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Streptococcal pharyngitis: current therapy and criteria for evaluation of new agents.

Penicillin has been the recommended drug of choice in most cases of group A streptococcus (GAS) pharyngitis for nearly 40 years based on its efficacy in the prevention of acute rheumatic fever. Since trials of other drugs for the prevention of rheumatic fever are no longer feasible in the United States, eradication of GAS pharyngitis has become the surrogate for their evaluation. On the basis of this criterion, specific therapeutic regimens have been recommended, and numerous other drugs have gained approval as alternatives to penicillin. Current therapeutic issues include possible decreased efficacy of penicillin, timing of the initiation of therapy, and drugs of choice for patients whose treatment fails, who are chronic carriers, or who have frequent infections. Criteria for assessment of new drugs include clinical response, likelihood of prevention of rheumatic fever, rates of relapse and recurrent infection, and drug safety. The establishment of uniform guidelines and definitions of response for new drug evaluations by the Infectious Diseases Society of America should aid in the further assessment of new antibacterial agents as therapy for GAS pharyngitis. However, no data yet suggest that any of these drugs should replace penicillin as the drug of choice.

Anti-Bacterial Agents↗

Nontyphoidal salmonellal septicemia in Gabonese children infected with Schistosoma intercalatum.

Relapses of enteric fever induced by Schistosoma intercalatum have been observed to occur in central Africa. In Libreville, Gabon, 70 children (ages, 2.1-15.9 years) who were seronegative for human immunodeficiency virus and were hospitalized for septicemic salmonellosis underwent rectal biopsy for diagnosis of S. intercalatum infection. A nontyphoidal Salmonella species was isolated from 53 of the 70 patients: Salmonella typhimurium in 14 cases; Salmonella enteritidis in 7 cases; Salmonella galiema in 4 cases; Salmonella arizonae in 3 cases; and other species in 25 cases. Schistosomal eggs were present in the rectal mucosa of 48 (90.6%) of these 53 patients, in 11 (64.7%) of 17 patients with septicemia due to Salmonella typhi or Salmonella paratyphi, and in 21 (38.2%; P < .001) of 55 controls. Clinical symptoms were not different among patients coinfected with S. intercalatum and nontyphoidal Salmonella vs. those with enteric fever. Treatment with antibiotics induced apyrexia only after administration of antiparasitic therapy in 30 patients. These data strongly suggest interactions between S. intercalatum and Salmonella in infected children with clinically severe nontyphoidal salmonellal septicemia.

Adolescent↗

Infectious endocarditis due to non-typhi Salmonella in patients infected with human immunodeficiency virus: report of two cases and review.

Endocarditis is not usually considered a complication of AIDS. Because salmonellal bacteremia is common in HIV-infected patients and because salmonellae have a propensity to adhere to endothelial cells, these patients are at risk of endocarditis and endarteritis. We report two cases of endocarditis due to Salmonella enteritidis and review three previously reported cases. All five patients had underlying heart valve disease and developed fever, breakthrough or relapsing bacteremia, heart murmurs, and cardiac failure; four of five patients were older than 45 years. One patient died, but the other four were successfully treated with beta-lactam agents alone or in combination with aminoglycosides or with ofloxacin (valve replacement was not required). As AIDS patients get older, the number of cases of endocarditis or endarteritis due to Salmonella species may increase, particularly in geographic areas where Salmonella species are prevalent.

AIDS-Related Opportunistic Infections↗

Dobutamine-induced fever.

OBJECTIVE: To report a case of dobutamine-induced fever. PATIENT: A 71-year-old woman with congestive heart failure who developed a fever after receiving dobutamine during two separate hospital admissions. RESULTS: Other possible causes of the fever during the first admission included relapse of staphylococcal sepsis and drug fever from vancomycin or metoclopramide. However, rechallenge with dobutamine on a subsequent admission demonstrated a highly probable relationship between dobutamine and fever. CONCLUSIONS: A strong temporal relationship between dobutamine and fever was noted during the patient's second admission and the case was not complicated by other new medications. No underlying infectious or noninfectious cause of the fever was found. Therefore, when patients receiving dobutamine become febrile, dobutamine should be considered as a possible cause.

Aged↗

[Characteristics of clinical features of tick-borne encephalitis in Crimea].

The analysis of data collected from the clinical epidemiological and virological surveys in 1985-1988 on the incidence of arbovirus infection in population provided evidence for circulation of tick-borne encephalitis (TBE) virus in the Crimea. Etiological relevance of TBE virus in the onset of the diseases was revealed. Clinical picture of TBE in the Crimea is characterized by severe forms and diphasic fever with the relapse running more grave and protracted course.

Disease Reservoirs↗

[Pathogenetic and immunological characteristics of different forms of the Salmonella typhi carrier state].

Infectious granulomas with macrophages containing Salmonella typhi have been detected in the immune organs of the intestine of typhoid patients by means of morphological investigation techniques, immunofluorescent and electron microscopy. This suggests that typhoid granulomas form the basis of S. typhi primary carriership complicated by the relapses of this infection in cases of weakened cell-mediated immunity, which is proved by a decrease in the level of T-lymphocytes and by increased leukocyte migration index in relapses of typhoid fever and in S. typhi primary carriership. At the same time, the formation of S. typhi secondary carriership occurs in the process of the colonization of the altered organs and tissues of the body by S. typhi. This secondary carriership differs from the primary one by a number of pathogenetic signs. The detailed characterization of these two forms of S. typhi carriership is presented.

Bacteriuria↗

Aortic root replacement with pulmonary autograft in children.

Between September 1988 and February 1993, 14 patients whose ages ranged from 3 months to 16 years (mean 11.1 +/- 4.3 years) underwent replacement of the aortic root with the autologous pulmonary root for aortic valve disease. The follow-up was 4 years (cumulative total of 25.2 patient-years). There was no early mortality. Late mortality (one patient) was 7.1% (95% confidence limits 0% to 21%). This patient had juvenile rheumatoid arthritis and died of consequent congestive heart failure with autograft failure 6 months after operation. Event-free survival after 4 years was 78.6% (95% confidence limits 50% to 95%). One patient was reoperated on because of autograft failure caused by a relapse of rheumatic fever. One patient operated on for critical neonatal aortic stenosis has subnormal exercise tolerance because of restrictive cardiomyopathy and pulmonary homograft regurgitation. The other 12 patients were in New York Heart Association functional class I at the end of follow-up. There was no prevalence of bacterial endocarditis. There were no signs of primary structural degeneration of the pulmonary autograft. During follow-up, in eight patients, increased anulus diameter of the pulmonary autograft could be demonstrated by precordial two-dimensional echocardiography, suggesting growth of the autograft. Our experience shows that aortic root replacement with the pulmonary autograft can be done with low mortality and morbidity in children with aortic valve disease. The operation seems to be contraindicated in children with juvenile rheumatoid arthritis because of the risk of recurrence of rheumatic disease in the autograft. The pulmonary autograft has also been shown to be susceptible to recurrence of rheumatic inflammation in children with a history of acute rheumatic fever. Despite pulmonary autograft replacement of the aortic valve in infants with critical valvular aortic stenosis and endocardial fibroelastosis, clinical results may be poor. Growth of the autograft is suggested by echocardiographic follow-up. We consider aortic root replacement with the pulmonary autograft the procedure of choice in children who require aortic valve replacement.

Adolescent↗

The influence of HIV infection on clinical presentation, response to treatment, and outcome in adults with Tuberculous meningitis.

BACKGROUND: Tuberculous meningitis occurs more commonly in human immunodeficiency virus (HIV)-infected individuals than in HIV-uninfected individuals, but whether HIV infection alters the presentation and outcome of tuberculous meningitis is unknown. METHODS: We performed a prospective comparison of the presenting clinical features and response to treatment in 528 adults treated consecutively for tuberculous meningitis (96 were infected with HIV and 432 were uninfected with HIV) in 2 tertiary-care referral hospitals in Ho Chi Minh City, Vietnam. Logistic regression was used to model variables associated independently with HIV infection, 9-month survival, and the likelihood of having a relapse or an adverse drug event. Kaplan-Meier estimates were used to compare survival rates and times to fever clearance, coma clearance, relapse, and adverse events. RESULTS: HIV infection did not alter the neurological presentation of tuberculous meningitis, although additional extrapulmonary tuberculosis was more likely to occur in HIV-infected patients. The 9-month survival rate was significantly decreased in HIV-infected patients (relative risk of death from any cause, 2.91 [95% confidence interval, 2.14-3.96]; P < .001), although the times to fever clearance and coma clearance and the number or timing of relapses or adverse drug events were not significantly different between the groups. CONCLUSIONS: HIV infection does not alter the neurological features of tuberculous meningitis but significantly reduces the survival rate.

Adolescent↗

Unusual bone marrow relapse of Hodgkin's disease with typical Pel-Ebstein fever.

We report the unusual case of a 43-year-old man with a diagnosis of clinical stage I A mixed cellularity Hodgkin's disease (HD), who relapsed 4 years after diagnosis with exclusive bone marrow involvement and a cyclic variation in body temperature typical of Pel-Ebstein fever. In the absence of clinical and laboratory signs of infection, a restaging of the lymphoma was performed. Total-body CT scan revealed no parenchymal or lymph node involvement, while a bone-marrow biopsy was positive for the presence of Reed-Sternberg cells. Therefore, the patient was started on combination chemotherapy, which promptly induced a normalization of the temperature curve. The presence of typical Pel-Ebstein fever, which is reported to be very rare, in association with bone marrow localization as the only site of relapse, suggests a relationship between these two rare manifestations of the disease.

Adult↗

Delayed diagnosis of Ewing's sarcoma of the right humerus initially treated as chronic osteomyelitis: a case report.

We report a case of limited stage Ewing's sarcoma which was initially treated as chronic osteomyelitis for 3 years. A 24-year-old man presented with a one-week history of pain in the right arm and fever, with histology suggestive of osteomyelitis of the affected humerus. He developed multiple relapses of pain and fever; each episode responded to antibiotic treatment. A second biopsy was performed 3 years later and confirmed a diagnosis of Ewing's sarcoma. Despite a 3-year delay in diagnosis, the disease remained localised. This case report highlights an atypical facet of the natural history of Ewing's sarcoma: a response to antibiotic and anti-inflammatory agents, and the limited stage of the disease despite a misdiagnosis of 3 years. This suggests the possibility that anti-inflammatory agents exert an inhibitory effect on the tumour growth. We also highlight the newer histologic and immunologic staining used in the diagnosis of Ewing's sarcoma.

12E7 Antigen↗

Q fever--still a query and underestimated infectious disease.

Coxiella burnetii (C.b.) is a strictly intracellular, Gram-negative bacterium. It causes Q fever in humans and animals worldwide. The animal Q fever is sometimes designated "coxiellosis". This infection has many different reservoirs including arthropods, birds and mammals. Domestic animals and pets, are the most frequent source of human infections. Q fever may appear basically in two forms, acute and chronic (persistent). The latter form of Q fever in animals is characteristic by shedding C.b. into the environment during parturition or abortion. Human Q fever results usually from inhalation of contaminated aerosols originating mostly from tissue and body fluids of infected animals. Q fever may appear in humans either in an acute form accompanied mainly by fever (pneumonia, flu-like disease, hepatitis) or in a chronic form (mainly endocarditis). Diagnosis of Q fever is based on isolation of the agent in cell culture, its direct detection, namely by PCR, and serology. Detection of high phase II antibodies titers 1-3 weeks after the onset of symptoms and identification of IgM antibodies are indicative to acute infection. High phase I IgG antibody titers >800 as revealed by microimmunofluorescence offer evidence of chronic C.b. infection. For acute Q fever, a two-weeks-treatment with doxycycline is recommended as the first-line therapy. In the case of Q fever endocarditis a long-term combined antibiotic therapy is necessary to prevent relapses. Application of Q fever vaccines containing or prepared from phase I C.b. corpuscles should be considered at least for professionally exposed groups of the population. Infections caused by C.b. are spread worldwide and may pose serious and often underestimated health problems in human but also in veterinary medicine. Though during the last decades substantial progress in investigation of C.b. has been achieved and many data concerning this pathogen has been accumulated, some questions, namely those related to the pathogenesis of the disease, remain open.

Acute Disease↗

Recrudescence and relapse in bacterial meningitis of childhood.

Antibiotic therapy of bacterial meningitis in children may be complicated by reappearance of bacteria in cerebrospinal fluid during therapy (recrudescence) or within three weeks after therapy is stopped (relapse). Clinical and laboratory features of six children with recrudescence and of 21 children with relapse were reviewed. These complications occurred mainly in infants less than 2 years of age and comprised less than 1% of all cases of bacterial meningitis. Neither the initial nor the follow-up CSF findings were predictive of recrudescence or relapse. Prolonged or secondary fever was unrelated to these complications. Recrudescence was usually caused by inappropriate therapy whereas relapse after adequate therapy of bacterial meningitis was usually ascribed to persistence of infection in meningeal or parameningeal foci. Relapse did not become manifest until three or more days after discontinuation of therapy. It is concluded that routine examination of CSF at the end of adequate anti-microbial therapy is not necessary or useful when the patient has exhibited a satisfactory clinical response. Furthermore, the commonly recommended observation period of 48 hours in the hospital after discontinuation of therapy is not justified for a patient who has had an uneventful course.

Anti-Bacterial Agents↗

[In vivo evaluation of chloroquine therapeutic efficacy in uncomplicated Plasmodium falciparum malaria in Central African Republic ine 1997 and 1998].

The efficacy of oral chloroquine was assessed in 268 children aged from 6 to 59 months attending pediatric services in regional hospitals between September 1997 and December 1998, located in the five county towns of the sanitary regions of the Central African Republic. Chloroquine was prescribed at 25 mg per kg body weight, and administered over 3 days to patients suffering from uncomplicated malaria. Body temperature and blood smears including parasitaemia were recorded on days 0, 3, 7 and 14. The main objective of the present study was to evaluate the therapeutic efficacy of chloroquine in the treatment of uncomplicated malaria using in vivo tests according to the WHO protocol (1996). The secondary objective was to identify the predictive factors of chloroquine relapses. Early relapses rates were under 15% except in Bangui (40%). A recurrence of parasitaemia with fever, sign of late relapse, was noted in 9% of children in Bambari, 9% in Bangassou, 8% in Bangui, 5% in Bossangoa and 4% in Berberati. The rate of successfully treated patients was between 66% and 75% except in Bangui (36%). Only the places of study and anaemia in days 0 were significant predictive factors of therapeutic relapses. Since the emergence of chloroquine resistance cases to P. falciparum in 1983 in Central African Republic, the phenomenon has increased. According to our results, a strong chloroquine resistance appears in the capital Bangui. Therefore, chloroquine should be replaced there for the first line treatment of uncomplicated P. falciparum malaria. In the provinces, it doesn't seem necessary to change the current chloroquine-based first line treatment.

Administration, Oral↗

Epidemiology of typhoid fever in Mauritius.

BACKGROUND: The epidemiology of typhoid fever in Mauritius was studied to determine whether there was any need for tourists visiting Mauritius to be vaccinated against the disease, and where Mauritians with typhoid fever had been infected. Data on antibiotic susceptibility of Salmonella typhi isolates from Mauritius were also analyzed. METHODS: Since 1997 every time S. typhi is isolated from blood cultures at our laboratory, an epidemiologic inquiry is conducted to determine the likely origin of the infection and the outcome of treatment, and the information collected is recorded. Results of antibiotic susceptibility testing are also noted. Data recorded on cases between 1997 and 2004 were reviewed and analyzed. RESULTS: S. typhi was isolated on 25 occasions during the 8-year period. The infection was likely to have been acquired in Mauritius in only 6 cases (24%). Another 6 cases (24%) occurred in expatriate workers from the Indian subcontinent. Of the 13 Mauritians (52%) who probably acquired the infection abroad, 11 had a history of recent travel to India. Thirteen of 14 S. typhi isolates from cases acquired in India were resistant to nalidixic acid. Of the 6 cases acquired in Mauritius, 4 occurred in children under 12 years and 1 was caused by a multiply resistant strain. Twenty-two patients made an uneventful recovery. One death was indirectly caused by typhoid fever, and there was 1 case each of intestinal perforation and relapse. CONCLUSIONS: In Mauritius typhoid fever is mainly an imported disease, but indigenous cases of the illness occur rarely and sporadically. Travelers to Mauritius need not be vaccinated against typhoid fever as the risk of acquiring the disease in the country is negligible. Mauritians traveling to India must be made aware of the risk of typhoid fever and of preventive measures. Ceftriaxone should be used as the initial first-line treatment of infection acquired in India.

Adolescent↗

Enzyme immunoassay of antibody to Rochalimaea quintana: diagnosis of trench fever and serologic cross-reactions among other rickettsiae.

Enzyme immunoassay (EIA) tests were used to diagnose trench fever and to determine cross-reactions of Rochalimaea quintana with other rickettsiae. The results were compared with those obtained by counterimmunoelectrophoresis (CIE). All sera from cases of primary or relapsed forms of trench fever were positive both in EIA, with serum antibody titers of 1:20-1:640, and in CIE, giving one to three precipitin lines. Sera from patients with other rickettsial infections were also tested for reactivity with R. quintana antigen: typhus group (Rickettsia prowazekii, Ricketsia mooseri), 15 sera; spotted fever group (Ricketsia ricketsii, Rickettsia akari), eight sera; and scrub typhus (Rickettsia tsutsugamushi), six sera. Strong reactions occurred with four sera from patients with scrub typhus, giving one or two lines in CIE and EIA titers of 1:40-1:160; these results were extended to guinea pig antisera to R. tsutsugamushi. About 50% of typhus group sera reacted with a single line in CIE and had antibody titers of 1:20-1:80 by EIA. The results show that EIA is accurate for the diagnosis of trench fever and, with the results obtained by CIE, suggest that R. quintana is antigenically related to R. tsutsugamushi and possibly to rickettsiae in the typhus group as well.

Antibodies, Bacterial↗

Enteric fever: a clinicopathologic study of 104 cases.

The records of 104 patients with culture-proven enteric fever were reviewed and evaluated as to the clinical signs, laboratory findings, pathologic features and complications of the disease. One patient with fatal disseminated intravascular coagulation and enteric fever is also presented. Fever and bradycardia were the leading clinical signs followed by splenomegaly, hepatomegaly and rose spots. The principal complications of enteric fever included anemia, typhoid hepatitis, relapse and bleeding. Evidence of typhoid hepatitis was present in 30% of the patients tested. The pathology consisted of typhoid nodules of variable frequency and size depending upon the severity of the condition. The relationship of typhoid hepatitis to relapse seems to be more than coincidental as four out of seven patients who had relapse had abnormal liver tests. The occurrence of disseminated intravascular coagulation in enteric fever is rare; however, awareness of such a potential complication may be life-saving to the patient.

Adolescent↗

Comparison of ofloxacin and ceftriaxone for short-course treatment of enteric fever.

An open, randomized comparison of ofloxacin (200 mg, every 12 h) given orally for 5 days and ceftriaxone (3 g, once daily) given intravenously for 3 days in the treatment of uncomplicated enteric fever was conducted in Ho Chi Minh City, Vietnam. Salmonella paratyphi type A was isolated from six patients. Salmonella typhi was isolated from 41 patients; 63% of these isolates were resistant to multiple antibiotics: ampicillin, chloramphenicol, sulfamethoxazole, trimethoprim, and tetracycline. Of the culture-confirmed cases, treatment with ofloxacin resulted in complete cure of all 22 patients, whereas 18 of 25 patients treated with ceftriaxone were completely cured (P < 0.01). In the ceftriaxone group, there were six acute treatment failures and one relapse. Mean +/- standard deviation fever clearance times were 81 +/- 25 h for ofloxacin and 196 +/- 87 h for ceftriaxone (P < 0.0001). Short-course treatment with oral ofloxacin (5 days) is significantly better than that with ceftriaxone (3 days) and will be of particular benefit in areas where multiresistant strains of S. typhi are encountered.

Adolescent↗