Basic Research

A case-control study to identify risk factors associated with Human Papilloma Virus (HPV) associated lesions within the female reproductive tract

Cervical cancer, which is caused by persistent infection by High Risk HPV types, is the most frequent cancer in Tanzanian females, particularly affecting those co-infected with HIV. This study investigates risk factors associated with high-grade squamous intraepithelial lesion (HSIL) or squamous cell carcinoma (SCC) within the reproductive tract of Tanzanian women and identify High Risk (HR) HPVs that most frequently cause such disease in HIV +ve and HIV -ve women. This study focuses on HPV and HIV related factors, particularly on infecting HPV genotype(s) and immune system related factors, such as CD4 T-cell count, antiretroviral therapy (ART) status and HIV induced dysfunction of HPV-specific adaptive immunity. In addition, quality of life for cancer patients and socio-economic factors  (such as sexual behaviour, age and smoking) will be studied.

A longitudinal follow up of selected HIV +ve and HIV -ve 2H study participants will allow to study viral persistence and clearance rates, and lesion recurrence after treatment of precancerous lesions. Highly Active Antiretroviral Treatment (HAART) associated reconstitution of HPV-specific immunity will be studied in relation to viral clearance and disease progression in HIV +ve 2H study participants initiating HAART. 

A maximum of 600 adult women will be enrolled in four groups: 100 HIV positive and 100 HIV negative women with HSIL/SCC (Cases); 200 HIV positive and 200 HIV negative women with no cytological abnormalities or lower grade lesions (ASCUS, LSIL) will be enrolled as controls. 

The anticipated results of this study will provide the basis for rational improvement of immunotherapeutic interventions in a patient population most heavily affected by HPV associated cancers and precancerous lesions. 

Surveillance of lymphatic filariasis (SOLF) and the impact of annual Ivermectine-Albendazole mass treatment on LF prevalence  in Kyela District 

SOLF is generating prevalence data for lymphatic filariasis in Southwest Tanzania. Lymphatic Filariasis (LF) is a mosquito-transmitted disease which is found throughout the tropics. In Tanzania, six million people have debilitating manifestations of the disease. Eradication programs are conducted throughout the country. In the Mbeya district they commenced 2009 giving the opportunity to create pre-treatment prevalence data and also monitoring the success rate of the control program.

The SOLF study is conducted within the framework of the EMINI survey, an EU funded project which started in 2005 and is still ongoing. In the EMINI survey 10% of all households in selected sites are visited. Typical clinical manifestations of lymphatic filariasis were reported from one area of the EMINI study, Kyela, a town close to the lake Nyasa. Efforts are undertaken by the “Global Alliance to Eliminate Lymphatic Filariasis”, to eradicate the disease using repeated once annual mass drug treatment with a two drug combination of Albendazole and Ivermectine. In Southwest Tanzania, the campaign for eradication of LF started in Nov 2009. Mapping of the prevalence of different regions as well as evaluation of treatment is needed for the success of the programme.
The analysis of frozen samples from the EMINI cohort, which were collected before the government programme commenced, creats a first overview over the prevalence of LF infection in this area. A commercially available ELISA (TropBio® Og4C3 serum ELISA, Townsville, Australia) which detects the circulating filarial antigen (CFA) is used to test sera. CFA is secreted by fully developed worms of W. Bancrofti and can be found at similar levels during day and night. Antigen levels reflect the worm burden and have been previously used to monitor the efficacy of lymphatic filariasis elimination programs. 100 µl of sera are used for the ELISA.
Analysis of samples after the treatment will give valuable information about the treatment success of the governmental mass drug administration.

Dissecting the Immunological Interplay between Poverty Related Diseases and Helminth Infections: An African-European Initiative

There is wide geographic overlap in occurrence, co-infections between worms and HIV, TB and malaria that occur in tens of million of people in both children and adults. Preliminary epidemiological data indicated that globally about 25% of individuals affected by HIV, malaria or worm infections are co-infected. Although worm infections and HIV, TB and malaria have been extensively investigated, there has only recently been increased attention to the potential impact of co-infections between worms and HIV, TB and malaria. Indeed, there is little information on the effects of worm infections on the HIV-, TB- and malaria-specific immune responses in humans, and little evidence as to whether such effects are detrimental, neutral or even beneficial. There is limited knowledge of the influence of underlying worm infections on the clinical course of HIV, TB and malaria. Finally, the impact of worm infections on vaccination requires further investigation, as the very limited data available suggests reduced effectiveness of vaccines in subjects with worm infections.

The primary objective of IDEA is to determine whether and how the presence of worm infections modulate

• immune responses specific to HIV, TB and Malaria

• the clinical course of these diseases

• and vaccination and vaccine-induced immune responses

Modulation of Allergies Through Helminth Infections in South-Tanzania 

MATHIS is focusing on helminth diseases and their influence on allergic diseases. Epidemiological studies demonstrate the protective effect of infections
during early childhood on the development of allergies and autoimmune
diseases. The decreased incidence and prevalence of allergic disorders
observed in individuals infected with parasitic helminthes supports the hypothesis
that worms might possibly play a role in suppressing allergies. Three stages of
the study have been proposed

Part 1 To determine the prevalence of allergic diseases in 5 different sites in Mbeya Region.
Part 2 To assess the effects of helminths on allergic surrogate markers by comparison of different allergen-specific IgEs in participants with and without documented helminth infection
Part 3 To measure differences in the amount of regulatory or inflammatory cells and a combination of cytokines in participants with allergies or worms and possible changes after worm treatment

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