National Institute For Medical Research Research Articles

Meals, Education, and Gardens for In-School Adolescents (MEGA): study protocol for a cluster randomised trial of an integrated adolescent nutrition intervention in Dodoma, Tanzania

IntroductionSecondary schools have the transformative potential to advance adolescent nutrition and provide a unique entry point for nutrition interventions to reach adolescents and their families and communities. Integrated school nutrition...

Antiplasmodial effects of aqueous leaf extracts of Senna alata and Dennettia tripetalla in chloroquine-sensitive Plasmodium berghei berghei (NK65) infected mice

The antiplasmodial effects of Senna alata and Dennettia tripetalla on chloroquine-sensitive Plasmodium berghei berghei (NK65) were analysed. P. berghei was obtained from National Institute for Medical Research, Lagos, Nigeria, and maintained in the laboratory by serial passage in mice. Chemosuppressive, prophylactic, and curative procedures were used to evaluate the antiplasmodial potentials of the extracts against established infection. A total of 320 albino mice were used for this study. Twenty-five albino mice were divided into 5 groups and used for D. tripetalla acute toxicity study. Eighty-five albino mice were divided into 15 groups of five albino mice each and used for chemosuppressive tests while two hundred and ten mice were used for prophylactic and curative tests. The infected mice were orally treated daily with 5mg/kg chloroquine 500 mg/kg, 1000 mg/kg, 1500 mg/kg, and 2000 mg/kg body weight of S. alata, D. tripetalla, and S. alata + D. tripetalla respectively. The in vivo antiplasmodial effect of the extracts against P. berghei infection showed a significant (p?0.05) dose-dependent schizontocidal activity for the chemosuppressive, and prophylactic test. Results of the curative study showed that the combination of both S. alata and D. tripetalla exhibited a strong curative effect on malaria parasitaemia. There was a significant clearance (p?0.05) in parasiteamia level from day 1 to day 5 of treatment in a dose-dependent manner with a corresponding significant (p?0.05) percentage suppression. It was therefore concluded that the leaf extracts of S. alata and D. tripetalla possess antimalarial potencies which could be exploited for antimalarial therapy.

Editorial introductions.

Current Opinion in Supportive and Palliative Care was launched in 2007. It is one of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The fields of supportive and palliative care are divided into 12 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Journal's Section Editors for this issue. SECTION EDITORS Anthony H. DickensonAnthony H. DickensonAnthony H. Dickenson, BSc, PhD, FmedSci, FBPharmcolS is Professor of Neuropharmacology in the Department of Neuroscience, Physiology and Pharmacology at University College, London, UK. He gained his PhD at the National Institute for Medical Research, London, UK, and has held posts in Paris, California and Sweden. His research interests are pharmacology of the brain, including the mechanisms of pain and how pain can be controlled in both normal and pathophysiological conditions, and how to translate basic science to the patient. Prof. Dickenson is an Honorary Member of the British Pain Society, was a Member of the Council of the International Association for the Study of Pain for six years and is Section Editor for the journal Pain. He has authored more than 340 refereed publications and has an h index of 90, all due to his motivated and brilliant research team. He is a founding and continuing Member of the Wellcome Trust funded London Pain Consortium. Prof. Dickenson has given plenary lectures at the World Congress on Pain, the American Pain Society, the European Pain Congress, the Canadian Pain Society, the Belgium Pain Society, ASEAPs, the Scandinavian Pain Society, the British Pain Society, the Thailand Pain Society, the Irish Pain Society, the Singapore Pain Society, the Australian Pain Society, the New Zealand Pain Society and many other international and national meetings. He has also spoken at the Royal Institution, to GPs, and to schools on pain. Paul Farquhar-SmithPaul Farquhar-SmithPaul Farquhar-Smith has been a Consultant in pain and anaesthetics for 14 years and is a Fellow of the Faculty of Pain of the Royal College of Anaesthetists. He has a PhD in visceral pain and cannabinoids. He works in chronic cancer pain in close collaboration with supportive and palliative care services. A major interest of his is neuropathic pain in cancer survivors, such as chronic pain after surgery and chemotherapy-induced neuropathic pain (CIPN). He is involved in the London Cancer Vanguard project developing pathways and recommendations for CIPN. He has written in reference textbooks and in the British Pain Society guidelines for cancer pain and has lectured nationally and internationally on these subjects. He is currently co-Chair of the British Pain Society / Association for Palliative Medicine Joint Working Group on Pain in Cancer Patients. Kirsty BannisterKirsty BannisterAssociate Professor Dr Kirsty Bannister leads the Central Modulation of Pain laboratory at King's College London, UK. Her research team bridges the gap between bench and bedside pain research as they conduct exploratory experiments that seek to molecularly, anatomically and/or functionally define descending control pathways in animals and humans. Notably, Kirsty was recently awarded the 2022 Patrick D Wall prize for basic pain research from the International Association for the Study of Pain, and she performs section editor duties for Pain, Pain Reports and British Journal of Pharmacology. Kirsty has led multiple symposia at international meetings including the World Congress on Pain (IASP) and the European Pain Federation (EFIC). She is also part of the Scientific Programme Committee for IASP 2022.

Early empiric anti-Mycobacterium tuberculosis therapy for sepsis in sub-Saharan Africa: a protocol of a randomised clinical trial

IntroductionSub-Saharan Africa shoulders the highest burden of global sepsis and associated mortality. In high HIV and tuberculosis (TB) prevalent settings such as sub-Saharan Africa, TB is the leading cause of...

Implementation of the ‘Removed Injectable modified Short-course regimens for EXpert Multidrug Resistant Tuberculosis’ (RISE study) in Tanzania: a protocol for a mixed-methods process evaluation

IntroductionTanzania is adapting a shortened injectable-free multidrug resistant tuberculosis (MDR-TB) regimen, comprising new drugs such as bedaquiline and delamanid and repurposed drugs such as clofazimine and linezolid. The regimen is...

Study protocol for a pilot prospective, observational study investigating the condition suggestion and urgency advice accuracy of a symptom assessment app in sub-Saharan Africa: the AFYA-‘Health’ Study

IntroductionDue to a global shortage of healthcare workers, there is a lack of basic healthcare for 4 billion people worldwide, particularly affecting low-income and middle-income countries. The utilisation of AI-based...

Editorial introductions.

Editorial introductions.

Adolescent mental health research in Tanzania: a study protocol for a priority setting exercise and the development of an interinstitutional capacity strengthening programme

IntroductionPoor adolescent mental health is a barrier to achieving several sustainable development goals in Tanzania, where adolescent mental health infrastructure is weak. This is compounded by a lack of community...

A history of coronaviruses

The history of coronaviruses is an account of the discovery of coronaviruses and the diseases they cause. It starts with a report of a new type of upper-respiratory tract disease among chickens in North Dakota, US, in 1931. The causative agent was identified as a virus in 1933. By 1936, the disease and the virus were recognised as unique from other viral diseases. The virus became known as infectious bronchitis virus (IBV), but later officially renamed as Avian coronavirus. A new brain disease of mice (murine encephalomyelitis) was discovered in 1947 at Harvard Medical School in Boston. The virus was called JHM (after Harvard pathologist John Howard Mueller). Three years later a new mouse hepatitis was reported from the National Institute for Medical Research in London. The causative virus was identified as mouse hepatitis virus (MHV), later renamed Murine coronavirus. In 1961, a virus was obtained from a school boy in Epsom, England, who was suffering from common cold. The sample, designated B814, was confirmed as novel virus in 1965. New common cold viruses (assigned 229E) collected from medical students at the University of Chicago were also reported in 1966. Structural analyses of IBV, MHV, B18 and 229E using transmission electron microscopy revealed that they all belong to the same group of viruses. Making a crucial comparison in 1967, June Almeida and David Tyrrell invented the collective name coronavirus, as all those viruses were characterised by solar corona-like projections (called spikes) on their surfaces. Other coronaviruses have been discovered from pigs, dogs, cats, rodents, cows, horses, camels, Beluga whales, birds and bats. As of 2022, 52 species are described. Bats are found to be the richest source of different species of coronaviruses. All coronaviruses originated from a common ancestor about 293 million years ago. Zoonotic species such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV), Middle East respiratory syndrome-related coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a variant of SARS-CoV, emerged during the past two decades and caused the first pandemics of the 21st century.

A Prospective, observational cohort study to identify neonates and children at risk of postdischarge mortality in Dar es Salaam, Tanzania and Monrovia, Liberia: the PPDM study protocol

IntroductionOver half of the 5 million annual deaths among children aged 0–59 months occur in sub-Saharan Africa. The period immediately after hospitalisation is a vulnerable time in the life of...

Sir Dai Rees (28 April 1936 to 10 June 2021)

Sir Dai Rees (28 April 1936 to 10 June 2021)

Editorial introductions.

Current Opinion in Allergy and Clinical Immunology was launched in 2001. It is one of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The fields of allergy and clinical immunology are divided into 14 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Journal's Section Editors for this issue. SECTION EDITORS M. Teresa (Maite) de la MorenaM. Teresa (Maite) de la MorenaM. Teresa (Maite) de la Morena is Professor of Pediatrics in the Department of Pediatrics, Division of Immunology at University of Washington and Seattle Children's Hospital, USA. She graduated from medical school at Universidad Complutense de Madrid, Spain. This was followed by residency and fellowships training in pediatrics, allergy and immunology, and laboratory immunology at the University of South Florida, St. Petersburg, Florida, USA. Dr de La Morena has a clinical interest in allergy and immunology, clinical immunology with particular focus on the primary immunodeficiency diseases. Her research interests include long term clinical outcomes of patients with X-linked Hyper IgM syndrome, DiGeorge syndrome and microRNAs in primary immunodeficiency disorders, including their role in thymic development. Stephen JollesStephen JollesDr Jolles is a Consultant Clinical Immunologist and Honorary Professor at the University Hospital of Wales, UK. He is Clinical Lead in the Immunodeficiency Centre of Wales and Co-Director of the Hub Immunology Diagnostic Laboratory of Wales. Dr Jolles trained in immunology and allergy, and obtained his PhD on Langerhans cell migration at the National Institute for Medical Research, London. He has a particular interest in the clinical use of immunoglobulin and its mechanism of action and research interests include development of new therapeutic products, new screening strategies to improve the laboratory diagnosis of primary and secondary immunodeficiency and allergy, and better ways to monitor primary immunodeficiency disease and the impact of treatments. Giovanni PassalacquaGiovanni PassalacquaProf. Giovanni Passalacqua was born in Genoa in 1964, graduated in 1990 from the Genoa University Medical School, Italy, and was appointed by the specialty degrees in Allergy and Clinical Immunology and Respiratory Medicine in 1994 and 2002. He is the Co-Chairman of the Immunotherapy Scientific Committee of the WAO and member of the ARIA editorial board. Prof. Passalacqua serves as a section editor for Current Opinion in Allergy and Clinical Immunology, and also as a reviewer for Allergy, JACI, Clin Exp Allergy and ERJ. Prof. Passalacqua is the co-author of several international position papers, including ARIA guidelines, WAO Pos pap on SLIT, EAACI Pos Pap on local immunotherapy. His main fields of research are sublingual immunotherapy, mechanisms of allergic inflammation, antihistamines, corticosteroids, respiratory allergy, hymenoptera venom allergy. Under the chairmanship of Professor Canonica, he developed and investigated sublingual immunotherapy in the last 20 years. He has had 450 full articles published in peer reviewed journals indexed in MedLine plus 15 chapters in international handbooks. He currently heads the Allergy and Respiratory Diseases Department, and chairs the Specialty School in Respiratory Diseases, University of Genoa, Italy. Robert BushRobert BushDr Robert Bush received his MD degree from West Virginia University, USA. After completing his residency in internal medicine and fellowship in allergy and immunology at the University of Wisconsin – Madison, USA, he joined the faculty. He is currently Professor (Emeritus) of Medicine and was the former Chief of Allergy at the William S Middleton VA Hospital, Madison, Wisconsin, USA. His research interests include sublingual immunotherapy, allergen characterization, fungal allergy, food allergy, and occupational asthma.

Interactions between fecal gut microbiome, enteric pathogens, and energy regulating hormones among acutely malnourished rural Gambian children.

BackgroundThe specific roles that gut microbiota, known pathogens, and host energy-regulating hormones play in the pathogenesis of non-edematous severe acute malnutrition (marasmus SAM) and moderate acute malnutrition (MAM) during outpatient nutritional rehabilitation are yet to be explored.MethodsWe applied an ensemble of sample-specific (intra- and inter-modality) association networks to gain deeper insights into the pathogenesis of acute malnutrition and its severity among children under 5 years of age in rural Gambia, where marasmus SAM is most prevalent.FindingsChildren with marasmus SAM have distinct microbiome characteristics and biologically-relevant multimodal biomarkers not observed among children with moderate acute malnutrition. Marasmus SAM was characterized by lower microbial richness and biomass, significant enrichments in Enterobacteriaceae, altered interactions between specific Enterobacteriaceae and key energy regulating hormones and their receptors.InterpretationOur findings suggest that marasmus SAM is characterized by the collapse of a complex system with nested interactions and key associations between the gut microbiome, enteric pathogens, and energy regulating hormones. Further exploration of these systems will help inform innovative preventive and therapeutic interventions.FundingThe work was supported by the UK Medical Research Council (MRC; MC-A760-5QX00) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement; Bill and Melinda Gates Foundation (OPP 1066932) and the National Institute of Medical Research (NIMR), UK. This network analysis was supported by NIH U54GH009824 [CLD] and NSF OCE-1558453 [CLD].

Effect of scheduled antimicrobial and nicotinamide treatment on linear growth in children in rural Tanzania: A factorial randomized, double-blind, placebo-controlled trial.

BackgroundStunting among children in low-resource settings is associated with enteric pathogen carriage and micronutrient deficiencies. Our goal was to test whether administration of scheduled antimicrobials and daily nicotinamide improved linear growth in a region with a high prevalence of stunting and enteric pathogen carriage.Methods and findingsWe performed a randomized, 2 × 2 factorial, double-blind, placebo-controlled trial in the area around Haydom, Tanzania. Mother–child dyads were enrolled by age 14 days and followed with monthly home visits and every 3-month anthropometry assessments through 18 months. Those randomized to the antimicrobial arm received 2 medications (versus corresponding placebos): azithromycin (single dose of 20 mg/kg) at months 6, 9, 12, and 15 and nitazoxanide (3-day course of 100 mg twice daily) at months 12 and 15. Those randomized to nicotinamide arm received daily nicotinamide to the mother (250 mg pills months 0 to 6) and to the child (100 mg sachets months 6 to 18). Primary outcome was length-for-age z-score (LAZ) at 18 months in the modified intention-to-treat group. Between September 5, 2017 and August 31, 2018, 1,188 children were randomized, of whom 1,084 (n = 277 placebo/placebo, 273 antimicrobial/placebo, 274 placebo/nicotinamide, and 260 antimicrobial/nicotinamide) were included in the modified intention-to-treat analysis. The study was suspended for a 3-month period by the Tanzanian National Institute for Medical Research (NIMR) because of concerns related to the timing of laboratory testing and the total number of serious adverse events (SAEs); this resulted in some participants receiving their final study assessment late. There was a high prevalence of stunting overall (533/1,084, 49.2%). Mean 18-month LAZ did not differ between groups for either intervention (mean LAZ with 95% confidence interval [CI]: antimicrobial: −2.05 CI −2.13, −1.96, placebo: −2.05 CI −2.14, −1.97; mean difference: 0.01 CI −0.13, 0.11, p = 0.91; nicotinamide: −2.06 CI −2.13, −1.95, placebo: −2.04 CI −2.14, −1.98, mean difference 0.03 CI −0.15, 0.09, p = 0.66). There was no difference in LAZ for either intervention after adjusting for possible confounders (baseline LAZ, age in days at 18-month measurement, ward, hospital birth, birth month, years of maternal education, socioeconomic status (SES) quartile category, sex, whether the mother was a member of the Datoga tribe, and mother’s height). Adverse events (AEs) and SAEs were overall similar between treatment groups for both the nicotinamide and antimicrobial interventions. Key limitations include the absence of laboratory measures of pathogen carriage and nicotinamide metabolism to provide context for the negative findings.ConclusionsIn this study, we observed that neither scheduled administration of azithromycin and nitazoxanide nor daily provision of nicotinamide was associated with improved growth in this resource-poor setting with a high force of enteric infections. Further research remains critical to identify interventions toward improved early childhood growth in challenging conditions.Trial registrationClinicalTrials.gov NCT03268902.

Cell scientist to watch – Vivian Li

ABSTRACT Vivian Li obtained her PhD from the University of Hong Kong in 2008, where she investigated the molecular mechanisms of human colonic development and tumorigenesis. Funded by a Croucher Foundation Fellowship, she joined the lab of Hans Clevers at the Hubrecht Institute in the Netherlands for her postdoctoral work. There, she identified novel Wnt signalling mechanisms at different subcellular levels and characterised intestinal stem cell genes using newly created transgenic mouse models. Vivian established her group at the MRC National Institute for Medical Research, which is now part of the Francis Crick Institute, London, in February 2013. In her lab she uses genetic mouse models and organoids to investigate the regulation of intestinal homeostasis and cancer with a primary focus on the Wnt signalling pathway. Vivian was awarded a Future Leaders in Cancer Research Prize in 2018 by Cancer Research UK and is the winner of the 2021 Women in Cell Biology Early Career Medal awarded by the British Society for Cell Biology.

HIV-Associated Neurocognitive Disorders (HAND): The First Longitudinal Follow Up of a cART-Treated Cohort of Older People in Sub-Saharan Africa

Background: HIV-associated neurocognitive disorders (HAND) are a highly prevalent chronic complication in older people living with HIV (PLWH) in high-income countries (HICs). Although Sub-Saharan Africa (SSA) has a newly emergent population of older cART treated PLWH, HAND have not been studied longitudinally. We assessed longitudinal prevalence of HAND and have identified possible modifiable risk factors in a population of PLWH aged ≥50, over three years of follow-up. Methods: Detailed neuropsychological and clinical assessment was completed annually 2016-2019 in a baseline systematic sample of cART treated PLWH in Kilimanjaro, Tanzania. A consensus panel defined HAND using American Academy of Neurology criteria for asymptomatic neurocognitive impairment (ANI), mild neurocognitive disorder (MND) and HIV-associated dementia (HAD). HIV-disease severity and other factors associated with HAND progression, improvement and stability were evaluated in individuals fully assessed at baseline and in 2019. Findings: At baseline 47% of the cohort (n=253, 72·3% female) met HAND criteria despite good HIV-disease control [Y1 59.5% (n=185), Y2 61·7% (n=162), Y3 57·9% (n=121)]. Of participants fully assessed at baseline and year 3 (n=121) HAND remained stable in 54% (n=57), improved in 15% (n=16), and declined in 31% (n=33). Older age and lower education level significantly predicted HAND progression, whereas HIV-specific factors did not. Male gender and shorter cART-treatment predicted improvement. Interpretation: In this first longitudinal study characterising clinical course of HAND in older cART treated PLWH in SSA, HAND was highly prevalent with variable progression and reversibility. Progression may be more related to cognitive reserve than HIV-disease in cART-treated PLWH. Funding Information: This study was part-funded by the Academy of Medical Sciences, Grand Challenges Canada and the Newcastle University Master’s in Research Programme. Declaration of Interests: None. Ethics Approval Statement: Ethical approval was granted by Kilimanjaro Christian Medical College Research Ethics and Review Committee (N·896) and the Tanzanian National Institute for Medical Research (NIMR/HQ/R·8a/Vol·IX/2136). Participants were provided with written and verbal study information as appropriate by trained nurses. Where participants lacked capacity to consent due to cognitive impairment, assent was sought from a close relative. Consent was reviewed annually, and additional informed consent was requested to obtain an informant history for corroboration of cognitive and functional decline.

John W. Suttie (1934–2020)

John W. Suttie (1934–2020)

Henry Arnstein (12 June 1924 – 2 November 2020)

Henry Arnstein (12 June 1924 – 2 November 2020)

Soil transmitted helminth infection in primary school children varies with ecozone in the Ngorongoro Conservation Area, Tanzania

BackgroundSoil-transmitted helminthiasis is a neglected tropical disease, thriving in environments of poverty and disadvantage. Our objective was to determine the prevalence and intensity of four soil transmitted helminths (STH) among primary school children in the Ngorongoro Conservation Area (NCA), Tanzania.MethodsA cross-sectional study was performed between May 15th and June 2nd, 2014. Six of 20 primary schools were chosen, based on elevation, designated low elevation ecozone (LEE) or high elevation ecozone (HEE). A total of 340 children from standards one to four were recruited. Height and weight of each child was determined and body mass index (BMI) was calculated. Stool samples were analyzed using the Kato-Katz, Wisconsin, and Baermann techniques to detect STH eggs and larvae. An interviewer-administered questionnaire on socio-demographic variables was used to capture information from the school’s headmaster and a checklist was used to assess sanitation facilities.ResultsSTHs identified included Ascaris (presumably lumbricoides), Trichuris (presumably trichiura), hookworms (presumably Ancylostoma duodenale and/or Necator americanus), and Strongyloides (presumably stercoralis). The overall prevalence of STH infection was 29.0% in LEE and 34.0% in HEE. Prevalence was 34.3% and 28.2% in males versus females, respectively. Ascaris sp. were only identified in HEE, prevalence of Trichuris sp. and hookworms were significantly higher in HEE compared to LEE, and Strongyloides spp. prevalence was lower in HEE. Intensity of Trichuris sp. was significantly higher in HEE and lower for hookworms. We did not detect a significant relationship between BMI and helminth intensity; however, BMI was lower in lower elevations and in males vs. females. Sanitation practices are taught at the schools, but challenges were identified when implementing. Latrine facilities were available and latrine-cleaning routines were practiced; however, hand washing practices were challenging due to restricted water availability.ConclusionsSignificant differences in prevalence in HEE and LEE exist, and STH infections are still very common among school children suggesting that anthelminthic intervention and education may be necessary in this region. Based on this outcome, the study area in the NCA would be classified as a medium risk area, where periodic treatment recommendations should be based on prevalence estimations in the different ecozones.Trial registrationEthics approval was obtained from the Catholic University of Health and Allied Sciences (CUHAS; Lake Zone Institutional Review Board MR/53/100/307)); the Conjoint Health Research Ethics Board (CHREB) at the University of Calgary in Canada (Study ID REB14-0127); the National Institute of Medical Research (NIMR) of Tanzania; and the Tanzania Commission for Science and Technology (COSTEC).

Editorial introductions.

Editorial introductions.