Adhesion ofPlasmodium falciparum-infected erythrocytes to human cells: molecular mechanisms and therapeutic implications

Severe malaria has a high mortality rate (15–20%) despite treatment with effective antimalarial drugs. Adjunctive therapies for severe malaria that target the underlying disease process are therefore urgently required. Adhesion of erythrocytes infected withPlasmodium falciparumto human cells has a key role in the pathogenesis of life-threatening malaria and could be targeted with antiadhesion therapy. Parasite adhesion interactions include binding to endothelial cells (cytoadherence), rosetting with uninfected erythrocytes and platelet-mediated clumping of infected erythrocytes. Recent research has started to define the molecular mechanisms of parasite adhesion, and antiadhesion therapies are being explored. However, many fundamental questions regarding the role of parasite adhesion in severe malaria remain unanswered. There is strong evidence that rosetting contributes to severe malaria in sub-Saharan Africa; however, the identity of other parasite adhesion phenotypes that are implicated in disease pathogenesis remains unclear. In addition, the possibility of geographic variation in adhesion phenotypes causing severe malaria, linked to differences in malaria transmission levels and host immunity, has been neglected. Further research is needed to realise the untapped potential of antiadhesion adjunctive therapies, which could revolutionise the treatment of severe malaria and reduce the high mortality rate of the disease.

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Prise En Charge Des Péritonites Aiguës Dans Un Hôpital De District En Afrique Sub-saharienne : Cas Du Bénin

European Scientific Journal ESJ ◽

10.19044/esj.2017.v13n36p388 ◽

2017 ◽

Vol 13 (36) ◽

pp. 388

Author(s):

Bio Tamou Sambo ◽

Salako Alexandre Allodé ◽

Didier Sewadé Wekpon ◽

Djifid Morel Séto ◽

Montcho Adrien Hodonou ◽

...

Keyword(s):

Mortality Rate ◽

District Hospital ◽

Public Health Problem ◽

Sub Saharan Africa ◽

Prise En Charge ◽

Prospective Data ◽

Acute Peritonitis ◽

Generalized Peritonitis ◽

Sub Saharan ◽

Surgery Department

Introduction: Peritonitis remains a public health problem in Africa. We aim to describe the epidemiological, etiological and therapeutic aspects of acute peritonitis in a district hospital in Sub Saharan Africa. Methods: This was a descriptive study with prospective data collection over a period of 15 months from May 1 st 2015 to July 31st 2016 in Bembereke district hospital. It has taken into account all the patients managed in the general surgery department for acute generalized peritonitis that has been confirmed at laparotomy. Results: Fifty-three patients, 38 men (71.7 %) and 15 women (28.3 %) had been registered. The average age of the patients was 19.8 ± 16.9 years. The main etiologies were: non-traumatic ileal perforation from typhoid infection 52.8%; perforated gastric or duodenal ulcer 17%; complicated appendicitis and abdominal traumas 11.3% each one. Twenty nine patients (54.7%) have been operated by a surgeon and the 24 remaining (45.3%) by a general practitioner with surgical skills. Twenty one patients (39.6%) had postoperative complications of which 11 cases of parietal suppurations (52.4%). The mortality rate was 11.3%. The mean hospital stay was 22.5 ± 4 days. Conclusion: In northern-Benin, peritonitis remains dominated by the complications of typhoid fever. The mortality rate remains high. Prevention requires good hygiene and awareness of early consultations.

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Molecular Mechanisms and Biochemical Pathways for Micronutrient Acquisition and Storage in Legumes to Support Biofortification for Nutritional Security

Frontiers in Plant Science ◽

10.3389/fpls.2021.682842 ◽

2021 ◽

Vol 12 ◽

Author(s):

Manish Roorkiwal ◽

Sarita Pandey ◽

Dil Thavarajah ◽

R. Hemalatha ◽

Rajeev K. Varshney

Keyword(s):

Molecular Mechanisms ◽

Food System ◽

Significant Risk ◽

Nutrient Deficiency ◽

Nutrient Content ◽

Sub Saharan Africa ◽

Nutritional Security ◽

Legume Crops ◽

Sub Saharan ◽

Poor Nutrition

The world faces a grave situation of nutrient deficiency as a consequence of increased uptake of calorie-rich food that threaten nutritional security. More than half the world’s population is affected by different forms of malnutrition. Unhealthy diets associated with poor nutrition carry a significant risk of developing non-communicable diseases, leading to a high mortality rate. Although considerable efforts have been made in agriculture to increase nutrient content in cereals, the successes are insufficient. The number of people affected by different forms of malnutrition has not decreased much in the recent past. While legumes are an integral part of the food system and widely grown in sub-Saharan Africa and South Asia, only limited efforts have been made to increase their nutrient content in these regions. Genetic variation for a majority of nutritional traits that ensure nutritional security in adverse conditions exists in the germplasm pool of legume crops. This diversity can be utilized by selective breeding for increased nutrients in seeds. The targeted identification of precise factors related to nutritional traits and their utilization in a breeding program can help mitigate malnutrition. The principal objective of this review is to present the molecular mechanisms of nutrient acquisition, transport and metabolism to support a biofortification strategy in legume crops to contribute to addressing malnutrition.

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Psychomotor impairments and therapeutic implications revealed by a mutation associated with infantile Parkinsonism-Dystonia

eLife ◽

10.7554/elife.68039 ◽

2021 ◽

Vol 10 ◽

Author(s):

Jenny I Aguilar ◽

Mary Hongying Cheng ◽

Josep Font ◽

Alexandra C Schwartz ◽

Kaitlyn Ledwitch ◽

...

Keyword(s):

High Speed ◽

Molecular Mechanisms ◽

Motor Coordination ◽

Neurodegenerative Disorder ◽

Expression System ◽

Distinct Type ◽

Underlying Disease ◽

Deficiency Syndrome ◽

Motor Deficits ◽

Therapeutic Implications

Parkinson disease (PD) is a progressive, neurodegenerative disorder affecting over 6.1 million people worldwide. Although the cause of PD remains unclear, studies of highly penetrant mutations identified in early-onset familial parkinsonism have contributed to our understanding of the molecular mechanisms underlying disease pathology. Dopamine (DA) transporter (DAT) deficiency syndrome (DTDS) is a distinct type of infantile parkinsonism-dystonia that shares key clinical features with PD, including motor deficits (progressive bradykinesia, tremor, hypomimia) and altered DA neurotransmission. Here, we define structural, functional, and behavioral consequences of a Cys substitution at R445 in human DAT (hDAT R445C), identified in a patient with DTDS. We found that this R445 substitution disrupts a phylogenetically conserved intracellular (IC) network of interactions that compromise the hDAT IC gate. This is demonstrated by both Rosetta molecular modeling and fine-grained simulations using hDAT R445C, as well as EPR analysis and X-ray crystallography of the bacterial homolog leucine transporter. Notably, the disruption of this IC network of interactions supported a channel-like intermediate of hDAT and compromised hDAT function. We demonstrate that Drosophila melanogaster expressing hDAT R445C show impaired hDAT activity, which is associated with DA dysfunction in isolated brains and with abnormal behaviors monitored at high-speed time resolution. We show that hDAT R445C Drosophila exhibit motor deficits, lack of motor coordination (i.e. flight coordination) and phenotypic heterogeneity in these behaviors that is typically associated with DTDS and PD. These behaviors are linked with altered dopaminergic signaling stemming from loss of DA neurons and decreased DA availability. We rescued flight coordination with chloroquine, a lysosomal inhibitor that enhanced DAT expression in a heterologous expression system. Together, these studies shed some light on how a DTDS-linked DAT mutation underlies DA dysfunction and, possibly, clinical phenotypes shared by DTDS and PD.

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High mortality in subjects with both diabetes and HIV in sub-Saharan Africa

AIDS ◽

10.1097/qad.0000000000001929 ◽

2018 ◽

Vol 32 (14) ◽

pp. 2083-2084

Author(s):

Philip I. Burgess ◽

Simon P. Harding ◽

Petros C. Kayange ◽

Joep van Oosterhout ◽

Marta García-Fiñana ◽

...

Keyword(s):

High Mortality ◽

Sub Saharan Africa ◽

Sub Saharan

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OC 8494 DRIVING REDUCED AIDS-ASSOCIATED MENINGO-ENCEPHALITIS MORTALITY

BMJ Global Health ◽

10.1136/bmjgh-2019-edc.24 ◽

2019 ◽

Vol 4 (Suppl 3) ◽

pp. A10.2-A10

Author(s):

Angela Loyse ◽

Godfrey S Mfinanga ◽

Cecilia Kanyama ◽

Charles Kounfack ◽

Sokoine Lesikari ◽

...

Keyword(s):

High Mortality ◽

Routine Care ◽

Sub Saharan Africa ◽

Contributing Factors ◽

Train The Trainer ◽

Csf Analysis ◽

Laboratory Capacity ◽

Poor Access ◽

Microbiological Techniques ◽

Sub Saharan

BackgroundDREAMM is an implementation study aiming to reduce meningo-encephalitis related mortality. Delays in diagnosis and treatment through poor access to diagnostics and treatments are significant contributing factors to the ongoing high mortality of HIV-associated central nervous system (CNS) infections, causing up to 25% of all HIV-related deaths in sub-Saharan Africa.MethodsA before-after design is being implemented across 3 sites in Africa; Lilongwe, Malawi, Dar Es Salaam, Tanzania and Yaoundé, Cameroon. The study is composed of 3 phases: Observation, Training and Implementation.ResultsThe observation phase (audit of practice) happened between November 2016 – May 2017 in Malawi and Tanzania. Overall, 110 patients were included. Ten-week all-cause mortality was 64% (42/66) in Tanzania and 37% (13/35) in Malawi. Approximately 75% of patients were ART experienced. Across sites, 76.6% of patients presented with abnormal mental status, with a median baseline CD4 count of 50 cells/µL. Only 2/75 patients in Tanzania had a lumbar puncture ordered compared to 27/35 in Malawi. All patients in Tanzania received empirical Fluconazole monotherapy whereas almost 1/3 patients in Malawi (11/35) were treated with Amphotericin B which is not readily available in both countries.The training phase (completed in November 2017 for Malawi and Tanzania) used the train-the-trainer approach. Interactive workshops on using rapid diagnostic tests (RDTs), performing basic microbiological techniques and safe administration of medicines were chosen as the most pertinent to reducing mortality. Patient and laboratory pathways were optimised afterwards by increasing the routine laboratory capacity, performing CSF analysis, providing infectious diseases mentorship for clinicians and procuring RDTs and reagents not locally available.Implementation is underway in Malawi and Tanzania and the audit phase is scheduled for autumn in Cameroon. Upon completion, the project is expected to create a sustainable approach to reduce the high mortality of HIV-related meningo-encephalitis with the optimised patient and laboratory pathways embedded within routine care.

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Does economic freedom improve health outcomes in sub-Saharan Africa?

International Journal of Social Economics ◽

10.1108/ijse-01-2020-0008 ◽

2020 ◽

Vol 47 (12) ◽

pp. 1633-1649

Author(s):

Anand Sharma

Keyword(s):

Mortality Rate ◽

Life Expectancy ◽

Health Outcomes ◽

Economic Freedom ◽

Sub Saharan Africa ◽

African Countries ◽

Content Type ◽

The World ◽

Sub Saharan ◽

The Impact

PurposeThe purpose of this study is to examine the impact of economic freedom on four key health indicators (namely, life expectancy, infant mortality rate, under-five mortality rate and neonatal mortality rate) by using a panel dataset of 34 sub-Saharan African countries from 2005 to 2016.Design/methodology/approachThe study obtains data from the World Development Indicators (WDI) of the World Bank and the Fraser Institute. It uses fixed effects regression to estimate the effect of economic freedom on health outcomes and attempts to resolve the endogeneity problems by using two-stage least squares regression (2SLS).FindingsThe results indicate a favourable impact of economic freedom on health outcomes. That is, higher levels of economic freedom reduce mortality rates and increase life expectancy in sub-Saharan Africa. All areas of economic freedom, except government size, have a significant and positive effect on health outcomes.Research limitations/implicationsThis study analyses the effect of economic freedom on health at a broad level. Country-specific studies at a disaggregated level may provide additional information about the impact of economic freedom on health outcomes. Also, this study does not control for some important variables such as education, income inequality and foreign aid due to data constraints.Practical implicationsThe findings suggest that sub-Saharan African countries should focus on enhancing the quality of economic institutions to improve their health outcomes. This may include policy reforms that support a robust legal system, protect property rights, promote free trade and stabilise the macroeconomic environment. In addition, policies that raise urbanisation, increase immunisation and lower the incidence of HIV are likely to produce a substantial improvement in health outcomes.Originality/valueExtant economic freedom-health literature does not focus on endogeneity problems. This study uses instrumental variables regression to deal with endogeneity. Also, this is one of the first attempts to empirically investigate the relationship between economic freedom and health in the case of sub-Saharan Africa.

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Severe Case of Plasmodium falciparum Malaria in a Pregnant Woman from Nigeria

Case Reports in Infectious Diseases ◽

10.1155/2019/2630825 ◽

2019 ◽

Vol 2019 ◽

pp. 1-3

Author(s):

Kruti Yagnik ◽

Bilal Farooqi ◽

Molly W. Mandernach ◽

Anthony P. Cannella ◽

Gautam Kalyatanda

Keyword(s):

Pregnant Women ◽

Severe Malaria ◽

Plasmodium Falciparum Malaria ◽

Severe Case ◽

Pregnant Patient ◽

Sub Saharan Africa ◽

Blood Parasites ◽

Intrauterine Pregnancy ◽

Drug Of Choice ◽

Sub Saharan

Human malaria has arguably affected more of human history than any other pathogen. Pregnant women have a higher risk of developing severe malaria as well as the risk of severe complications. We present a case of severe malaria in a pregnant patient from sub-Saharan Africa who was treated successfully with artesunate. A 28-year-old Nigerian woman with a 20-week intrauterine pregnancy presented with a five-day history of fever and diffuse joint pains. Evaluation of peripheral thin blood smear demonstrated a parasitemia of 9.8%. The patient was admitted to the intensive care unit, and oral clindamycin/quinine was initiated until intravenous artesunate was obtained. The patient completed four doses of IV artesunate, and after the 4th dose of artesunate, no blood parasites were seen on peripheral smear. The patient was discharged home and, upon clinic follow-up, did not have any further complications associated with either her disease or therapy. A review on the treatment of severe malaria in all trimesters of pregnancy supports the WHO recommendation for intravenous artesunate as the drug of choice. This case illustrates the importance of recognizing malaria in pregnant women from endemic countries and shows that artesunate compounds can be used safely in pregnancy, particularly with high parasitemia.

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The age patterns of severe malaria syndromes in sub-Saharan Africa across a range of transmission intensities and seasonality settings

Malaria Journal ◽

10.1186/1475-2875-9-282 ◽

2010 ◽

Vol 9 (1) ◽

Cited By ~ 52

Author(s):

Arantxa Roca-Feltrer ◽

Ilona Carneiro ◽

Lucy Smith ◽

Joanna RM Armstrong Schellenberg ◽

Brian Greenwood ◽

...

Keyword(s):

Severe Malaria ◽

Sub Saharan Africa ◽

Age Patterns ◽

Sub Saharan

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Antimicrobial Resistance in Gram-negative bacteria from Urinary Specimens: a study of prevalence, risk factors and molecular mechanisms of resistance (ARGUS) in Zimbabwe – a study protocol

Wellcome Open Research ◽

10.12688/wellcomeopenres.15977.1 ◽

2020 ◽

Vol 5 ◽

pp. 140

Author(s):

Ioana D. Olaru ◽

Shunmay Yeung ◽

Rashida A. Ferrand ◽

Richard Stabler ◽

Prosper Chonzi ◽

...

Keyword(s):

Risk Factors ◽

Antimicrobial Resistance ◽

Clinical Outcomes ◽

Molecular Mechanisms ◽

Outpatient Setting ◽

Sub Saharan Africa ◽

Gram Negative ◽

Sub Saharan ◽

Few Data ◽

Tract Infections

Antimicrobial resistance (AMR) is compromising our ability to successfully treat infections. There are few data on gram-negative AMR prevalence in sub-Saharan Africa especially from the outpatient setting. This study aims to investigate the prevalence of and underlying molecular mechanisms for AMR in gram-negative bacilli causing urinary tract infections (UTIs) in Zimbabwe. Risk factors for AMR and how AMR impacts on clinical outcomes will also be investigated. Adults presenting with UTI symptoms at primary health clinics in Harare will be included. A questionnaire will be administered, and urine samples will be collected for culture. Participants with positive urine cultures will be followed up at 7-14 days post-enrolment. All participants will also be followed by telephone at 28 days to determine clinical outcomes. Bacterial identification and antibiotic susceptibility testing will be performed on positive cultures. The results from this study will be used to inform policy and development of treatment recommendations. Whole genome sequencing results will provide a better understanding of the prevalent resistance genes in Zimbabwe, of the spread of successful clones, and potentially will contribute to developing strategies to tackle AMR.

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Hospital Mortality in Trauma Patients

International Journal of Orthopaedics Research ◽

10.33140/ijor.04.03.09 ◽

2021 ◽

Vol 4 (3) ◽

Keyword(s):

Mortality Rate ◽

Hospital Mortality ◽

Traffic Accidents ◽

Causes Of Death ◽

Cardiopulmonary Arrest ◽

Lower Limbs ◽

Sub Saharan Africa ◽

Trauma Patients ◽

Road Accidents ◽

Sub Saharan

Introduction: The study of mortality in a community makes it possible to define the axes of disease prevention and to readjust public health policies. The achieve of our study was to assess hospital mortality in trauma patients in an orthopedic department of a teaching hospital in sub-Saharan Africa. Patients and Method: We conducted a retrospective prognostic study evaluating hospital mortality during the period from March 1, 2013 to February 29, 2018. The results were analyzed using Statistical Package for the Social Sciences (SPSS) version 26.0. Results: Hospital mortality rate was 1.43%. The Circumstances of death were dominated by road accidents with 48.2%. Trauma to the lower limbs, the spine and polytrauma were the most frequently observed lesions on admission of patients with 40%, 27.3% and 28.2% respectively. Neurovegetative complications (29.51 %) and cardiopulmonary arrest (18.03 %) were the main causes of death at autopsy. Results: Hospital mortality rate was 1.43%. The Circumstances of death were dominated by road accidents with 48.2%. Trauma to the lower limbs, the spine and polytrauma were the most frequently observed lesions on admission of patients with 40%, 27.3% and 28.2% respectively. Neurovegetative complications (29.51 %) and cardiopulmonary arrest (18.03 %) were the main causes of death at autopsy. Conclusion: Traffic accidents are the most common cause of death from trauma. They can be avoided or limited by a good road safety policy.

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