Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0348321 (Haemophilus)
 15,372 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Infections by parasitic protozoans and helminths are a major world-wide health concern, but no vaccines exist to the major human parasitic diseases, such as malaria, African trypanosomiasis, amebiasis, leishmaniasis, schistosomiasis, and lymphatic filariasis. Recent studies on a number of parasites indicate that immune responses to parasites in infected animals and humans are directed to glycan determinants within cell surface and secreted glycoconjugates and that glycoconjugates are important in host-parasite interactions. Because of the tremendous success achieved recently in generating carbohydrate-protein conjugate vaccines toward microbial infections, such as Haemophilus influenzae type b, there is renewed interest in defining parasite-derived glycans in the prospect of developing conjugate vaccines and new diagnostics for parasitic infections. Parasite-derived glycans are compelling vaccine targets because they have structural features that distinguish them from mammalian glycans. There have been exciting new developments in techniques for glycan analysis and the methods for synthesizing oligosaccharides by chemical or combined chemo-enzymatic approaches that now make it feasible to generate parasite glycans to test as vaccine candidates. Here, we highlight recent progress made in elucidating the immunogenicity of glycans from some of the major human and animal parasites, the potential for developing conjugate vaccines for parasitic infections, and the possible utilization of these novel glycans in diagnostics.
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PMID:Antigenic glycans in parasitic infections: implications for vaccines and diagnostics. 1515 69

The health burden and mortality caused by infections during childhood remain large in sub-Saharan Africa. We performed a review of the causes of hospitalization and death among children admitted to a pediatric teaching hospital in Bamako, Mali. Medical records of children admitted throughout 2000 were systematically sampled and abstracted for demographics, diagnosis, hospital course, and disposition. A sample of 1644 charts, from 5001 admitted children, were abstracted. The median age was 8 months. Half of the children had a febrile illness. All diagnoses were made clinically. The annual incidence per 100,000 and case fatality rates of the four most common serious infections, excluding malaria, were as follows: pneumonia, 165 (12 per cent); sepsis, 75 (37 per cent); meningitis, 71 (20 per cent); and enteric fever, 14 (12 per cent). An estimated 1300 children were admitted with thick-smear confirmed malaria; at least 64 per cent met World Health Organization criteria for severe malaria and 11 per cent died. Seventy-one per cent of admissions were due to infections. Overall 21 per cent of children admitted died in the hospital, most within the first 3 days of admission. Infectious diseases remain the primary cause of hospitalization among Malian children and frequently lead to death. A substantial proportion of this morbidity and mortality is probably attributable to vaccine-preventable diseases, such as Haemophilus influenzae type B, Streptococcus pneumoniae, and Neisseria meningitidis. Prospective surveillance using microbiological data is needed to delineate the organism-specific burdens.
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PMID:The causes of hospital admission and death among children in Bamako, Mali. 1523 92

Biodegradable microspheres may represent a potential tool for the delivery of combination vaccines. We demonstrate strong immunogenicity of five co-encapsulated antigens after a single subcutaneous inoculation in guinea pigs. Tetanus- and diphtheria-specific antibodies were not significantly affected by the presence of either antigen or by the presence of pertussis or Haemophilus influenzae type b (Hib) antigens. Microsphere formulations gave better protection against diphtheria toxin than did two injections of a licensed tetravalent vaccine. Finally, a synthetic malaria peptide antigen (PfCS) also encapsulated in PLGA microspheres increased diphtheria and tetanus-specific immunity and improved protection against diphtheria. These findings demonstrate the potential of microspheres as an alternative and promising strategy for combination vaccines with a further aptitude in reducing the number of inoculations required to gain functional immunity.
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PMID:Childhood and malaria vaccines combined in biodegradable microspheres produce immunity with synergistic interactions. 1545 93

Vaccines are a key contributor to public health, especially in developing countries. Despite numerous demonstrations of the cost-effectiveness of immunisation, vaccines spending accounted for only 1.7% of the total pharmaceutical market in 2002, when UNICEF estimated that 34 million children were not reached by routine immunisation, most of them in developing countries. Several international organizations or initiatives, like the Global Alliance for Vaccines and Immunisation (GAVI), have defined a long-term goal of universal immunisation in developing countries. There is an urgent need to estimate the financial resources required to meet this goal. The objective of this study was to anticipate the funding needs for childhood immunisation in developing countries over the 2004-2014 period. The study scope includes all the 75 countries eligible for support from GAVI, and covers existing vaccines that are considered as a priority for GAVI (DTP (diphtheria, tetanus, pertussis), hepatitis B, Haemophilus influenzae type b (as a stand alone presentation or in combination with DTP) and yellow fever) as well as future vaccines (meningitis A and C, rotavirus, human papilloma virus (HPV), malaria, Streptococcus pneumoniae and tuberculosis) likely to be available within the 10-year period. We developed a methodology to estimate the number of doses required, based on disease prevalence and incidence, target populations, introduction dates of new vaccines, coverage dynamics and dosing regimen. The introduction price and price evolution of vaccines over time were modelled, taking into account the type of vaccine, the expected return on investment from vaccine manufacturers and the competitive landscape. Non-vaccine costs (capital costs and non-vaccine recurrent costs) were estimated based on the number of people immunised and number of doses dispensed, using available case studies as a reference. According to the optimal scenario that would consider the provision of all vaccines to all relevant developing countries as soon as they are available, funding requirements to cover the associated total costs over the 10-year period were estimated to be about US$ 30 billion. Vaccines-related costs represent the largest share, with estimated costs of US$ 21 billion (among which 18 billion for new vaccines), the remaining needs being split between capital costs and other recurrent costs. Accounting for the main imponderables (such as delay in vaccines launch compared to industry plans) as well as probable phasing of vaccine introduction in countries, the total costs of immunisation would be reduced to US$ 14-17 billion over the same period. Vaccines-related costs represent the largest share (US$ 7.1-9.3 billion, among which 4.3-6.5 billion for new vaccines). This study advocates for the anticipation of the substantial financial resources needed to (a) purchase and introduce these vaccines in the developing countries in order to reduce the time lag between availability in industrialised and developing countries; and (b) stimulate vaccine researchers and manufacturers to continue research and development of much needed vaccines for the developing world.
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PMID:Financial requirements of immunisation programmes in developing countries: a 2004-2014 perspective. 1597 69

Resistance of the most virulent human malaria parasite, Plasmodium falciparum, to antifolates is spreading with increasing speed, especially in Africa. Antifolate resistance is mainly caused by point mutations in the P. falciparum dihydropteroate synthase (DHPS) and dihydrofolate reductase (DHFR) target proteins. Homology models of the bifunctional P. falciparum dihydropterin pyrophosphokinase-dihydropteroate synthase (PPPK-DHPS) enzyme as well as the separate domains complete with bound substrates were constructed using the crystal structures of Saccharomyces cerevisiae (PPPK-DHPS), Mycobacterium tuberculosis (DHPS), Bacillus anthracis (DHPS), and Escherichia coli (PPPK) as templates. The resulting structures were subsequently solvated and refined using molecular dynamics. The active site residues of DHPS are highly conserved in S. cerevisiae, M. tuberculosis, E. coli, S. aureus, and B. anthracis, an attribute also shared by P. falciparum DHPS. Sulfadoxine was superimposed into the equivalent position of the p-aminobenzoic acid substrate and its binding parameters were refined using minimization and molecular dynamics. Sulfadoxine appears to interact mainly with P. falciparum DHPS mainly through hydrophobic interactions. Rational explanations are provided by the model for the sulfadoxine resistance-causing effects of four of the five known mutations in P. falciparum DHPS. A possible structure for the bifunctional PPPK-DHPS was derived from the structure from the S. cerevisiae bifunctional enzyme. The active site residues of P. falciparum PPPK are also conserved when compared to S. cerevisiae, Haemophilus influenzae, and E. coli. The informative nature of these models opens up avenues for structure-based drug design approaches toward the development of alternative and more effective inhibitors of P. falciparum PPPK-DHPS.
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PMID:Elucidation of sulfadoxine resistance with structural models of the bifunctional Plasmodium falciparum dihydropterin pyrophosphokinase-dihydropteroate synthase. 1651 68

Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: ABT-510, adalimumab, alefacept, alemtuzumab, AMG-531, anakinra, armodafinil, asenapine maleate, atazanavir sulfate, atorvastatin; Bortezomib, bosentan; CEB-1555, cetuximab, ciclesonide, clodronate, CT-011; Darifenacin hydrobromide, desloratadine; E-7010, ecallantide, eculizumab, efalizumab, eltrombopag, erlotinib hydrochloride, eslicarbazepine acetate, eszopiclone, ezetimibe; Febuxostat, fosamprenavir calcium, fulvestrant; Gefitinib, genistein; Haemophilus influenzae B vaccine, human papillomavirus vaccine; Imatinib mesylate, insulin glargine; Lenalidomide, liposomal cisplatin; MAb G250, mapatumumab, midostaurin, MP4, mycophenolic acid sodium salt; Natalizumab, neridronic acid, NSC-330507; Oblimersen sodium, ofatumumab, omalizumab, oral insulin, oregovomab; Paliperidone, parathyroid hormone (human recombinant), peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pegylated arginine deiminase 20000, pemetrexed disodium, pimecrolimus, pitavastatin, pneumococcal 7-valent conjugate vaccine, prasterone, pregabalin, pumosetrag hydrochloride; Recombinant malaria vaccine, retigabine, rivaroxaban, Ro-26-9228, romidepsin, rosuvastatin calcium, rotavirus vaccine; SGN-30, sitaxsentan sodium, solifenacin succinate, sorafenib, sunitinib malate; Tadalafil, tegaserod maleate, temsirolimus, TER-199, tifacogin, tiludronic acid, tiotropium bromide; Vildagliptin, VNP-40101M, vorinostat; YM-150, yttrium 90 (90Y) ibritumomab tiuxetan; Zanolimumab, zoledronic acid monohydrate.
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PMID:Gateways to clinical trials. 1681 Mar 45

Sickle cell disease is a genetic disease most common in blacks. We retrospectively collected records for patients with sickle cell disease who were seen from January 2002 through September 2006 to assess the care provided for this disease at Charles de Gaulle University Children's Hospital of Ouagadougou. In all, 88 patients were monitored quarterly at outpatient visits for sickle cell disease, in the absence of any crisis. Their age ranged from 6 months to 16 years, with an average age of 7. There were more boys than girls, with a sex ratio of 1.44. The distribution according to sickle cell genotype showed that SC accounted for 62% of cases, while SS forms were more frequent until the age of 5. All children have received the immunizations in the standard Expanded Programme on Immunization (EPI) [diphtheria, tetanus, pertussis, polio, measles and yellow fever]. The immunization rates for non-EPI vaccines including hepatitis B, Haemophilus influenzae B, Salmonella typhi, meningitis, pneumonia and the combined vaccine against measles, mumps and rubella ranged from 94 to 100%. A prophylactic anti-anaemic agent was made with folic acid often associated with iron. In addition, patients receive malaria chemoprophylaxis. Chloroquine was initially provided, and since 2006, children have been receiving sulfadoxine-pyrimethamine. Our encouraging results deserve reinforcement in the short-term - at the local level by neonatal screening, the creation of an immunization unit, and the systematization of antibiotic prophylaxis, and in the medium-term by implementation of a National sickle cell disease programme to help meet the objective of a 40% reduction in mortality among affected children younger than 5 years by 2015, set by the Sickle Cell Disease International Organization.
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PMID:[Pediatric management of sickle cell disease: experience at the Charles de Gaulle University Children's Hospital in Ouagadougou (Burkina Faso)]. 1918 29

The complement system comprises several fluid-phase and membrane-associated proteins. Under physiological conditions, activation of the fluid-phase components of complement is maintained under tight control and complement activation occurs primarily on surfaces recognized as "nonself" in an attempt to minimize damage to bystander host cells. Membrane complement components act to limit complement activation on host cells or to facilitate uptake of antigens or microbes "tagged" with complement fragments. While this review focuses on the role of complement in infectious diseases, work over the past couple of decades has defined several important functions of complement distinct from that of combating infections. Activation of complement in the fluid phase can occur through the classical, lectin, or alternative pathway. Deficiencies of components of the classical pathway lead to the development of autoimmune disorders and predispose individuals to recurrent respiratory infections and infections caused by encapsulated organisms, including Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae. While no individual with complete mannan-binding lectin (MBL) deficiency has been identified, low MBL levels have been linked to predisposition to, or severity of, several diseases. It appears that MBL may play an important role in children, who have a relatively immature adaptive immune response. C3 is the point at which all complement pathways converge, and complete deficiency of C3 invariably leads to severe infections, including those caused by meningococci and pneumococci. Deficiencies of the alternative and terminal complement pathways result in an almost exclusive predisposition to invasive meningococcal disease. The spleen plays an important role in antigen processing and the production of antibodies. Splenic macrophages are critical in clearing opsonized encapsulated bacteria (such as pneumococci, meningococci, and Escherichia coli) and intraerythrocytic parasites such as those causing malaria and babesiosis, which explains the fulminant nature of these infections in persons with anatomic or functional asplenia. Paramount to the management of patients with complement deficiencies and asplenia is educating patients about their predisposition to infection and the importance of preventive immunizations and seeking prompt medical attention.
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PMID:Infections of people with complement deficiencies and patients who have undergone splenectomy. 2093 72

In 2010 the Bill & Melinda Gates Foundation announced a $10 billion commitment over the next ten years to increase access to childhood vaccines in the world's poorest countries. The effort was labeled the "Decade of Vaccines." This study estimates both the short- and long-term economic benefits from the introduction and increased use of six vaccines in seventy-two of the world's poorest countries from 2011 to 2020. Increased rates of vaccination against pneumococcal and Haemophilus influenzae type b pneumonia and meningitis, rotavirus, pertussis, measles, and malaria over the next ten years would save 6.4 million lives and avert 426 million cases of illness, $6.2 billion in treatment costs, and $145 billion in productivity losses. Monetary estimates based on this type of analysis can be used to determine the return on investment in immunization from both the international community and local governments, and they should be considered in policy making.
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PMID:Estimated economic benefits during the 'decade of vaccines' include treatment savings, gains in labor productivity. 2197 49

Pneumonia kills more children than any other disease--more than HIV/AIDS, malaria, and measles combined. Introduction of vaccines against pneumococcus and Haemophilus influenzae type b (the most important causes of severe pneumonia in young children), increasing resistance to antibiotics, and changes in HIV prevalence will likely change patterns of pneumonia etiology in developing countries. Studies such as Pneumonia Etiology Research for Child Health (PERCH) that take advantage of new diagnostic technologies are needed to provide an updated and more precise description of the microbial causes of pneumonia and to inform decisions around treatment algorithms and vaccine development and introduction. In recognition of its importance for global health and especially its significance as an ongoing cause of gross inequity in risks, The Bill & Melinda Gates Foundation has made pneumonia an important part of its global health strategy and PERCH a centerpiece of its Pneumonia Program.
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PMID:Childhood pneumonia as a global health priority and the strategic interest of the Bill & Melinda Gates Foundation. 2240 37


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