries and will conduct phase 1 trials in Antwerp.

The Immunology Unit and the STD/HIV Research and Intervention Unit are also collaborating in a European consortium that will submit a major grant application to the 6^th Framework Programme of the European Commission.

In May 2002 the unit organised and hosted the Microbicides 2002 Conference. Marie Laga was the conference chair and Lut Van Damme the scientific coordinator (see also "Focus on").

• Epidemiology of Trichomonas vaginalis: prevalence of Trichomonas sp., and sexual and hygienic risk factors associated with genital trichomoniasis

Trichomonas vaginalis (Tv) is highly prevalent in women in Africa. Tv is believed to be sexually transmitted. However, the Multicentre study on factors determining the differential spread of HIV in four African Cities, showed a high prevalence of Tv infection in girls in Ndola (Zambia), who denied that they had ever had sex. Data from a study in Mwanza on young girls also indicates a high prevalence of Tv while the prevalence in men is relatively low. This led us to postulate that not all of these vaginal infections in young girls were due to Tv but that – at least a certain proportion of them - are caused by related species such as P. hominis and/or T. tenax which colonise the vagina from the digestive tract. These parasites do grow on conventional media (own data, unpublished) and can not be distinguished from Tv by direct microscopy. The objectives of this project are to develop PCR techniques for the differentiation of different species of trichomonads and to use these techniques to study the epidemiology of the different species and risk factors for the acquisition of the parasite.

There is no funding yet for this project and in 2002 the work concentrated on developing the PCR techniques.

• At present staff members of the unit are regular consultants for the Belgian Cooperation, Family Health International (IMPACT), UNAIDS, The World Bank, International Family Health.

• Several staff members of the Unit are regularly asked to review papers submitted to international journals (AIDS, Genitourinary Medicine, The Lancet, Health Policy and Planning, Sexually Transmitted Diseases, European Journal of Microbiology and Infectious Diseases).

• The Unit is represented in scientific committees of international conferences (international AIDS conferences, conferences on AIDS and STD in Africa, International Conference on Home and Commuity Care for persons living with HIV/AIDS). Several staff of the Unit are asked to review abstracts submitted to these international conferences.

• Staff members of the unit are part of review committees for funding agencies for research (World AIDS Foundation, European Union, HIVNET, Agence Nationale de Recherche sur le SIDA, Wellcome Trust, UNAIDS/SDI).

• The unit is also sollicited by African organisations for technical advise and support to the organisation of conferences and meetings. Most of this support is provided on behalf of UNAIDS.