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Showing papers by "Makerere University published in 2019"


Journal ArticleDOI
TL;DR: Given the high disease burden caused by hypertension in LMICs, nationally representative hypertension care cascades, as constructed in this study, are an important measure of progress towards achieving universal health coverage.

276 citations


Journal ArticleDOI
TL;DR: In this paper, the authors assimilated a state-of-the-art terrestrial water storage product derived from Gravity Recovery and Climate Experiment (GRACE) satellite observations into NASA's Catchment land surface model (CLSM) at the global scale, with the goal of generating groundwater storage time series that are useful for drought monitoring and other applications.
Abstract: The scarcity of groundwater storage change data at the global scale hinders our ability to monitor groundwater resources effectively. In this study, we assimilate a state-of-the-art terrestrial water storage product derived from Gravity Recovery and Climate Experiment (GRACE) satellite observations into NASA's Catchment land surface model (CLSM) at the global scale, with the goal of generating groundwater storage time series that are useful for drought monitoring and other applications. Evaluation using in situ data from nearly 4,000 wells shows that GRACE data assimilation improves the simulation of groundwater, with estimation errors reduced by 36% and 10% and correlation improved by 16% and 22% at the regional and point scales, respectively. The biggest improvements are observed in regions with large interannual variability in precipitation, where simulated groundwater responds too strongly to changes in atmospheric forcing. The positive impacts of GRACE data assimilation are further demonstrated using observed low-flow data. CLSM and GRACE data assimilation performance is also examined across different permeability categories. The evaluation reveals that GRACE data assimilation fails to compensate for the lack of a groundwater withdrawal scheme in CLSM when it comes to simulating realistic groundwater variations in regions with intensive groundwater abstraction. CLSM-simulated groundwater correlates strongly with 12-month precipitation anomalies in low-latitude and midlatitude areas. A groundwater drought indicator based on GRACE data assimilation generally agrees with other regional-scale drought indicators, with discrepancies mainly in their estimated drought severity.

186 citations


Journal ArticleDOI
Robert Edwards1, Alejandro A. Vega1, Holly M. Norman1, Maria Ohaeri1, Kyle Levi1, Elizabeth A. Dinsdale1, Ondrej Cinek2, Ramy K. Aziz3, Katelyn McNair1, Jeremy J. Barr4, Kyle Bibby5, Stan J. J. Brouns6, Adrian Cazares7, Patrick A. de Jonge8, Patrick A. de Jonge9, Christelle Desnues10, Samuel L. Díaz Muñoz11, Samuel L. Díaz Muñoz12, Peter C. Fineran13, Alexander Kurilshikov14, Rob Lavigne15, Karla Mazankova2, David Thomas McCarthy4, Franklin L. Nobrega6, Alejandro Reyes Muñoz16, German Tapia17, Nicole Trefault18, Alexander V. Tyakht19, Pablo Vinuesa20, Jeroen Wagemans15, Alexandra Zhernakova14, Frank Møller Aarestrup21, Gunduz Ahmadov, Abeer Alassaf22, Josefa Antón23, Abigail E. Asangba24, Emma Billings1, Vito Adrian Cantu1, Jane M. Carlton11, Daniel Cazares20, Gyu Sung Cho, Tess Condeff1, Pilar Cortés25, Mike Cranfield12, Daniel A. Cuevas1, Rodrigo De la Iglesia26, Przemyslaw Decewicz27, Michael P. Doane1, Nathaniel J. Dominy28, Lukasz Dziewit27, Bashir Mukhtar Elwasila29, A. Murat Eren30, Charles M. A. P. Franz, Jingyuan Fu14, Cristina García-Aljaro31, Elodie Ghedin11, Kristen M. Gulino11, John M. Haggerty1, Steven R. Head32, Rene S. Hendriksen21, Colin Hill33, Heikki Hyöty34, Elena N. Ilina, Mitchell T. Irwin35, Thomas C. Jeffries36, Juan Jofre31, Randall E. Junge37, Scott T. Kelley1, Mohammadali Khan Mirzaei38, Martin M. Kowalewski, Deepak Kumaresan39, Steven R. Leigh40, David A. Lipson1, Eugenia S. Lisitsyna, Montserrat Llagostera25, Julia M. Maritz11, Linsey C. Marr41, Angela McCann33, Shahar Molshanski-Mor42, Silvia Monteiro43, Benjamin Moreira-Grez39, Megan M. Morris1, Lawrence Mugisha44, Maite Muniesa31, Horst Neve, Nam Nguyen45, Olivia D. Nigro46, Anders S. Nilsson47, Taylor O'Connell1, Rasha Odeh22, Andrew Oliver48, Mariana Piuri49, Aaron J. Prussin41, Udi Qimron42, Zhe Xue Quan50, Petra Rainetova, Adán Ramírez-Rojas, Raúl R. Raya, Kim Reasor1, Gillian A.O. Rice28, Alessandro Rossi51, Alessandro Rossi8, Ricardo Santos43, John Shimashita41, Elyse Stachler52, Lars C. Stene17, Ronan Strain33, Rebecca M. Stumpf24, Pedro J. Torres1, Alan Twaddle11, Mary Ann Ugochi Ibekwe53, Nicolás A. Villagra54, Stephen Wandro48, Bryan A. White24, Andrew S. Whiteley39, Katrine Whiteson48, Cisca Wijmenga14, María Mercedes Zambrano, Henrike Zschach55, Bas E. Dutilh8, Bas E. Dutilh56 
San Diego State University1, Charles University in Prague2, Cairo University3, Monash University4, University of Notre Dame5, Delft University of Technology6, University of Liverpool7, Utrecht University8, Kavli Institute of Nanoscience9, Aix-Marseille University10, New York University11, University of California, Davis12, University of Otago13, University of Groningen14, Katholieke Universiteit Leuven15, University of Los Andes16, Norwegian Institute of Public Health17, Universidad Mayor18, Saint Petersburg State University of Information Technologies, Mechanics and Optics19, National Autonomous University of Mexico20, Technical University of Denmark21, University of Jordan22, University of Alicante23, University of Illinois at Urbana–Champaign24, Autonomous University of Barcelona25, Pontifical Catholic University of Chile26, University of Warsaw27, Dartmouth College28, University of Khartoum29, University of Chicago30, University of Barcelona31, Scripps Research Institute32, University College Cork33, University of Tampere34, Northern Illinois University35, University of Sydney36, Columbus Zoo and Aquarium37, McGill University38, University of Western Australia39, University of Colorado Boulder40, Virginia Tech41, Tel Aviv University42, Instituto Superior Técnico43, Makerere University44, University of California, San Diego45, Hawaii Pacific University46, Stockholm University47, University of California, Irvine48, University of Buenos Aires49, Fudan University50, University of Padua51, University of Pittsburgh52, Ebonyi State University53, Andrés Bello National University54, University of Copenhagen55, Radboud University Nijmegen56
TL;DR: It is concluded that crAssphage is a benign cosmopolitan virus that may have coevolved with the human lineage and is an integral part of the normal human gut virome.
Abstract: Microbiomes are vast communities of microorganisms and viruses that populate all natural ecosystems. Viruses have been considered to be the most variable component of microbiomes, as supported by virome surveys and examples of high genomic mosaicism. However, recent evidence suggests that the human gut virome is remarkably stable compared with that of other environments. Here, we investigate the origin, evolution and epidemiology of crAssphage, a widespread human gut virus. Through a global collaboration, we obtained DNA sequences of crAssphage from more than one-third of the world's countries and showed that the phylogeography of crAssphage is locally clustered within countries, cities and individuals. We also found fully colinear crAssphage-like genomes in both Old-World and New-World primates, suggesting that the association of crAssphage with primates may be millions of years old. Finally, by exploiting a large cohort of more than 1,000 individuals, we tested whether crAssphage is associated with bacterial taxonomic groups of the gut microbiome, diverse human health parameters and a wide range of dietary factors. We identified strong correlations with different clades of bacteria that are related to Bacteroidetes and weak associations with several diet categories, but no significant association with health or disease. We conclude that crAssphage is a benign cosmopolitan virus that may have coevolved with the human lineage and is an integral part of the normal human gut virome.

167 citations


Journal ArticleDOI
TL;DR: Health system performance for management of diabetes showed large losses to care at the stage of being tested, and low rates of diabetes control along the care cascade, indicating large unmet need for diabetes care across 28 LMICs.
Abstract: CITATION: Manne-Goehler, J., et al. 2019. Health system performance for people with diabetes in 28 low- and middle-income countries : a cross-sectional study of nationally representative surveys. PLoS Medicine, 16(3):e1002751, doi:10.1371/journal.pmed.1002751.

155 citations


Journal ArticleDOI
TL;DR: A cohort of Ugandan individuals who were household contacts of patients with TB are reported, revealing a distinctive adaptive immune profile among Mtb-exposed subjects, supporting an expanded definition of the host response to Mtb exposure, with implications for public health and the design of clinical trials.
Abstract: Exposure to Mycobacterium tuberculosis (Mtb) results in heterogeneous clinical outcomes including primary progressive tuberculosis and latent Mtb infection (LTBI). Mtb infection is identified using the tuberculin skin test and interferon-γ (IFN-γ) release assay IGRA, and a positive result may prompt chemoprophylaxis to prevent progression to tuberculosis. In the present study, we report on a cohort of Ugandan individuals who were household contacts of patients with TB. These individuals were highly exposed to Mtb but tested negative by IFN-γ release assay and tuberculin skin test, ‘resisting’ development of classic LTBI. We show that ‘resisters’ possess IgM, class-switched IgG antibody responses and non-IFN-γ T cell responses to the Mtb-specific proteins ESAT6 and CFP10, immunologic evidence of exposure to Mtb. Compared to subjects with classic LTBI, ‘resisters’ display enhanced antibody avidity and distinct Mtb-specific IgG Fc profiles. These data reveal a distinctive adaptive immune profile among Mtb-exposed subjects, supporting an expanded definition of the host response to Mtb exposure, with implications for public health and the design of clinical trials. New immune biomarkers of exposure to tuberculosis may require a rethink of evidence of Mycobacterium tuberculosis infection and control.

155 citations


Journal ArticleDOI
07 Aug 2019-Nature
TL;DR: It is shown that levels of aridity dictate the predominant recharge processes, whereas local hydrogeology influences the type and sensitivity of precipitation–recharge relationships, and that a drier climate does not necessarily mean less recharge.
Abstract: Groundwater in sub-Saharan Africa supports livelihoods and poverty alleviation1,2, maintains vital ecosystems, and strongly influences terrestrial water and energy budgets3. Yet the hydrological processes that govern groundwater recharge and sustainability—and their sensitivity to climatic variability—are poorly constrained4,5. Given the absence of firm observational constraints, it remains to be seen whether model-based projections of decreased water resources in dry parts of the region4 are justified. Here we show, through analysis of multidecadal groundwater hydrographs across sub-Saharan Africa, that levels of aridity dictate the predominant recharge processes, whereas local hydrogeology influences the type and sensitivity of precipitation–recharge relationships. Recharge in some humid locations varies by as little as five per cent (by coefficient of variation) across a wide range of annual precipitation values. Other regions, by contrast, show roughly linear precipitation–recharge relationships, with precipitation thresholds (of roughly ten millimetres or less per day) governing the initiation of recharge. These thresholds tend to rise as aridity increases, and recharge in drylands is more episodic and increasingly dominated by focused recharge through losses from ephemeral overland flows. Extreme annual recharge is commonly associated with intense rainfall and flooding events, themselves often driven by large-scale climate controls. Intense precipitation, even during years of lower overall precipitation, produces some of the largest years of recharge in some dry subtropical locations. Our results therefore challenge the ‘high certainty’ consensus regarding decreasing water resources4 in such regions of sub-Saharan Africa. The potential resilience of groundwater to climate variability in many areas that is revealed by these precipitation–recharge relationships is essential for informing reliable predictions of climate-change impacts and adaptation strategies.

149 citations


Journal ArticleDOI
TL;DR: An overview of the challenges of adaptation tracking is provided and a comprehensive conceptual framework for assessing adaptation progress by governments that is scalable over time and across contexts is proposed.
Abstract: The Paris Agreement and Katowice Climate Package articulate a clear mandate for all parties to undertake and document adaptation progress. Yet persistent challenges have prevented substantive developments in tracking adaptation and the assessment of adaptation actions and their outcomes. Here, we provide an overview of the challenges of adaptation tracking and propose a comprehensive conceptual framework for assessing adaptation progress by governments that is scalable over time and across contexts. The framework addresses the core components of adaptation assessment (vulnerability, goals and targets, adaptation efforts, and adaptation results) and characterizes subcomponents focused on adaptation effort (leadership, organizations and policy). In particular, we highlight how critical insights can be uncovered by systematically tracking policy efforts over time, and discusses novel approaches to data collection. The Paris Agreement places new emphasis on the need to take stock of adaptation progress. This Perspective discusses the conceptual and methodological challenges associated with monitoring adaptation and provides a comprehensive framework for tracking progress among governments.

135 citations


Journal ArticleDOI
David Bishop1, Robert A. Dyer2, Salome Maswime3, Reitze N. Rodseth1  +1058 moreInstitutions (16)
TL;DR: Maternal mortality after caesarean delivery in Africa is 50 times higher than that of high-income countries and is driven by peripartum haemorrhage and anaesthesia complications, which is double the global average.

128 citations


Journal ArticleDOI
TL;DR: This study has demonstrated that age ≤19 years, female gender, married individuals, genitourinary tract abnormalities, diabetes, hospitalization, indwelling catheter <6 days, and indwelled catheter >6 days had statistically significant relationships with UTI.
Abstract: Urinary tract infections (UTIs) are one of the major causes of morbidity and comorbidities in patients with underlying conditions, and it accounts for the majority of the reasons for hospital visit globally. Sound knowledge of factors associated with UTI may allow timely intervention that can easily bring the disease under control. This study was designed to determine the prevalence of UTI by isolating and characterizing the different bacterial etiological agents and to evaluate the factors associated with UTI. In this cross-sectional study, a total of 267, clean catch midstream urine (MSU) samples were collected aseptically and analyzed using standard microbiology methods. Data for the factors associated with UTI were obtained by use of questionnaires and standard laboratory tests for selected underlying conditions. The study revealed 86/267 (32.2%) UTI prevalence among patients attending hospitals in Bushenyi District, Uganda. Escherichia coli was the most prevalent bacterial uropathogen with 36/86 (41.9%) followed by Staphylococcus aureus 27/86 (31.4%), Klebsiella pneumoniae 10/86 (11.6%), Klebsiella oxytoca 6/86 (7.0%), Proteus mirabilis 3/86 (3.5%), Enterococcus faecalis 3/86 (3.5%), and Proteus vulgaris 1/86 (1.2%). This study has demonstrated that age ≤19 years, female gender, married individuals, genitourinary tract abnormalities, diabetes, hospitalization, indwelling catheter 6 days had statistically significant relationships (p < 0.05) with UTI. Screening for UTI in hospitalized patients, female gender, married individuals, genitourinary tract abnormalities, indwelling catheter, and diabetics should be adopted.

101 citations


Journal ArticleDOI
TL;DR: The findings indicate that direct land application of chicken litter could be harming animal, human, and environmental health.
Abstract: Chicken litter application on land as an organic fertilizer is the cheapest and most environmentally safe method of disposing of the volume generated from the rapidly expanding poultry industry worldwide. However, little is known about the safety of chicken litter for land application and general release into the environment. Bridging this knowledge gap is crucial for maximizing the benefits of chicken litter as an organic fertilizer and mitigating negative impacts on human and environmental health. The key safety concerns of chicken litter are its contamination with pathogens, including bacteria, fungi, helminthes, parasitic protozoa, and viruses; antibiotics and antibiotic-resistant genes; growth hormones such as egg and meat boosters; heavy metals; and pesticides. Despite the paucity of literature about chicken litter safety for land application, the existing information was scattered and disjointed in various sources, thus making them not easily accessible and difficult to interpret. We consolidated scattered pieces of information about known contaminants found in chicken litter that are of potential risk to human, animal, and environmental health and how they are spread. This review tested the hypothesis that in its current form, chicken litter does not meet the minimum standards for application as organic fertilizer. The review entails a meta-analysis of technical reports, conference proceedings, peer-reviewed journal articles, and internet texts. Our findings indicate that direct land application of chicken litter could be harming animal, human, and environmental health. For example, counts of pathogenic strains of Eschericia coli (105–1010 CFU g−1) and Coliform bacteria (106–108 CFU g−1) exceeded the maximum permissible limits (MPLs) for land application. In Australia, 100% of broiler litter tested was contaminated with Actinobacillus and re-used broiler litter was more contaminated with Salmonella than non-re-used broiler litter. Similarly, in the US, all (100%) broiler litter was contaminated with Eschericia coli containing genes resistant to over seven antibiotics, particularly amoxicillin, ceftiofur, tetracycline, and sulfonamide. Chicken litter is also contaminated with a vast array of antibiotics and heavy metals. There are no standards set specifically for chicken litter for most of its known contaminants. Even where standards exist for related products such as compost, there is wide variation across countries and bodies mandated to set standards for safe disposal of organic wastes. More rigorous studies are needed to ascertain the level of contamination in chicken litter from both broilers and layers, especially in developing countries where there is hardly any data; set standards for all the contaminants; and standardize these standards across all agencies, for safe disposal of chicken litter on land.

86 citations


Posted ContentDOI
Robert Edwards1, Alejandro A. Vega1, Holly M. Norman1, Maria Ohaeri1, Kyle Levi1, Elizabeth A. Dinsdale1, Ondrej Cinek2, Ramy K. Aziz3, Katelyn McNair1, Jeremy J. Barr4, Kyle Bibby5, Stan J. J. Brouns6, Adrian Cazares7, Patrick A. de Jonge6, Patrick A. de Jonge8, Christelle Desnues9, Samuel L. Díaz Muñoz10, Samuel L. Díaz Muñoz11, Peter C. Fineran12, Alexander Kurilshikov13, Rob Lavigne14, Karla Mazankova2, David Thomas McCarthy4, Franklin L. Nobrega6, Alejandro Reyes Muñoz15, German Tapia16, Nicole Trefault17, Alexander V. Tyakht18, Pablo Vinuesa19, Jeroen Wagemans14, Alexandra Zhernakova13, Frank Møller Aarestrup20, Gunduz Ahmadov, Abeer Alassaf21, Josefa Antón22, Abigail E. Asangba23, Emma Billings1, Vito Adrian Cantu1, Jane M. Carlton10, Daniel Cazares19, Gyu Sung Cho, Tess Condeff1, Pilar Cortés24, Mike Cranfield11, Daniel A. Cuevas1, Rodrigo De la Iglesia25, Przemyslaw Decewicz26, Michael P. Doane1, Nathaniel J. Dominy27, Lukasz Dziewit26, Bashir Mukhtar Elwasila28, A. Murat Eren29, Charles M. A. P. Franz, Jingyuan Fu13, Cristina García-Aljaro30, Elodie Ghedin10, Kristen M. Gulino10, John M. Haggerty1, Steven R. Head31, Rene S. Hendriksen20, Colin Hill32, Heikki Hyöty33, Elena N. Ilina, Mitchell T. Irwin34, Thomas C. Jeffries35, Juan Jofre30, Randall E. Junge36, Scott T. Kelley1, Martin M. Kowalewski37, Deepak Kumaresan38, Steven R. Leigh39, Eugenia S. Lisitsyna, Montserrat Llagostera24, Julia M. Maritz10, Linsey C. Marr40, Angela McCann32, Mohammadali Khan Mirzaei41, Shahar Molshanski-Mor42, Silvia Monteiro43, Ben Moreira-Grez38, Megan M. Morris1, Lawrence Mugisha44, Maite Muniesa30, Horst Neve, Nam Nguyen11, Olivia D. Nigro45, Anders S. Nilsson41, Taylor O'Connell1, Rasha Odeh21, Andrew Oliver11, Mariana Piuri46, Aaron J. Prussin40, Udi Qimron42, Zhe Xue Quan47, Petra Rainetova, Adán Ramírez-Rojas, Raúl R. Raya, Gillian A.O. Rice27, Alessandro Rossi8, Alessandro Rossi48, Ricardo Santos43, John Shimashita40, Elyse Stachler49, Lars C. Stene16, Ronan Strain32, Rebecca M. Stumpf23, Pedro J. Torres1, Alan Twaddle10, Mary Ann Ugochi Ibekwe50, Nicolás A. Villagra51, Stephen Wandro11, Bryan A. White23, Andrew S. Whiteley38, Katrine Whiteson11, Cisca Wijmenga13, María Mercedes Zambrano, Henrike Zschach20, Bas E. Dutilh8, Bas E. Dutilh52 
San Diego State University1, Charles University in Prague2, Cairo University3, Monash University4, University of Notre Dame5, Delft University of Technology6, University of Liverpool7, Utrecht University8, Aix-Marseille University9, New York University10, University of California, Berkeley11, University of Otago12, University Medical Center Groningen13, Katholieke Universiteit Leuven14, University of Los Andes15, Norwegian Institute of Public Health16, Universidad Mayor17, Saint Petersburg State University of Information Technologies, Mechanics and Optics18, National Autonomous University of Mexico19, Technical University of Denmark20, University of Jordan21, University of Alicante22, University of Illinois at Urbana–Champaign23, Autonomous University of Barcelona24, Pontifical Catholic University of Chile25, University of Warsaw26, Dartmouth College27, University of Khartoum28, University of Chicago29, University of Barcelona30, Scripps Research Institute31, University College Cork32, University of Tampere33, Northern Illinois University34, University of Sydney35, Columbus Zoo and Aquarium36, National Scientific and Technical Research Council37, University of Western Australia38, University of Colorado Boulder39, Virginia Tech40, Stockholm University41, Tel Aviv University42, Instituto Superior Técnico43, Makerere University44, Hawaii Pacific University45, University of Buenos Aires46, Fudan University47, University of Padua48, University of Pittsburgh49, Ebonyi State University50, Andrés Bello National University51, Radboud University Nijmegen52
26 Jan 2019-bioRxiv
TL;DR: It is concluded that crAssphage is a benign globetrotter virus that may have co-evolved with the human lineage and an integral part of the normal human gut virome.
Abstract: Microbiomes are vast communities of microbes and viruses that populate all natural ecosystems. Viruses have been considered the most variable component of microbiomes, as supported by virome surveys and examples of high genomic mosaicism. However, recent evidence suggests that the human gut virome is remarkably stable compared to other environments. Here we investigate the origin, evolution, and epidemiology of crAssphage, a widespread human gut virus. Through a global collaboratory, we obtained DNA sequences of crAssphage from over one-third of the world’s countries, and showed that its phylogeography is locally clustered within countries, cities, and individuals. We also found colinear crAssphage-like genomes in both Old-World and New-World primates, challenging genomic mosaicism and suggesting that the association of crAssphage with primates may be millions of years old. We conclude that crAssphage is a benign globetrotter virus that may have co-evolved with the human lineage and an integral part of the normal human gut virome.

Journal ArticleDOI
TL;DR: Evaluating the available evidence on postharvest processes for edible insects in Africa is evaluated, with the aim of identifying areas that need research impetus and drawing attention to potential postHarvest technology options for overcoming hurdles associated with utilization of insects for food and feed.
Abstract: In many African cultures, insects are part of the diet of humans and domesticated animals. Compared to conventional food and feed sources, insects have been associated with a low ecological foot print because fewer natural resources are required for their production. To this end, the Food and Agriculture Organization of the United Nations recognized the role that edible insects can play in improving global food and nutrition security; processing technologies, as well as packaging and storage techniques that improve shelf-life were identified as being crucial. However, knowledge of these aspects in light of nutritional value, safety, and functionality is fragmentary and needs to be consolidated. This review attempts to contribute to this effort by evaluating the available evidence on postharvest processes for edible insects in Africa, with the aim of identifying areas that need research impetus. It further draws attention to potential postharvest technology options for overcoming hurdles associated with utilization of insects for food and feed. A greater research thrust is needed in processing and this can build on traditional knowledge. The focus should be to establish optimal techniques that improve presentation, quality and safety of products, and open possibilities to diversify use of edible insects for other benefits.


Journal ArticleDOI
TL;DR: The risks associated with initiation of isoniazid preventive therapy during pregnancy appeared to be greater than those associated with Initiation of therapy during the postpartum period.
Abstract: Background The safety, efficacy, and appropriate timing of isoniazid therapy to prevent tuberculosis in pregnant women with human immunodeficiency virus (HIV) infection who are receiving a...

Journal ArticleDOI
TL;DR: Sertraline did not reduce mortality and should not be used to treat patients with HIV-associated cryptococcal meningitis, and the reasons for sertralines inactivity appear to be multifactorial and might be associated with insufficient duration of therapeutic sertrals.
Abstract: Summary Background Identifying new antifungals for cryptococcal meningitis is a priority given the inadequacy of current therapy. Sertraline has previously shown in vitro and in vivo activity against cryptococcus. We aimed to assess the efficacy and cost-effectiveness of adjunctive sertraline in adults with HIV-associated cryptococcal meningitis compared with placebo. Methods In this double-blind, randomised, placebo-controlled trial, we recruited HIV-positive adults with cryptococcal meningitis from two hospitals in Uganda. Participants were randomly assigned (1:1) to receive standard therapy with 7–14 days of intravenous amphotericin B (0·7–1·0 mg/kg per day) and oral fluconazole (starting at 800 mg/day) with either adjunctive sertraline or placebo. Sertraline was administered orally or via nasogastric tube at a dose of 400 mg/day for 2 weeks, followed by 200 mg/day for 12 weeks, then tapered off over 3 weeks. The primary endpoint was 18-week survival, analysed by intention-to-treat. This study is registered with ClinicalTrials.gov , number NCT01802385 . Findings Between March 9, 2015, and May 29, 2017, we screened 842 patients with suspected meningitis and enrolled 460 of a planned 550 participants, at which point the trial was stopped for futility. Three patients in the sertraline group and three patients in the placebo group were lost to follow-up and therefore discontinued before study end. At 18 weeks, 120 (52%) of 229 patients in the sertraline group and 106 (46%) of 231 patients in the placebo group had died (hazard ratio 1·21, 95% CI 0·93–1·57; p=0·15). The fungal clearance rate from cerebrospinal fluid was similar between groups (0·43 –log10 CFU/mL per day [95% CI 0·37–0·50] in the sertraline group vs 0·47 –log10 CFU/mL per day [0·40–0·54] in the placebo group; p=0·59), as was occurrence of grade 4 or 5 adverse events (72 [31%] of 229 vs 75 [32%] of 231; p=0·98), most of which were associated with amphotericin B toxicity. Interpretation Sertraline did not reduce mortality and should not be used to treat patients with HIV-associated cryptococcal meningitis. The reasons for sertraline inactivity appear to be multifactorial and might be associated with insufficient duration of therapeutic sertraline concentrations. Funding National Institutes of Health and Medical Research Council, Wellcome Trust.

Journal ArticleDOI
TL;DR: Monthly intermittent preventive treatment with dihydroartemisinin-piperaquine was safe but did not lead to significant improvements in birth outcomes compared with sulfadoxine-pyrimethamine.

Journal ArticleDOI
Jens H. Kuhn1, Takuya Adachi, Neill K. J. Adhikari2, Jose R. Arribas3, Ibrahima Elhadj Bah4, Daniel G. Bausch, Nahid Bhadelia5, Matthias Borchert6, Arne Broch Brantsæter7, David M. Brett-Major8, Timothy Burgess8, Daniel S. Chertow1, Christopher G. Chute9, Theodore J. Cieslak10, Robert Colebunders11, Ian Crozier12, Richard T. Davey1, Hilde De Clerck13, Rafael Delgado14, Laura Evans15, Mosoka Fallah, William A. Fischer, Tom Fletcher16, Robert A. Fowler2, Thomas Grünewald17, Andy Hall18, Angela L. Hewlett10, Andy I. M. Hoepelman19, Catherine F Houlihan20, Giuseppe Ippolito, Shevin T. Jacob21, Michael Jacobs22, Robert Jakob23, Frederique Jacquerioz24, Laurent Kaiser, Andre C. Kalil10, Rashidatu F Kamara, Jimmy Kapetshi, Hans-Dieter Klenk25, Gary P. Kobinger26, Mark G. Kortepeter10, Colleen S. Kraft27, Thomas Kratz6, Henry S Kyobe Bosa28, Marta Lado29, Francois Lamontagne30, H Cliff Lane1, Leslie Lobel31, Julius J. Lutwama32, G. Marshall Lyon27, Moses Massaquoi, Thomas A Massaquoi33, Aneesh K. Mehta27, Vital Mondonge Makuma23, Srinivas Murthy34, Tonny Seikikongo Musoke, Jean-Jacques Muyembe-Tamfum35, Phiona Nakyeyune36, Carolina Nanclares13, Miriam Nanyunja23, Justus Nsio-Mbeta, Tim O'Dempsey21, Janusz T. Paweska, Clarence J. Peters37, Peter Piot36, Christophe Rapp, Bertrand Renaud38, Bruce S. Ribner27, Pardis C. Sabeti39, John S. Schieffelin40, Werner Slenczka25, Moses J Soka, Armand Sprecher13, James E. Strong41, Robert Swanepoel42, Timothy M. Uyeki43, Michel Van Herp13, Pauline Vetter, David A. Wohl44, Timo Wolf45, Anja Wolz13, Alie H. Wurie, Zabulon Yoti23 
TL;DR: The recent large outbreak of Ebola virus disease in Western Africa resulted in greatly increased accumulation of human genotypic, phenotypic and clinical data, and improved the understanding of the spectrum of clinical manifestations, so that the WHO disease classification of EVD underwent major revision.
Abstract: The recent large outbreak of Ebola virus disease (EVD) in Western Africa resulted in greatly increased accumulation of human genotypic, phenotypic and clinical data, and improved our understanding of the spectrum of clinical manifestations. As a result, the WHO disease classification of EVD underwent major revision.

Journal ArticleDOI
TL;DR: Two simultaneous outbreaks of two distinct human respiratory viruses, human metapneumovirus (MPV) and human respirovirus 3 (HRV3), in two chimpanzee communities in the same forest in Uganda in December 2016 and January 2017 are reported.
Abstract: Respiratory viruses of human origin infect wild apes across Africa, sometimes lethally. Here we report simultaneous outbreaks of two distinct human respiratory viruses, human metapneumovirus (MPV; ...

Journal ArticleDOI
01 Aug 2019
TL;DR: Wang et al. as discussed by the authors reviewed the feasibility and impact of non-manipulative and manipulative measures for carbon sequestration in wetland ecosystems and concluded that successful implementation of such measures will require attachment of economic incentives that are not only foreseeable, but also adequate to match returns from competing land uses.
Abstract: Wetlands are among the most important ecosystems in the response strategy to climate change, through carbon sequestration (CS). Nevertheless, their current CS potential is declining due to human disturbance, with further decrease expected under global population growth and climate change scenarios. Literature has documented various measures that seek to enhance CS by wetlands and therefore enable these ecosystems remain vital in global carbon (C) balance and climate change mitigation. The objective of this review is to critically analyse these measures with respect to their feasibility and impact on wetland functioning, both in ecological and socio-economic perspectives. In doing this, we strive to address the concerns of wetland scientists, managers and other stakeholders pertaining CS by wetlands. Findings indicate that CS can be enhanced through both non-manipulative and manipulative measures. Non-manipulative measures aim at enhancing CS by increasing wetlands’ spatial extent, while manipulative ones aim at altering characteristics of certain wetland components that influence CS. Their overall target is to increase organic matter input, apportion C to longer-lived pools, and increase residence times of C pools. Based on the identified research gaps, we recommend that CS actions for wetlands should prioritize conservation of existing natural wetlands. Additional measures should consider associated risks such as those on wetland flora and fauna, soil and hydrological regimes, and competing services. We further believe that successful implementation of non-manipulative measures for CS will require attachment of economic incentives that are not only foreseeable, but also adequate to match returns from competing land uses.

Journal ArticleDOI
TL;DR: For example, the authors found that acute kidney injury (AKI) is a recognized complication of pediatric severe malaria, but its long-term consequences are unknown, and AKI is a risk factor for longterm neurocognitive impairment and CKD in children with severe malaria.
Abstract: Acute kidney injury (AKI) is a recognized complication of pediatric severe malaria, but its long-term consequences are unknown. Ugandan children with cerebral malaria (CM, n = 260) and severe malaria anemia (SMA, n = 219) or community children (CC, n = 173) between 1.5 and 12 years of age were enrolled in a prospective cohort study. Kidney Disease: Improving Global Outcomes (KDIGO) criteria were used to retrospectively define AKI and chronic kidney disease (CKD). Cognitive testing was conducted using the Mullen Scales of Early Learning in children < 5 and Kaufman Assessment Battery for Children (K-ABC) second edition in children ≥ 5 years of age. The prevalence of AKI was 35.1%, ranging from 25.1% in SMA to 43.5% in CM. In-hospital mortality was 11.9% in AKI compared to 4.2% in children without AKI (p = 0.001), and post-discharge mortality was 4.7% in AKI compared to 1.3% in children without AKI (p = 0.030) corresponding to an all-cause adjusted hazard ratio of 2.30 (95% CI 1.21, 4.35). AKI was a risk factor for short- and long-term neurocognitive impairment. At 1 week post-discharge, the frequency of neurocognitive impairment was 37.3% in AKI compared to 13.5% in children without AKI (adjusted odds ratio (aOR) 2.31 [95% CI 1.32, 4.04]); at 1-year follow-up, it was 13.3% in AKI compared to 3.4% in children without AKI (aOR 2.48 [95% CI 1.01, 6.10]), and at 2-year follow-up, it was 13.0% in AKI compared to 3.4% in children without AKI (aOR 3.03 [95% CI 1.22, 7.58]). AKI was a risk factor for CKD at 1-year follow-up: 7.6% of children with severe malaria-associated AKI had CKD at follow-up compared to 2.8% of children without AKI (p = 0.038) corresponding to an OR of 2.81 (95% CI 1.02, 7.73). The presenting etiology of AKI was consistent with prerenal azotemia, and lactate dehydrogenase as a marker of intravascular hemolysis was an independent risk factor for AKI in CM and SMA (p < 0.0001). In CM, AKI was associated with the presence and severity of retinopathy (p < 0.05) and increased cerebrospinal fluid albumin suggestive of blood-brain barrier disruption. AKI is a risk factor for long-term neurocognitive impairment and CKD in pediatric severe malaria.

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TL;DR: Improved HTN control was achieved in an integrated HIV and chronic care model similar to HIV care, visit frequency determined by drug supply chain rather than clinical indication is associated with worseHTN control.
Abstract: There is an increasing burden of hypertension (HTN) across sub-Saharan Africa where HIV prevalence is the highest in the world, but current care models are inadequate to address the dual epidemics. HIV treatment infrastructure could be leveraged for the care of other chronic diseases, including HTN. However, little data exist on the effectiveness of integrated HIV and chronic disease care delivery systems on blood pressure control over time. Population screening for HIV and HTN, among other diseases, was conducted in ten communities in rural Uganda as part of the SEARCH study (NCT01864603). Individuals with either HIV, HTN, or both were referred to an integrated chronic disease clinic. Based on Uganda treatment guidelines, follow-up visits were scheduled every 4 weeks when blood pressure was uncontrolled, and either every 3 months, or in the case of drug stock-outs more frequently, when blood pressure was controlled. We describe demographic and clinical variables among all patients and used multilevel mixed-effects logistic regression to evaluate predictors of HTN control. Following population screening (2013–2014) of 34,704 adults age ≥ 18 years, 4554 individuals with HTN alone or both HIV and HTN were referred to an integrated chronic disease clinic. Within 1 year 2038 participants with HTN linked to care and contributed 15,653 follow-up visits over 3 years. HTN was controlled at 15% of baseline visits and at 46% (95% CI: 44–48%) of post-baseline follow-up visits. Scheduled visit interval more frequent than clinical indication among patients with controlled HTN was associated with lower HTN control at the subsequent visit (aOR = 0.89; 95% CI 0.79–0.99). Hypertension control at follow-up visits was higher among HIV-infected patients than uninfected patients to have controlled blood pressure at follow-up visits (48% vs 46%; aOR 1.28; 95% CI 0.95–1.71). Improved HTN control was achieved in an integrated HIV and chronic care model. Similar to HIV care, visit frequency determined by drug supply chain rather than clinical indication is associated with worse HTN control. The SEARCH Trial was prospectively registered with ClinicalTrials.gov : NCT01864603.

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TL;DR: In this article, the authors present a systematic documentation of IK, and a framework for integrating IK and scientific weather forecasting from national meteorological agencies can improve accuracy, uptake, and use of weather forecasts.
Abstract: Climate information and agro-advisory services are crucial in helping smallholder farmers and pastoralists in East Africa manage climate-related risks and adapt to climate change. However, significant gaps exist in provision of climate information that effectively addresses the needs of farmers and pastoralists. Most farmers and pastoralists, therefore, rely on indigenous knowledge (IK), where local indicators and experiences are used to observe and forecast weather conditions. While IK-based forecasting is inbuilt and established in many communities in East Africa, coordinated research and systematic documentation of IK for weather forecasting, including accuracy and reliability of IK is largely lacking. This paper documents and synthesizes existing IK for weather forecasting in East Africa using case studies from Ethiopia, Tanzania, and Uganda. The results show that farmers and pastoralists use a combination of meteorological, biological, and astrological indicators to forecast local weather conditions. IK weather forecasting is, therefore, crucial in supporting efforts to improve access to climate information in East Africa, especially in resource-poor and vulnerable communities. The paper draws valuable lessons on how farmers and pastoralists in East Africa use IK weather forecasts for making crop and livestock production decisions and demonstrates that the trust and willingness to apply scientific forecasts by farmers and pastoralists is likely to increase when integrated with IK. Therefore, a systematic documentation of IK, and a framework for integrating IK and scientific weather forecasting from national meteorological agencies can improve accuracy, uptake, and use of weather forecasts.

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14 Feb 2019-PLOS ONE
TL;DR: Immunization services in Hoima District require urgent improvement in the following areas: vaccine supply, expanding service delivery points, more health workers, transport and tailored mechanisms to ensure adequate communication between health workers and caretakers.
Abstract: Introduction Hoima, one of the largest districts in mid- western Uganda, has persistently performed poorly with low immunization coverage, high immunization drop outs rates and repeated outbreaks of vaccine preventable diseases especially measles. The objectives of this study were to evaluate the state of immunization services and to identify the gaps in immunization health systems that contribute to low uptake and completion of immunization schedules in Hoima District. Methods This was a cross sectional mixed methods study, utilizing both qualitative and quantitative approaches. A situation analysis of the immunization services was carried out using in-depth interviews with vaccinators, focus group discussions and key informant interviews with ethno-videography. Secondary data was sourced from records at headquarters and vaccination centres within Hoima District. The quantitative component utilized cluster random sampling with sample size estimated using the World Health Organization's 30 cluster sampling technique. Results A total of 311 caretaker/child pairs were included in the study. Immunization completion among children of age at least 12 months was 95% for BCG, 96% for OPV0, 93% for DPT1, 84.5% for DPT2, 81% for DPT3 and 65.5% for measles vaccines. Access to immunization centres is difficult due to poor road terrain, which affects effectiveness of outreach program, support supervision, mentorship and timely delivery of immunization program support supplies especially refrigerator gas and vaccines. Some facilities are under-equipped to effectively support the program. Adverse Events Following Immunization (AEFI) identification, reporting and management is poorly understood. Conclusion Immunization services in Hoima District require urgent improvement in the following areas: vaccine supply, expanding service delivery points, more health workers, transport and tailored mechanisms to ensure adequate communication between health workers and caretakers.

Journal ArticleDOI
TL;DR: Clinicians should be aware that patients with current or past HAP exposure are at increased risk for respiratory diseases or malignancies and may want to consider earlier screening in this population, and better environmental exposure monitoring is critical.
Abstract: Approximately three billion individuals are exposed to household air pollution (HAP) from the burning of biomass fuels worldwide. Household air pollution is responsible for 2.9 million annual deaths and causes significant health, economic and social consequences, particularly in low- and middle-income countries. Although there is biological plausibility to draw an association between HAP exposure and respiratory diseases, existing evidence is either lacking or conflicting. We abstracted systematic reviews and meta-analyses for summaries available for common respiratory diseases in any age group and performed a literature search to complement these reviews with newly published studies. Based on the literature summarized in this review, HAP exposure has been associated with acute respiratory infections, tuberculosis, asthma, chronic obstructive pulmonary disease, pneumoconiosis, head and neck cancers, and lung cancer. No study, however, has established a causal link between HAP exposure and respiratory disease. Furthermore, few studies have controlled for tobacco smoke exposure and outdoor air pollution. More studies with consistent diagnostic criteria and exposure monitoring are needed to accurately document the association between household air pollution exposure and respiratory disease. Better environmental exposure monitoring is critical to better separate the contributions of household air pollution from that of other exposures, including ambient air pollution and tobacco smoking. Clinicians should be aware that patients with current or past HAP exposure are at increased risk for respiratory diseases or malignancies and may want to consider earlier screening in this population.

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TL;DR: It was observed that high levels of PCDD/Fs and dl-PCBs were reported in environmental and biological samples near densely populated urban and industrialised areas compared to those in rural settings, and the concentrations of dioxin-like compounds in the atmosphere in Africa were comparable to and/or higher than those in developed countries.

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TL;DR: Viral deep-sequencing can be used to reconstruct HIV-1 transmission networks and to infer the direction of transmission in these networks and is sufficiently low for population-level inferences into the sources of epidemic spread.
Abstract: To prevent new infections with human immunodeficiency virus type 1 (HIV-1) in sub-Saharan Africa, UNAIDS recommends targeting interventions to populations that are at high risk of acquiring and passing on the virus. Yet it is often unclear who and where these 'source' populations are. Here we demonstrate how viral deep-sequencing can be used to reconstruct HIV-1 transmission networks and to infer the direction of transmission in these networks. We are able to deep-sequence virus from a large population-based sample of infected individuals in Rakai District, Uganda, reconstruct partial transmission networks, and infer the direction of transmission within them at an estimated error rate of 16.3% [8.8-28.3%]. With this error rate, deep-sequence phylogenetics cannot be used against individuals in legal contexts, but is sufficiently low for population-level inferences into the sources of epidemic spread. The technique presents new opportunities for characterizing source populations and for targeting of HIV-1 prevention interventions in Africa.

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TL;DR: Financial support to ensure treatment access and education of treatment benefits are needed to improve treatment access for breast cancer patients across sub-Saharan Africa, especially at regional treatment centres, for lower socio-economic groups, and for the HIV-positive woman with breast cancer.
Abstract: Improving breast cancer survival in sub-Saharan Africa (SSA) is urgently needed, requiring early diagnosis and improved access to treatment. However, data on the types of and barriers to receiving breast cancer therapy in this region are limited and have not been compared between different SSA countries and treatment settings. In different health care settings across Uganda, Nigeria and Namibian sites of the prospective African Breast Cancer - Disparities in Outcomes cohort study, we assessed the percentage of newly diagnosed breast cancer patients who received treatment (systemic, surgery and/or radiotherapy) for cancer and their socio-demographic and clinical determinants. Treatment data were systematically extracted from medical records, as well as self-reported by women during 6-month follow-up interviews, and were used to generate a binary indicator of treatment received within 12 months of diagnosis (yes/no), which was analysed via logistic regression. Of 1325 women, cancer treatment had not been initiated treatment within 1 year of diagnosis for 227 (17%) women and 185 (14%) of women with stage I–III disease. Untreated percentages were highest in two Nigerian regional hospitals where 38% of 314 women were not treated (32% among stage I–III). At a national referral hospital in Uganda, 18% of 430 women were not treated (15% among stage I–III). In contrast, at a cancer care centre in Windhoek, Namibia, where treatment is provided free to the patient, all non-black (100%) and almost all (98.7%) black women had initiated treatment. Percentages of untreated women were higher in women from lower socio-economic groups, women who believed in traditional medicine and, in Uganda, in HIV+ women. Self-reported treatment barriers confirmed treatment costs and treatment refusal as contributors to not receiving treatment. Financial support to ensure treatment access and education of treatment benefits are needed to improve treatment access for breast cancer patients across sub-Saharan Africa, especially at regional treatment centres, for lower socio-economic groups, and for the HIV-positive woman with breast cancer.

Journal ArticleDOI
20 Jun 2019-PLOS ONE
TL;DR: The near complete genome of a highly divergent orthobunyavirus, tentatively named Nyangole virus, is identified from the serum of a child diagnosed with malaria and pneumonia, a Bwamba orthob UNavirus in the nasopharynx of a children with rash and sepsis, and the genomes of two novel human rhinovirus C species are reported.
Abstract: Febrile illness is a major burden in African children, and non-malarial causes of fever are uncertain. In this retrospective exploratory study, we used metagenomic next-generation sequencing (mNGS) to evaluate serum, nasopharyngeal, and stool specimens from 94 children (aged 2-54 months) with febrile illness admitted to Tororo District Hospital, Uganda. The most common microbes identified were Plasmodium falciparum (51.1% of samples) and parvovirus B19 (4.4%) from serum; human rhinoviruses A and C (40%), respiratory syncytial virus (10%), and human herpesvirus 5 (10%) from nasopharyngeal swabs; and rotavirus A (50% of those with diarrhea) from stool. We also report the near complete genome of a highly divergent orthobunyavirus, tentatively named Nyangole virus, identified from the serum of a child diagnosed with malaria and pneumonia, a Bwamba orthobunyavirus in the nasopharynx of a child with rash and sepsis, and the genomes of two novel human rhinovirus C species. In this retrospective exploratory study, mNGS identified multiple potential pathogens, including 3 new viral species, associated with fever in Ugandan children.

Journal ArticleDOI
TL;DR: The prevalence of chloroquine resistance alleles among Plasmodium falciparum parasites have steadily declined since discontinuation of chlorquine use, however, Pfcrt K76T and Pfmdr-1 N86Y mutations still persist at moderate frequencies in most malaria affected countries.
Abstract: Chloroquine, a previous highly efficacious, easy to use and affordable anti-malarial agent was withdrawn from malaria endemic regions due to high levels of resistance. This review collated evidence from published-reviewed articles to establish prevalence of Pfcrt 76T and Pfmdr-1 86Y alleles in malaria affected countries following official discontinuation of chloroquine use. A review protocol was developed, registered in PROSPERO (#CRD42018083957) and published in a peer-reviewed journal. Article search was done in PubMed, Scopus, Lilacs/Vhl and Embase databases by two experienced librarians (AK, RS) for the period 1990-to-Febuary 2018. Mesh terms and Boolean operators (AND, OR) were used. Data extraction form was designed in Excel spread sheet 2007. Data extraction was done by three reviewers (NL, BB and MO), discrepancies were resolved by discussion. Random effects analysis was done in Open Meta Analyst software. Heterogeneity was established using I2-statistic. A total of 4721 citations were retrieved from article search (Pubmed = 361, Lilac/vhl = 28, Science Direct = 944, Scopus = 3388). Additional targeted search resulted in three (03) eligible articles. After removal of duplicates (n = 523) and screening, 38 articles were included in the final review. Average genotyping success rate was 63.6% (18,343/28,820) for Pfcrt K76T and 93.5% (16,232/17,365) for Pfmdr-1 86Y mutations. Prevalence of Pfcrt 76T was as follows; East Africa 48.9% (2528/5242), Southern Africa 18.6% (373/2163), West Africa 58.3% (3321/6608), Asia 80.2% (1951/2436). Prevalence of Pfmdr-1 86Y was; East Africa 32.4% (1447/5722), Southern Africa 36.1% (544/1640), West Africa 52.2% (1986/4200), Asia 46.4% (1276/2217). Over half, 52.6% (20/38) of included studies reported continued unofficial chloroquine use following policy change. Studies done in Madagascar and Kenya reported re-emergence of chloroquine sensitive parasites (IC50 95%). The prevalence of chloroquine resistance alleles among Plasmodium falciparum parasites have steadily declined since discontinuation of chloroquine use. However, Pfcrt K76T and Pfmdr-1 N86Y mutations still persist at moderate frequencies in most malaria affected countries.

Journal ArticleDOI
TL;DR: Despite low plasma DTG exposures in the third trimester, transfer across the placenta and through breastfeeding was observed in this study, with persistence in infants likely due to slower metabolic clearance.
Abstract: Background The global transition to use of dolutegravir (DTG) in WHO-preferred regimens for HIV treatment is limited by lack of knowledge on use in pregnancy. Here we assessed the relationship between drug concentrations (pharmacokinetics, PK), including in breastmilk, and impact on viral suppression when initiated in the third trimester (T3). Methods and findings In DolPHIN-1, HIV-infected treatment-naive pregnant women (28–36 weeks of gestation, age 26 (19–42), weight 67kg (45–119), all Black African) in Uganda and South Africa were randomised 1:1 to dolutegravir (DTG) or efavirenz (EFV)-containing ART until 2 weeks post-partum (2wPP), between 9th March 2017 and 16th January 2018, with follow-up until six months postpartum. The primary endpoint was pharmacokinetics of DTG in women and breastfed infants; secondary endpoints included maternal and infant safety and viral suppression. Intensive pharmacokinetic sampling of DTG was undertaken at day 14 and 2wPP following administration of a medium-fat breakfast, with additional paired sampling between maternal plasma and cord blood, breastmilk and infant plasma. No differences in median baseline maternal age, gestation (31 vs 30 weeks), weight, obstetric history, viral load (4.5 log10 copies/mL both arms) and CD4 count (343 vs 466 cells/mm3) were observed between DTG (n = 29) and EFV (n = 31) arms. Although DTG Ctrough was below the target 324ng/mL (clinical EC90) in 9/28 (32%) mothers in the third trimester, transfer across the placenta (121% of plasma concentrations) and into breastmilk (3% of plasma concentrations), coupled with slower elimination, led to significant infant plasma exposures (3–8% of maternal exposures). Both regimens were well-tolerated with no significant differences in frequency of adverse events (two on DTG-ART, one on EFV-ART, all considered unrelated to drug). No congenital abnormalities were observed. DTG resulted in significantly faster viral suppression (P = 0.02) at the 2wPP visit, with median time to <50 copies/mL of 32 vs 72 days. Limitations related to the requirement to initiate EFV-ART prior to randomisation, and to continue DTG for only two weeks postpartum. Conclusion Despite low plasma DTG exposures in the third trimester, transfer across the placenta and through breastfeeding was observed in this study, with persistence in infants likely due to slower metabolic clearance. HIV RNA suppression <50 copies/mL was twice as fast with DTG compared to EFV, suggesting DTG has potential to reduce risk of vertical transmission in mothers who are initiated on treatment late in pregnancy. Trial registration clinicaltrials.gov NCT02245022