INTERNS (8 September 2011)
INT014
Assessing whether a Plasmodium falciparum tyrosine kinase-like protein kinase (PfTKL2) expressed
on the surface of infected red blood cells is a target of natural immunity to malaria
City:
KILIFI
Supervisor: Abdirahman Abdi & Pete Bull
Background
Development of an effective malaria vaccine remains a global public health priority. Children who grow
up in stable malaria transmission areas acquire antibody-mediated disease protective immunity (Marsh
1992) but the critical targets of this immunity remain unknown. A malaria vaccine that can elicit a response
similar to that acquired after repeated natural infections could save millions of lives especially of children
under 5 years of age. Development of such a vaccine requires identification of the parasite molecules
responsible for inducing these protective responses. The P. falciparum genome encodes approximately
5300 proteins, many of which could be targets of the observed disease protective immune response.
Identification of potential targets of this immunity is closely linked to efforts to develop malaria vaccines.
However, only a small fraction of these potential targets have been evaluated as vaccine candidates
(
http://who.int/vaccine_research/links/Rainbow/en/index.html). So far efforts have been directed to two
main class of proteins: (1) surface proteins of the liver (sporozoite) and blood (merozoite) invasive stages
and those secreted during the invasion process, (2) proteins exported to the surface of infected red blood
cell (iRBC). A conserved P. falciparum tyrosine kinase-like kinase, PfTKL2 (PF11_0220) was recently shown
to be exported to the surface of the iRBC (Singh, Mukherjee et al. 2009). We will express recombinant
fragments of PF11_0220 in Escherichia coli and assess whether this protein is a target of natural immunity
and hence a vaccine candidate.
QUESTION TO BE ADDRESSED BY INTERN
Overall objective: To determine whether PfTKL2, an exported P. falciparum protein kinase is a target of
naturally acquired antibodies.
Specific Objectives:
• Clone and express fragments derived from the sequence encoding PfTKL2 as soluble recombinant
proteins in E. coli.
• Assess whether these fragments are targets of naturally acquired antibodies using archived
plasma samples collected from well-established cohorts for immuno-epidemiological studies.
• Determine whether the magnitude of the antibody response against PfTKL2 fragment correlates
with clinical protection against malaria.
SKILLS TO BE ACQUIRED BY INTERN
Molecular and biochemical techniques such cloning and in vitro expression of recombinant proteins, protein
purifications, western blotting, enzyme-linked immunosorbent assay (ELISA) and statistic skills necessary for
the data analysis
TRAINING BACKGROUND OF REQUIRED INTERN
Basic degree in Molecular Biology, Biochemistry, Zoology
REFERENCES
Marsh, K. (1992). "Malaria--a neglected disease?" Parasitology 104 Suppl: S53-69.
Singh, M., P. Mukherjee, et al. (2009). "Proteome analysis of Plasmodium falciparum extracellular
secretory antigens at asexual blood stages reveals a cohort of proteins with possible roles in immune
modulation and signaling." Mol Cell Proteomics 8(9): 2102-2118.
To apply, please follow the link below:
http://careers.kemri-wellcome.org/frontpage
INT015
Molecular characterization of Adenovirus in Kilifi and the role of the different serotypes in respiratory
illness
City:
KILIFI
Supervisor: Clayton Onyango
BACKGROUND
Adenoviruses cause a broad spectrum of clinical disease and are responsible for approximately 7 to 8%
of reported childhood viral respiratory infections worldwide. Other than respiratory tract infections,
adenoviruses are also associated with pharyngoconjuctival fever, conjunctivitis, hemorrhagic cystitis and
gastroenteritis in humans. Most adenoviral infections are self limiting, but some have been associated with
severe and in some cases fatal outcomes in both immunocompromised and healthy individuals. Up to
adenovirus serotypes have been identified and these are classified into 7 species. Serotypes 1-7 have
been associated mainly with respiratory illnesses, while serotypes 40 and 41 have been associated with
gastroenteritis. There is little information on the epidemiology of adenovirus species and serotypes
prevalent in sub Saharan Africa. It is therefore important to identify the different adenoviruses in
nasopharyngeal swabs collected from pneumonia admissions (at Kilifi district hospital) as well as those
collected at the community level (house hold study) with the aim of establishing their role in respiratory
illnesses. Recently, innovative molecular techniques have been modified to rapidly identify the different
serotypes with a better precision than the traditional methods of neutralization assays. By targeting
adenovirus hexon gene, up-to 51 serotypes can be identified and these include those viruses involved in
respiratory illnesses.
QUESTION TO BE ADDRESSED BY INTERN
• What are the dominant adenovirus serotypes in Kilifi?
• What role does a particular serotype play in a subsequent infection of the same host?
Skills to be acquired by intern
• PCR primer design
• RT-PCR of viral substrates
• Gene sequencing and sequence analysis
TRAINING BACKGROUND OF REQUIRED INTERN
BSc Biomedical sciences
Advantages include basic knowledge in:
DNA/RNA extraction techniques,
Polymerase chain reaction and
DNA sequencing
To apply, please follow the link below:
http://careers.kemri-wellcome.org/frontpage
INT016
Developing a Socio-economic Index for Kilifi Health Demographic Surveillance System
City:
KILIFI
Supervisor: Evasius Bauni & Jane Chuma
BACKGROUND
Socio-economic status (SES) has long been a predictive variable in studies on population health status and
access to health care services. How to ensure both the poor and the rich benefit from health interventions
remains a major concern in health and development debates. The KEMRI-Welcome Trust has had a Health
Demographic Surveillance System (HDSS) for the last 10 years. The KHDSS is an important resource for
researchers within the programme. Quite often many researchers have expressed interest in having a
socioeconomic index that categorises households in the KHDSS into various socio-economic groups. Until
recently (January 2011), complete data on socio-economic variables were not available from the KHDSS.
A socio-economic index will enable researchers to explore the relationship between socio-economic status
and various health outcomes. The overall aim of this project is to develop a socio-economic index that can
clearly distinguish households within the Kilifi HDSS.
QUESTION TO BE ADDRESSED BY INTERN
• The intern will be expected to conduct a scientific literature review on the range of variables used
to measure socio-economic status in developing countries
• Define and model a socio-economic index that clearly distinguishes households within the Kilifi
HDSS
• Compare the performance of the socio-economic index developed with others identified in the
literature, especially those used in Kenya.
SKILLS TO BE ACQUIRED BY INTERN
• Scientific literature review
• Data cleaning and management with support from Norbert Kihuha and George Oando.
• Data analysis
• Writing skills
TRAINING BACKGROUND OF REQUIRED INTERN
A Bachelors Degree in Economics and Statistics, Economics and Mathematics, or Economics
To apply, please follow the link below:
http://careers.kemri-wellcome.org/frontpage
INT018
A comparison of 2 methods used in estimating the mid-point in measuring the Mid Upper Arm
Circumference; Its implication to accuracy
City:
KILIFI
Supervisor: Martha Mwangome & James Berkley
BACKGROUND
It is common practice for health workers in a busy rural health clinic to identify and use simplified nonvalidated
procedures in measuring anthropometry among children. These summarized but informal
procedures which are largely borrowed from the long formal procedure, are normally aimed at shortening
the measuring processes and also at omitting steps perceived to be “irrelevant”. Regularly, health workers
measure the weight of a fully/half dressed children contrary to the instructions or measure the length of
children with one leg pressing onto the leg board and not two legs as instructed or using “eyeballing” to
estimate the mid- point of the upper arm in taking MUAC instead of using the tape measure/string as
instructed.
There is currently little information on how these informal procedures affect the accuracy of the outcome
measure and eventually their effect on their interpretation.
QUESTION TO BE ADDRESSED BY INTERN
Are there significant differences in the estimation of MUAC using the formal compared to informal
procedure of estimating the midpoint?
SKILLS TO BE ACQUIRED BY INTERN
Study design, Research methods, statistical analysis and fundamentals in nutritional assessment
TRAINING BACKGROUND OF REQUIRED INTERN
BSc Food, Nutrition and dietetics
BSc Nursing
To apply, please follow the link below:
http://careers.kemri-wellcome.org/frontpage
INT019
Understanding the factors that enhance and constrain the effective delivery and uptake of ANC and
MCH services in Kilifi District
City:
KILIFI
Supervisor: Caroline Jones & Bryn Kemp
AIM
To investigate the factors that influence the use of ANC and MCH services by women in Kilifi District and to
understand the challenges and facilitating factors that affect health care provider practices and impact on
the quality of services they provide.
BACKGROUND
Kenya has identified the need to improve birth outcomes as a public health priority. Based on current
estimates, deaths during the first 28 days of life exceed the entire Millennium Develop Goal target for
childhood mortality (MDG4). Whilst prematurity and fetal growth restriction are two of the key
determinants of newborn survival, their relative prevalence in the majority of Kenya and sub-Saharan
Africa remains unknown and data reporting the causes of stillbirth and perinatal death are limited.
However, at least 60% of the 4 million neonatal deaths each year are associated with low birth weight
(LBW). Causes of LBW include intrauterine growth restriction (IUGR), preterm delivery and
genetic/chromosomal abnormalities. The contribution of risk factors such as malaria, maternal
undernutrition, HIV and anaemia to abnormal fetal growth, and how the latter relates to infant growth
patterns in sSA is not known. A greater understanding of how these risk factors interact with fetal growth is
required to guide interventions targeted at reducing the burden of perinatal morbidity and mortality.
Recently, Kilifi District hospital (KDH) became one of the sites for INTERGROWTH-21st, an international
study which uses ultrasound to date pregnancies and assess fetal growth accurately. By measuring
neonatal/infant growth accurately and collecting data on the health status of the pregnant women, the
study will provide the first comprehensive description of the impact of maternal under-nutrition, malaria,
HIV and anaemia upon birthweight and pregnancy outcomes in Kenya and other parts of the world. A
unique feature of the study as it is being implemented in Kilifi is an assessment of how the introduction of
ultrasound technology for routine antenatal care (ANC) will affect care pathways for patients within KDH.
This socio-behavioral component of the Intergrowth study is concerned with investigating the factors that
influence the use of ANC and maternal and child health services (MCH) and the impact of the introduction
of ultrasound scans on the perceptions and behaviours of women attending these services. It is also
concerned with the perceptions and practices of the providers of care and identification of factors that
enhance and/or constrain the delivery of quality services and may impact on the implementation of
ultrasound scanning under routine ANC conditions. Data for this component of the study is being collected
through a combination of quantitative and qualitative methods such as observations (structured and unstructured),
in-depth interviews (with providers and pregnant women) and group discussions.
This internship will utilize part of the qualitative data already collected and will take part in additional
qualitative data collection activities to provide information on the factors that influence the use of ANC and
MCH services by women in Kilifi District and to understand the challenges and facilitating factors that
affect health care provider practices and impact on the quality of services they provide. The intern will
also conduct a literature review of relevant studies and undertake qualitative data analysis. The intern will
be supported by a senior social scientist (Dr Caroline Jones), and the PI of the broader study (Dr Bryn
Kemp).
SKILLS TO BE ACQUIRED BY THE INTERN
• Reviewing the literature;
• An understanding of the concepts and methods used in qualitative research
• Qualitative data collection; analysis & interpretation
• Scientific writing and presentation skills.
TRAINING BACKGROUND OF REQUIRED INTERN
• Social science training
• Experience in in-depth interviews and FGDs
• Ability to work independently
• Excellent communication skills and good team player
• Giriama speaker
To apply, please follow the link below:
http://careers.kemri-wellcome.org/frontpage
INT020
Relationship between patients’ educational level and anti-epileptic drug adherence amongst adults in
Kilifi District
City:
KILIFI
Supervisor: Michael Kihara & Caroline Kathomi
BACKGROUND
Non-adherence to epilepsy medications can interfere with treatment and may adversely affect clinical
outcomes. There are a number of studies on the strategies for improving adherence to anti-epileptic drugs
(AEDs) in patients with epilepsy (PWE). Interventions of education and counselling of PWE have shown
mixed success. However, behavioural interventions such as the use of intensive reminders and
'implementation intention' interventions provided more positive effects on adherence (Ai-Aqeel & Al-
Shabhan, 2011).
Studies have however overlooked the potential confounding effects of education level of the PWE in
adherence studies. A recent study in the US showed that the main cause of non-adherence was socioeconomic
status (Modi et al., 2011) while another pointed to forgetfulness as the reason for non-adherence
(Hovinga et al., 2008). Forgetfulness is a cognitive trait and so we speculate that level of education could
be associated with adherence to AEDs.
We have drug levels of PWE in the Kilifi DSS which were collected as part of a previous study. We intend
to invite these PWE to undertake a brief cognitive test and answer questions on their education
background.
QUESTION TO BE ADDRESSED BY INTERN
• Is there a relationship between AED drug adherence and education level
• Is there a relationship between AED drug adherence and performance on cognitive test.
• What are the contributing factors of poor adherence amongst adult patients with epilepsy
SKILLS TO BE ACQUIRED BY INTERN
• Development of a cognitive impairment tool
• Administration of assessment tools
• Statistical analysis using SPSS
• How to write systematic reviews
TRAINING BACKGROUND OF REQUIRED INTERN
• Graduate in Sociology or Nursing
• Knowledge of Mijikenda (added advantage)
To apply, please follow the link below:
http://careers.kemri-wellcome.org/frontpage
INT021
Validation of immuno-adaptive genes by real-time PCR
City:
KILIFI
Supervisor: Margaret Mackinnon & Martin Rono
BACKGROUND
We have identified some genes in malaria parasites that are associated with high levels of immunity. This
was done by comparing gene transcription levels in parasites taken from a high malaria transmission
(Kisumu) vs. a low transmission area (Kilifi) using whole-genome microarrays. We found some of the
parasites gene’s were consistently up-regulated in high transmission areas suggesting that these genes may
be adaptive to high levels of immunity.
QUESTION TO BE ADDRESSED BY INTERN
Using real-time PCR, transcription levels on each of these candidate adaptive genes will be performed on
samples taken from an independent sample from these populations. This will confirm whether the results
from the microarray assays are representative of what is found in the parasite populations from these high
and low transmission areas.
SKILLS TO BE ACQUIRED BY INTERN
