Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
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Stand-by treatment is the use of anti-malaria drugs carried for self-administration when fever and flu-like symptoms occur and prompt medical attention is not available. This paper aims to review the rationale for the stand-by therapy concept, the range of options available, the factors influencing the choice of therapy and the efficacy and toxicity of the various agents available in the light of ever increasing resistance to conventional drugs. The use of chloroquine as a possible stand-by treatment is limited because of widespread chloroquine resistance and the problem is further compounded by the increasing prevalence of parasites resistant to antifolate/sulpha drug combinations, particularly in South-East Asia and South America. Mefloquine is a promising agent for presumptive malarial treatment with limited foci of drug resistance, notably in Thailand. Mefloquine therapy has been associated with adverse events, mostly minor but with occasional neuropsychiatric events. The use of halofantrine, hitherto often recommended as a stand-by treatment, has been curtailed after recent research reports demonstrated that the drug may cause prolongation of the QTc interval. Current experience with stand-by therapy is limited and studies are in progress to elucidate the exact circumstances under which travellers actually use their emergency medication. Stand-by treatment is an option for clearly defined situations while prophylaxis remains the safest choice for travellers to areas of high transmission.
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PMID:Stand-by treatment of malaria in travellers: a review. 800 55

In Kenya, health professionals compared prospective data on 193 suspected malaria patients at the Eldoret District Hospital during February-March, 1992, with retrospective data on 120 suspected malaria cases at the same hospital during November-December, 1991, to examine the protocol on the management of suspected malaria cases. Between these 2 periods, physicians introduced a simple algorithm to follow in suspected malaria cases. The use of quinine as the 1st choice drug fell considerably between the 2 periods (54.2-19%). There was an increase in the use of chloroquine as the 1st choice drug for uncomplicated malaria (38.4-63.9%). The proportion of blood smear positive patients increased (27.5-51.3%), probably because the department technician was more careful conducting repeat blood smears than were technicians at the busy hospital laboratory. Blood smear negative patients were less likely to automatically receive any antimalarial treatment or quinine in 1992 than in 1991 (14.6% vs. 47.5% and 4.1% vs. 30.9%, respectively). The proportion of patients whose final diagnosis was an illness other than malaria was higher in 1992 than in 1991 (19.7% vs. 15.8%). No clear diagnosis other than flu-like illness was the case for 28 (14.5%) of the prospective patients. The tendency for clinicians to accept a diagnosis of malaria without enough evidence to confirm it can have the damaging effect of masking other serious diagnoses (e.g., dysentery [8 cases], meningitis [6 cases], and HIV infection [2 case]). These findings show that hospital physicians should develop simple protocols for inpatient management of suspected malaria cases, a properly quantified blood smear should be done of all suspected malaria cases to confirm or refute the diagnosis, and chloroquine should be the 1st line of treatment in the Kenyan highlands, until considerable parasite resistance is confirmed.
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PMID:Management of malaria before and after introduction of a treatment protocol at the Eldoret District Hospital. 805 55

Mankind has been stricken with "major" epidemic diseases throughout its history. The most serious among them immediately threaten man's life e.g. plague, cholera, smallpox, typhus, and dysentery, besides, there are others which take a slower course e.g. lues, leprosy, leishmaniasis, tuberculosis, and malaria. Yet, the "lesser" epidemic diseases like diphtheria, scarlet fever, mumps, pneumococcosis, influenza, and most recently AIDS may also turn into "major" ones. Originally, man exclusively depended on his genetic makeup for protection, and being particularly prone to attacks of disease he was subject to natural selection. Thus, only one human species survived, the homo sapiens. Interbreeding achieved biologic adaptation and created a balanced genetic polymorphism. Advancing in his degree of civilization, man formed groups, developed clothing, fire, houses, and tools, and his increasing cultural awareness allowed him to migrate from the tropical climates to more temperate, and less disease-infested zones. Immigration and wars, and the accompanying infections jeopardized and diminished entire populations and eradicated highly developed cultures like that of the American Indians. The plague, coming from Asia, and lues, from America, as well as cholera, influenza, and smallpox spread around the whole globe. Fear and terror led to irrational conclusions and triggered persecutions. The attitude of accepting disease as a God-sent fate (Hiob), or a God-sent punishment suppressed reasonable measures against disease. The necessary official measures have increasingly restricted liberty, and this patronizing treatment needs to be opposed with a higher sense of responsibility. Medical art has developed from more healing towards prophylactic and predictive medicine, which prognosticates the individual susceptibility to particular infections, and other risk factors.
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PMID:[Effect of major epidemics on cultural awareness]. 857 53

Sialic acid on the red cell surface plays a major role in invasion by the malaria parasite Plasmodium falciparum. The NeuAc(alpha 2,3) Gal motif on the O-linked tetrasaccharides of the red cell glycophorins is a recognition site for the parasite erythrocyte-binding antigen (EBA-175). Consequently, the interaction of P. falciparum and the red cell might share homology with that of the influenza virus. The cellular interactions of P. falciparum were examined for their sensitivity to 4-guanidino-2,3-didehydro-D-N-acetyl neuraminic acid (4-guanidino Neu5Ac2en), a potent inhibitor of influenza virus sialidase. Parasite invasion and subsequent development was unaffected by the sialidase inhibitor. The inhibitor did not affect rosette formation of parasite-infected erythrocytes with uninfected cells nor their cytoadherence to C32 melanoma cells. Furthermore, we were unable to confirm the presence of a previously reported parasite sialidase using sensitive fluorometric or haemagglutination assays, neither was any malarial trans-sialidase identified. We conclude that P. falciparum possesses neither sialidase nor trans-sialidase activity and that an inhibitor of influenza virus sialidase has no effect on important cellular interactions of this parasite.
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PMID:Plasmodium falciparum lacks sialidase and trans-sialidase activity. 867 33

B cell deficient animals obtained by various strategies of gene targeting were used to study the B cell development and examine the role of different immune compartments in the immune response to microbes. Study of muMT, JHD, lambda 5T and JHT models of B cell deficiency, was essential in order to understand the role of pre-B cell receptor in B cell development, allelic exclusion and variable gene rearrangement regulation. In the immune response to influenza virus, a protective role of T cells in a total absence of B cell compartment, was revealed by studying the JHD -/- model. Further, it was established that a T cell compartment is sufficient to mediate the recovery from influenza infection. Examination of immune response in muMT and JHD models of definitive B cell deficiency to various blood stage Plasmodia species, showed that whereas B cells are not required for recovery from infection with P. chabaudi adami, P. vinckei petteri and P. chabaudi chabaudi (CB), B cell compartment is important in the later stages of infection with P. chabaudi chabaudi (AS). Studies carried out in muMT model suggested a possible role for T gamma delta subpopulation in the immune response to blood stage malaria parasite. B cell deficiency models are valuable for understanding the normal and pathological immune response. Studies carried out in muMT model indicated that T cell responses are not significantly affected in the absence of B cells. These data can neither rule out a role for B cells in T cell priming, nor in triggering an effective T cell help for humoral response. Study of double homozygous mice deficient for B cells and FAS or IL-2 gene, pinpointed the role of B cells in pathogenesis of lupus-like nephritis and vasculitis from lpr mouse and in hemolytic anemia from IL-2 -/- mouse model, respectively.
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PMID:Immunoglobulin deficient mice generated by gene targeting as models for studying the immune response. 888 29

Antimicrobials are frequently used to prevent infections. Principles of prophylaxis, and antimicrobial prophylaxis in surgery, tuberculosis, acquired immunodeficiency syndrome, influenza A, traveller's diarrhoea, malaria, recurrent otitis media, Haemophilus influenzae type b infection, pertussis, rheumatic fever, and urinary tract infection are described. Various strategies to improve the prophylactic use of antibiotics are discussed. Collaborative efforts among health care disciplines are needed to assure optimal antimicrobial prophylaxis. This should maximize efficacy and minimize adverse effects, the development of bacterial resistance and associated costs.
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PMID:Guidelines for antimicrobial prophylaxis. 893

A little over a decade ago, novel immunostimulating complexes (ISCOMs) were described. This review examines the position and progress that ISCOM technology has achieved in the fields of vaccine research and medicine over this period. Much of the work on ISCOMs has remained in the area of vaccine research where there is still an urgent need for improved adjuvants to help combat important diseases such as AIDS, malaria and influenza. Currently the only widely licensed adjuvants for human use are the aluminium salts, but with the trend towards highly purified subunit vaccines, which are inherently less immunogenic than some of the older vaccines, potent adjuvants capable of promoting specific immune responses are required. ISCOMs are one such technology that offers many of these requirements and as their use in vaccines enters its second decade clinical trials are commencing that will establish whether these submicron, non-living particles composed of saponin, cholesterol, phospholipid and in many cases protein, are useful components for a range of human vaccines.
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PMID:ISCOMs (immunostimulating complexes): the first decade. 893 49

The immunogenicity of a recombinant replication defective adenovirus expressing a major malaria Ag, the circumsporozoite (CS) protein (AdPyCS), was determined using a rodent malaria model. A single immunizing dose of this construct induced a large number of CS-specific CD8+ and CD4+ T cells in the spleens of these animals, particularly when given by the s.c. or i.m. route. A single dose of AdPyCS also induced high titers of Abs to Plasmodium yoelii sporozoites in mice. No other form of presentation of the CS protein given as a single immunizing dose, i.e., irradiated sporozoites, recombinant vaccinia, or influenza virus, etc., elicits comparably high numbers of CS-specific CD8+ T cells. The high concentration of CS-specific CD8+ T cells in the spleen was relatively short-lived, decreasing to half of its original value by 4 wk and to one-third at 8 wk after AdPyCS inoculation. The decrease in splenic CS-specific CD4+ T cells was even more rapid. Most importantly, a single dose of inoculation of AdPyCS into mice rendered them highly resistant to sporozoite challenge, resulting in a 93% inhibition of liver stage development of the parasites. This protective effect was primarily mediated by CD8+ T cells, as shown by depletion of this T cell population, while depletion of the CD4+ T cell population had only a minor effect on anti-plasmodial activity. Moreover, the inoculation of mice with AdPyCS induces sterile immunity in a significant proportion of mice, preventing the occurrence of parasitemia.
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PMID:Single immunizing dose of recombinant adenovirus efficiently induces CD8+ T cell-mediated protective immunity against malaria. 901 69

The current status and future prospects of vaccines for adults are discussed. For every child in America who dies of a vaccine-preventable disease, about 400 adults die of such a disease. Evidence of the merit of influenza vaccination continues to accumulate, yet < 30% of high-risk people younger than 65 have been vaccinated. Use of pneumococcal vaccine lags behind that of influenza vaccine. Serious discrepancies in immunization levels exist among different segments of U.S. adult society. A vaccination status assessment is now recommended for everyone reaching the age of 50. New vaccines are available to prevent varicella, hepatitis A, and typhoid fever. There are now two formulations of hepatitis A virus vaccine; adult users of these vaccines include travelers, people relocating to areas with poor sanitation, military personnel, laboratory workers, and hemophiliacs. New rabies vaccines may be the next vaccines to be used primarily in adults. Vaccines against pertussis, Lyme disease, cholera, herpes simplex, malaria, other infectious diseases, and cancer are in various stages of development. For health care personnel in areas where there is a strong likelihood of Mycobacterium tuberculosis transmission and infection, BCG vaccination is recommended. The risk of immunization to a person infected with the human immunodeficiency virus is likely outweighed by the protection offered against other health threats. Health systems should select tetanus-diphtheria toxoids adsorbed for their formularies for immunizing adults, not monovalent tetanus toxoid. Vaccines are available to prevent a growing list of infectious diseases but are underused in adults.
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PMID:Status and future of vaccines for adults. 904 59

The preeminent infectious threat to unwary tropical travelers, malaria is a preventable, mosquito-borne protozoan infection of red blood cells, which causes fever, anemia, respiratory failure, coma, and death. Malaria is a true medical emergency that requires rapid diagnosis and treatment. Unfortunately, in two thirds of tropical travelers who die of malaria, either treatment is delayed or the diagnosis is simply missed. Every tropical traveler with fever or unexplained, flu-like illness must be assumed to have life-threatening malaria and must have thick and thin blood smears immediately examined to confirm the diagnosis.
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PMID:Malaria. 905 73


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