Ongoing Research Activities

Evaluation of microbial causes of fever in patients admitted with blood smear negative for malaria parasites at Bombo Regional Hospital, Tanga, Tanzania
To establish the probable diagnoses in fever patients who present with negative blood smear for malaria parasites.

To carry-out blood and urine culture, and sensitivity tests for blood smear negative cases.
To determine HIV status by serological tests for all BS negative cases.
To determine the proportion of malaria positive specimens by RDT in BS negative cases.
Interactions between ACTs for malaria and cART for HIV/AIDS in co-infected patients in Muheza, Tanzania. (InterACT)

The aim of InterACT project is to conduct a series of observational studies of clinical safety, therapeutic efficacy and pharmacokinetic interactions between the current nationally recommended first-line treatments for uncomplicated malaria and HIV/AIDS in Tanzania. These involve artemether-lumefantrine (AL) for uncomplicated malaria and antiretrovral combination treatments for HIV/AIDS, which is primarily Nevirapine+Stavudine+Lamivudine (Triomune®). The studies are being conducted among patients with uncomplicated malaria, who attend the HIV/AIDS Care and Treatment Clinic and Muheza District Hospital in Muheza. InterACT is within the ACT Consortium and funded through the Bill and Melinda Gates Foundation.

Multisite evaluation of highly active antiretroviral treatment (HAART) response and associated factors among HIV infected patients in Tanzania
This project was funded through Global Fund Round 8 with the overall goal being to evaluate patients’ response to HAART. At the end of the project, we will establish data related to the relationships between viral load, circulating HIV subtypes and drug resistance mutations in Tanzania. It is coordinated under a virtue network named Tz-HAART M&E Net for Tanzania HAART Monitoring and Evaluation Network. The project is currently running at five member institutions: Kilimanjaro Clinical Research Institute (KCRI), National Institute for Medical Research (NIMR Tanga and Mwanza Centres), Ifakara Health Institute (IHI) and Bugando Medical Centre (BMC). Over one thousand (1000) patients both ARV-naïve and ARV-experienced will be recruited. From these patients, blood samples will be collected and analysed. Tanga site has started enrolling patients at Bombo Regional Hospital CTC. Subject to funding availability, this baseline, cross-sectional study will be followed by a follow-up study to assess drug-induced mutations that are likely to confer HIV resistance to currently used ARVs. The main objective of this project is to monitor and evaluate the responses to HAART, drug failure and pattern of drug resistance among HIV-infected patients in Tanzania. Specifically, the project aims:

To determine baseline prevalence and incidence of HIV-1 resistance to the currently used ARV drugs among HIV treatment naïve patients in Tanzania.
To determine the prevalence of HIV-1 subtypes and circulating recombinant forms (CRF’s) among treatment naïve patients in Tanzania.
To determine the association between HIV-1 subtypes and other factors on immunological response among patients initiated on HAART regime during the study period in sentinel zonal health facilities.
To determine the association between HIV-1 subtypes and other factors on virological response (viral load) among patients initiated on HAART regime during the study period in sentinel zonal health facilities.
To determine patterns of baseline prevalence of HIV -1 drug resistance among naïve HIV patients starting HAART regimen in sentinel zonal health facilities.
Levels of Antiretroviral Drugs in Cervico-vaginal secretions and Sexual Transmitted Infections in relation to Mother-to-child transmission of HIV-1 among pregnant women in Tanga, north-eastern Tanzania.

This sub study is part of the ComTru project. Collaborating Institutions are Rigshospitalet and CMP, Copenhagen. Project duration is 3 years with funding from EDCTP. The main objective of this MTCT study is to determine levels of antiretroviral drugs in Cervicovaginal secretions and Sexually Transmitted Infections among pregnant women in Tanga and relate these to MTCT of HIV. Laboratory work is still on going, preliminary results from the STI part of the study are available and have been accepted for publication. Syphilis prevalence is declining while HIV prevalence is stable among pregnant women in Tanga. Other STIs/RTIs are common and more prevalent among HIV-infected than uninfected pregnant women. Major challenge remains with regard to getting partners to report for testing and treatment.

Establishment and strengthening of sites for malaria vaccine trials in Korogwe district, Tanga region, northeastern Tanzania: Passive Case detection of fever by Community Owned Resource Persons (CORPs)
This is an ongoing activity supported by Centre resources since January 2009. Roll Back Malaria/WHO has advocated early diagnosis and prompt treatment of cases as the mainstay of malaria control in Africa. In February 2006, we introduced a system for documenting fever of any origin by Passive case detection (PCD) using Community Owned Resource Persons (CORPs) with the main aim being to estimate the burden of malaria in the selected villages for inclusion in malaria vaccine trial. It involves 4 villages of which 2 are from the highlands (Kwamhanya and Magundi) and the other Kwashemshi and Mng’aza located in the lowlands in Korogwe district. Trained CORPs have continued to provide early and prompt malaria treatment, at a selected post within the villages, using standard protocol. To ensure adherence to treatment protocol by CORPs, they are supervised once weekly by a laboratory technician and clinical officer.

Development of PfEMP1 Based Malaria Vaccines (ENRECA-Immunology)

The main objective of the project is to establish or identify the parts of the PfEMP1 that are targets for protective immunity for inclusion in the vaccine construct. Establishing the parts of the PfEMP1 molecule which are targets for protective antibodies is key to vaccine development. This study is currently being conducted at the Korogwe District Hospital, the NIMR Korogwe Research Laboratory and 2 villages in Korogwe – Mkokola and Kwamasimba. Assays using clinicalPlasmodium falciparum isolates are on going with the over all aim of identifying P.
falciparum erythrocyte membrane protein 1 (PfEMP1)-based vaccines for children and pregnant women. It has been difficult to produce cross reactive PfEMP1-antibodies.

Phase III, double blind, randomized, controlled multi-centre study to evaluate, in infants and children, the efficacy of the RTS,S/ASO1E candidate vaccine against malaria disease caused by P. falciparum infection, across diverse malaria transmission settings in Africa: MAL 55
The study population include children 5-17 months at the time of receiving the first dose of RTS,S/AS01E or control vaccine. The other age category is infant aged 6-12 weeks who receives the study vaccines co-administered with the EPI vaccines. Main study objective is to evaluate efficacy against clinical malaria disease when primary immunization starts at 6 weeks, or 5 to 17 months of age. Recruitment was completed at all 11 sites in Africa by 31st Jan 2011. At
Korogwe, 912 participants had been enrolled in the age category 5-17 months at the time of receiving the first dose. In the infant cohort (6-12 weeks at the first vaccination), 593 participants had been enrolled. During this reporting period the site continued with vaccination, clinic visit for blood draw and monitoring of adverse events among study participants. Activities in the different laboratory sections continued at high standards. Paediatric ward and radiology unit continued to improved quality of care at Magunga hospital. Four papers related to the vaccine trial were published this quarter. Primary results on vaccine efficacy were released in Oct. 2011. The vaccine was found to have a protective efficacy of 56% against the first or only episode of malaria.

Targeting on the values of Wolbachia endosymbionts as novel feasible anti-filarial chemotherapeutic approach to prevent/reduce/clear disease in lymphatic filariasis and interrupt transmission in endemic communities of Tanzania

Lymphoedema (LE) of the lower limbs/legs is a major complication of lymphatic filariasis due to
Wuchereria bancrofti infection; however, the pathogenesis of this condition is still unresolved.
The objective of this work is to determine inter-digital skin lesions (dermatitis) in rice farming contribute to progression of LE.