UZBCS

1. The population of Sub-Saharan Africa endures health challenges regarding poor hygiene, lack of access to clean water, malnutrition, as well as non-communicable and infectious diseases such as HIV. The University of Zimbabwe birth cohort study (UZBCS) is investigating the impact of these conditions on the highly vulnerable population of pregnant women, young mothers, and infants. UZBCS compares HIV-exposed, but uninfected children with HIV-unexposed uninfected children. Our collaboration aims to support these efforts by providing financial support, scientific training, and advice to the study team.
2. While the infant's gut is almost sterile at birth, its microbiota develops within the first 2-5 years of life, supported by interactions with the mother including breastfeeding. The trajectory of the infant microbiota maturation impacts on growth and development of the child, and susceptibility to diseases including gut infections. We aim to understand the development of the infant intestinal microbiota in UZBCS infants in comparison with healthy Bernese children from the BeBiCo study to appreciate common pathways and important differences and the impact on infant health.
3. In addition, the comprehensive biomaterials, and deep clinical metadata of UZBCS and BeBiCo allow addressing many additional questions for future translational research.

Malnutrition, poor hygiene, lack of access to clean water, infectious diseases, and low access to medicine limit the life expectancy and developmental potential of infants in Sub-Saharan Africa (SSA) including Zimbabwe [1]. These adverse conditions can severely affect infant growth and neurodevelopment, especially within the first 1000 days of life and infants might never reach their full development potential later in life [2, 3]. The interaction of the mother with the infant shapes the trajectory of the intestinal microbiota as well as the development of the infant intestine and its immune system. This interaction is considered crucial for healthy infant development [4-6] but the success of interventions remains limited [7, 8].

Since 1985, SSA endures an HIV epidemic and in Zimbabwe, out of 1.3 million people living with immune deficiency virus (HIV) in 2016, 72’000 were children under the age of 15. Without treatment, >30% of HIV-infected mothers transmitted the virus to their infants by 6 months of age and most infants progress to acquired immunodeficiency syndrome (AIDS) rapidly, with only 50% surviving beyond the age of two [9]. The introduction of combined antiretroviral therapy has greatly improved the outcome of mothers and infants [9]; however, a growing number of studies indicate challenges in HIV-exposed uninfected children regarding neurodevelopment [10], defense against pathogens [11], as well as growth and metabolism [12] and these risks need to be continuously investigated.

The University of Zimbabwe Birth Cohort study (UZBCS) has recruited pregnant women (50% HIV infected) of at least 20 weeks gestational age since 2016 [13]. Participants were recruited in four municipality health clinics, namely Kuwadzana, Dzivaresekwa (Rujeko), Glenview, and Budiriro in South West of Harare in a high-density area in a low-resource setting facing challenges in nutrition and clean water and sanitation as exemplified by a cholera outbreak in 2018 involving two of the study sites [14]. Participants are followed as mother-baby pairs until 6 years so far and later into  adulthood of the offspring. So far, 1200 mothers and infants have been investigated with deep clinical phenotyping and biosampling.

The study team enrolled mothers during pregnancy when baseline environmental and societal conditions and HIV status are evaluated. After the birth of the baby regular follow-up visits are scheduled, where health data are updated and biosamples, including breast milk, blood, and fecal samples are collected from mothers and babies respectively. All interested subsequent pregnancies/babies continue to be enrolled.

The Bern birth cohort (BeBiCo)-study is recruiting healthy pregnant women from the Bern area since 2020. Following a similar study design as UZBCS, mothers and infants are followed until 10 years of age with the acquisition of clinical meta-data and biosampling. In May 2023, 103 active participants remain included in BeBiCo with active enrolment at the maternity clinic of Inselspital.

The study design of UZBCS has been published [13]. In our first analyses, we addressed viral suppression in pregnant women and risk factors for lack of HIV suppression [15] and the role of cytomegalovirus in pregnancy in women with HIV infection [16]. Together, these analyses provide a comprehensive characterization of pregnant HIV-infected women, a highly vulnerable population in Zimbabwe that is also of great interest to public health authorities. Additional analyses with infant outcome data are pending.

To study the biology of HIV infection, we performed a pilot study, analyzing inflammatory markers in the serum of pregnant and non-pregnant women, with and without HIV infection [17]. In another pilot study, we described the microbiota of HIV-infected and uninfected women [18]. A separate project addressed immune-metabolic dysregulation in children born to women living with HIV [19, 20].

We recently completed testing of the mental health of UZBCS children 2-5 years of age with the child behavioral checklist (CBCL), which will be the first usage of CBCL in Sub-Saharan Africa (results pending).

In the future, we are aiming for a comprehensive analysis of the microbiota in the intestine and in breastmilk in UZBCS and BeBiCo to understand the differences in the trajectory of microbiota development in both settings and the impact of the environment. Results will be correlated with infant outcomes. Dense biosampling and deep phenotyping in UZBCS and BeBiCo will also make additional studies possible.   

Our transcontinental collaboration occurs in personal visits and online meetings.

Meetings in person

The Zimbabwean study team members visited our laboratory in Bern in 2019, 2021, and 2022. Zimbabwean master’s students and PhD students stay in Switzerland for approximately 3 months. A Zimbabwean PhD student's visit was involuntarily prolonged to 5 months due to the COVID-19-related shut-down of air traffic in 2019. During their visits, Zimbabwean students learned laboratory techniques such as bacterial DNA extraction and sequencing and participate in laboratory meetings.

Prof. Kerina Duri, the PI of UZBCS, visited our laboratory for 1 month in 2019. During this time, Prof. Duri also visited the Botnar Foundation which has been funding our collaboration. https://brc.ch/insights-into-the-university-of-zimbabwe-birth-cohort-study/

Prof. Benjamin Misselwitz visited Zimbabwe yearly from 2018-2023, meeting all collaboration partners in person, auditing the study’s finances, and discussing the study's progress and future projects.

Online meetings

We are performing weekly online meetings (on Wednesdays from 9-10 am). Meetings involve the Zimbabwean study team and Swiss researchers. During meetings, we discuss the progress of the study, results, next experiments, and the budget.
 

We are also performing online training for the Zimbabwean study team. All statistical analyses for our project are done using the open-source platform R. Our training has enabled Zimbabwean students to perform basic statistics and multivariable regression analyses independently for epidemiological data, which were used in recent publications [15-17]. Microbiota analyses of 16S sequencing data using QIIME 2 and MaAsLin are also done by Zimbabweans and have been/ will be used in past [18] and ongoing work. 

African capacity building is an important aspect of our collaboration.

• With funds from the Botnar Foundation, we provided critical infrastructure to the Zimbabwean study team including a -80°C freezer, DNA extraction kits, and lab equipment such as microcentrifuges and pipettes. 
• Our project supports the training of two Zimbabwean master’s students and one Zimbabwean PhD student.
• We are performing onsite training in Switzerland and regular online training to the benefit of our Zimbabwean collaboration partners. Abilities in open-source tools in R will enable the Zimbabwean team to complete a number of projects without the direct involvement of the Swiss partners (see technology transfer above).  

Principles of transboundary collaboration have been outlined in the “Nagoya protocol on Access to Genetic Resources and the Fair and Equitable Sharing of Benefits Arising from their Utilization” (https://www.cbd.int/abs/), as well as in the “Guide for Transboundary Research Partnerships” of the Swiss academy of sciences (https://kfpe.scnat.ch/en/11_principles_7_questions), and are followed in our collaboration. Specifically,

• UZBCS is a local Zimbabwean initiative, designed to study locally relevant clinical and scientific questions regarding the health of a highly vulnerable population and results have already been used to inform and shape local policies. Current projects are shaped by intense discussions between partners from both continents.
• All projects are approved by the local Swiss and Zimbabwean Ethics Committees and all participants provide written informed consent.
• All essential steps of the projects including wet-lab techniques as well as bioinformatics analyses of African material and data are performed either by or with direct participation of Zimbabwean scientists.
• Training is an integral of all projects and we enable local training of students, as well as online training and hands-on teaching and exposure, respectively, for all Zimbabwean students including senior scientists.

African capacity building is a crucial objective of our collaboration (see above).

• Data are available to all participants without restrictions. Data ownership resides with the researches generating the biosamples and clinical data and those performing sample processing and analyses.
• All collaborative UZBCS publications are jointly written with shared or exclusive Zimbabwean first/ last authorship with a Zimbabwean corresponding author.

The University of Zimbabwe Birth Cohort Team

• Professor K. Duri (Principle investigator: PI)
• Professor F.Z. Gumbo (coPI)
• Professor E. Gomo (coPI)
• Professor S. Rusakaniko (coPI)
• Dr. F. Chikwanha
• Dr. A. Ziruma
• Dr. T. Marere
• Dr. P. Kuona
• Dr. Chimhuya

Completed DrPhil Sub-studies within the cohort

• Dr. Agness Nhidza
• Dr. Doreen Mhandire

On-going DrPhil sub-studies within the cohort

• Mr. Privilege Munjoma (Funded by Bern University/ Botnar Foundation)
  • Research title: “Maternal gut and breast milk microbiota diversity: influences on infant gut microbiota colonization and health within the first two years of life”- Data analysis stage.
• Ms. Hope Muchatuta (funded by DFG, HIV TRUST)
  • • Research title:“Role of maternal HIV infection and life-long combination antiretroviral therapy use on the natural killer cell functional profiles and metabolic dysregulation among HIV exposed uninfected infants within the first two years of life”-Data analysis stage.
• Mr. Clive Tatenda Murashiki (Funded by HIV TRUST)
  • • Research title:”Burden of mycotoxins exposure, associated with cytokine profiles, anaemia and adverse pregnancy outcomes among pregnant women from high density urban populations of Harare”-Data analysis stage.
• Ms. Rudo Nyamakura

Completed MPhil sub-studies within the cohort

• Mr. Ray Chikwati

On-going MPhil sub-studies within the cohort

• Mr. Arthur Mazhandu (Funded by Bern University/ Botnar Foundation)
  • • Research title. ”Helicobactor pylori infection rates and risk in pregnant women and children under 5 years in a low resource setting”- Data analysis stage.
• Mr. Panashe Chandiwana (Funded by Bern University/ Botnar Foundation)
  • • Research title“Microbiome profiles in pregnant women and pregnancy outcomes: roles of HIV infection and malnutrition”- Submitted thesis for marking.

Support Staff

• Sister Mercy Ngoweni (study nurse)
• Sister Nyaradzo Sibiya (study nurse)
• Ndega “Sekuru” Taremeredzwa (supporting scientist)
• Mr. McLeod Madhaka (finance officer)
• Ms. Progress Muzire (data entry clerk)
• Sr. Mary Maria Chipiti
• Ms. Precious Chandiwana

Attachees

• Panashe Chandiwana (2017-2018)
• Tanaka
• Mcdonald
• Blessed
• Patience
• Sarah Gwaradzima (Attachee since August 2022)
• Shigirai Mudzviti (Attachee since August 2022)

• Prof. Benjamin Misselwitz
• Prof. Bahtiyar Yilmaz
• Prof. Stephanie Ganal-Vonarburg
• Prof. Ziad Al Nabhani
• Prof. Andrew Macpherson
• Prof. Michael Kaess
• Dr. Annekatrin Steinhoff
• PD Dr. Christiane Sokollik
• Sebastian Jordi (MD PhD student)

• Dr. med. Jacqueline Wyss (MD PhD student)
• Isabel Bärtschi (PhD student)
• Jiaqi Li (PhD student)

UZBCS is currently funded by the Botnar Foundation via a grant to Prof. R. Platt, ETH Basel, Prof. U. Sauer, ETH Zurich, Prof. D. Bumann, ETH Basel and A.J. Macpherson, Inselpital Bern, and the University of Bern. Funding covers the costs for the clinical study as well as consumables and equipment for the microbiota analysis.

Additional costs of our collaboration are funded by UVCM, Inselspital Bern. Tests for mental health of children using the Child Behavioural Check List (CBCL) are funded by UPD Bern.  

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