KEMRI-Wellcome Trust Research Programme (KWTRP) is offering sponsored opportunities for talented masters students to undertake their research projects at the Programmes’ facilities in Nairobi or Kilifi, Kenya. The placement will provide opportunities for recipients to carry out their projects within a high-quality research environment and, under the supervision and mentorship of internationally renowned KWTRP-scientists. Interested applicants must be registered at a local university in Kenya and will be offered (if successful) a stipend for up to 12 months.

AVAILABLE RESEARCH PROJECTS

Interested applicants can apply to undertake either of these research projects.

Background & aim of RESEARCH PROJECT 1

In July 2014, Kenya introduced the Rotarix™ rotavirus vaccine into its national immunisation programme. WHO recommends use of antigen detection approach (mainly ELISA) for rotavirus diagnosis in the post-vaccine introduction era. In Kenya, the overall 2-dose effectiveness of Rotarix™ vaccine was found to be only 64% in under-5-year-olds with rotavirus positives identified using the ELISA diagnostic approach. However, data from our virus research laboratory at KWTRP consistently indicate that ELISA

misses a significant number of rotavirus positives detected by nucleic acid amplification test (NAATs) e.g., real-time RT-PCR. For instance, using the TaqMan array cards, the positivity rate of rotavirus in admitted children at Kilifi county hospital did not appear to change pre-(2013) vs post (2016-2018) rotavirus vaccine introduction era; 27.4% vs. 23.5% (p = 0.253). Motivated by Rotarix™ vaccine shortages and a lower price per dose, Kenya recently (in early 2023) changed its recommended rotavirus vaccine brand in public outlets from Rotarix™ to Rotavac™ which has had few phase III clinical trials to date and is known to have slightly lower efficacy compared Rotarix™. Our research team has sustained rotavirus surveillance among children under 13-years admitted with diarrhea in Kilifi county hospital for more than a decade (since 2009). Further, since 2019, we have also sustained parallel testing of stool samples from recruited participants by both ELISA and real-time RT-PCR NAAT. Positives are genotyped by whole genome sequencing followed by classification by phylogenetic analysis and established bioinformatic algorithms. This MSc project will specifically seek to answer these questions; (i) Does the diagnostic method have a significant impact on the observed rotavirus vaccine effectiveness? (ii) How does effectiveness of Rotavac™ and Rotarix™ vaccines compare in the coast of Kenya? and (iii) Can the lower rotavirus vaccine effectiveness observed in Kenya e.g. for Rotarix™ be explained by the circulating rotavirus vaccine strains? Interested applicants must have studied medical/applied statistics, epidemiology, public health, data science, clinical sciences or other related field for their undergraduate degree.

Background & aim of RESEARCH PROJECT 2

The decline in malaria burden in Africa has stalled in recent years. We are now faced with significant threats to the diagnosis and treatment of malaria; Plasmodium falciparum histidine rich protein (Pfhrp) 2/3 deletions,making parasites invisible to most rapid diagnostic tests (RDT), and the emergence and spread of mutations in Pf kelch 13 (Pfk13), resulting in resistance to the major frontline antimalarial artemisinin. Pfk13 mutations (i.e. R561H, P574L and A675V) associated with artemisinin resistance in Southeast Asia are now present in Africa. The Oxford Nanopore Technology (ONT), MinION, gives fewer sequence reads per run, but its reagents and overall cost per run is cheaper than the MiSeq illumine platform. We intend to explore pooling strategies of for instance 1000 samples in one sequencing run or 10 samples per pool for a rapid approach to screen thousands of samples by TADS or MinION. Different pooling and library strategies will be compared against individual sample assays to test the accuracy of these approaches in determining prevalence of drug resistance alleles. The successful candidate will specifically examine prevalence levels of drug resistance markers in samples obtained from a primary healthcare facility in Kilifi using ONT. Interested applicants must have theoretical knowledge of molecular biology, biochemistry, and basic bioinformatics.

Background & aim of RESEARCH PROJECT 3

The Government of Kenya has made great investments aimed at reducing maternal and neonatal deaths. These have largely been aimed at increasing coverage of facility-based services which include increased contraceptive use to reduce unwanted pregnancies, increased antenatal care, and skilled deliveries. Despite these investments and increasing coverage, the expected reduction on maternal and neonatal deaths has not been realized. To reduce maternal and neonatal mortality, WHO, UNICEF, and UNFPA jointly recommend having for every 500,000 population at least five health facilities that can provide basic emergency obstetric care and one that can provide comprehensive care. Basic emergency obstetric care (BEmONC) includes capacity to provide all of seven key services: (i) Parenteral administration of oxytocics (ii) Manual removal of placenta (iii) Manual removal of retained products of conception (iv) Assisted vaginal delivery (v) Parenteral administration of anticonvulsants (vi) Parenteral administration of antibiotics and (vii) neonatal resuscitation. Comprehensive emergency obstetric care (CEmONC) includes two additional services: (viii) caesarean section and (ix) blood transfusion. The WHO quality of care framework recommends that good quality of care is achieved by use of eight key pillars. This MSc project will focus on the 7th and 8th pillar regarding availability of competent and motivated human resources and essential physical resources, respectively. The overall aim will be to examine health provider clinical knowledge and practices of essential maternal and new-born care with emphasis on post-delivery care. The project will complement and be embedded within an ongoing project: the QuEST (Quality Evidence for Health System Transformation) e-Cohort study. The e-Cohort study aims to develop and validate a tool for measuring quality of MNH care by using phone surveys to follow up women over the course of pregnancy, delivery, postpartum and new-born periods. Interested applicants must have studied nursing or clinical medicine in their undergraduate studies and currently undertaking a masters programme in public health, health systems, implementation science, medical statistics, or other related field. Experience serving in a public hospital and in quantitative data collection, analysis and dissemination is desirable.

Background & aim of RESEARCH PROJECT 4

The nutritional status of non-pregnant women can significantly impact their future reproductive health and their ability to have a healthy pregnancy when the time comes due to impaired immune function and increased susceptibility to chronic diseases. Adequate micronutrient intake contributes to eradicating poverty and hunger by increasing learning ability and intellectual potential, leading to better-educated citizens due to reduced burden of morbidity and mortality making resources more available in the household and provide more time for income generation. In developing countries like Kenya, micronutrient deficiencies are prevalence. Studies have found anemia and Vitamin A deficiency among pregnant women to be as high as 47% and 51.2% respectively in different counties in Kenya. Poor diets are major contributors to these deficiencies. In Kenya for example – among most population, diets are mainly plant-based with low micronutrient content. The small quantities of micronutrients that are in these foods are not readily available to the body due to a high content of antinutrients for example phytates which bind with the micronutrients making them unavailable to the body. Similarly, inadequate dietary intake and poor nutritional status among pregnant women are prevalent. This is coupled by poverty resulting in poor dietary practices, limited access to diverse and nutritious foods, and inadequate knowledge about optimal nutrition. In addition, utilization, socio-cultural traditions and disparities in households contribute to under nutrition in women. Data on diet patterns, dietary intakes, and micronutrient adequacy of diets for women across the county is also scarce. There is ample evidence showing that dietary diversity is indeed strongly associated with nutrient adequacy and is an essential element of diet quality however evidence confirming this association specifically among women of reproductive age is limited. This research project will evaluate the contribution of dietary intake to micronutrient status of pregnant and non-pregnant women in Kilifi, Kenya. Interested applicants must have studied nutrition in their undergraduate studies and undertaking a masters programme in nutrition studies or other related field. Research experience particularly in dietary assessments is desirable.

Background & aim of RESEARCH PROJECT 5

Streptococcus pneumoniae is thought to be a major cause of community acquired pneumonia (CAP) among adults. However, diagnosis of pneumococcal pneumonia is hampered by the poor sensitivity of blood culture and the substantial contribution of non-bacteremic pneumococcal pneumonia. Urinary pneumococcal antigen detection tests (both serotype-specific and non-specific) have higher sensitivity than blood cultures for detection of pneumococcal pneumonia and have been successfully employed for diagnosis and surveillance of pneumococcal pneumonia predominantly in high income settings. Serotype-specific urinary antigen detection (ssUAD) tests have the added benefit of generating evidence on the serotype-specific burden of disease, which is important for informing pneumococcal vaccine policy. The burden of pneumococcal pneumonia in low- and middle-income settings is not well understood; ssUAD could potentially inform our understanding of the burden in these settings. However, prior to implementation of their widespread use for surveillance in low- and middle-income settings, the performance of ssUAD tests would need to be validated as host factors – such as relatively high asymptomatic nasopharyngeal carriage of pneumococcus, co-infections, and comorbidities – may impact their performance. The Nottingam University Hospitals NHS Trust (NUH-NHST) have implemented a 24-valent ssUAD test for the detection of pneumococcal pneumonia due to serotypes 1, 2, 3, 4, 5, 6A, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F or 33F. The sensitivity and specificity of the 24-valent ssUAD test are 94.3% and 93.6%, respectively, as measured among UK patients. This MSc project will constitute testing urine samples collected as part of KWTRP’s community- and hospital-based studies at the NUH-NHST lab using the 24-valent ssUAD test, and subsequent assessment of the assay’s performance. This is the first step in a series of planned work that is hoped to culminate in the establishment of a ssUAD at KWTRP. Interested applicants must have studied epidemiology, microbiology, statistics, biostatistics or other related fieldin their undergraduate studies. Previous experience in epidemiological research of microbial diseases is desirable.

Background & aim of RESEARCH PROJECT 6

Major progress has been made globally to slow down the spread of COVID-19 in the human population. However, emergence of variants which could evade immunity mounted following vaccination or infection with earlier variants threaten this progress. Therefore, timely discovery through genomics and rapid assessment of newly circulating variants on host immunity through serology is important to inform public health interventions (WHO, 2023). This project is part of a larger project performing continuous surveillance of SARS-CoV-2 variants circulating in Kenya and the Eastern Africa region with aim to rapidly characterize the variants of interest and their impact on natural and vaccine induced immunity. This specific MSc project will answer this question; “Are the variants of interest circulating locally evasive to immune responses mounted by vaccination and natural infection by earlier SARS-CoV-2 variants”? Interested applicants must have theoretical knowledge of molecular biology, immunology and basic bioinformatics.