The University of Zimbabwe Birth Cohort study (UZBCS) has been recruiting pregnant women (50% HIV infected) since 2016 [13]. Participants are 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 hygiene as exemplified by a cholera outbreak in 2018 involving two of the study sites [14]. Participants are followed as mother-baby pairs until the adulthood of the offspring. So far, 1200 mothers and infants have been investigated with deep clinical phenotyping and dense biosampling.
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.
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,
African capacity building is a crucial objective of our collaboration (see above).
The University of Zimbabwe Birth Cohort Team
Completed DrPhil Sub-studies within the cohort
On-going DrPhil sub-studies within the cohort
Completed MPhil sub-studies within the cohort
On-going MPhil sub-studies within the cohort
Support Staff
Attachees
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.
1. Agyepong IA, Sewankambo N, Binagwaho A, Coll-Seck AM, Corrah T, Ezeh A, et al. The path to longer and healthier lives for all Africans by 2030: the Lancet Commission on the future of health in sub-Saharan Africa. Lancet. 2017;390(10114):2803-59. Epub 2017/09/18. doi: 10.1016/S0140-6736(17)31509-X. PubMed PMID: 28917958.
2. Alderman H, Behrman JR, Glewwe P, Fernald L, Walker S. Evidence of Impact of Interventions on Growth and Development during Early and Middle Childhood. In: Bundy DAP, Silva ND, Horton S, Jamison DT, Patton GC, editors. Child and Adolescent Health and Development. 3rd ed. Washington (DC)2017.
3. Perkins JM, Kim R, Krishna A, McGovern M, Aguayo VM, Subramanian SV. Understanding the association between stunting and child development in low- and middle-income countries: Next steps for research and intervention. Soc Sci Med. 2017;193:101-9. Epub 2017/10/14. doi: 10.1016/j.socscimed.2017.09.039. PubMed PMID: 29028557.
4. Smith MI, Yatsunenko T, Manary MJ, Trehan I, Mkakosya R, Cheng J, et al. Gut microbiomes of Malawian twin pairs discordant for kwashiorkor. Science. 2013;339(6119):548-54. Epub 2013/02/01. doi: 10.1126/science.1229000. PubMed PMID: 23363771; PubMed Central PMCID: PMCPMC3667500.
5. Kau AL, Planer JD, Liu J, Rao S, Yatsunenko T, Trehan I, et al. Functional characterization of IgA-targeted bacterial taxa from undernourished Malawian children that produce diet-dependent enteropathy. Sci Transl Med. 2015;7(276):276ra24. Epub 2015/02/27. doi: 10.1126/scitranslmed.aaa4877. PubMed PMID: 25717097; PubMed Central PMCID: PMCPMC4423598.
6. Gehrig JL, Venkatesh S, Chang HW, Hibberd MC, Kung VL, Cheng J, et al. Effects of microbiota-directed foods in gnotobiotic animals and undernourished children. Science. 2019;365(6449). Epub 2019/07/13. doi: 10.1126/science.aau4732. PubMed PMID: 31296738; PubMed Central PMCID: PMCPMC6683325 diet-by-microbiota interactions in animal health. L.D.S. is currently a scientific sales representative at STEMCELL Technologies.
7. Keats EC, Das JK, Salam RA, Lassi ZS, Imdad A, Black RE, et al. Effective interventions to address maternal and child malnutrition: an update of the evidence. Lancet Child Adolesc Health. 2021;5(5):367-84. Epub 2021/03/11. doi: 10.1016/S2352-4642(20)30274-1. PubMed PMID: 33691083.
8. Humphrey JH, Mbuya MNN, Ntozini R, Moulton LH, Stoltzfus RJ, Tavengwa NV, et al. Independent and combined effects of improved water, sanitation, and hygiene, and improved complementary feeding, on child stunting and anaemia in rural Zimbabwe: a cluster-randomised trial. Lancet Glob Health. 2019;7(1):e132-e47. Epub 2018/12/18. doi: 10.1016/S2214-109X(18)30374-7. PubMed PMID: 30554749; PubMed Central PMCID: PMCPMC6293965.
9. Shepherd BL, Ferrand R, Munyati S, Folkard S, Boyd K, Bandason T, et al. HLA Correlates of Long-Term Survival in Vertically Infected HIV-1-Positive Adolescents in Harare, Zimbabwe. AIDS Res Hum Retroviruses. 2015;31(5):504-7. Epub 2015/01/07. doi: 10.1089/AID.2014.0338. PubMed PMID: 25560566; PubMed Central PMCID: PMCPMC4426308.
10. Wedderburn CJ, Weldon E, Bertran-Cobo C, Rehman AM, Stein DJ, Gibb DM, et al. Early neurodevelopment of HIV-exposed uninfected children in the era of antiretroviral therapy: a systematic review and meta-analysis. Lancet Child Adolesc Health. 2022;6(6):393-408. Epub 2022/04/29. doi: 10.1016/S2352-4642(22)00071-2. PubMed PMID: 35483380; PubMed Central PMCID: PMCPMC9090907 Centre for Child Health independent external review board and is a member of several data and safety monitoring boards with no payment, none of which relate to the current research. DJS has received research grants or consultancy honoraria from Discovery, Johnson & Johnson, Lundbeck, Sanofi, Servier, Takeda, and Vistagen. All other authors declare no competing interests.
11. le Roux SM, Abrams EJ, Donald KA, Brittain K, Phillips TK, Zerbe A, et al. Infectious morbidity of breastfed, HIV-exposed uninfected infants under conditions of universal antiretroviral therapy in South Africa: a prospective cohort study. Lancet Child Adolesc Health. 2020;4(3):220-31. Epub 2020/01/15. doi: 10.1016/S2352-4642(19)30375-X. PubMed PMID: 31932246; PubMed Central PMCID: PMCPMC7235356.
12. le Roux SM, Abrams EJ, Donald KA, Brittain K, Phillips TK, Nguyen KK, et al. Growth trajectories of breastfed HIV-exposed uninfected and HIV-unexposed children under conditions of universal maternal antiretroviral therapy: a prospective study. Lancet Child Adolesc Health. 2019;3(4):234-44. Epub 2019/02/19. doi: 10.1016/S2352-4642(19)30007-0. PubMed PMID: 30773459.
13. Duri K, Gumbo FZ, Munjoma PT, Chandiwana P, Mhandire K, Ziruma A, et al. The University of Zimbabwe College of Health Sciences (UZ-CHS) BIRTH COHORT study: rationale, design and methods. BMC Infect Dis. 2020;20(1):725. Epub 2020/10/04. doi: 10.1186/s12879-020-05432-6. PubMed PMID: 33008316; PubMed Central PMCID: PMCPMC7532096.
14. Mashe T, Chaibva BV, Nair P, Sani KA, Jallow M, Tarupiwa A, et al. Descriptive epidemiology of the cholera outbreak in Zimbabwe 2018-2019: role of multi-sectorial approach in cholera epidemic control. BMJ Open. 2023;13(1):e059134. Epub 2023/01/31. doi: 10.1136/bmjopen-2021-059134. PubMed PMID: 36717140; PubMed Central PMCID: PMCPMC9887696.
15. Duri K, Munjoma PT, Mazhandu AJ, Marere T, Gomo E, Banhwa S, et al. Predictors and Timing to Viral Suppression in HIV-Infected Pregnant Women in the University of Zimbabwe Birth Cohort Study During the Era of Lifelong Antiretroviral Therapy (Option B+ Treatment Strategy). Frontiers in Virology 2022;2. doi: https://doi.org/10.3389/fviro.2022.838234.
16. Duri K, Chimhuya S, Gomo E, Munjoma PT, Chandiwana P, Yindom LM, et al. Role of antenatal plasma cytomegalovirus DNA levels on pregnancy outcome and HIV-1 vertical transmission among mothers in the University of Zimbabwe birth cohort study (UZBCS). Virol J. 2021;18(1):30. Epub 2021/01/31. doi: 10.1186/s12985-021-01494-3. PubMed PMID: 33514390; PubMed Central PMCID: PMCPMC7846993.
17. Chandiwana P, Munjoma PT, Mazhandu AJ, Mazengera LR, Misselwitz B, Jordi SBU, et al. Antenatal and postpartum immunological markers levels in women with HIV infection and malnutrition in a low resource setting: A pilot study. European Journal of Inflammation. 2022;20. doi: 10.1177/1721727X221139261.
18. Chandiwana P, Munjoma PT, Mazhandu AJ, Li J, Baertschi I, Wyss J, et al. Antenatal gut microbiome profiles and effect on pregnancy outcome in HIV infected and HIV uninfected women in a resource limited setting. BMC Microbiol. 2023;23(1):4. Epub 2023/01/06. doi: 10.1186/s12866-022-02747-z. PubMed PMID: 36604616; PubMed Central PMCID: PMCPMC9817306.
19. Zhang Z, Duri K, Duisters KLW, Schoeman JC, Chandiwana P, Lindenburg P, et al. Altered methionine-sulfone levels are associated with impaired growth in HEU-children. AIDS. 2023. Epub 2023/04/19. doi: 10.1097/QAD.0000000000003574. PubMed PMID: 37070556.
20. Mataramvura H, Bunders MJ, Duri K. Human immunodeficiency virus and antiretroviral therapy-mediated immune cell metabolic dysregulation in children born to HIV-infected women: potential clinical implications. Front Immunol. 2023;14:1182217. Epub 2023/06/23. doi: 10.3389/fimmu.2023.1182217. PubMed PMID: 37350953; PubMed Central PMCID: PMCPMC10282157.