1. The document summarizes biomedical research activities at the Ifakara Health Institute (IHI) in Tanzania, including past and current laboratory-based research in malaria, tuberculosis, HIV, and other infectious diseases. 2. Key areas of research mentioned include monitoring anti-malarial drug resistance, evaluating malaria vaccines and biomarkers, population genetics of malaria vectors, and molecular monitoring of HIV drug resistance. 3. Future research directions discussed are non-communicable diseases, genetic determinants of infectious diseases, mapping and characterizing pathogens/emerging pathogens, drug efficacy monitoring, gene expression profiling, diagnostic development, and understanding pathogen co-infections. The document highlights strengths like laboratory facilities, clinical trial platforms,

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BIOMEDICAL THEMATIC
GROUP
Dr. Moses Gwamaka
2012 RETREAT
Stake-holders meeting

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Outline
Biomedical research activities at IHI
(Past and current)
Research potential
Prospects

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IHI Biomedical scientists
Lab based
Two laboratories
Ifakara and Bagamoyo
Significant contribution to the basic and applied research
- Treatment policy change
Molecular biology
-Monitoring parasite resistance to anti malaria drugs
Biomedical research at IHI

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Mugittu et al 2004 Am J Trop Med. 2004
IHI biomedical research
Prevalence of sulfadoxine-pyrimethamine (SP) resistance parasite
genotypes in Tanzania

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Temporal trend of the alleles with greatest significance for SP efficacy,
the double dhfr and triple dhfr mutant and their combination in Morogoro
IHI biomedical research
Malisa et al., Afr Health Sci. 2011

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IHI biomedical research
Pathophysiology
- Pathophysiological features of malaria
sTfR , Anemia
- Evaluating biomarkers for malaria infection
(CRP, Haptoglobin, MRP 8/14, IL-2 and TNF-alpha
soluble receptors)
(Hurt et al., 1994,1995, Bordmann et al., 1997)
Immunology
-Immunological monitoring of HIV progression
- Malaria vaccines immunogenicity
- SPf66 – Teuscher et al., 1994
- RTS,S/AS02D – Abdulla et al., 2008

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The science 2012
3 Infectious diseases
Malaria
Tuberculosis
HIV

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The science 2012 - MALARIA
A rapid scale-up of a range of malaria
control measures
- Insecticide-treated mosquito nets
- Indoor spraying - IRS
- Fast and accurate diagnosis and
- Access to anti-malaria drugs
The burden of malaria in countries
in sub-Saharan Africa is scaling
down
WHO report 2010

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The science 2012 Malaria research

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Malaria vector:
ITNs, IRS – target the vector
Population structure?
Potential barriers to vector gene flow exist
-Tanzania mainland/Zanzibar
- Ecological islands on either side of Great Lift
valley
? Success and sustainability of vector control activities
Study: Population genetics of malaria vectors and determine the
insecticide resistance status using molecular methods
The science 2012 Malaria research

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Near infrared spectroscopy (NIRS) has been shown to be
useful to determine the age of fresh mosquitoes
- Quick and non destructively
How to use for non - fresh samples – preservation?
Study: Develop a preservation method that will be used to
preserve mosquitoes for successful use with NIRs
The science 2012 Malaria research

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The science 2012 Malaria research
The parasite:
Malaria parasite cultivation for In-
vitro drugs sensitivity assays
Advantages
- No interference of host factors
-Test several anti-malarial drugs
against the same isolate

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RTS,S vaccine candidate has been proved to be safe and
induce significant protection against Plasmodium falciparum
infections.
But the mechanism of protection is not clearly defined
1. Gene Expression profiling (rt-PCR) from the PBMC
stimulated in-vitro in presence of components of RTS,S
malaria vaccine antigens
2. Dissecting the functional profile of vaccine induced
protective cellular immune and humoral responses in
volunteers participating in malaria (RTS, S vaccine) and
Tuberculosis (H1/CS31 vaccine) clinical trials – Flow
cytometric
The science 2012 Malaria research

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The science 2012 Co- infections
IDEA project : An African-European Research Initiative
(engages 21 institutes from Europe and Sub-Sahara Africa)
Wide geographic overlap in occurrence, co-infections
between worms and HIV, TB and malaria occur in many
people.
The potential impact of co-infections between worms and
HIV, TB and malaria is not known.
Study: Monitoring innate immune responses following
Malaria, Tuberculosis and helmith co-infection

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The science 2012 HIV
1. Molecular monitoring of HIV drug resistance in Tanzania
(Partnership project between Swiss TPH/ IHI)
Objectively
- Molecular characterization of HIV-1 subtypes
- Prevalence of HIV drug resistance
- Compare HIV drug resistance and HIV subtypes
-Association of drug resistance and treatment regimen
2. Studying the immunological mechanisms in HIV infections
Role of micronutrients in the progression of HIV:
Focusing on the effects of iron on immune activation in
ART naïve HIV infected individuals

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The science 2012 Tuberculosis
In most developing countries, Mycobacterium tuberculosis
drug susceptibility testing is not conducted prior to treatment,
leading to the prescription of inappropriate drugs.
Play a key role in the emergence of multi-drug resistant TB
MDR strains hamper – TB treatment efforts
1. Development and implementation of a molecular tool to
provide rapid drug resistance profiling and genotyping of TB
clinical isolates in endemic countries of Southern Africa

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2. Developing a comprehensive molecular tool for large-
scale TB drug resistance surveillance
TB Diagnosis
3. Analysis of Inducible protein 10 (IP10) and T -cell
activation markers interferon-gamma release assays (TAM-
IGRA) for the detection of latent Tuberculosis
The science 2012 Tuberculosis

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S/N Strength Reason
1. The group is growing
Number and skills
1. Senior scientists - skills
2. Good number of middle cadre scientists
currently on training, others in preparation for
further studies.
2. Ifakara DSS in which all
household are geo-
referenced
This provides a unique setup for the long term
studies
KIULARCO project-
serving over 5000
clients
Provides a good platform for all kinds of
classical HIV studies and HIV co-infection
studies, NCDs in HIV infections
Close vicinity to the
Hospital services
Provides us an opportunity for a 2 way street -
between clinical and basic research i.e. from
bedside to the bench vice versa
The coming Mzima
cohort
An open adult health community cohort
lodged in the Ifakara urban HDSS, focusing
first on surveillance for HIV and NCDs
3. Laboratories Modern equipment to carry most of current
lab analyses, BSL3 Labs in Bagamoyo
OUR STRENGTH

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Bacteriology and Virology BSL3 - Bagamoyo

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FCM – for phenotypic and functional analyses of immune cells
Currently - is the only technology platform that suitably can analyze
the complex components of the immune system
FACSCALIBUR (3 or 4 color) 8 color flow cytometer
FLOW CYTOMETER (FCM)

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A system of nucleic acids amplification – uses rRNA as template
- 10X more sensitive than conventional PCR
- Currently we use for diagnosis of STDs
GEN PROBE system

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DNA Sequencer
Determine the order of the nucleotide bases
- biotechnology, forensic medicine and biological systematics

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MassArray for Genotyping, Comparative Sequencing & Quantitative Gene Analysis
MassArray

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BACTEC for blood culture
BACTERIOLOGY

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Electrolyte analysis using (1) Cobas integra and (2) Vitrous DT
BIOCHEMISTRY

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Research direction Reasons Comments
Non communicable
diseases
- Public health problem
- Unique in SSA- at younger age <10
years than elsewhere
- Change of life style, diet
Available skills
and equipments
Genetic
determinants of
infectious diseases
Example – RBC disorders vs. malaria –
What about other infectious diseases e.g.
HIV and TB?
Available skills
and equipments
Mapping and
characterizing
pathogens/emerging
pathogens
Kilombero valley presents complex
ecosystem: rich diversity of wildlife,
domestic animals, human settlements,
agricultural activities and flood plains, and
mosquito vectors
One health
approach
4. Lab based studies Developing molecular assays, developing
SOPs
FUTURE DIRECTION

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Research direction Specific area
Drug efficacy monitoring i. ACT in vivo efficacy monitoring
ii. ACT in vitro efficacy monitoring
iii. Anti-TB Drug sensitivity testing
Gene-specific expression
profiling – massarray
i. Gene copy number variation
ii. Assessment of TB resistance by SNPs
typing
iii. TB strain profiling using strain-specific
SNPs - M. Tb genetic diversity
Development of diagnostics i. Malaria RDTs
ii. Magnetic deposition microscopy: for
submicroscopic gametocytes detection
iii. DNA microchip for malaria diagnosis
iv. One platform for HIV-1, TB, Malaria and
Hepatitis
Understanding the role of
pathogen co- infections Tb and
HIV, malaria Hepatitis C
Expression profile of biomarkers ie micro
RNA

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THANKS