scholarly journals Molecular Aspects ofPlasmodium falciparumInfection during Pregnancy

2007 ◽  
Vol 2007 ◽  
pp. 1-13 ◽  
Author(s):  
Nicaise Tuikue Ndam ◽  
Philippe Deloron
Keyword(s):  
Molecular Basis ◽  
Protective Immunity ◽  
Surface Antigens ◽  
Pathological Process ◽  
Sub Saharan Africa ◽  
Variant Surface Antigens ◽  
Important Exception ◽  
Sub Saharan ◽  
Molecular Aspects ◽  
Poor Outcomes

Cytoadherence ofPlasmodium-falciparum-parasitized red blood cells (PRBCs) to host receptors is the key phenomenon in the pathological process of the malaria disease. Some of these interactions can originate poor outcomes responsible for 1 to 3 million annual deaths mostly occurring among children in sub-Saharan Africa. Pregnancy-associated malaria (PAM) represents an important exception of the disease occurring at adulthood in malaria endemic settings. Consequences of this are shared between the mother (maternal anemia) and the baby (low birth weight and infant mortality). Demonstrating that parasites causing PAM express specific variant surface antigens (VSAPAM), including theP. falciparumerythrocyte membrane protein 1 (PfEMP1) variant VAR2CSA, that are targets for protective immunity has strengthened the possibility for the development of PAM-specific vaccine. In this paper, we review the molecular basis of malaria pathogenesis attributable to the erythrocyte stages of the parasites, and findings supporting potential anti-PAM vaccine components evidenced in PAM.

scholarly journals Presentation and Outcomes of Childhood Cancer Patients at Uganda Cancer Institute

2019 ◽  
Vol 6 ◽  
pp. 2333794X1984974 ◽  
Author(s):  
Innocent Mutyaba ◽  
Henry R. Wabinga ◽  
Jackson Orem ◽  
Corey Casper ◽  
Warren Phipps
Keyword(s):  
Childhood Cancer ◽  
Lymphoblastic Leukemia ◽  
Kaposi Sarcoma ◽  
Sub Saharan Africa ◽  
Children With Cancer ◽  
Non Hodgkin Lymphoma ◽  
Cox's Regression ◽  
Sub Saharan ◽  
Poor Outcomes ◽  
Histological Confirmation

Introduction. Limited data suggest that children with cancer in sub-Saharan Africa have poor survival. We aimed to describe the presentation, treatment outcomes, and factors associated with survival among children with cancer managed at Uganda Cancer Institute. Methods. We retrospectively evaluated patients with childhood cancer (age ≤19 years) from Kyadondo County treated at Uganda Cancer Institute from 2006 to 2009. Cox’s regression and Kaplan-Meier methods were used to study 1-year survival. Results. Among 310 patients studied, median age was 7 years (range = 0.25-19 years), 64% were boys, and 92% had histological confirmation of cancer diagnosis. The commonest diagnoses were Burkitt lymphoma (BL, N = 87), Kaposi sarcoma (KS, N = 68), non-BL non-Hodgkin lymphoma (NHL, N = 32), acute lymphoblastic leukemia (ALL, N = 28), Wilms (N = 28), and Hodgkin disease (HD, N = 20). Advanced disease at diagnosis was common for all cancers (ranging from 45% for KS to 83% for non-BL NHL). Overall, 33.2% abandoned treatment. One-year survival was 68% for HD (95% confidence interval [CI] = 11.3-40.6), 67% for KS (95% CI = 52.1-77.9), 55% for BL (95% CI = 42-66.9), 44% for Wilms (95% CI = 22.5-63), 43% for non-BL NHL (95% CI = 23.3-61.3), and 20% for ALL (95% CI = 6.4-38.7). In univariate and multivariate analysis, anemia and thrombocytopenia were associated with mortality for several cancers. Conclusion. Survival among children with cancer in Uganda is poor. Advanced stage disease and loss to follow-up likely contribute to poor outcomes. Anemia and thrombocytopenia may augment traditional staging methods to provide better prognostic factors in Uganda and warrant further evaluation.

Neoliberal Reforms in Sub-Saharan Africa's Electricity Sector

2021 ◽  
pp. 410-430
Author(s):  
Chigozie Nweke-Eze
Keyword(s):  
Electricity Markets ◽  
Electricity Sector ◽  
Sub Saharan Africa ◽  
Weak Institutions ◽  
Neoliberal Reforms ◽  
Regulatory Measures ◽  
Sub Saharan ◽  
Poor Outcomes ◽  
Implementation Status ◽  
Ssa Countries

Based on literature review and documents analyses, this contribution discusses the processes, implementation, experiences and impacts of the neoliberal electricity-sector reform in Sub-Saharan Africa (SSA). The study generally finds poor implementation status and experiences as well as little improvement in the performance of the electricity sector as a result of the reforms, in the reviewed and analyzed SSA countries. The study identifies the reasons for the general poor outcomes of the reforms to be non-existence of truly independent electricity regulatory agencies, weak institutions and non-existence of unhampered competition among players in the electricity markets in most SSA context. The study suggests implementation of more tailored reform alternatives which suit existing political, social, and institutional characteristics and conditions of the SSA countries, namely: hybrid electricity markets and complementary regulatory measures.

scholarly journals Geographical and Temporal Conservation of Antibody Recognition of Plasmodium falciparum Variant Surface Antigens

2004 ◽  
Vol 72 (6) ◽  
pp. 3531-3535 ◽  
Author(s):  
Morten A. Nielsen ◽  
Lasse S. Vestergaard ◽  
John Lusingu ◽  
Jørgen A. L. Kurtzhals ◽  
Haider A. Giha ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Protective Immunity ◽  
Surface Antigens ◽  
African Countries ◽  
Variant Surface Antigens ◽  
Antibody Recognition ◽  
Specific Immunoglobulin ◽  
Life Threatening ◽  
Specific Igg ◽  
Plasma Collection

ABSTRACT The slow acquisition of protection against Plasmodium falciparum malaria probably reflects the extensive diversity of important antigens. The variant surface antigens (VSA) that mediate parasite adhesion to a range of host molecules are regarded as important targets of acquired protective immunity, but their diversity makes them questionable vaccine candidates. We determined levels of VSA-specific immunoglobulin G (IgG) in human plasma collected at four geographically distant and epidemiologically distinct localities with specificity for VSA expressed by P. falciparum isolates from three African countries. Plasma levels of VSA-specific IgG recognizing individual parasite isolates depended on the transmission intensity at the site of plasma collection but were largely independent of the geographical origin of the parasites. The total repertoire of immunologically distinct VSA thus appears to be finite and geographically conserved, most likely due to functional constraints. Furthermore, plasma samples frequently had high IgG reactivity to VSA expressed by parasites isolated more than 10 years later, showing that the repertoire is also temporally stable. Parasites from patients with severe malaria expressed VSA (VSASM) that were better recognized by plasma IgG than VSA expressed by other parasites, but importantly, VSASM-type antigens also appeared to show substantial antigenic homogeneity. Our finding that the repertoire of immunologically distinct VSA in general, and in particular that of VSASM, is geographically and temporally conserved raises hopes for the feasibility of developing VSA-based vaccines specifically designed to accelerate naturally acquired immunity, thereby enhancing protection against severe and life-threatening P. falciparum malaria.

scholarly journals Iron deficiency anaemia: experiences and challenges

2018 ◽  
Vol 78 (1) ◽  
pp. 19-26 ◽  
Author(s):  
Isabella Stelle ◽  
Anastasia Z. Kalea ◽  
Dora I. A. Pereira
Keyword(s):  
Iron Deficiency ◽  
Bacterial Infections ◽  
Iron Deficiency Anaemia ◽  
Sub Saharan Africa ◽  
Deficiency Anaemia ◽  
Poor Countries ◽  
Resource Poor ◽  
Physiological Approach ◽  
Sub Saharan ◽  
Poor Outcomes

Iron deficiency remains the largest nutritional deficiency worldwide and the main cause of anaemia. Severe iron deficiency leads to anaemia known as iron deficiency anaemia (IDA), which affects a total of 1·24 billion people, the majority of whom are children and women from resource-poor countries. In sub-Saharan Africa, iron deficiency is frequently exacerbated by concomitant parasitic and bacterial infections and contributes to over 120 000 maternal deaths a year, while it irreparably limits the cognitive development of children and leads to poor outcomes in pregnancy.Currently available iron compounds are cheap and readily available, but constitute a non-physiological approach to providing iron that leads to significant side effects. Consequently, iron deficiency and IDA remain without an effective treatment, particularly in populations with high burden of infectious diseases. So far, despite considerable investment in the past 25 years in nutrition interventions with iron supplementation and fortification, we have been unable to significantly decrease the burden of this disease in resource-poor countries.If we are to eliminate this condition in the future, it is imperative to look beyond the strategies used until now and we should make an effort to combine community engagement and social science approaches to optimise supplementation and fortification programmes.

scholarly journals Outcomes of ventriculoperitoneal shunt insertion in Sub-Saharan Africa

2010 ◽  
Vol 6 (4) ◽  
pp. 329-335 ◽  
Author(s):  
Esther Gathura ◽  
Dan Poenaru ◽  
Richard Bransford ◽  
A. Leland Albright
Keyword(s):  
Sub Saharan Africa ◽  
Complication Rates ◽  
Long Term Outcomes ◽  
Shunt Insertion ◽  
Vp Shunt ◽  
Good Outcome ◽  
Sub Saharan ◽  
Poor Outcomes

Object Ventriculoperitoneal (VP) shunts in Sub-Saharan Africa are traditionally associated with high complication rates and poor outcomes. The aim of this study was to review one large institutional experience with VP shunts, to evaluate the feasibility of shunt insertion procedures with acceptable long-term outcomes in Africa, and to identify factors correlated with good and/or poor outcomes. Methods A retrospective study was conducted by reviewing the charts of all children who underwent primary (93%) or subsequent VP shunt insertions at the Kijabe Hospital between November 2004 and March 2007. Epidemiological data, clinical investigations, etiology of the hydrocephalus, details of the VP shunt insertion, outcome at follow-up, and morbidity and mortality data were collected. Outcomes were graded as good, fair, or poor, according to visual, motor, and seizure criteria. Results The authors analyzed 593 VP shunt insertions in 574 patients. The sex distribution was 53% male and 47% female. The mean age at shunt insertion was 8.5 months (range 0–309 months). The commonest etiologies for hydrocephalus were spina bifida (43.4%) and postinfectious (27.7%). Follow-up was available in 76% of children, with a mean follow-up period of 8.9 months (range 2–30.5 months). The median patient age was 3.3 months. The overall shunt function rate at 2 years was 65%, and the complication rate per procedure was 20%, with infection encountered in 9.1% and shunt malfunction in 11%. Complications were significantly related to hydrocephalus etiology and to sex (p = 0.03 and p = 0.01, respectively). Overall outcomes were good in 40.2% and poor in 59.8%. Overall mortality in the group was 7.1%. Younger patients who survived had an overall good outcome (p = 0.0001). Only 10% of patients with a head circumference greater than 60 cm had a good outcome. Conclusions Despite limited resources, VP shunt procedures can be carried out in Sub-Saharan Africa with acceptable complication rates and fair long-term outcomes.

scholarly journals Pediatric Solid Tumors in Resource-Constrained Settings: A Review of Available Evidence on Management, Outcomes, and Barriers to Care

Children ◽  
2018 ◽  
Vol 5 (11) ◽  
pp. 143 ◽  
Author(s):  
Nicholas Carter ◽  
Andrew Avery ◽  
Jaime Libes ◽  
Harold Lovvorn ◽  
Erik Hansen
Keyword(s):  
Solid Tumors ◽  
Barriers To Care ◽  
Wilms Tumor ◽  
Tumor Biology ◽  
Sub Saharan Africa ◽  
Pediatric Care ◽  
Middle Income ◽  
Pediatric Solid Tumors ◽  
Sub Saharan ◽  
Poor Outcomes

International disparities in outcomes from pediatric solid tumors remain striking. Herein, we review the current literature regarding management, outcomes, and barriers to care for pediatric solid tumors in low- and middle-income countries (LMICs). In sub-Saharan Africa, Wilms Tumor represents the most commonly encountered solid tumor of childhood and has been the primary target of recent efforts to improve outcomes in low-resource settings. Aggressive and treatment-resistant tumor biology may play a role in poor outcomes within certain populations, but socioeconomic barriers remain the principal drivers of preventable mortality. Management protocols that include measures to address socioeconomic barriers have demonstrated early success in reducing abandonment of therapy. Further work is required to improve infrastructure and general pediatric care to address disparities.

Clinical disease, immunity and protection against Plasmodium falciparum malaria in populations living in endemic areas

1998 ◽  
Vol 1 (4) ◽  
pp. 1-10 ◽  
Author(s):  
Lars Hviid
Keyword(s):  
Immune Responses ◽  
Protective Immunity ◽  
Plasmodium Falciparum Malaria ◽  
Clinical Disease ◽  
Sub Saharan Africa ◽  
Immunological Mechanism ◽  
Endemic Setting ◽  
Natural Exposure ◽  
Resistance To Infection ◽  
Sub Saharan

Malaria remains one of the biggest health problems in large parts of the world. In sub-Saharan Africa alone, it is currently estimated that there are more than 150 million clinical cases annually, and that about 2 million people die from the disease every year. The bulk of malaria-related morbidity and mortality in an endemic setting (malaria is regularly found) is concentrated in children below the age of five years, and the increasing resistance to infection and disease with age is conventionally thought to reflect a slow and gradual acquisition of protective immunity. Many recent and comprehensive reviews of malarial immunity exist; rather than attempting to add another, this review summarises some of the recent evidence on how protective immunity is acquired in humans and what precipitates clinical disease, specifically as it relates to populations living in areas where the disease is endemic. It is becoming increasingly clear that naturally acquired protective immunity depends largely on responses directed against highly variable parasite antigens. This implies that a successful blood-stage vaccine against this disease must be able to either induce protective responses against many of these variants, or artificially initiate protective immune responses that do not normally occur following natural exposure to the parasites. Such protective immune responses might either rely on a different immunological mechanism, or be directed against other antigens, other than those seen in naturally acquired protective immunity. It remains to be seen whether it will be possible to induce protective responses such as these by ‘artificially’ immunising humans.

scholarly journals Plasmodium falciparum Infection Elicits Both Variant-Specific and Cross-Reactive Antibodies against Variant Surface Antigens

2003 ◽  
Vol 71 (2) ◽  
pp. 597-604 ◽  
Author(s):  
Rana Chattopadhyay ◽  
Amit Sharma ◽  
Vinod K. Srivastava ◽  
Sudhanshu S. Pati ◽  
S. K. Sharma ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Membrane Protein ◽  
Molecular Basis ◽  
Transmission Rate ◽  
Surface Antigens ◽  
Cross Reactivity ◽  
Falciparum Infection ◽  
Variant Surface Antigens ◽  
Convalescent Phase ◽  
Low Malaria Transmission

ABSTRACT Naturally acquired antibodies to Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP-1), the variant surface antigens expressed on the surface of infected erythrocytes, are thought to play a role in protection against P. falciparum malaria. Here, we have studied the development of antibodies to PfEMP-1 in adult malaria patients living in Rourkela, India, an area with a low malaria transmission rate, and prevalence of antibodies to PfEMP-1 in residents of San Dulakudar, India, a village in which P. falciparum malaria is hyperendemic. Convalescent-phase sera from adult malaria patients from Rourkela agglutinate homologous P. falciparum isolates as well as some heterologous isolates, suggesting that they develop partially cross-reactive antibodies to PfEMP-1 following infection. Adult sera from San Dulakudar agglutinate diverse P. falciparum isolates, suggesting that they have antibodies with wide recognition of diverse PfEMP-1. Mixed-agglutination assays using pairs of P. falciparum isolates confirm the presence of both variant-specific and partially cross-reactive antibodies in convalescent-phase sera from Rourkela and adult sera from San Dulakudar. Analysis of PfEMP-1 sequences suggests a molecular basis for the observed cross-reactivity.

scholarly journals VAR2CSA and protective immunity against pregnancy-associated Plasmodium falciparum malaria

Parasitology ◽  
2007 ◽  
Vol 134 (13) ◽  
pp. 1871-1876 ◽  
Author(s):  
L. HVIID ◽  
A. SALANTI
Keyword(s):  
Immune Response ◽  
Plasmodium Falciparum ◽  
Pregnant Women ◽  
Protective Immunity ◽  
Plasmodium Falciparum Malaria ◽  
Surface Antigens ◽  
Variant Surface Antigens ◽  
Important Target ◽  
First Time ◽  
Stable Transmission

SUMMARYPeople living in areas with stable transmission of P. falciparum parasites acquire protective immunity to malaria over a number of years and following multiple disease episodes. Immunity acquired this way is mediated by IgG with specificity for parasite-encoded, clonally variant surface antigens (VSA) on the surface of infected erythrocytes (IEs). However, women in endemic areas become susceptible to P. falciparum infection when they become pregnant, particularly for the first time, regardless of previously acquired protective immunity. This conundrum was resolved when it was observed that the selective placental accumulation of IEs that characterizes pregnancy-associated malaria (PAM) is caused by an immunologically and functionally unique subset of VSA (VSAPAM) that is only expressed by parasites infecting pregnant women, and that protective immunity to PAM is mediated by IgG with specificity for VSAPAM. In this review we summarize the research leading to the identification of the distinctly structured PfEMP1 variant VAR2CSA as the dominant PAM-type VSA and as the clinically most important target of the protective immune response to placental P. falciparum infection.

scholarly journals Malaria-Induced Acquisition of Antibodies to Plasmodium falciparum Variant Surface Antigens

2002 ◽  
Vol 70 (6) ◽  
pp. 2982-2988 ◽  
Author(s):  
Michael F. Ofori ◽  
Daniel Dodoo ◽  
Trine Staalsoe ◽  
Jørgen A. L. Kurtzhals ◽  
Kwadwo Koram ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Protective Immunity ◽  
Surface Antigens ◽  
Specific Antibodies ◽  
Variant Surface Antigens ◽  
Detailed Kinetics ◽  
Antibody Levels ◽  
Kinetics Of ◽  
Malaria Episodes ◽  
Sustained Increase

ABSTRACT In areas of intense Plasmodium falciparum transmission, protective immunity is acquired during childhood in parallel with acquisition of agglutinating antibodies to parasite-encoded variant surface antigens (VSA) expressed on parasitized red blood cells. In a semi-immune child in such an area, clinical disease is caused mainly by parasites expressing VSA not recognized by preexisting VSA-specific antibodies in that child. Such malaria episodes are known to cause an increase in agglutinating antibodies specifically recognizing VSA expressed by the parasite isolate causing the illness, whereas antibody responses to other parasite isolates are relatively unaffected. However, the detailed kinetics of this VSA antibody acquisition are unknown and hence were the aim of this study. We show that P. falciparum malaria in Ghanaian children generally caused a rapid and sustained increase in variant-specific VSA antibody levels, while more transient and limited increases in levels of antibodies to VSA expressed by other parasite isolates were also seen. Plasma VSA antibody levels were positively correlated with the age of the healthy plasma donors but negatively correlated with the age of the parasite donors (the malaria patient). The data from this first detailed longitudinal study of acquisition of VSA antibodies support the hypothesis that naturally acquired protective immunity to P. falciparum malaria is mediated, at least in part, by VSA-specific antibodies.

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