Familial transmission of a serious disease--producing group A streptococcus clone: case reports and review

Invasive group A streptococcus (GAS) infections are emerging diseases; however, person-to-person transmission of invasive GAS producing life-threatening infection has been observed rarely. We report a small intrafamilial cluster of life-threatening GAS infections. A previously healthy 47-year-old father developed necrotizing fasciitis of the neck. Two days later, his 16-year-old daughter developed streptococcal angina, pneumonia, and pleural empyema. Both patients had signs of streptococcal toxic shock syndrome. Pulsed field gel electrophoresis revealed that the M6 strains of GAS isolated from the father and daughter had identical patterns. Cases of person-to-person transmission of invasive GAS infection reported in the literature are also reviewed.     

An international evaluation of the cancer-preventive potential of nonsteroidal anti-inflammatory drugs

The most common complication in children with varicella is cutaneous superimposed infection with pyogenic bacteria. Group A beta-hemolytic streptococci, which are known to cause life-threatening infections in both previously healthy children and those with underlying diseases, are the most frequently associated pathogens. A newly recognized disease, called streptococcal toxic shock syndrome, is associated with severe morbidity and mortality. We report a 3-year-old boy with a diagnosis of this syndrome who presented with increasing fever, vomiting, and lethargy 7 days after the development of a classic varicella skin lesion. In spite of aggressive fluid supply, administration of inotropic agents, and cardiopulmonary resuscitation, a rapidly deteriorating clinical course led to death 4 hours after hospitalization. This is the first report of this association in Taiwan. Pediatricians evaluating children with varicella must be mindful of the potential for Group A beta-hemolytic streptococcal infection.     

Group A beta-hemolytic streptococcal infections

GABHS is the most common bacterial cause of tonsillopharyngitis, but this organism also produces acute otitis media; pneumonia; skin and soft-tissue infections; cardiovascular, musculoskeletal, and lymphatic infections; bacteremia; and meningitis. Most children and adolescents who develop a sore throat do not have GABHS as the cause; their infection is viral in etiology. Other bacterial pathogens produce sore throat infrequently (e.g., Chlamydia pneumoniae and Mycoplasma pneumoniae), and when they do, other concomitant clinical illness is present. Classic streptococcal tonsillopharyngitis has an acute onset; produces concurrent headache, stomach ache, and dysphagia; and upon examination is characterized by intense tonsillopharyngeal erythema, yellow exudate, and tender/enlarged anterior cervical glands. Unfortunately only about 20% to 30% of patients present with classic disease. Physicians overdiagnose streptococcal tonsillopharyngitis by a wide margin, which almost always leads to unnecessary treatment with antibiotics. Accordingly, use of throat cultures and/or rapid GABHS detection tests in the office is strongly advocated. Their use has been shown to be cost-effective and to reduce antibiotic overprescribing substantially. Penicillin currently is recommended by the American Academy of Pediatrics and American Heart Association as first-line therapy for GABHS infections; erythromycin is recommended for those allergic to penicillin. Virtually all patients improve clinically with penicillin and other antibiotics. However, penicillin treatment failures do occur, especially in tonsillopharyngitis in which 5% to 35% of patients do not experience bacteriologic eradication. Penicillin treatment failures are more common among patients who have been treated recently with the drug. Cephalosporins or azithromycin are preferred following penicillin treatment failures in selected patients as first-line therapy, based on a history of penicillin failures or lack of compliance and for impetigo. GABHS remain exquisitely sensitive to penicillin in vitro. There are several explanations for penicillin treatment failures, but the possibility of copathogen co-colonization in vivo has received the most attention. Treatment duration with penicillin should be 10 days to optimize cure in GABHS infections. A 5-day regimen is possible and approved by the United States Food and Drug Administration for cefpodoxime (a cephalosporin) and azithromycin (a macrolide). Prevention of rheumatic fever is the primary objective for antibiotic therapy of GABHS infections, but a reduction in contagion and faster clinical improvement also can be achieved. Development of streptococcal toxic shock syndrome and necrotizing fasciitis ("flesh-eating bacteria") are rising concerns. The portal of entry for these invasive GABHS strains is far more often skin and soft tissue than the tonsillopharynx.     

Necrotizing group A streptococcal infections associated with streptococcal toxic shock syndrome

BACKGROUND: Group A streptococci (GAS) cause a variety of life-threatening infectious complications, including necrotizing fasciitis (NF), purpura fulminans (PF), and streptococcal toxic shock syndrome (strepTSS), in which bacteremia is associated with shock and organ failure. METHODS: We reviewed our experience in the management of patients with necrotizing GAS infections from 1991 to 1995. RESULTS: Eight adult patients (6 NF, 2 PF) were identified. Patients presented with fever, leukocytosis, and severe pain, and rapidly developed shock and organ dysfunction. The diagnosis of strepTSS was confirmed in 6 cases. A total of 54 surgical procedures were required, including widespread debridements and amputations. Two patients died (25%). CONCLUSIONS: Recognition of the need for aggressive diagnosis and surgical treatment of this most rapidly progressive surgical infection is necessary for successful management.     

Invasive streptococcal infection as a complication of chickenpox

Two girls aged 11 months and 6 years, presented with an invasive group A streptococcal (GAS) infection during the course of primary varicella. The infant had severe cellulitis of the left arm and leg, fever and bacteraemia. She developed osteomyelitis of ulna and tibia. The 6-year-old girl had a fever > 38.5 degrees C, hypotension, an acute respiratory distress syndrome, liver function abnormalities, and positive cultures of blood and joints. Her clinical picture was compatible with a GAS-associated toxic shock syndrome. If during the course of primary varicella persistent fever, secondary fever or pain in one or more extremities occurs, invasive bacterial infection by GAS or Staphylococcus aureus should be considered, even in the absence of skin infection or cellulitis.     

Musculoskeletal complications of varicella

Varicella, commonly known as chickenpox, is a common viral infection in children. An estimated 3.5 million cases occur annually in the United States. Serious musculoskeletal complications such as osteomyelitis and necrotizing fasciitis, although uncommon, can be life and limb-threatening. The purpose of the current study was to determine the association between varicella and serious musculoskeletal complications necessitating operative treatment and to characterize these infections in otherwise healthy children. We retrospectively reviewed the records of all patients who had been admitted to the Children's Hospital in San Diego because of varicella and its complications during the eleven-year period from 1984 through 1994. All records with an inpatient discharge diagnosis code for varicella were identified. Twenty-seven (6 per cent) of the 417 admissions for varicella were for musculoskeletal complications of the disease necessitating operative treatment. There were seven admissions for osteomyelitis, four for septic arthritis, five for necrotizing fasciitis, ten for a deep-tissue abscess, and one for toxic shock syndrome leading to multiple limb amputations. Seventy-nine (19 per cent) of the 417 admissions occurred in 1994. Eleven (41 per cent) of the twenty-seven musculoskeletal complications that led to operative treatment occurred in 1994, representing a significant increase in the number of such complications compared with the numbers in previous years of the study (p < 0.01). Bacterial pathogens were identified as the cause of twenty-five of the twenty-seven complications that led to operative treatment. Of these twenty-five, twenty-one (84 per cent) were found, on culture, to be caused by group-A beta-hemolytic streptococcus. This pathogen was the cause of the infection in five of the seven patients who had osteomyelitis while Staphylococcus aureus was the cause in only one. Group-A beta-hemolytic streptococcus was also the causative organism in two of the four patients who had septic arthritis, three of the five who had necrotizing fasciitis, and all ten who had a deep-tissue abscess. Nine of the eleven musculoskeletal complications leading to operative treatment in 1994 had group-A beta-hemolytic streptococcus as the causative organism. An understanding of the trends of and a high level of suspicion for potentially serious secondary infections in children who have varicella is necessary for prompt recognition and appropriate treatment.     

Toxin-mediated streptococcal and staphylococcal disease

After several decades of seemingly decreasing virulence, streptococcal and staphylococcal infections have reemerged as a major source of morbidity and mortality. Within the past 2 decades, not only have well-established diseases such as rheumatic fever begun to reappear. but also many new entities, such as toxic shock syndrome, streptococcal toxic shock syndrome, recurrent toxin-mediated perineal erythema, and recalcitrant erythematous desquamating disorder have been described. Central to the renewed importance of these bacteria has been the production of circulating toxins, which often function as superantigens in causing the clinical manifestations, morbidity and mortality associated with these diseases.     

Early onset group B streptococcal disease: clinical, roentgenographic, and pathologic features

Thirty-one neonates with early onset of serious group B streptococcal infections were observed in a four-year period. The mortality was 52%. Premature infants with clinical signs of respiratory distress syndrome were at highest risk of death; clinical signs of RDS were typical until apnea, shock, respiratory failure, and worsening of the radiographic pattern unexpectedly intervened. Pathologic material from infants with radiographic evidence either of RDS or of pneumonia showed both typical hyaline membrane disease and pneumonia in most instances. Factors which may be helpful in recognizing premature infants at risk for GBS disease in the much larger group of premature infants with uncomplicated RDS include: history of artificial, premature, or prolonged rupture of membranes; localized pulmonary infiltrates on chest roentgenogram; low absolute neutrophil count; and an unusually rapid progression of RDS.     

Specific T cell recognition of peptides derived from prostate-specific antigen in patients with prostate cancer

Active, population-based surveillance for invasive group A streptococcal (GAS) disease was conducted in laboratories in metropolitan Atlanta from 1 January 1994 through 30 June 1995. Clinical and laboratory records were reviewed and isolates characterized. One hundred and eighty-three cases of invasive GAS disease were identified (annual incidence, 5.2 cases/100,000). The incidence was highest among blacks (9.7/100,000 per year; relative risk (RR), 1.92; confidence interval (CI), 1.69-2.19; P < .0001) and the elderly, particularly nursing home residents (RR, 13.66; CI, 7.07-26.40; P < .0001). The mean age of patients was 41.3 years (range, 0-95 years). Skin and soft-tissue infections were most common. Mortality was 14.4%; risk of death was significantly higher for patients with streptococcal toxic shock syndrome (STSS) (RR, 9.73; CI, 3.34-29; P = .0008) and individuals infected with M-type 1 (RR, 7.40; CI, 1.5-16; P = .0084). Fourteen percent of invasive GAS infections were STSS and 3% were necrotizing fasciitis. Invasive GAS disease was associated with varicella infection in children (RR, 12.19; CI, 5.58-26.62; P < .0001). M (or emm) types included M1 (16%), M12 (12%), and M3 (11%). Continued study of GAS disease is essential to further define risk factors and risk of secondary cases and to develop effective prevention strategies.     

Molecular analysis of glycogen storage disease type Ib: identification of a prevalent mutation among Japanese patients and assignment of a putative glucose-6-phosphate translocase gene to chromosome 11

BACKGROUND: Varicella pneumonia that results in respiratory failure or progresses to the institution of mechanical ventilation carries a significant morbidity and mortality despite intensive respiratory support and antiviral therapy. There has been no reported study of the role of corticosteroids in life-threatening varicella pneumonia. DESIGN AND METHODS: This was an uncontrolled retrospective and prospective study of all adult patients with a diagnosis of varicella pneumonia who were admitted to the ICUs of the Johannesburg group of academic hospitals in South Africa between 1980 and 1996. Patient demographics, clinical and laboratory features, necessity for mechanical ventilation, and complications were reviewed. The outcome and therapy of varicella pneumonia was evaluated with particular reference to the use of corticosteroids. Patients with comorbid disease and those already taking immunosuppressive agents were excluded. Key endpoints included length of ICU and hospital stay and mortality. MEASUREMENTS AND RESULTS: Fifteen adult patients were evaluated, six of whom received corticosteroids in addition to antiviral and supportive therapy. These six patients demonstrated a clinically significant therapeutic response. They had significantly shorter hospital (median difference, 10 days; p<0.006) and ICU (median difference, 8 days; p=0.008) stays and there was no mortality, despite the fact that they were admitted to the ICU with significantly lower median ratios between PaO2 and fraction of inspired oxygen than those patients (n=9) who did not receive corticosteroid therapy (86.5 vs 129.5; p=0.045). CONCLUSION: When used in addition to appropriate supportive care and early institution of antiviral therapy, corticosteroids appear to be of value in the treatment of previously well patients with life-threatening varicella pneumonia. The observations presented in this study are important and should form the basis for a randomized controlled trial, as no other relevant studies or guidelines are available.     

Microbiology of common infections in the upper respiratory tract

The management of upper respiratory tract infections has become more difficult because of the recent increase in the number of penicillin-resistant organisms. The bacteria that predominate in otitis media and sinusitis can resist penicillin through the production of the enzyme beta-lactamase (Haemophilus influenzae and Moraxella catarrhalis in acute infections and Staphylococcus aureus and Prevotella and Fusobacteria spp in chronic infections) or through changes in penicillin-binding sites (Streptococcus pneumoniae). beta-lactamase-producing bacteria can express their pathogenicity directly through their ability to cause infections and indirectly by production of the enzyme, thus protecting penicillin-susceptible pathogens from penicillins. This phenomenon may explain penicillin's failure in the treatment of Group A beta-hemolytic streptococcal (GABHS) tonsillitis. An additional cause for penicillin failure is the absence among the normal tonsillar bacterial flora of streptococcal species that are capable of interfering with the growth of GABHS. Proper use of antimicrobial therapy, including those therapies that are effective against penicillin-resistant bacteria, is the cornerstone of management of upper respiratory tract infections.     

Infections due to group A streptococcus: new concepts and potential treatment strategies

Important new information has been gained on the pathogenesis and treatment of life-threatening invasive infections caused by group A streptococci (GAS), i.e. the streptococcal toxic shock syndrome (STSS) and necrotizing fasciitis (NF). Both STSS and NF lead to superantigen reactions with activation of up to 10% of the CD4+ lymphocytes and release of large amounts of cytokines; mainly tumour necrosing factor beta, interferon gamma, interleukin 1 and interleukin 6. Streptococcal products known to trigger the superantigen reactions are the pyrogenic exotoxins, spe A, spe B and spe C and the M-proteins. Therapeutically clindamycin has been shown to reduce mortality in animal experiments in comparison to penicillin treatment. A possible mechanism is the effect of clindamycin on protein synthesis which might decrease the production of superantigens. In man, the use of intravenous immunoglobulin has been shown to significantly reduce mortality in STSS and NF. The most probable mechanism is neutralisation of superantigens by antibodies in the immunoglobulin preparations used.     

Streptococcal pyrogenic exotoxins A (SpeA) and C (SpeC) stimulate the production of inducible nitric oxide synthase (iNOS) protein in RAW 264.7 macrophages

Streptococcal pyrogenic exotoxins A (SpeA) and C (SpeC) are members of a family of superantigens produced by group A streptococci that appear to play a key role in the pathogenesis of streptococcal toxic shock syndrome. Since it is known that nitric oxide (NO) and tumor necrosis factor (TNF) are largely responsible for the shock and multiple organ dysfunction of Gram-negative sepsis, we hypothesized that SpeA and/or SpeC could trigger the production of inducible nitric oxide synthase (iNOS) and/or TNF by murine macrophages. We exposed RAW 264.7 macrophages to increasing concentrations of SpeA or SpeC alone and in combination with recombinant murine interferon-gamma (rIFN gamma) for 16-24 h. We found that both SpeA and SpeC triggered iNOS production in the presence of low concentrations of rIFN gamma, while neither provoked iNOS accumulation in the absence of rIFN gamma. Neither SpeA nor SpeC (with or without rIFN gamma) reproducibly induced TNF production by these murine macrophages. These data indicate that two streptococcal exotoxins up-regulate iNOS production by murine macrophages and suggest that nitric oxide production may play an important role in the pathogenesis of streptococcal toxic shock syndrome.     

Markedly elevated cytokines in pleural effusion during the ovarian hyperstimulation syndrome: transudate or ascites?

OBJECTIVE: To study levels of proinflammatory cytokines in pleural fluid during the severe ovarian hyperstimulation syndrome (OHSS). DESIGN: Case report. SETTING: Tertiary academic medical center. PATIENT(S): A 35-year-old female with a 6-year history of unexplained infertility on menotropin therapy and 28 healthy normal controls. INTERVENTION(S): Thoracentesis for severe pleural effusion and venipunctures. MAIN OUTCOME MEASURE(S): Interleukin-1 beta (IL-beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) levels were measured by ELISA and compared between pleural effusion and serum from normal controls. RESULT(S): Pleural effusion IL-1 beta and IL-6 levels were higher than serum. Interleukin-6 levels were elevated particularly in pleural effusion (1,961.89 pg/mL) compared with serum (3.9 +/- 0.41 pg/mL). CONCLUSION(S): Our results confirm the high cytokine levels observed in OHSS. Cytokines have been implicated in capillary permeability, extravasation of fluid, oliguria, and shock. We have postulated that these mediators are released from the corpora lutea into the peritoneum and systemic circulation. Alternatively, the presence of high cytokine levels in pleural fluid maybe the result of diaphragmatic defects, which allow for the migration of ascites into the pleural space.     

Impact of imported beverages on fluoridated and nonfluoridated communities

In the last 10 years an increasing number of cases of group A streptococcal toxic shock syndrome have appeared in various clinical settings. The manifestation of this syndrome includes rapidly progressive multiorgan failure and soft-tissue necrosis. This report presents a case of streptococcal toxic shock syndrome caused by Streptococcus pyogenes with severe necrotizing fasciitis of the abdominal wall following hysterectomy. Aggressive surgical intervention with debridement of all necrotic tissue necessitated resection of the complete abdominal wall (skin, subcutaneous tissue, muscle and peritoneum). The abdominal wall defect was covered with free myocutaneous flaps and split-skin grafts. Optimal treatment, including adequate antibiotic therapy and radical surgical intervention, is an indispensable prerequisite of successful outcome.     

The vascular compartment hampers accurate determination of teniposide penetration into brain tumor tissue

Pleural effusion represents a frequent feature both of Hodgkin's (HL) and non-Hodgkin's (NHL) lymphoma. The aims of the present study were: 1) to analyse the diagnostic accuracy of thoracoscopy as compared to pleural cytology in patients with lymphoma and concurrent pleural effusion; and 2) to evaluate the effectiveness of chemical pleurodesis with the tetracycline derivative, rolitetracycline. Seventeen patients with pleural effusion and concurrent lymphoma (10 NHL and seven HL) were studied. Analysis of pleural fluid revealed the presence of lymphoma cells in six cases (four NHL and two HL); histopathological examination of samples obtained by thoracoscopy was consistent with pleural infiltration by NHL in eight cases and by HL in six cases. Overall sensitivities of pleural cytology and histology were 35 and 82%, respectively. Following chemical pleurodesis, complete response was observed in five of the 17 cases (two NHL and three HL), partial response in four cases (two NHL and two HL), whereas failure was observed in the remaining eight cases. Two patients who had presented failure underwent subsequent pleurectomy by thoracotomy (one case of HL) or video-thoracoscopy (one case of NHL). Complete response was observed in both cases following this treatment. No major complication was recorded after chemical pleurodesis or pleurectomy. Thoracoscopy may be considered a useful tool to evaluate the involvement of pleural space in patients presenting with pleural effusion in the course of lymphoma. Chemical pleurodesis plays an important role in the palliative treatment of this condition. Further studies are necessary to assess the role of pleurectomy in the treatment of such patients.     

Acute eosinophilic pneumonia: radiographic and CT findings in six patients

OBJECTIVE: Our objective was to assess the radiographic and CT findings of acute eosinophilic pneumonia. CONCLUSION: Initial and follow-up chest radiographs, chest CT scans (n = 5) and clinical data in six patients with acute eosinophilic pneumonia were reviewed by two chest radiologists. The predominant initial radiographic finding was diffuse bilateral reticular densities (four [67%] of six patients). Areas of ground-glass opacity were observed on CT scans in all patients (5 of 5) and were bilateral, random, and patchy in distribution in four (80%) of five patients. Smooth septal thickening and pleural effusions were observed in four patients. The disease manifested as rapid onset of severe dyspnea and fever and rapid resolution with (n = 3) or without (n = 3) steroid therapy. Bilateral reticular densities on chest radiographs and, on CT scans, ground-glass opacity with smooth septal thickening and pleural effusion associated with acute fever and dyspnea may suggest the diagnosis of acute eosinophilic pneumonia.     

Radiolabelled monoclonal antibodies (McAb): an alternate approach to the conventional methods for the assessment of cardiomyocyte damage in an experimental brain-death pig model

BACKGROUND: According to the Ministry of Health and Welfare AIDS Surveillance Committee's report on vertically transmitted human immunodeficiency virus (HIV) infection, there have been eight children with acquired immune deficiency syndrome (AIDS) and 18 children with HIV infection in Japan, totalling 26 in all as of February 1997. A search of the literature fails to reveal any report that deals with many cases of vertically transmitted HIV infection in Japan. METHODS: A primary questionnaire survey was taken of the main medical institutions across the country, followed by a secondary questionnaire survey of physicians and pediatricians who treated the disease. A clinical review was made of 19 children with vertically transmitted HIV infection (including eight AIDS children) according to the 1994 Revised Classification System for HIV Infection in Children. RESULTS: The mean age at diagnosis was 14.5 months and the diagnosis was made at less than 18 months of life in approximately 70% of infected children. In the mean observation period of 16 months, six of eight AIDS children (75%), and one child of group B died. The mean period of observation for the seven dead children was 7 months, and six of seven children died by 36 months of life. The survival period after the diagnosis of AIDS was 15 months. The diagnosis of HIV infection was made based on the clinical symptoms of all children with AIDS. Of 11 children, six (45%) presented with symptoms of HIV infection by 6 months of life, and 10 of 11 children (91%) presented with symptoms by 26 months of life. The noteworthy clinical findings included hepatomegaly, splenomegaly, recurrent respiratory tract infection, lymph node swelling, oral candidiasis, hepatitis, wasting syndrome, HIV encephalopathy and severe pneumonia. The favored age for the start of complications and the magnitude of decrease in the HIV helper cell count varied with each case of complications of HIV infection (wasting syndrome, HIV encephalopathy) or opportunistic infections (cytomegalovirus infection, Mycobacterium avium complex infection). Anti-HIV drugs (mainly zidovudine) had been used in five of eight children with AIDS and were effective in two long survivors alone. CONCLUSIONS: Children who are diagnosed with HIV infection, based on their clinical symptoms, carry a poor prognosis. In this respect, early diagnosis and progress in anti-HIV therapy are necessary.     

Spontaneous tibial artery thrombosis associated with varicella pneumonia and free protein S deficiency

Pneumonia is the most common serious complication of varicella infection in adults. A variety of thrombotic complications including purpura fulminans and disseminated intravascular coagulation have been reported in children with varicella but not in adults. Two men with varicella pneumonia who had profound lower extremity ischemia caused by thrombosis of the profunda femoris and tibial arteries are reported. Both patients had free protein S deficiency and vascular thrombosis in association with varicella pneumonia without overt evidence of disseminated intravascular coagulation or purpura fulminans. Antiphospholipid immunoglobulin G and immunoglobulin M antibodies were present in one, whereas the other had evidence of the lupus anticoagulant. The proposed pathogenesis and management options including intraarterial thrombolytic therapy with urokinase and the need for long-term anticoagulation are discussed.     

Two patients with polymyositis or dermatomyositis complicated with massive pleural effusion

Two patients with polymyositis (PM) or dermatomyositis (DM) complicated with massive pleural effusion are reported here. Both patients presented a high-grade fever, pleural effusion prominent on the right, and good response to steroid therapy. In a 50-year-old woman with PM, combined process of pleural inflammation, cardiomyopathy and coexisting hypothyroidism were considered to be responsible for the accumulation of the massive pleural effusion. However, in a 34-year-old man with DM, pleural inflammation associated with interstitial pneumonia or pleural microvasculopathy in DM was considered to be responsible for the accumulation of the massive pleural effusion.