Bio

Prof Ruth Nduati

Ruth Nduati is a Professor of Paediatrics at the School of Medicine, College of Health Sciences, University of Nairobi. She is a Paediatrician and Epidemiologist who has taught at the University of Nairobi for many years.  Her major achievement is her contribution to the understanding of the epidemiology and biology of breast milk transmission of HIV and in integration of prevention of mother-to-child transmission (PMTCT) of HIV in resource constrained settings.

Publications


Submitted

2017

Newman, LP, Njoroge A, Magaret A, Chohan BH, Gitomea VW, Wald A, Gorstein J, Overbaugh J, Dalton Wamalwa, Maleche-Obimbo E, Ruth Nduati, Farquhar C.  2017.  Sustained Responses to Measles Revaccination at 24 Months in HIV-Infected Children on Antiretroviral Therapy in Kenya., 2017 Feb 13. The Pediatric infectious disease journal. Abstract

There are limited data on whether HIV-infected children in resource-limited countries who are receiving antiretroviral therapy (ART) are able to produce sustained, protective levels of measles antibody after multiple measles vaccinations.

Buttolph, J, Inwani I, Agot K, Cleland CM, Cherutich P, Kiarie JN, Osoti A, Celum CL, Baeten JM, Ruth Nduati, John Kinuthia, James N Kiarie, Hallett TB, Alsallaq R, Kurth AE.  2017.  Gender-Specific Combination HIV Prevention for Youth in High-Burden Settings: The MP3 Youth Observational Pilot Study Protocol., 2017 Mar 08. JMIR research protocols. 6(3):e22. Abstract

Nearly three decades into the epidemic, sub-Saharan Africa (SSA) remains the region most heavily affected by human immunodeficiency virus (HIV), with nearly 70% of the 34 million people living with HIV globally residing in the region. In SSA, female and male youth (15 to 24 years) are at a disproportionately high risk of HIV infection compared to adults. As such, there is a need to target HIV prevention strategies to youth and to tailor them to a gender-specific context. This protocol describes the process for the multi-staged approach in the design of the MP3 Youth pilot study, a gender-specific, combination, HIV prevention intervention for youth in Kenya.

2016

Rustagi, AS, Gimbel S, Ruth Nduati, de Cuembelo MF, Wasserheit JN, Farquhar C, Gloyd S, Sherr K.  2016.  Health facility factors and quality of services to prevent mother-to-child HIV transmission in Côte d'Ivoire, Kenya, and Mozambique., 2016 Sep 02. International journal of STD & AIDS. Abstract

This study aimed to identify facility-level characteristics associated with prevention of mother-to-child HIV transmission service quality. This cross-sectional study sampled 60 health facilities in Mozambique, Côte d'Ivoire, and Kenya (20 per country). Performance score - the proportion of pregnant women tested for HIV in first antenatal care visit, multiplied by the proportion of HIV-positive pregnant women who received appropriate antiretroviral medications - was calculated for each facility using routine data from 2012 to 2013. Facility characteristics were ascertained during on-site visits, including workload. Associations between facility characteristics and performance were quantified using generalized linear models with robust standard errors, adjusting for country. Over six months, facilities saw 38,611 first antenatal care visits in total. On-site CD4 testing, Pima CD4 machine, air conditioning, and low or high (but not mid-level) patient volume were each associated with higher performance scores. Each additional first antenatal care visit per nurse per month was associated with a 4% (95% confidence interval: 1%-6%) decline in the odds that an HIV-positive pregnant woman would receive both HIV testing and antiretroviral medications. Physician workload was only modestly associated with performance. Investments in infrastructure and human resources - particularly nurses - may be critical to improve prevent mother-to-child HIV transmission service delivery and protect infants from HIV.

Richardson, BA, John-Stewart G, Atkinson C, Ruth Nduati, Ásbjörnsdóttir K, Boeckh M, Overbaugh J, Emery V, Slyker JA.  2016.  Vertical Cytomegalovirus Transmission From HIV-Infected Women Randomized to Formula-Feed or Breastfeed Their Infants., 2016 Mar 15. The Journal of infectious diseases. 213(6):992-8. Abstract

Cytomegalovirus (CMV) is associated with morbidity and mortality in human immunodeficiency virus (HIV)-exposed infants. We assessed the effect of and relative contribution of breastfeeding to CMV acquisition among infants delivered by HIV-infected mothers.

Milligan, C, Omenda MM, Chohan V, Odem-Davis K, Richardson BA, Ruth Nduati, Overbaugh J.  2016.  Maternal Neutralization-Resistant Virus Variants Do Not Predict Infant HIV Infection Risk., 2016. mBio. 7(1):e02221-15. Abstract

Mother-to-child transmission (MTCT) of HIV provides a setting for studying immune correlates of protection. Neutralizing antibodies (NAbs) are suggested to contribute to a viral bottleneck during MTCT, but their role in blocking transmission is unclear, as studies comparing the NAb sensitivities of maternal viruses have yielded disparate results. We sought to determine whether transmitting mothers differ from nontransmitting mothers in the ability to neutralize individual autologous virus variants present at transmission. Ten transmitting and 10 nontransmitting HIV-infected mothers at high risk of MTCT were included in this study. Full-length HIV envelope genes (n = 100) were cloned from peripheral blood mononuclear cells obtained near transmission from transmitting mothers and at similar time points from nontransmitting mothers. Envelope clones were tested as pseudoviruses against contemporaneous, autologous maternal plasma in neutralization assays. The association between transmission and the log2 50% inhibitory concentration (IC50) for multiple virus variants per mother was estimated by using logistic regression with clustered standard errors. t tests were used to compare proportions of neutralization-resistant viruses. Overall, transmitting mothers had a median IC50 of 317 (interquartile range [IQR], 202 to 521), and nontransmitting mothers had a median IC50 of 243 (IQR, 95 to 594). Transmission risk was not significantly associated with autologous NAb activity (odds ratio, 1.25; P = 0.3). Compared to nontransmitting mothers, transmitting mothers had similar numbers of or fewer neutralization-resistant virus variants, depending on the IC50 neutralization resistance cutoff. In conclusion, HIV-infected mothers harbor mostly neutralization-sensitive viruses, although resistant variants were detected in both transmitting and nontransmitting mothers. These results suggest that MTCT during the breastfeeding period is not driven solely by the presence of maternal neutralization escape variants.

Bosire, R, Betz B, Aluisio A, Hughes JP, Ruth Nduati, Kiarie J, Chohan BH, Merkel M, Lohman-Payne B, John-Stewart G, Farquhar C.  2016.  High Rates of Exclusive Breastfeeding in Both Arms of a Peer Counseling Study Promoting EBF Among HIV-Infected Kenyan Women.. Breastfeeding medicine : the official journal of the Academy of Breastfeeding Medicine. 11:56-63. Abstract

Exclusive breastfeeding (EBF) is recommended for 6 months after delivery as the optimal infant feeding method and is especially important for prevention of mother-to-child HIV transmission (PMTCT). However, EBF promotion efforts among HIV-infected mothers in sub-Saharan Africa have achieved mixed success and require context-specific interventions.

Rustagi, AS, Gimbel S, Ruth Nduati, de Cuembelo MF, Wasserheit JN, Farquhar C, Gloyd S, Sherr K.  2016.  Implementation and Operational Research: Impact of a Systems Engineering Intervention on PMTCT Service Delivery in Côte d'Ivoire, Kenya, Mozambique: A Cluster Randomized Trial., 2016 Jul 1. Journal of acquired immune deficiency syndromes (1999). 72(3):e68-76. Abstract

Efficacious interventions to prevent mother-to-child HIV transmission (PMTCT) have not translated well into effective programs. Previous studies of systems engineering applications to PMTCT lacked comparison groups or randomization.

Odeny, BM, Pfeiffer J, Farquhar C, Igonya EK, Gatuguta A, Kagwaini F, Ruth Nduati, Kiarie J, Bosire R.  2016.  The Stigma of Exclusive Breastfeeding Among Both HIV-Positive and HIV-Negative Women in Nairobi, Kenya., 2016 Jun. Breastfeeding medicine : the official journal of the Academy of Breastfeeding Medicine. 11:252-8. Abstract

Exclusive breastfeeding (EBF) means giving only breast milk to an infant. Although it is the optimal mode of feeding for infants younger than 6 months, its prevalence is low in HIV-endemic regions. Extensive promotion of EBF for 6 months in prevention of mother-to-child HIV transmission (PMTCT) programs could inadvertently result in stigma due to women's perceived association of EBF with HIV infection. In this qualitative study, we describe how stigma impacts the uptake of EBF among HIV-positive and -negative women.

Aluisio, AR, Bosire R, Betz B, Gatuguta A, Kiarie JN, Nduati R, John-Stewart G, Farquhar C.  2016.  Male Partner Participation in Antenatal Clinic Services is Associated with Improved HIV-free survival Among Infants in Nairobi, Kenya: A Prospective Cohort Study.. Journal of acquired immune deficiency syndromes (1999). Abstract

This prospective study investigated the relationship between male antenatal clinics (ANC) involvement and infant HIV-free survival.

Nduati, EW, Nkumama IN, Gambo FK, Muema DM, Knight MG, Hassan AS, Jahangir MN, Etyang TJ, Berkley JA, Urban BC.  2016.  HIV-exposed uninfected infants show robust memory B cell responses in spite of a delayed accumulation of memory B cells: An observational study in the first two years of life., 2016 May 11. Clinical and vaccine immunology : CVI. Abstract

Improved HIV care has led to an increase in the number of HIV-exposed uninfected (HEU) infants born to HIV infected women. Although uninfected, these infants experience increased morbidity and mortality. One explanation may be that their developing immune system is altered by HIV-exposure predisposing them to increased post-natal infections.

Simonich, CA, Williams KL, Verkerke HP, Williams JA, Ruth Nduati, Lee KK, Overbaugh J.  2016.  HIV-1 Neutralizing Antibodies with Limited Hypermutation from an Infant., 2016 Jun 22. Cell. Abstract

HIV-1 broadly neutralizing antibodies (bnAbs) develop in a subset of infected adults and exhibit high levels of somatic hypermutation (SHM) due to years of affinity maturation. There is no precedent for eliciting highly mutated antibodies by vaccination, nor is it practical to wait years for a desired response. Infants develop broad responses early, which may suggest a more direct path to generating bnAbs. Here, we isolated ten neutralizing antibodies (nAbs) contributing to plasma breadth of an infant at ∼1 year post-infection, including one with cross-clade breadth. The nAbs bind to envelope trimer from the transmitted virus, suggesting that this interaction may have initiated development of the infant nAbs. The infant cross-clade bnAb targets the N332 supersite on envelope but, unlike adult bnAbs targeting this site, lacks indels and has low SHM. The identification of this infant bnAb illustrates that HIV-1-specific neutralization breadth can develop without prolonged affinity maturation and extensive SHM.

2015

Cournil, A, Van de Perre P, Cames C, de Vincenzi I, Read JS, Luchters S, Meda N, Naidu K, Newell M-L, Bork K.  2015.  Early infant feeding patterns and HIV-free survival: findings from the Kesho-Bora trial (Burkina Faso, Kenya, South Africa).. The Pediatric infectious disease journal. 34(2):168-74. Abstract

To investigate the association between feeding patterns and HIV-free survival in children born to HIV-infected mothers and to clarify whether antiretroviral (ARV) prophylaxis modifies the association.

Muema, DM, Nduati EW, Uyoga M, Bashraheil M, Scott JAG, Hammitt LL, Urban BC.  2015.  10-valent pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine (PHiD-CV) induces memory B cell responses in healthy Kenyan toddlers., 2015 Aug. Clinical and experimental immunology. 181(2):297-305. Abstract

Memory B cells are long-lived and could contribute to persistence of humoral immunity by maintaining the plasma-cell pool or making recall responses upon re-exposure to an antigen. We determined the ability of a pneumococcal conjugate vaccine to induce anti-pneumococcal memory B cells. Frequencies of memory B cells against pneumococcal capsular polysaccharides from serotypes 1, 6B, 14, 19F and 23F were determined by cultured B cell enzyme-linked immunospot (ELISPOT) in 35 children aged 12-23 months who received pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine (PHiD-CV). The relationships between plasma antibodies and memory B cell frequencies were also assessed. After two doses of PHiD-CV, the proportion of subjects with detectable memory B cells against pneumococcal capsular polysaccharides increased significantly for serotypes 1 (3-45%; P < 0·01), 19F (21-66%; P < 0·01) and 23F (13-36%; P = 0·02), but not serotypes 6B (24-42%; P = 0·24) and 14 (21-40%; P = 0·06). Correlations between antibodies and memory B cells were weak. Carriage of serotype 19F at enrolment was associated with poor memory B cell responses against this serotype at subsequent time-points (day 30: non-carriers, 82% versus carriers, 0%, P < 0·01; day 210: non-carriers, 72% versus carriers, 33%, P = 0·07). PHiD-CV is capable of inducing memory B cells against some of the component pneumococcal capsular polysaccharides.

Milligan, C, Richardson BA, John-Stewart G, Ruth Nduati, Overbaugh J.  2015.  Passively acquired antibody-dependent cellular cytotoxicity (ADCC) activity in HIV-infected infants is associated with reduced mortality., 2015 Apr 8. Cell host & microbe. 17(4):500-6. Abstract

In addition to direct effects on virus infectivity, antibodies mediate antibody-dependent cellular cytotoxicity (ADCC), the killing of an antibody-coated virus-infected cell by cytotoxic effector cells. Although ADCC has been suggested to protect against HIV, the relationship between HIV-specific ADCC antibodies at the time of HIV exposure and infection outcome in humans remains to be assessed. We evaluated the ADCC activity of passively acquired antibodies in infants born to HIV-infected mothers. ADCC levels were higher in uninfected than infected infants, although not significantly. Increase in ADCC antibody activity in infected infants was associated with reduced mortality risk. Infant ADCC positively correlated with the magnitude of IgG1 binding, and IgG1 levels were associated with survival in infected infants. Infant IgG3-binding antibodies were not associated with infected infant survival. These data suggest a therapeutic benefit of pre-existing HIV-specific ADCC antibodies and support a role for eliciting ADCC-mediating IgG1 in HIV vaccines.

Pope, WH, Bowman CA, Russell DA, Jacobs-Sera D, Asai DJ, Cresawn SG, Jacobs WR, Hendrix RW, Lawrence JG, Hatfull GF.  2015.  Whole genome comparison of a large collection of mycobacteriophages reveals a continuum of phage genetic diversity., 2015. eLife. 4:e06416. Abstract

The bacteriophage population is large, dynamic, ancient, and genetically diverse. Limited genomic information shows that phage genomes are mosaic, and the genetic architecture of phage populations remains ill-defined. To understand the population structure of phages infecting a single host strain, we isolated, sequenced, and compared 627 phages of Mycobacterium smegmatis. Their genetic diversity is considerable, and there are 28 distinct genomic types (clusters) with related nucleotide sequences. However, amino acid sequence comparisons show pervasive genomic mosaicism, and quantification of inter-cluster and intra-cluster relatedness reveals a continuum of genetic diversity, albeit with uneven representation of different phages. Furthermore, rarefaction analysis shows that the mycobacteriophage population is not closed, and there is a constant influx of genes from other sources. Phage isolation and analysis was performed by a large consortium of academic institutions, illustrating the substantial benefits of a disseminated, structured program involving large numbers of freshman undergraduates in scientific discovery.

Daniels, J, Ruth Nduati, Kiarie J, Farquhar C.  2015.  Supporting early career health investigators in Kenya: A qualitative study of HIV/AIDS research capacity building., 2015. The Pan African medical journal. 20:192. Abstract

Strategies to transfer international health research training programs to sub-Saharan African institutions focus on developing cadres of local investigators who will lead such programs. Using a critical leadership theory framework, we conducted a qualitative study of one program to understand how collaborative training and research can support early career investigators in Kenya toward the program transfer goal.

Muema, DM, Macharia GN, Hassan AS, Mwaringa SM, Fegan GW, Berkley JA, Nduati EW, Urban BC.  2015.  Control of Viremia Enables Acquisition of Resting Memory B Cells with Age and Normalization of Activated B Cell Phenotypes in HIV-Infected Children., 2015 Aug 1. Journal of immunology (Baltimore, Md. : 1950). 195(3):1082-91. Abstract

HIV affects the function of all lymphocyte populations, including B cells. Phenotypic and functional defects of B cells in HIV-infected adults have been well characterized, but defects in children have not been studied to the same extent. We determined the proportion of B cell subsets and frequencies of Ag-specific memory B cells in peripheral blood from HIV-infected children and healthy controls, using flow cytometry and B cell ELISPOT, respectively. In addition, we measured the quantities and avidities of plasma Abs against various Ags by ELISA. We also determined plasma levels of BAFF and expression of BAFF receptors on B cells. Children with high HIV viremia had increased proportions of activated mature B cells, tissue-like memory B cells and plasmablasts, and low proportions of naive B cells when compared with community controls and children with low HIV viremia, similar to adults infected with HIV. HIV-infected groups had lower proportions of resting memory B cells than did community controls. Notably, high HIV viremia prevented the age-dependent accumulation of class-switched resting memory B cells. HIV-infected children, regardless of the level of viremia, showed lower quantities and avidities of IgG and lower frequencies of memory B cells against Expanded Program on Immunization vaccines. The HIV-infected children had an altered BAFF profile that could have affected their B cell compartment. Therefore, B cell defects in HIV-infected children are similar to those seen in HIV-infected adults. However, control of HIV viremia is associated with normalization of activated B cell subsets and allows age-dependent accumulation of resting memory B cells.

Kibaru, EG, Ruth Nduati, Dalton Wamalwa, Kariuki N.  2015.  Impact of highly active antiretroviral therapy on hematological indices among HIV-1 infected children at Kenyatta National Hospital-Kenya: retrospective study., 2015. AIDS research and therapy. 12:26. Abstract

HIV infected children experience a range of hematological complications which show marked improvement within 6 months of initiating anti-retroviral therapy. The Objectives of the study was to describe the changes in hematological indices of HIV-1 infected children following 6 months of treatment with first line antiretroviral drugs (ARVs) regimen.

Nduati, EW, Hassan AS, Knight MG, Muema DM, Jahangir MN, Mwaringa SL, Etyang TJ, Rowland-Jones S, Urban BC, Berkley JA.  2015.  Outcomes of prevention of mother to child transmission of the human immunodeficiency virus-1 in rural Kenya--a cohort study., 2015. BMC public health. 15:1008. Abstract

Success in prevention of mother-to-child transmission (PMTCT) raises the prospect of eliminating pediatric HIV infection. To achieve global elimination, however, strategies are needed to strengthen PMTCT interventions. This study aimed to determine PMTCT outcomes and identify challenges facing its successful implementation in a rural setting in Kenya.

Garcia-Knight, MA, Nduati E, Hassan AS, Gambo F, Odera D, Etyang TJ, Hajj NJ, Berkley JA, Urban BC, Rowland-Jones SL.  2015.  Altered Memory T-Cell Responses to Bacillus Calmette-Guerin and Tetanus Toxoid Vaccination and Altered Cytokine Responses to Polyclonal Stimulation in HIV-Exposed Uninfected Kenyan Infants., 2015. PloS one. 10(11):e0143043. Abstract

Implementation of successful prevention of mother-to-child transmission of HIV strategies has resulted in an increased population of HIV-exposed uninfected (HEU) infants. HEU infants have higher rates of morbidity and mortality than HIV-unexposed (HU) infants. Numerous factors may contribute to poor health in HEU infants including immunological alterations. The present study assessed T-cell phenotype and function in HEU infants with a focus on memory Th1 responses to vaccination. We compared cross-sectionally selected parameters at 3 and 12 months of age in HIV-exposed (n = 42) and HU (n = 28) Kenyan infants. We measured ex vivo activated and bulk memory CD4 and CD8 T-cells and regulatory T-cells by flow cytometry. In addition, we measured the magnitude, quality and memory phenotype of antigen-specific T-cell responses to Bacillus Calmette-Guerin and Tetanus Toxoid vaccine antigens, and the magnitude and quality of the T cell response following polyclonal stimulation with staphylococcal enterotoxin B. Finally, the influence of maternal disease markers on the immunological parameters measured was assessed in HEU infants. Few perturbations were detected in ex vivo T-cell subsets, though amongst HEU infants maternal HIV viral load positively correlated with CD8 T cell immune activation at 12 months. Conversely, we observed age-dependent differences in the magnitude and polyfunctionality of IL-2 and TNF-α responses to vaccine antigens particularly in Th1 cells. These changes mirrored those seen following polyclonal stimulation, where at 3 months, cytokine responses were higher in HEU infants compared to HU infants, and at 12 months, HEU infant cytokine responses were consistently lower than those seen in HU infants. Finally, reduced effector memory Th1 responses to vaccine antigens were observed in HEU infants at 3 and 12 months and higher central memory Th1 responses to M. tuberculosis antigens were observed at 3 months only. Long-term monitoring of vaccine efficacy and T-cell immunity in this vulnerable population is warranted.

Milligan, C, Richardson BA, John-Stewart G, Ruth Nduati, Overbaugh J.  2015.  FCGR2A and FCGR3A Genotypes in Human Immunodeficiency Virus Mother-to-Child Transmission., 2015 Dec. Open forum infectious diseases. 2(4):ofv149. Abstract

Background.  Fc-mediated effector functions have been suggested to influence human immunodeficiency virus (HIV) acquisition and disease progression. Analyzing the role of host Fc gamma receptor (FcγR) polymorphisms on HIV outcome in mother-to-child transmission (MTCT) will increase our understanding of how host genetics may alter immune responses in prevention, therapy, and disease. This study analyzed the impact of FCGR2A and FCGR3A genotypes on MTCT in a cohort in which Fc-mediated antibody functions are predictive of infant HIV outcome. Methods.  Human immunodeficiency virus-positive mothers and their infants from a historical MTCT cohort were genotyped for FCGR2A and FCGR3A. We assessed the impact of these genotypes on transmission and acquisition of HIV and disease progression using χ(2) tests, survival analyses, and logistic regression. Results.  Among 379 mother-infant pairs, infant FCGR2A and FCGR3A genotypes were not associated with infant HIV infection or disease progression. Maternal FCGR2A was not associated with transmission, but there was a trend between maternal FCGR3A genotype and transmission (P = .07). When dichotomizing mothers into FCGR3A homozygotes and heterozygotes, heterozygotes had a 64.5% higher risk of transmission compared with homozygotes (P = .02). This risk was most evident in the early breastfeeding window, but a trend was only observed when restricting analyses to breastfeeding mothers (hazards ratio, 1.64; P = .064). Conclusions.  Infant FCGR2A and FCGR3A genotypes were not associated with HIV infection or disease progression, and, thus, host FcγR genotype may not significantly impact vaccination or therapeutic regimens that depend on Fc-mediated antibody functions. Maternal FCGR3A genotype may influence early breastfeeding transmission risk, but more studies should be conducted to clarify this association and its mechanism.

Kurth, AE, Inwani I, Wangombe A, Ruth Nduati, Owuor M, Njiri F, Akinyi P, Cherutich P, Osoti A, John Kinuthia, James N Kiarie, Chhun N, Kiarie J.  2015.  The Gender Context of HIV Risk and Pregnancy Goals in Western Kenya., 2015. East African medical journal. 92(4):163-169. Abstract

Intentional childbearing may place heterosexual couples at risk of HIV infection in resource-limited settings with high HIV prevalence areas where society places great value on having children.

2014

Afran, L, Garcia Knight M, Nduati E, Urban BC, Heyderman RS, Rowland-Jones SL.  2014.  HIV-exposed uninfected children: a growing population with a vulnerable immune system?, 2014 Apr Clinical and experimental immunology. 176(1):11-22. Abstract

Through the successful implementation of policies to prevent mother-to-child-transmission (PMTCT) of HIV-1 infection, children born to HIV-1-infected mothers are now much less likely to acquire HIV-1 infection than previously. Nevertheless, HIV-1-exposed uninfected (HEU) children have substantially increased morbidity and mortality compared with children born to uninfected mothers (unexposed uninfected, UU), predominantly from infectious causes. Moreover, a range of phenotypical and functional immunological differences between HEU and UU children has been reported. As the number of HEU children continues to increase worldwide, two questions with clear public health importance need to be addressed: first, does exposure to HIV-1 and/or ART in utero or during infancy have direct immunological consequences, or are these poor outcomes simply attributable to the obvious disadvantages of being born into an HIV-affected household? Secondly, can we expect improved maternal care and ART regimens during and after pregnancy, together with optimized infant immunization schedules, to reduce the excess morbidity and mortality of HEU children?

Goo, L, Chohan V, Ruth Nduati, Overbaugh J.  2014.  Early development of broadly neutralizing antibodies in HIV-1-infected infants., 2014 Jun. Nature medicine. 20(6):655-8. Abstract

Eliciting protective neutralizing antibodies (NAbs) against HIV-1 is daunting because of the extensive genetic and antigenic diversity of HIV-1. Moreover, broad and potent responses are uncommon even during persistent infection, with only a subset of adults developing broadly neutralizing antibodies (bNAbs) that recognize viral variants from different HIV-1 clades. It is not known whether bNAbs can also arise in HIV-1-infected infants, who typically progress to disease faster than adults, presumably in part due to an immature immune system. Here, we show that bNAbs develop at least as commonly in infants as in adults. Cross-clade NAb responses were detected in 20/28 infected infants, in some cases within 1 year of infection. Among infants with breadth of responses within the top quartile, neutralization of tier 2 or 3 variants from multiple clades was detected at 20 months after infection. These findings suggest that, even in early life, there is sufficient B cell functionality to mount bNAbs against HIV-1. Additionally, the relatively early appearance of bNAbs in infants may provide a unique setting for understanding the pathways of B cell maturation leading to bNAbs.

Kiarie, JN, Farquhar C, Redfield R, Bosire K, Nduati RW, Mwanda W, M'Imunya JM, Kibwage I.  2014.  Strengthening health systems by integrating health care, medical education, and research: University of Nairobi experience., 2014 Aug. Academic medicine : journal of the Association of American Medical Colleges. 89(8 Suppl):S109-10.
Child, MJ, Kiarie JN, Allen SM, Ruth Nduati, Wasserheit JN, Kibore MW, John-Stewart G, Njiri FJ, O'Malley G, Kinuthia R, Norris TE, Farquhar C.  2014.  Expanding clinical medical training opportunities at the University of Nairobi: adapting a regional medical education model from the WWAMI program at the University of Washington., 2014 Aug. Academic medicine : journal of the Association of American Medical Colleges. 89(8 Suppl):S35-9. Abstract

A major medical education need in Sub-Saharan Africa includes expanding clinical training opportunities to develop health professionals. Medical education expansion is a complicated process that requires significant investment of financial and human resources, but it can also provide opportunities for innovative approaches and partnerships. In 2010, the U.S. President's Emergency Plan for AIDS Relief launched the Medical Education Partnership Initiative to invest in medical education and health system strengthening in Africa. Building on a 30-year collaborative clinical and research training partnership, the University of Nairobi in Kenya developed a pilot regional medical education program modeled on the WWAMI (Washington, Wyoming, Alaska, Montana, and Idaho) medical education program at the University of Washington in the United States. The University of Nairobi adapted key elements of the WWAMI model to expand clinical training opportunities without requiring major capital construction of new buildings or campuses. The pilot program provides short-term clinical training opportunities for undergraduate students and recruits and trains clinical faculty at 14 decentralized training sites. The adaptation of a model from the Northwestern United States to address medical education needs in Kenya is a successful transfer of knowledge and practices that can be scaled up and replicated across Sub-Saharan Africa.

Kibore, MW, Daniels JA, Child MJ, Ruth Nduati, Njiri FJ, Kinuthia RM, O'Malley G, John-Stewart G, Kiarie J, Farquhar C.  2014.  Kenyan medical student and consultant experiences in a pilot decentralized training program at the University of Nairobi., 2014 May-Aug. Education for health (Abingdon, England). 27(2):170-6. Abstract

Over the past decade, the University of Nairobi (UoN) has increased the number of enrolled medical students threefold in response to the growing need for more doctors. This has resulted in a congested clinical training environment and limited opportunities for students to practice clinical skills at the tertiary teaching facility. To enhance the clinical experience, the UoN Medical Education Partnership Initiative Program Undertook training of medical students in non-tertiary hospitals around the country under the mentorship of consultant preceptors at these hospitals. This study focused on the evaluation of the pilot decentralized training rotation.

Monroe-Wise, A, Kibore M, Kiarie J, Ruth Nduati, Mburu J, Drake FT, Bremner W, Holmes K, Farquhar C.  2014.  The Clinical Education Partnership Initiative: an innovative approach to global health education., 2014. BMC medical education. 14:1043. Abstract

Despite evidence that international clinical electives can be educationally and professionally beneficial to both visiting and in-country trainees, these opportunities remain challenging for American residents to participate in abroad. Additionally, even when logistically possible, they are often poorly structured. The Universities of Washington (UW) and Nairobi (UoN) have enjoyed a long-standing research collaboration, which recently expanded into the UoN Medical Education Partnership Initiative (MEPI). Based on MEPI in Kenya, the Clinical Education Partnership Initiative (CEPI) is a new educational exchange program between UoN and UW. CEPI allows UW residents to partner with Kenyan trainees in clinical care and teaching activities at Naivasha District Hospital (NDH), one of UoN's MEPI training sites in Kenya.

Cames, C, Cournil A, de Vincenzi I, Gaillard P, Meda N, Luchters S, Ruth Nduati, Naidu K, Newell M-L, Read JS, Bork K.  2014.  Postpartum weight change among HIV-infected mothers by antiretroviral prophylaxis and infant feeding modality in a research setting., 2014 Jan 2. AIDS (London, England). 28(1):85-94. Abstract

To assess the relationship between infant feeding, triple-antiretroviral prophylaxis and weight from 2 weeks (baseline) to 6 months postpartum among HIV-infected mothers in a mother-to-child transmission (MTCT) of HIV-prevention trial in five sub-Saharan African sites.

Daniels, J, Ruth Nduati, Farquhar C.  2014.  Right from primary school, I liked science: understanding health research capacity building in sub-Saharan Africa through Kenyan training experiences., 2014 Feb 20. Global health promotion. 21(2):32-42. Abstract

Defining research career paths that enable Africans to address local and global health issues is essential for population health. This study was conducted to better understand how international health training programs contribute to human resource capacity building in health research. Research career motivations, decision-making and experiences were explored among a small group of Kenyan HIV/AIDS researchers who had completed an international training program. We found that intersecting social dynamics within specific geographic spaces influenced individual training decision-making and motivated research career decisions over time. The concept that 'geo-social motivation' is an important determinant of success for an African considering a research career developed from this study, and may be used to tailor future health research human resource capacity-building programs.

Newman, LP, Njoroge A, Ben-Youssef L, Merkel M, Gatuguta A, Ton Q, Elizabeth Maleche Obimbo, Dalton Wamalwa, Lohman-Payne B, Richardson BA, Ruth Nduati, Farquhar C.  2014.  Measles Seropositivity in HIV-Infected Kenyan Children on Antiretroviral Therapy., 2014 Mar 10. The Pediatric infectious disease journal. Abstract

This paper describes results from a cross-sectional study among HIV-infected children 15 months to 12 years of age who were receiving antiretroviral therapy. We found a low prevalence of measles IgG seropositivity (45.7%) and identified CD4% ≥ 25 as a predictor. Most HIV-infected children on ART were not measles seropositive and might benefit from revaccination.

Sherr, K, Gimbel S, Rustagi A, Ruth Nduati, Cuembelo F, Farquhar C, Wasserheit J, Gloyd S.  2014.  Systems analysis and improvement to optimize pMTCT (SAIA): a cluster randomized trial., 2014. Implementation science : IS. 9:55. Abstract

Despite significant increases in global health investment and the availability of low-cost, efficacious interventions to prevent mother-to-child HIV transmission (pMTCT) in low- and middle-income countries with high HIV burden, the translation of scientific advances into effective delivery strategies has been slow, uneven and incomplete. As a result, pediatric HIV infection remains largely uncontrolled. A five-step, facility-level systems analysis and improvement intervention (SAIA) was designed to maximize effectiveness of pMTCT service provision by improving understanding of inefficiencies (step one: cascade analysis), guiding identification and prioritization of low-cost workflow modifications (step two: value stream mapping), and iteratively testing and redesigning these modifications (steps three through five). This protocol describes the SAIA intervention and methods to evaluate the intervention's impact on reducing drop-offs along the pMTCT cascade.

Marangu, D, Jowi C, Aswani J, Wambani S, Ruth Nduati.  2014.  Prevalence and associated factors of pulmonary hypertension in Kenyan children with adenoid or adenotonsillar hypertrophy., 2014 Jun 16. International journal of pediatric otorhinolaryngology. Abstract

Adenotonsillar hypertrophy is a common condition in childhood, whose serious complications of pulmonary hypertension and cor pulmonale are devastating but local prevalence is unknown. This study determined the prevalence and associated factors of pulmonary hypertension in children with adenoid or adenotonsillar hypertrophy at Kenyatta National Hospital, Kenya.

2013

Daniels, J, Ruth Nduati, Farquhar C.  2013.  Kenyan women medical doctors and their motivations to pursue international research training., 2013 May-Aug. Education for health (Abingdon, England). 26(2):89-97. Abstract

There is a need to understand the factors that influence African women medical doctors to pursue international health research training because they remain under-represented in research fields but increasingly represented in medicine.

Cournil, A, de Vincenzi I, Gaillard P, Cames C, Fao P, Luchters S, Rollins N, Newell M-L, Bork K, Read JS.  2013.  Relationship between mortality and feeding modality among children born to HIV-infected mothers in a research setting: the Kesho Bora study., 2013 Jun 19. AIDS (London, England). 27(10):1621-30. Abstract

To assess the relationship between infant feeding practices and mortality by 18 months of age among children born to HIV-infected mothers in the Kesho Bora trial (Burkina-Faso, Kenya and South Africa).

Slyker, JA, Casper C, Tapia K, Richardson B, Bunts L, Huang M-L, Maleche-Obimbo E, Ruth Nduati, John-Stewart G.  2013.  Clinical and virologic manifestations of primary Epstein-Barr virus (EBV) infection in Kenyan infants born to HIV-infected women., 2013 Jun 15. The Journal of infectious diseases. 207(12):1798-806. Abstract

Human immunodeficiency virus (HIV) infection is a risk factor for Epstein-Barr virus (EBV)-associated lymphomas. Characterizing primary infection may elucidate risk factors for malignancy.

Omenda, MM, Milligan C, Odem-Davis K, Ruth Nduati, Richardson BA, Lynch J, John-Stewart G, Overbaugh J.  2013.  Evidence for efficient vertical transfer of maternal HIV-1 envelope-specific neutralizing antibodies but no association of such antibodies with reduced infant infection., 2013 Oct 1. Journal of acquired immune deficiency syndromes (1999). 64(2):163-6. Abstract

: Little is known about the efficiency of vertical transfer of HIV-1-specific antibodies. Antibody levels in plasma from 60 mother-infant pairs near the time of birth, including 14 breast-feeding transmission pairs, were compared. The envelope-binding titers were strongly correlated (r = 0.91, P < 0.0001) and similar (1.4-fold greater in maternal plasma) between a mother and her corresponding infant as were the neutralizing antibody (Nab) levels (r = 0.80, P < 0.0001; 1.3-fold higher), suggesting efficient transfer. There was no significant difference in Nab responses between transmitting and nontransmitting mothers, although there was a trend for transmitting mothers to have higher HIV-1-specific Nabs.

Mabuka, J, Goo L, Omenda MM, Ruth Nduati, Overbaugh J.  2013.  HIV-1 maternal and infant variants show similar sensitivity to broadly neutralizing antibodies, but sensitivity varies by subtype., 2013 Jun 19. AIDS (London, England). 27(10):1535-44. Abstract

To protect against HIV infection, passively transferred and/or vaccine-elicited neutralizing antibodies (NAbs) need to effectively target diverse subtypes that are transmitted globally. These variants are a limited subset of those present during chronic infection and display some unique features. In the case of mother-to-child transmission (MTCT), transmitted variants tend to be resistant to neutralization by maternal autologous NAbs.

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