NIMR - Mbeya Medical Research Programme

Quick Information

NIMR - Mbeya Medical
Research Center

P.O Box 2410
Hospital Hill rd, Mbeya Tanzania

Tel    +255 25 250 3364
Fax   +255 25 250 3134
Working hours:
Mon   -  Fri
08:00 - 16:30 EAT (GMT + 3)

Human cohort studies

NVBD: Epidemiology of Neglected Viral and Bacterial Diseases in the Mbeya Region

MMRC:Co-Principal Investigator: Nyanda Elias, MD

Munich: Principal Investigator: Norbert Heinrich

Collaborators: Nina Weller, Tatjana Dill

Purpose
NVBD (Epidemiology of Neglected Viral and Bacterial Diseases in the Mbeya Region) is a substudy of the EMINI project. Within NVBD, 1300 blood samples from selected EMINI participants are examined to establish epidemiological data on six arbovirus infections (Chikungunya, Dengue, Yellow Fever, Rift Valley Fever, O' nyong nyong), as well on bacterial zoonotic diseases which affect human health as well as lifestock breeding success. Among the latter are Plague, Rickettsioses and Brucellosis.

Approach
1300 blood samples have been examined for antibodies against the mentioned diseases. Sera from febrile patients will be selected and further examined by nucleic acid amplification methods and viral culture to detect the pathogens.

Results: High seropositivity rates have been detected for Chikungunya, Flaviviridae and Rift Valley Fever from sites with a proximity to large water bodies.

Sponsors: the study is sponsored by the German Ministry for Education and Research (BMBF). EMINI is sponsored by EU-AIDCO.

Partners: Gerhard Dobler, MD, Bundeswehr (German Federal Armed Forces) Institute of Microbiology, Munich, Germany

Publications

Weller N: Epidemiology of Neglected Arthropod-Borne Viral Diseases in the Mbeya Region,

South Western Tanzania; poster presentation at NIMR conference, Arusha 2010,

Dobler G: Seroprevalence of Antibodies Against Rift Valley Fever Virus in Humans in Southwestern Tanzania, poster presentation at American Society for Tropical Medicine and Hygiene meeting, Atlanta 2010,

Dobler G: Seroprevalence of Antibodies Against Rickettsiae of the Spotted Fever Group and of the Typhus Group in Humans in Southwestern Tanzania, American Society of Rickettsiology Meeting, Stevenson, 2010

 

RV 217

Local PI: Dr Lucas Maganga
Study Coordinator: Dr. Inge Kroidl
Description
This is a multi-center, non-randomised clinical observational study conducted in three East African contries (Tanzania, Kenya, Uganda) and Thailand.
The research collaboration outlined in this study measures the epidemiology of HIV in a volunteer cohort drawn from high-risk populations in these contries.  The primary objective of the study is to estimate HIV-1 incidence and retention in a volunteer cohort established to test vaccine strategies. The study focus more on acute infection acquisition rather than high risk cohort development alone.
The aim is to develop a cohort of 2,000 individuals at high-risk of HIV infection in Uganda (subtype D, A, A/D), Tanzania (subtype C, A, A/C), Kenya (subtype A), and Thailand (subtype CRF_01 AE, B). Volunteers are screened in each country from populations with very high prevalence (20-70%) to yield incidence rates of >3%.This study also defines the prevalence of HIV-1 in this volunteer cohort, determine the distribution of HIV-1 genotypes and different host genetic backgrounds, assess the range of CD4 and viral load in HIV-1 infected volunteers, characterize behavioral and other risk factors associated with HIV-1 infection, and augment HIV-1 prevention and education programs, human resources, and laboratory infrastructure to support future vaccine trials.
 

WHIS Project

WHIS - Intestinal helminth infections and schistosomiasis and their relation to HIV-1 incidence, disease progression and immunology in Mbeya Region, Tanzania

Team

MMRC: Petra Clowes (study coordinator), Mkunde Chachage (junior scientist, immunology laboratory), Lilli Podola (supervisor, immunology laboratory), Anthony Nsojo (helminth diagnostics, EMINI laboratory), Dickens Kowuor (data department) and Leonard Maboko (site principle investigator)

MUHAS: Zulfiqarali G. Premji (collaborator from Muhimbili College of Health and Allied Sciences)

LMU: Elmar Saathoff (principal investigator) and Christof Geldmacher (immunologist)

Purpose

WHIS aims to examine the influence of helminth infections on the epidemiology and immunology of HIV infection. Specific objectives are

i. to assess the possible influence of different Helminth infections (Ascaris lumbricoides, Trichuris trichiura, Hookworm, Schistosoma haematobium and S. mansoni) on HIV prevalence, incidence and disease progression.

ii. to investigate whether and how different kinds of helminth infections change the human immune response to HIV, TB and other infectious diseases and to examine the possibility that helminth-infection increases the susceptibility of CD25 and CD4 T cells to infection with the Human Immunodeficiency Virus.

Furthermore WHIS includes a capacity building component that aims to provide PhD and MSc training to two young scientists from Tanzania.

Approach

The WHIS study is conducted within the framework of the EMINI survey, an EU funded project which was initiated in June 2006 and is still ongoing. To achieve the above objectives WHIS is made up of an epidemiology component (WHIS_Epi) that only uses data that are routinely being collected as per EMINI protocol and an immunology component (WHIS_Imu) that equally uses EMINI data but also requires collection of additional samples and data.

WHIS_Epi includes all ~17,000 EMINI participants. The third round of the EMINI survey (July 2008 to June 2009) included 50% of the participants for stool examinations and possible worm treatment, where the other 50% were planned to be examined for intestinal helminth infections one year later. Therefore, since July 2009 – the begin of the 4th survey round - all participants from both groups are examined and if necessary treated for intestinal worm infections. No additional visits to the study subjects are necessary for this part of WHIS; data collected during the annual EMINI visits will be used for the WHIS _Epi study. Subsequently, HIV incidence and disease progression over one year between groups can be compared.

WHIS_Imu includes a maximum of 480 participants from the EMINI cohort. Participants are chosen according to their present helminth infection and HIV status. 3 visits are planned for each participant where 40 ml of blood, a urine sample and a stool sample are being collected. Visits are conducted after identifying the participants through the EMINI survey (F0), six weeks later (F1) and one year later (F2). At F0 participants will receive, if indicated, worm treatment, F1 and 2 are therefore post treatment visits.

Viral load determination, CD4 counts and most of the immunology laboratory work is carried out at the well equipped NIMR-MMRC laboratory.

Results

The study is still ongoing and no results regarding our main outcomes are available yet. An interim analysis is planned for early 2011.

The study is going well and participants for the WHIS_Imu part are steadily being recruited. It is difficult however to retain participants but every effort is made to explain the overall benefit of the study to the study subjects. There are not as many HIV-helminth co-infections in the EMINI study area as anticipated which might result in a smaller number of participants as originally planned.

Sponsor

WHIS is funded by the German Science Foundation (DFG) and also relies on data that are collected during the EC funded EMINI study.

Partners

The projected is a collaboration of the following institutions:

NIMR-Mbeya Medical Research Center in Mbeya, Tanzania.
The Division of Infectious Diseases and Tropical Medicine, Medical Center of the University of Munich (LMU), Germany 
Muhimbili College of Health and Allied Sciences, Dar es Salaam, Tanzania.

Publications

First publications are expected in 2011.

 

 

 

Active Detection of Tuberculosis in Children

Study Coordinator

Dr Petra Clowes

Background

The diagnosis of childhood tuberculosis remains a major challenge of TB control, especially in developing countries. Causes of misdiagnosis include non-specific clinical signs or symptoms and low sensitivities of e.g. AFB microscopy, especially in HIV co-infected children.

This pilot study started in May 2008 with the objective to provide an improved approach to TB diagnosis in HIV infected and uninfected children through evaluation of emerging innovative diagnostic methods. Furthermore, in an extension to the original study, a closer look is taken at the clinical and immunological treatment outcome of TB infected children and at the diagnosis and prevalence of immune reconstitution inflammatory syndromes (IRIS) in HIV co-infected children.

Date of first enrolment was the 29th May 2008. Eligible participants are all children between the age of 6 weeks and 14 years of age with clinical suspicion of having either intra- or extra-pulmonary TB.

Objectives

The overall objective of this study is to provide an improved approach to TB diagnosis in HIV infected and uninfected children through evaluation of emerging innovative diagnostic methods.

Methods

A prospective clinical study, enrolling suspected TB-infected Children of more than 6 weeks and less than 14 years of age. Children with clinically suspected TB are screened using standard microscopy and culture (MGIT, LJ, HAIN Assay) for Mycobacterium tuberculosis from induced sputum, other body fluid or histology samples. Results are related to clinical/radiological signs and symptoms. New diagnostic approaches (e.g. INF-gamma release assays (IGRA), mycobacterial lipoarabinomannan (LAM) detection from urine and PCR-based MTBDR-plus assay from Hain Company are compared to the standard microbiology tests and clinical findings at baseline and evaluated during a 12 months follow-up period. Follow-up visits are scheduled to monitor the treatment outcome (after 3, 6, 12 months). HIV testing is performed and TB treatment and/or ART initiated when indicated, according to the Tanzanian National guidelines.

Preliminary findings

The amended number of participants aimed for was 175 Tb suspects. This target was achieved by the 1st November 2010. Of the 175 TB suspects, 37 had confirmed TB; in 25 cases the results were still outstanding. In 48 cases TB could be ruled out as an alternative diagnosis was established or the children recovered on treatment other than TB treatment.

Progress

Recruitment has been rather slow but picked up in the third quarter of this year again. Collaboration with the hospital and other referring facilities is good and well established. The initial aim of enrolling 250 participants was changed to 175 as less new diagnostic tools were evaluated as initially planned.

Future plans

The study is still ongoing although new recruitments have been completed recently. However, all participants will have at least one year of follow up visits which will bring the end of the study to November 2011. Data evaluation has started and first conclusions are being drawn, but final recommendations will have to wait until the end of the study.

Sponsors

The TB Diagnosis in children study is part of the ADAT (Active Detection of Active Tuberculosis) project, which is funded by the European Union as part of EuropAid, contract number SANTE/2006/129-931.

 

EMINI Project

EMINI - Establishment of the infrastructure for the Evaluation and Monitoring of the Impact of New Interventions

Team

MMRC: Petra Clowes (study coordinator), Anthony Nsojo (laboratory), Dickens Kowuor (data) and Leonard Maboko (site principle investigator)

LMU: Elmar Saathoff (epidemiologist) and Michael Hoelscher (principal investigator)

Purpose

The overall objective of the EMINI project is to contribute to the overall improvement of health by trying to help control two of the three major communicable diseases in Africa. This overall objective should be achieved through two specific objectives. These are

i. The reinforcement of the existing health care structures so they become conducive to new interventions

ii. The establishment of an up-to-date capacity to evaluate and monitor the impact of improved health care infrastructure and new interventions.

These new interventions include drugs and vaccines for HIV, TB and malaria and active TB case finding; just to mention some of them. The target group for this action is the general population of the Mbeya Region.
As part of the second objective the study aims to describe the epidemiology of infectious diseases, including HIV, TB, malaria, schistosomiasis and helminth infections and causes of morbidity in the studied population. The study shall also establish the data that are required for community randomized controlled trials.

Approach

The initial EMINI study was a 3 year EC funded project which started in May 2005. The initial funding by the EC has been completed, however, the survey of the EMINI study is still ongoing under another EC funded project (ADAT). The EMINI survey is a closed population based cohort with annual visits of 18,000 individuals (age 1 and above) enrolled from 10% of all households, randomly selected in 9 dedicated EMINI sites (urban, semi urban and rural). The project sites were chosen according to the specific characteristics in the Mbeya Region in order to give a good representation of the geographic diversity of the Region

Embedded into EMINI are several focused studies such as NVBD that determines the presence of antibodies against numerous viral and bacterial febrile diseases, including Chikungunya, Dengue, O`nyong nyong, West Nile, Yellow Fever, Rift Valley-Fever as well as other tropical Arboviruses, but also rickettsia, yersinia pestis, anthrax and brucellosis. Other studies embedded into the EMINI survey are WHIS, SOLF and MATHIS. WHIS concentrates on the influence of helminth infection on HIV epidemiology and immunology. The SOLF study aims to assess the prevalence of lymphatic filariasis (LF) and the impact of annual Ivermectine-Albendazole mass treatment on LF prevalence in Southwest Tanzania, whereas the MATHIS study examines the effects of helminth infections on allergy specific parameters in a well characterized cohort in Southwest Tanzania. All these smaller studies are described separately in this web page.

Results

The reinforcement part of the EMINI study was completed with the end of the initial funding by the EC in 2008. The survey itself is still being conducted under another EC funded project (ADAT) and going well. The 5th survey round has started on the 19th July 2010. This round, which will be the last survey round, is expected to be completed by the middle of 2011.
The HIV prevalence stayed stable throughout the first three annual surveys with a slight decline in prevalence. The prevalences were 7.4%, 7.21% and 7.23% in survey 1 to 3. Malaria prevalences have declined considerably during the course of the project, most probably due to the introduction of ALU as the new first line treatment. Schistosoma haematobium infection has equally declined in the study population. Other helminth infections show marked differences between age groups and sites.

Sponsor

EMINI is funded by the European Union through EuropAid, contract numbers SANTE/2004/078-545 EMINI and SANTE/2006/129-931.

Partners

The project is a collaboration of

NIMR-Mbeya Medical Research Center in Mbeya, Tanzania.
Division of Infectious Diseases and Tropical Medicine, Medical Center of the University of Munich (LMU), Germany.

Publications

Findings of the HIV prevalence for the first three years of the survey (2006 to 2009) have already been presented at several venues, such as the NIMR 24th Annual Joint Scientific Conference in Arusha from 16.-18 March 2010.

Publications regarding these and other results of the EMINI study are presently in preparation.

 

 

 

 

 

 

Cohort Development (CODE) Project

Project Coordinator L. Maboko

Description

This study was realised in collaboration with Walter Reed Army Institute of Research. Three different kinds of cohort recruiting were compared. Over a four year period, HIV incidence and prevalence rates were determined, basal data for viral load, cd4 and cd8 kinetics, risk behaviour and follow-up rates was generated.
Through an information campaign, knowledge about vaccine studies, and willingness to participate in such studies has been improved. In September 2005, the 3,000 participants have been observed for three years. HIV prevalence was determined to be 18,4% in urban and 12,2% in rural population, incidence of new infection was 1,6%, and interestingly was higher in rural than in urban areas. Follow-up rate after three years was 85%.

 

HIV Super Infection Study (HISIS)

Project Coordinator: L. Maboko

Decription

basing on samples obtained from 600 prostitutes in during the HISIS study, correlates of protective immunity are evaluated. In a case-control-study, cellular immunity is examined using ELISPOT and intracellular cytokine staining (ICC) in three subgroups:
Women massively exposed to HIV during three years as prostitutes, who are HIV-negative;
Women infected with HIV once, whose immune response is preventing superinfection with another HIV strain;
Women whose immune response is insufficient to prevent infection, resulting in several infections with HIV.
Thus, correlates of protective immunity shall be identified. First results how certain HLA alleles (B5801, B8101, B0702) to induce a borader immunity in gag, which contributes to a long-term reduction in viral load by two log steps.

LMU Department of Infectious Diseases and Tropical Medicine is participating in this activity through its immunologists L. Podola, PhD and C. Geldmacher, PhD, who are planning and analysing this study together with colleagues in the NIMR-MMRC immunology laboratory.

 

Bar workers health project (BHP)

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