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Brazilian purpuric fever

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Brazilian purpuric fever ( BPF ) is an illness of children caused by the bacterium Haemophilus influenzae biogroup aegyptius which is ultimately fatal due to sepsis . BPF was first recognized in the São Paulo state of Brazil in 1984. At this time, young children between the ages of 3 months and 10 years were contracting a strange illness which was characterized by high fever and purpuric lesions on the body. These cases were all fatal, and originally thought to be due to meningitis . It was not until the autopsies were conducted that the cause of these deaths was confirmed to be infection by H. influenzae aegyptius . Although BPF was thought to be confined to Brazil, other cases occurred in Australia and the United States during 1984–1990.

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36-396: Haemophilus species are non-spore-forming gram-negative coccobacilli . They lack motility and are aerobic or facultatively anaerobic. They require preformed growth factors that are present in blood, specifically hemin (X factor) and NAD or NADP (V factor). The bacterium grows best at 35–37 °C and has an optimal pH of 7.6. Haemophilus species are obligate parasites and are part of

72-437: A common case of conjunctivitis, H. aegyptius is not susceptible to the antibiotic eye drops that are being used to treat it. This treatment is ineffective because it treats only the local ocular infection, whereas if it progresses to BPF, systemic antibiotic treatment is required. Although BPF is susceptible to many commonly used antibiotics, including ampicillin , cefuroxime , cefotaxime , rifampin , and chloramphenicol , by

108-471: A follow-up to an IM or IV injection. For IV and IM injections, ampicillin is kept as a powder that must be reconstituted. IV injections must be given slowly, as rapid IV injections can lead to convulsive seizures . Ampicillin is one of the most used drugs in pregnancy, and has been found to be generally harmless both by the Food and Drug Administration in the U.S. (which classified it as category B ) and

144-798: A skin rash. Ampicillin is comparatively less toxic than other antibiotics, and side effects are more likely in those who are sensitive to penicillins and those with a history of asthma or allergies . In very rare cases, it causes severe side effects such as angioedema , anaphylaxis, and C. difficile infection (that can range from mild diarrhea to serious pseudomembranous colitis ). Some develop black "furry" tongue . Serious adverse effects also include seizures and serum sickness . The most common side effects, experienced by about 10% of users are diarrhea and rash. Less common side effects can be nausea , vomiting , itching , and blood dyscrasias . The gastrointestinal effects, such as hairy tongue, nausea, vomiting, diarrhea, and colitis, are more common with

180-416: A study conducted by Barbosa et al. , a 60 kilodalton hemagglutinating extracellular product was suggested to be the major pathogenic factor linked to the hemorrhagic manifestations of BPF. This molecule was found to be absorbable by human O-type erythrocytes. After the molecule had been injected into rabbits, they showed reactions similar to that of BPF patients. Further research is being conducted to determine

216-413: Is contraindicated in those with a hypersensitivity to penicillins , as they can cause fatal anaphylactic reactions. Hypersensitivity reactions can include frequent skin rashes and hives , exfoliative dermatitis , erythema multiforme , and a temporary decrease in both red and white blood cells . Ampicillin is not recommended in people with concurrent mononucleosis, as over 40% of patients develop

252-457: Is distributed through most tissues, though it is concentrated in the liver and kidneys. It can also be found in the cerebrospinal fluid when the meninges become inflamed (such as, for example, meningitis). Some ampicillin is metabolized by hydrolyzing the beta-lactam ring to penicilloic acid , though most of it is excreted unchanged. In the kidneys, it is filtered out mostly by tubular secretion ; some also undergoes glomerular filtration , and

288-525: Is endogenously produced in the human body, for example during the turnover of old red blood cells . It can form inappropriately as a result of hemolysis or vascular injury. Several proteins in human blood bind to hemin, such as hemopexin and serum albumin . A lyophilised form of hemin is used as a pharmacological agent in certain cases for the treatment of porphyria attacks, particularly in acute intermittent porphyria . Administration of hemin can reduce heme deficits in such patients, thereby suppressing

324-440: Is normally used to treat cholera and typhoid fever, lowering the immunological response that the body has to mount. Ampicillin is in the penicillin group of beta-lactam antibiotics and is part of the aminopenicillin family. It is roughly equivalent to amoxicillin in terms of activity. Ampicillin is able to penetrate gram-positive and some gram-negative bacteria. It differs from penicillin G , or benzylpenicillin, only by

360-612: Is not well established but it is thought that patients become pharyngeal or conjunctival carriers of H. aegyptius , which is followed by spreading to the bloodstream. This hypothesis is supported by the isolation of from both the conjunctiva and oropharynx of documented BPF cases with H. aegyptius bacteremia. Possible virulence factors of H. aegyptius include lipooligosaccharides (LOS), capsular polysaccharides, pilus proteins (mediates adhesion to mucosal membrane), immunoglobulin A1 (IgA1), membrane associated proteins, and extracellular proteins. In

396-410: Is sometimes used in combination with other antibiotics that have different mechanisms of action, like vancomycin , linezolid , daptomycin , and tigecycline . Ampicillin can be administered by mouth , an intramuscular injection (shot) or by intravenous infusion . The oral form, available as capsules or oral suspensions, is not given as an initial treatment for severe infections, but rather as

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432-455: Is used by mouth, by injection into a muscle , or intravenously. Common side effects include rash, nausea, and diarrhea. It should not be used in people who are allergic to penicillin . Serious side effects may include Clostridioides difficile colitis or anaphylaxis . While usable in those with kidney problems , the dose may need to be decreased. Its use during pregnancy and breastfeeding appears to be generally safe. Ampicillin

468-407: Is used to treat infections by many gram-positive and gram-negative bacteria . It was the first "broad spectrum" penicillin with activity against gram-positive bacteria, including Streptococcus pneumoniae , Streptococcus pyogenes , some isolates of Staphylococcus aureus (but not penicillin-resistant or methicillin-resistant strains ), Trueperella , and some Enterococcus . It is one of

504-549: The Therapeutic Goods Administration in Australia (which classified it as category A ). It is the drug of choice for treating Listeria monocytogenes in pregnant women, either alone or combined with an aminoglycoside. Pregnancy increases the clearance of ampicillin by up to 50%, and a higher dose is thus needed to reach therapeutic levels. Ampicillin crosses the placenta and remains in

540-422: The amniotic fluid at 50–100% of the concentration in maternal plasma ; this can lead to high concentrations of ampicillin in the newborn. While lactating mothers secrete some ampicillin into their breast milk, the amount is minimal. In newborns, ampicillin has a longer half-life and lower plasma protein binding. The clearance by the kidneys is lower, as kidney function has not fully developed. Ampicillin

576-488: The hemoglobin of human blood. Hemin is protoporphyrin IX containing a ferric iron (Fe ) ion with a coordinating chloride ligand. Chemically, hemin differs from the related heme-compound hematin chiefly in that the coordinating ion is a chloride ion in hemin, whereas the coordinating ion is a hydroxide ion in hematin. The iron ion in haem is ferrous (Fe ), whereas it is ferric (Fe ) in both hemin and hematin. Hemin

612-403: The activity of delta-amino-levulinic acid synthase (a key enzyme in the synthesis of the porphyrins) by biochemical feedback, which in turn reduces the production of porphyrins and of the toxic precursors of heme. In such pharmacological contexts, hemin is typically formulated with human albumin prior to administration by a medical professional, to reduce the risk of phlebitis and to stabilize

648-568: The cell wall. It inhibits the third and final stage of bacterial cell wall synthesis in binary fission , which ultimately leads to cell lysis ; therefore, ampicillin is usually bacteriolytic . Ampicillin is well-absorbed from the GI tract (though food reduces its absorption), and reaches peak concentrations in one to two hours. The bioavailability is around 62% for parenteral routes. Unlike other penicillins, which usually bind 60–90% to plasma proteins , ampicillin binds to only 15–20%. Ampicillin

684-487: The compound, which is potentially reactive if allowed to circulate in free-form. Such pharmacological forms of hemin are sold under a range of trade names including the trademarks Panhematin and Normosang. Hemin was first crystallized out of blood in 1853, by Ludwik Karol Teichmann . Teichmann discovered that blood pigments can form microscopic crystals. Thus, crystals of hemin are occasionally referred to as 'Teichmann crystals'. Hans Fischer synthesized hemin, for which he

720-399: The conjunctival secretions of the children who were infected with conjunctivitis. 19 of those children developed BPF following the conjunctivitis. Other modes of transmission include contact with the conjunctival discharges of infected people, ophthalmic instruments which have not been properly sterilized, sharing eye makeup applicators or multiple-dose eye medications. The pathogenesis of BPF

756-561: The face and extremities, cyanosis , rapid necrosis of soft tissue, particularly the hands, feet, nose, and ears. Analysis of the fatalities due to BPF showed hemorrhage in the skin, lungs, and adrenal glands. Histopathology showed hemorrhage, intravascular microthrombi and necrosis in the upper dermis, renal glomeruli, lungs, and hepatic sinusoids. The risk factors associated with BPF are not well known. However, it has been suggested that children under 5 years of age are more susceptible to BPF since they lack serum bactericidal activity against

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792-589: The few antibiotics that works against multidrug resistant Enterococcus faecalis and E. faecium . Activity against gram-negative bacteria includes Neisseria meningitidis , some Haemophilus influenzae , and some of the Enterobacteriaceae (though most Enterobacteriaceae and Pseudomonas are resistant). Its spectrum of activity is enhanced by co-administration of sulbactam , a drug that inhibits beta lactamase , an enzyme produced by bacteria to inactivate ampicillin and related antibiotics. It

828-493: The growth of Haemophilus influenzae . Ampicillin Ampicillin is an antibiotic belonging to the aminopenicillin class of the penicillin family. The drug is used to prevent and treat several bacterial infections , such as respiratory tract infections , urinary tract infections , meningitis , salmonellosis , and endocarditis . It may also be used to prevent group B streptococcal infection in newborns. It

864-476: The infected person resides in Brazil, it is mandatory that the infection is reported to the health authority so that a proper investigation of the contacts can be completed. This investigation will help to determine the probable source of the infection. It is extremely difficult to successfully treat BPF, mainly because of the difficulty obtaining a proper diagnosis. Since the disease starts out with what seems to be

900-467: The infection. Older children and adults have much higher titers of bactericidal antibodies, which serve as a protective measure. Also children residing in warmer geographic areas have been associated with a higher risk of BPF infection. The eye gnat ( Liohippelates ) was thought to be the cause of the conjunctivitis epidemic which occurred in Mato Grosso do Sul in 1991. These gnats were extracted from

936-498: The mechanisms involved with the other virulence factors of H. aegyptius. The overall pathogenesis of BPF probably involves multiple steps and a number of bacterial factors. A positive BPF diagnosis includes the clinical symptoms (mainly the fever, purpuric lesions, and rapid progression of the disease), isolation of Haemophilus Influenzae Biogroup aegyptius from blood, and negative laboratory tests for Neisseria meningitidis . The negative tests for Neisseria meningitidis rules out

972-447: The normal flora of the human upper respiratory tract. In documented BPF cases, the symptoms include high fever (101.3 °F/38,5 °C or higher), nausea, vomiting, severe abdominal pain, septic shock, and ultimately death. A history of conjunctivitis 30 days prior to the onset of fever was also present in the documented BPF cases. The physical presentation of children infected with BPF include purpuric skin lesions affecting mainly

1008-404: The oral form of penicillin. Other conditions may develop up several weeks after treatment. Ampicillin overdose can cause behavioral changes, confusion , blackouts, and convulsions, as well as neuromuscular hypersensitivity, electrolyte imbalance , and kidney failure . Ampicillin reacts with probenecid and methotrexate to decrease renal excretion . Large doses of ampicillin can increase

1044-417: The possibility of the symptoms being caused by meningitis, since the clinical presentations of the two diseases are similar. The basic method for control of the conjunctivitis includes proper hygiene and care for the affected eye. If the conjunctivitis is found to be caused by H. aegyptius Biogroup III then prompt antibiotic treatment preferably with rifampin has been shown to prevent progression to BPF. If

1080-404: The presence of an amino group. This amino group, present on both ampicillin and amoxicillin, helps these antibiotics pass through the pores of the outer membrane of gram-negative bacteria, such as Escherichia coli , Proteus mirabilis , Salmonella enterica , and Shigella . Ampicillin acts as an irreversible inhibitor of the enzyme transpeptidase , which is needed by bacteria to make

1116-670: The rest is excreted in the feces and bile . Hetacillin and pivampicillin are ampicillin esters that have been developed to increase bioavailability. Ampicillin has been used extensively to treat bacterial infections since 1961. Until the introduction of ampicillin by the British company Beecham , penicillin therapies had only been effective against gram-positive organisms such as staphylococci and streptococci . Ampicillin (originally branded as "Penbritin") also demonstrated activity against gram-negative organisms such as H. influenzae , coliforms , and Proteus spp. Ampicillin

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1152-441: The risk of bleeding with concurrent use of warfarin and other oral anticoagulants, possibly by inhibiting platelet aggregation. Ampicillin has been said to make oral contraceptives less effective, but this has been disputed. It can be made less effective by other antibiotic, such as chloramphenicol , erythromycin , cephalosporins , and tetracyclines . For example, tetracyclines inhibit protein synthesis in bacteria, reducing

1188-416: The target against which ampicillin acts. If given at the same time as aminoglycosides, it can bind to it and inactivate it. When administered separately, aminoglycosides and ampicillin can potentiate each other instead. Ampicillin causes skin rashes more often when given with allopurinol . Both the live cholera vaccine and live typhoid vaccine can be made ineffective if given with ampicillin. Ampicillin

1224-480: The time it is diagnosed the disease has progressed too much to be effectively treated. However, with the fast rate of progression of BPF it is unlikely that it will be successfully treated. With antibiotic therapy, the mortality rate of BPF is around 70%. Hemin Hemin ( haemin ; ferric chloride heme) is an iron -containing porphyrin with chlorine that can be formed from a heme group, such as heme B found in

1260-519: Was awarded the Nobel Prize in Chemistry in 1930. Fischer's procedure involves treating defibrinated blood with a solution of sodium chloride in acetic acid. Hemin can be produced from hemoglobin by the so-called Teichmann test , when hemoglobin is heated with glacial acetic acid (saturated with saline). This can be used to detect blood traces. Hemin is considered the "X factor" required for

1296-485: Was discovered in 1958 and came into commercial use in 1961. It is on the World Health Organization's List of Essential Medicines . The World Health Organization classifies ampicillin as critically important for human medicine. It is available as a generic medication . Ampicillin used to also be used to treat gonorrhea , but there are now too many strains resistant to penicillins. Ampicillin

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