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While most agree that vaccination is one of the most important public health practices, vaccines continue to be underused and undervalued, and vaccine-preventable diseases remain a threat to world health. Perhaps one reason this gap remains is that decision-making generally is made on a vaccine-by-vaccine basis. There has been less attention to the value of vaccination in general. To more clearly identify this value, this paper reviews the cost-effectiveness literature and calculates the annual benefits of vaccination on a global scale.

Two hundred and ten newborns from among a high risk group were examined for intrauterine infections by polymerase chain reaction (PCR) with the aim of assessing the clinical information density of the method in the diagnostic sphere. The patients were examined for the presence of DNA/RNA viruses and bacteria. Genetic samples of various causative agents were detected in 49% of the newborns. No correlation was established between the clinical pattern and the presence of DNA of certain microorganisms. The most severe condition of newborns was noted in cases when a DNA causative agent was found in several different biological samples. The highest mortality (in per cent) was registered in the group of newborns with detected DNA of Herpesviridae viruses. The PCR clinical value was affirmed for establishing a disease etiology in newborns.

Intra- and inter-specific effects of cotton, soybean, and clover on the time until death of Helicoverpa zea (Boddie) and Heliothis virescens (F.) larvae lethally infected with H. zea nucleopolyhedrovirus (HzSNPV) were evaluated in the laboratory. In the first test, on second instar only, the time until death of lethally infected larvae of both species differed with the plant tissues (vegetative or reproductive) and plant species. The total viral activity produced per larva in LC(50) units (occluded viral bodies (OBs) per larva/LC(50) in OBs/mm(2) of diet surface) was greater from H. virescens larvae fed vegetative than reproductive tissues of all host plants, but from H. zea virus production was greater only when fed vegetative tissue of soybean. In a second test that compared second and fourth instar H. virescens on cotton, total viral activity from larvae treated in both instars was greater when fed vegetative than reproductive tissues. Results of these tests suggest that the ability of host plants to influence baculovirus disease is more complex than previously believed. When examining the epizootic potential of a baculovirus, more attention must be given to the effects of the host plant on the insect-virus interactions.

The postmortem findings in 274 kittens were reviewed. The kittens were grouped by age at death: perinatal (< one day), neonatal (one to 14 days), preweaning (15 to 34 days) and postweaning (35 to 112 days); 203 (74 per cent) of the kittens were postweaning and 38 (14 per cent) were preweaning. Infectious disease was identified in 55 per cent of the kittens, and 71 per cent of the infectious disease was viral and detected significantly more frequently in rescue shelter kittens than in kittens from private homes. Twenty-five per cent of all kitten mortality was due to feline parvovirus (FPV). During the neonatal and preweaning periods, the main viral infections were feline herpesvirus and calicivirus. Feline infectious peritonitis caused the death of 17 kittens in the postweaning period. The rescue shelter kittens were significantly younger than the kittens from private homes (median survival 49 and 56 days) and were more likely to have FPV. The non-pedigree kittens were significantly younger than the pedigree kittens (42 v 56 days), and the pedigree kittens were significantly less likely to originate from rescue shelters. There was no significant difference between the age distribution of the male and female kittens. No diagnosis could be found in 33 per cent of the kittens, and this failure was correlated significantly with the submission of tissue samples as opposed to the whole carcase.

Purpose of Review: The leading cause of death in solid organ and hematopoietic stem cell transplant recipients is infection. The respiratory viruses, particularly respiratory syncytial virus, influenza, parainfluenza, adenovirus, and picornaviruses, are increasingly recognized as significant pathogens in these populations., Recent Findings: Respiratory syncytial virus has again been found to be the most common of the respiratory viruses causing severe infections in transplant recipients. Advances in prevention, particularly with regard to infection control practices, and to lesser extent treatment have had a substantial impact on the frequency and outcomes of this infection. New studies have clarified the impact of influenza in the hematopoietic stem cell transplant recipients and have provided evidence to support the use of M2 and neuraminidase inhibitors for early treatment. The epidemiology of parainfluenza and adenovirus in transplant recipients has been clarified, although therapeutic modalities are still limited and understudied. New antiviral medications may bring improved outcomes of picornavirus infections in this population. Finally, a new virus, the human metapneumovirus, has recently been described and may be a significant respiratory pathogen in immunocompromised transplant recipients., Summary: Studies published over the past year have documented a new respiratory pathogen. They have also resulted in improved understanding of the epidemiology of all of the respiratory virus pathogens, and have contributed to improve management of respiratory syncytial virus and influenza infection in hematopoietic stem cell transplant and solid organ transplant recipients.

Hispanic immigrants are an increasing portion of the United States (US) population. In addition to being at risk for diseases common in the US-born population, Hispanic immigrants also are at risk for infections that do not usually occur in the US-born population. Thus, such diseases as tuberculosis, neurocysticercosis, brucellosis, typhoid fever, malaria, amebiasis, viral exanthems, and hepatitis need to be considered in Hispanics who present with fever or focal lesions. When included in the differential diagnosis, most of these infections can be readily diagnosed and treated with currently available methods.

Objective: To classify 239 cases of perinatal death in a newly introduced classification system for underlying causes of perinatal death., Design: Prospective, descriptive., Setting: Dutch healthcare region Delft-Westland-Oostland (DWO)., Materials and Methods: In 10 years (1983-1992), all cases of perinatal death with a birthweight above 500 g (n=239) were included into the study. We used a classification model based upon the underlying cause of death using simple principles of obstetrical and neonatal pathology. A team consisting of a gynaecologist, neonatologist and pathologist classified all cases of perinatal death into seven groups to determine the "most-probable" cause of death., Results: Birth trauma was seen in two cases (0.8%). Infections were seen in 16 cases (6.8%). Acute/subacute placental pathology in 77 cases (32.2%) and chronic placental pathology in 50 cases (21%). Bloodtype antagonism was seen in two cases (0.8%). Lethal congenital malformations in 55 cases (23%). Complications of pre-viable delivery in 20 cases (8.4%). Unclassifiable were 17 cases (7%): two cases could not be classified despite thorough investigation (1%) and 15 cases were lost for follow-up (6%)., Conclusions: Classification of perinatal death causes by using our fundamental classification system gives insight in the possible underlying causes of death. The results of such a classification can be used as guidelines for preventive measures in the future.

Myocarditis is a common cause of cardiomyopathy and is thought to account for 25% of all cases in humans. Unfortunately, the disease is difficult to detect clinically before a myopathic process ensues. Management of myocarditis-induced heart failure includes the standard regimen of diuretics, digoxin, angiotensin-converting enzyme inhibitors, angiotensin-II receptor blockers, and beta-adrenergic blockers. The management of myocarditis itself is dependent on the etiology of the illness. Treatments that are currently under investigation include immunosuppressants, nonsteroidal antiinflammatory agents, immunoglobulins, immunomodulation, antiadrenergics, calcium-channel blockers, angiotensin-converting enzyme inhibitors, nitric oxide inhibitors (e.g., aminoguanidine), and antivirals. Despite advances in treatment, more work needs to be done in the early detection of myocarditis. Additionally, better means need to be established for distinguishing between viral and noninfectious autoimmune forms of the disease, so that appropriate treatment can be instituted.

Between the years 1990 and 2000, an attempt was made to determine the causes of death of 55 harbour porpoises stranded along the Belgian and northern French coasts. From 1990 to 1996, only five carcasses were collected as against seven in 1997, eight in 1998, 27 in 1999 and eight in 2000. The sex ratio was normal and most of the animals were juvenile. The most common findings were emaciation, severe parasitosis and pneumonia. A few cases of fishing net entanglement were observed. The main microscopical lesions were acute pneumonia, massive lung oedema, enteritis, hepatitis and gastritis. Encephalitis was observed in six cases. No evidence of morbillivirus infection was detected. Pneumonia was associated with bacteria or parasites, or both. The causes of death and the lesions were similar to those previously reported in other countries bordering the North Sea. The cause of the increased numbers of carcasses in 1999 was unclear but did not include viral epizootics or net entanglement. A temporary increase in the porpoise population in the southern North Sea may have been responsible., (Copyright 2002 Elsevier Science Ltd. All rights reserved.)

Population-based surveillance for unexplained death and critical illness possibly due to infectious causes (UNEX) was conducted in four U.S. Emerging Infections Program sites (population 7.7 million) from May 1, 1995, to December 31, 1998, to define the incidence, epidemiologic features, and etiology of this syndrome. A case was defined as death or critical illness in a hospitalized, previously healthy person, 1 to 49 years of age, with infection hallmarks but no cause identified after routine testing. A total of 137 cases were identified (incidence rate 0.5 per 100,000 per year). Patients' median age was 20 years, 72 (53%) were female, 112 (82%) were white, and 41 (30%) died. The most common clinical presentations were neurologic (29%), respiratory (27%), and cardiac (21%). Infectious causes were identified for 34 cases (28% of the 122 cases with clinical specimens); 23 (68%) were diagnosed by reference serologic tests, and 11 (32%) by polymerase chain reaction-based methods. The UNEX network model would improve U.S. diagnostic capacities and preparedness for emerging infections.

Objective: To collect accurate data on disease- and microbial-specific causes and avoidable factors in child deaths in a developing country., Methods: A systematic prospective audit of deaths of children seen at Goroka Hospital in the highlands of Papua New Guinea was carried out. Over a 24-month period, we studied 353 consecutive deaths of children: 126 neonates, 186 children aged 1-59 months, and 41 children aged 5-12 years., Findings: The most frequent age-specific clinical diagnoses were as follows: for neonates--very low birth weight, septicaemia, birth asphyxia and congenital syphilis; for children aged 1-59 months--pneumonia, septicaemia, marasmus and meningitis; and for children aged 5-12 years--malignancies and septicaemia. At least one microbial cause of death was identified for 179 (50.7%) children and two or more were identified for 37 (10.5%). Nine microbial pathogens accounted for 41% of all childhood deaths and 76% of all deaths that had any infective component. Potentially avoidable factors were identified for 177 (50%) of deaths. The most frequently occurring factors were as follows: no antenatal care in high-risk pregnancies (8.8% of all deaths), very delayed presentation (7.9%), vaccine-preventable diseases (7.9%), informal adoption or child abandonment leading to severe malnutrition (5.7%), and lack of screening for maternal syphilis (5.4%). Sepsis due to enteric Gram-negative bacilli occurred in 87 (24.6%). The strongest associations with death from Gram- negative sepsis were adoption/abandonment leading to severe malnutrition, village births, and prolonged hospital stay., Conclusions: Reductions in child mortality will depend on addressing the commonest causes of death, which include disease states, microbial pathogens, adverse social circumstances and health service failures. Systematic mortality audits in selected regions where child mortality is high may be useful for setting priorities, estimating the potential benefit of specific and non-specific interventions, and providing continuous feedback on the quality of care provided and the outcome of health reforms.

Seasonal variation has been documented in the frequency and attributable mortality of a number of medical illnesses and infections in the nontransplantation setting. Whether similar trends exist in transplant recipients is not known. Seasonal rates of overall and early mortality and contributory variables stratified by season were assessed in 190 consecutive liver transplant recipients who underwent transplantation over a 10-year period. The frequency of infectious complications and rejection was also assessed and stratified by season of transplantation. Early (deaths occurring in the first year posttransplantation), but not overall, mortality correlated significantly with seasonality. Of patients with early mortality, 43% (13 of 30 patients) died in winter; 23% (7 of 30 patients), in spring; 13% (4 of 30 patients), in summer; and 20% (6 of 30 patients), in fall. The frequency of deaths in winter was significantly greater than for all other seasons (P = .022). The high wintertime mortality could not be explained by previously recognized risk factors portending a poor outcome, e.g., United Network for Organ Sharing status, Child-Pugh score, surgical time, blood loss, pretransplantation and posttransplantation dialysis, infections, rejection, or increased immunosuppression. Strong trends toward a higher rate of cytomegalovirus disease in patients who underwent transplantation in fall (P = .09) and bacterial infections in those who underwent transplantation in winter were documented (P = .09). There was no correlation between seasonality and rejection. Early mortality in winter in liver transplant recipients was significantly greater than if the deaths were totally random. Whether the seasonal clustering of deaths and infections is triggered by respiratory viruses, yet unrecognized viruses, or unknown exogenous factors remains to be determined.

Background: Over the last decades, better drinking water and hygiene, improved nutrition and vaccines and antibiotics have greatly reduced child mortality and morbidity. Still, 11 million children under the age of five die every year, many of them from diseases that could have been prevented or treated, given existing knowledge and technology., Materials and Methods: On the basis of a review of recent literature, this paper discusses current strategies to reduce childhood morbidity and mortality., Results: Sufficient knowledge and technology exist to further improve the health of the worlds' children. Poverty and its consequences--weak implementation and organisation of health services--is a major obstacle., Interpretation: In order to improve health services in developing countries, additional resources are needed. There is also a need for better quality of service. This will require increased efforts in the field of health policy and systems research.

We compared the occurrence of severe infections following 71 reduced-intensity conditioning (RIC) allogeneic peripheral blood stem cell transplants (PBSCT) and 123 standard myeloablative PBSCT (MINI and STAND groups, respectively) from HLA-identical siblings. The probability of 1-year infection-related mortality (IRM) was 19% in the STAND group and 10% in the MINI group (log-rank, P = 0.3). On multivariate analysis the only significant variable associated with a higher risk of IRM was the development of moderate-to-severe GVHD (P = 0.005). The probability of developing CMV infection was 39% in the STAND group and 21% in the MINI group (P = 0.03) (43% and 21%, respectively, in seropositive donor/recipient pairs, P = 0.01), and the probability of developing CMV disease was 9.5% and 1%, respectively (P = 0.05) (11% and 1%, respectively, in seropositive donor/recipient pairs, P = 0.03). Multivariate analysis of CMV infection identified four variables associated with a higher risk: CMV positive serostatus (P = 0.05), STAND transplant group (P = 0.02), the development of moderate-to-severe GVHD (P < 0.001) and a dose of CD34(+) cells infused below 6 x 10(6)/kg (P = 0.01). Invasive fungal infections and pneumonias of unknown origin did not differ between groups, and neither did other severe non-CMV viral infections and bacterial infections. Our results suggest that RIC allogeneic PBSCT may decrease the risk of dying from an opportunistic infection and reduces the occurrence of CMV infection and disease. Overall, the development of GVHD (acute or chronic) is an important risk factor for these complications. Other infections continue to pose a significant threat to recipients of RIC allografts, stressing that prophylactic and supportive measures are an important aspect in their care.

In the last 20 years, the survival rate for children with acute lymphoblastic leukaemia (ALL) has markedly improved, largely owing to a decrease in relapses. However, children still die from complications of treatment and these are potentially preventable. We have analysed data from three large consecutive national protocols for ALL from 1980 to 1997 [Medical Research Council United Kingdom ALL (MRC UKALL) trials VIII, X and XI] to compare the incidence and causes of treatment-related deaths (TRD). The percentage of TRD has fallen from 9% to 2% (UKALL VIII to XI), largely as a result of a decrease in fatal infections. Deaths during induction have fallen from 3% to 1%, the main causes of death being bacterial, followed by fungal infection, while other causes, chiefly haemorrhage, have not declined. Remission deaths also decreased from 6% to 1%, particularly those deaths due to measles and pneumocystis carinii. More guidelines for surveillance and treatment of infections have been included within progressively more intensive protocols. Risk factor analysis showed increased TRD in patients with Down's syndrome, high leucocyte count and older age in UKALL XI. In contrast, the introduction of blocks of intensification was not associated with an increased death rate. While improved supportive care has reduced the incidence of TRD, there is still scope for further reduction by prompt treatment of suspected infection. Maintenance of herd immunity remains of vital importance in avoiding deaths from measles.

The frequency of and survival from community-acquired respiratory virus (CRV) infections among patients undergoing allogeneic or autologous stem cell transplantation (SCT) were evaluated in a prospective study conducted at 37 medical centers affiliated with the European Group for Blood and Marrow Transplantation. Of the 40 CRV infections diagnosed in 1863 patients (739, allogeneic SCT; 1124, autologous SCT), 20 were attributed to respiratory syncytial virus (RSV), 4 to parainfluenza viruses, and 16 to influenza virus A. The overall survival rate among SCT recipients with CRV infections was 76%; 8 patients, all recipients of allogeneic transplants, died after diagnosis of CRV infection, but only 5 of these deaths (3, RSV; 2, influenza A virus) were attributable to the infection. The overall rate of death directly attributable to RSV and influenza A virus infections in allogeneic SCT recipients was 1.1%. In an 18-month extension, an additional 53 patients with CRV were identified. Results for the combined data were similar to those from the first phase of the study.

Drawing on the notion of the drench hypothesis proposed by Greenberg (1988), the author proposes a preliminary theoretical framework to explain "drenching" effects of dramatic media. Three drench variables-perceived realism, role identification, and media involvement-were identified and tested regarding their role in mediating the impact of virus disease portrayals on health locus-of-control belief orientations. Participants in the experimental condition watched the movie Outbreak (a portrayal of an outbreak of a deadly virus disease). Perceived realism, role identification, and media involvement were measured concerning the movie depiction of the virus disease. The findings indicate that the dramatized portrayal significantly weakened the viewers' beliefs in self-controllability over health and strengthened their beliefs in chance outcomes of health. Beliefs in provider control over health were affected by the viewers' perception of realism regarding the movie portrayals. Effects of role identification were different between male and female viewers. The results are discussed in relation to drench analysis as a theoretical approach to media effects.

The interaction between virus multiplication and host development was studied by determining the survival time of Trichoplusia ni larvae inoculated with a wide range of doses of Autographa californica nucleopolyhedrovirus and incubated at five different temperatures spanning the biologically relevant range. The results support earlier findings that the course of baculovirus infection follows the mathematical description of the birth-death model. Both in vivo rate of virus increase and larval growth rate increased linearly with increasing temperature from 14 to 29 degrees C; developmental zeros for virus replication and larval growth were estimated from these data to be 10.2 and 10.4 degrees C, respectively. The data were used to generate a description of the combined effects of dose and temperature on median survival time at doses greater than the LD(50). Implications of the lag times before onset of viral replication and between cessation of replication and larval death with respect to model-based estimation of the critical population level (i.e., amount of virus in the host just prior to death) are discussed., (Copyright 2000 Academic Press.)

To assess the expected benefits of rapid reporting of respiratory viruses, we compared patients whose samples were processed using standard techniques such as enzyme immunoassays, shell vial assays, and culture tube assays (year 1) to patients whose samples were processed with the same standard techniques in addition to immunofluorescent testing (FA) directly on cytocentrifuged samples (year 2). The cytospin FA screened for influenza A and B viruses, respiratory syncytial virus (RSV), parainfluenza viruses 1 to 3, and adenovirus (DAKO Diagnostics Ltd.). The specificity of the cytospin FA for all viruses was 100%. The sensitivities for influenza A virus and RSV were 90 and 98%, respectively, but the sensitivities for influenza B virus and adenovirus were unacceptable (14.3 and 0%, respectively). However, since the former viruses account for >85% of our isolates from clinical specimens, the cytospin FA is an excellent screening test since the positive result was available within hours. The mean turnaround time for all positive viruses was 4.5 days in year 1 and 0.9 day in year 2 (P = 0.001). This rapid reporting resulted in physicians having access to information sooner, enabling more appropriate treatment. The mean length of stay in the hospital for inpatients with respiratory viral isolates was 10.6 days for year 1 versus 5.3 days for year 2. Mean variable costs for these patients was $7,893 in year 1 and $2,177 in year 2. After subtracting reagent costs and technological time, the savings in variable costs was $144,332/year. Summarizing, the cytospin FA markedly decreased turnaround time and was associated with decreased mortality, length of stay, and costs and with better antibiotic stewardship.

In studies of chronic viral infections, the objective is to estimate probabilities of developing viral eradication and resistance. Complications arise as the laboratory methods used to assess eradication status result in unusual types of censored observations. This paper proposes nonparametric methods for the one-sample analysis of viral eradication/resistance data. We show that the unconstrained nonparametric maximum likelihood estimator of the subdistributions of eradication and resistance are obtainable in closed form. In small samples, these estimators may be inadmissible; thus, we also present an algorithm for obtaining the constrained MLEs based on an isotonic regression of the unconstrained MLEs. Estimators of several functionals of the eradication and resistance subdistributions are also developed and discussed. The methods are illustrated with results from recent hepatitis C clinical trials.

In the last months of the second World War, 250,000 German refugees landed in Denmark. A third of them were children under the age of 15. Seven thousand German refugee children under the age of five died in Denmark in 1945. Using birth certificates and death certificates from the Danish national archives and burial lists from the German refugee cemetaries I have collected data to reveal causes of death, age distributions and time of the deaths of the 7000 fatal cases among children under the age of five. Three thousand children under the age of one, 2000 children one year old and 2000 children 2-4 years old died. Most of them died just before and after the German surrender, but many died in the months following the German surrender. The infant mortality was extremely high all during 1945. The infants died from diseases due to malnutrition, but the older the children the more likely the causes of death were due to infectious diseases such as pneumonia, measles, diphtheria and gastroenteritis.

Objectives: To assess whether a previously established low sexually transmitted infection/HIV risk in prostitutes in London has been sustained, and to measure other occupational risks, including mortality., Design: 9 year prospective study in west London., Subjects: 402 prostitutes recruited from 1985 to 1991, 320 were followed up for 675 person years to 1994., Main Outcome Measures: Condom use in commercial and non-commercial sex; viral and bacterial sexually transmitted infection at initial and follow up visits; death., Results: Condom use increased significantly from 1986 to 1993 and protected the majority of commercial sexual contacts. Baseline prevalence: HIV 1.3%, hepatitis C 6.7%, hepatitis B 6.6%, syphilis 2.3%, HTLV-I/II 0.4%, gonorrhoea 3.0%, chlamydia 8.2%, genital herpes 16.8%. Incidence (per 100 person years): HIV 0.2, hepatitis C 0.3, gonorrhoea 5.6, chlamydia 12.6, genital herpes 6.5. Viral infections were associated with injecting drug use and non-British nationality; bacterial infections were associated with numbers of non-commercial partners but not with sexual contacts at work. Four women died during the course of the study; two had AIDS, two were murdered. This mortality of 5.93 per 1000 person years was 12 times the expected rate for women of a similar age., Conclusions: This study shows that it is possible to have a larger number of sexual partners and remain free from sexually transmitted infections provided that condoms are used consistently: there has been a sustained increase in condom use in the sex industry. None the less, prostitutes are at increased risk of sexually transmitted infections, primarily through non-commercial sexual partnerships. Infectious diseases are only one of the risks facing prostitutes, as illustrated by the mortality from violence as well as from HIV infection.

Background and Objective: The main difficulty of PCR-based clonality studies for B-cell lymphoproliferative disorders (B-LPD) is discrimination between monoclonal and polyclonal PCR products, especially when there is a high background of polyclonal B cells in the tumor sample. Actually, PCR-based methods for clonality assessment require additional analysis of the PCR products in order to discern between monoclonal and polyclonal samples. Heteroduplex analysis represents an attractive approach since it is easy to perform and avoids the use of radioactive substrates or expensive equipment., Design and Methods: We studied the sensitivity and specificity of heteroduplex PCR analysis for monoclonal detection in samples from 90 B-cell non Hodgkin's lymphoma (B-NHL) patients and in 28 individuals without neoplastic B-cell disorders (negative controls). Furthermore, in 42 B-NHL and in the same 28 negative controls, we compared heteroduplex analysis vs the classical PCR technique. We also compared ethidium bromide (EtBr) vs. silver nitrate (AgNO(3)) staining as well as agarose vs. polyacrylamide gel electrophoresis (PAGE)., Results: Using two pair consensus primers sited at VH (FR3 and FR2) and at JH, 91% of B-NHL samples displayed monoclonal products after heteroduplex PCR analysis using PAGE and AgNO(3) staining. Moreover, no polyclonal sample showed a monoclonal PCR product. By contrast, false positive results were obtained when using agarose (5/28) and PAGE without heteroduplex analysis: 2/28 and 8/28 with EtBr and AgNO(3) staining, respectively. In addition, false negative results only appeared with EtBr staining: 13/42 in agarose, 4/42 in PAGE without heteroduplex analysis and 7/42 in PAGE after heteroduplex analysis., Interpretation and Conclusions: We conclude that AgNO(3) stained PAGE after heteroduplex analysis is the most suitable strategy for detecting monoclonal rearrangements in B-NHL samples because it does not produce false-positive results and the risk of false-negative results is very low.

Background: Single-donor platelets (SDPs) are frequently preferred over pooled random-donor platelets (RDPs) to reduce donor exposures and the risk for virus transmission or HLA alloimmunization. Transfusion-associated virus-transmission risks have significantly decreased, which suggests that white cell reduction by filtration eliminates any difference in the risk of alloimmunization in transfused leukemic patients. Health care reform pressures of make it appropriate to examine the cost-effectiveness of SDPs versus RDPs in reducing donor exposures., Study Design and Methods: A decision analysis model was developed and sensitivity analyses were used to assess the incremental cost (dollars/quality-adjusted life-year) associated with the use of SDPs versus RDPs for adult patients undergoing hematopoietic progenitor cell transplantation or primary coronary artery bypass grafting (CABG)., Results: Among transplant patients, the incremental cost of choosing SDPs as opposed to RDPs ranged from $168,700 to $519,822 per quality-adjusted life-year. For patients undergoing primary CABG, the incremental cost was $192,415 (females) and $216,280 (males). Variations in the cost differential between SDPs and RDPs, the number of random-donor platelets in the RDP, and the risk of bacterial sepsis markedly influenced cost-effectiveness. The model was minimally affected by variations in the risks of transmission of HIV and hepatitis B and C, and human T-lymphotropic viruses., Conclusion: In comparison with other accepted medical interventions, the use of SDPs as opposed to RDPs may not be a cost-effective method of reducing donor exposures in the adult patient populations studied. SDPs were more cost-effective in patients undergoing primary CABG than in leukemia patients undergoing hematopoietic progenitor cell transplantation. Regardless of diagnosis, decreasing the acquisition cost differential would have the greatest impact on improving the cost-effectiveness of SDPs, as opposed to RDPs, to decrease donor exposures.

Infectious agent(s) causing the fatal Sarawak acute childhood viral infection (SACVI) has not been identified. In the present study, results indicating that inocula prepared from the fatal cases of SACVI induced apoptosis in Vero cell cultures are presented. These findings suggest the possible involvement of apoptotic cellular responses in SACVI.

The improved survival of SLE patients since the 1950s is the result of not only better treatment, but also supportive treatment of renal failure and the wealth of antibiotics now available. Ironically, the wider use of immunosuppressives, especially the alkylating drugs, and the longer survival of patients with renal insufficiency and renal failure have made the identification and appropriate treatment of infection in SLE an ongoing challenge.

Objective: To assess the risk of infection in patients with systemic lupus erythematosus (SLE) treated with plasmapheresis in addition to intravenous (I.V.) pulse cyclophosphamide (CYC)., Methods: We searched the records of all our SLE patients for those who had undergone plasmapheresis plus I.V. CYC treatment (n = 9). Consecutive patients with similarly high SLE activity who underwent I.V. CYC therapy but not plasmapheresis were included as controls (n = 12). We evaluated both groups for severe infections, outcome, and confounding clinical variables., Results: Seven of 9 plasmapheresis-treated patients had serious bacterial or viral infections, including 3 cases of cytomegalovirus infections. Among the 12 patients treated with I.V. CYC alone, only 2 had severe infections (P < 0.01). Three patients in the plasmapheresis group and none in the control group died of infections. Treatment efficacy, however, was similar for both groups., Conclusion: Among SLE patients treated with plasmapheresis and I.V. CYC, life-threatening bacterial and viral infections and mortality occur more frequently than among patients with similarly active SLE treated with I.V. CYC alone.

Patients with acute leukemia treated with intensive chemotherapy and recipients of bone marrow or peripheral blood stem cell transplants are at high risk of serious viral disease. Recent progress in diagnostic methods and in antiviral drug treatment has permitted the development of efficient management strategies particularly for infections due to herpes simplex virus, varicella-zoster virus, and cytomegalovirus in these patients. By contrast, specific treatment of other virus infections in immunocompromised cancer patients remains an unresolved issue. The emergence of herpesvirus resistance to antiviral drugs is a matter of concern, and its clinical importance among patients with malignancy needs to be elucidated. Future investigations may furthermore help to clarify the role of novel antiviral agents, such as cidofovir, lobucavir, and compound 1263W94, and of the adoptive immunotherapy with virus-specific CTL clones in severely immunodeficient cancer patients.

Background: Detailed information regarding the spectrum and predictors of infection after heart transplantation in children is limited because of relatively small numbers of patients at any single institution. We therefore used combined data obtained from the Pediatric Heart Transplant Study Group to gain additional information regarding infectious complications in the pediatric population., Methods: To determine the time-related risk of infection and death related to infection in a large pediatric patient population, we analyzed data related to 332 pediatric patients (undergoing heart transplantation between January 1, 1993, and December 31, 1994) from 22 institutions in the Pediatric Heart Transplant Study Group., Results: Among the 332 total patients, 276 infections were identified in 136 patients. Of those patients with development of infection, a single infection episode was reported in 54% of patients, 21% had two infections, and 25% had three or more infections. Of the 276 infections, 164 (60%) were bacterial, 51 (18%) were due to cytomegalovirus, 35 (13%) were other viral (noncytomegalovirus) infections, 19 (7%) were fungal, and 7 (2%) were protozoal. Bacterial infections were more common in infants younger than 6 months of age at time of transplantation, comprising 73% of all infections as compared with 49% in patients older than 6 months of age. The incidence of bacterial infection peaked during the first month after transplantation, with the actuarial likelihood of a bacterial infection among all patients reaching 25% at 2 months. The most common sites of bacterial infection were blood and lung (74% of bacterial infections). Cytomegalovirus accounted for 59% of viral infections, with a peak hazard occurring at 2 months after transplantation. Among all infections, cytomegalovirus was less common in infants younger than 6 months of age (8% of all infections) than in older patients (25%). By multivariate analysis, risk factors for early infection included younger recipient age (p = 0.05), mechanical ventilation at time of transplantation (p = 0.0002), positive donor cytomegalovirus serologic study result with negative recipient result (p = 0.004), and longer donor ischemic time (p = 0.04). The overall mortality rate from infection was 5%, with an actuarial freedom from death related to infection of 92% at 1 year after transplantation. The mortality rate was high in patients with fungal infections (52%), yet was low for those with cytomegalovirus infection (6%). Infections accounted for 27% of the overall mortality rate in infants younger than 6 months of age, compared with 16% for older patients., Conclusions: Although most infections in pediatric heart transplant recipients are successfully treated, infection remains an important cause of posttransplantation morbidity and death, especially in infants. Bacterial infections predominate within the first month after transplantation, whereas the peak hazard for viral infections occurs approximately 2 months after transplantation. Cytomegalovirus infections are common in the pediatric transplant population, but death related to cytomegalovirus is low.

Objective: To evaluate drug survival, efficacy, side effects, and longterm toxicity of azathioprine treatment in patients with juvenile chronic arthritis (JCA)., Methods: In an uncontrolled, prospective study we evaluated 129 consecutive patients with JCA refractory to therapy in whom azathioprine treatment was begun during 1980-1989. In the first 29 patients, a 2 year trial was planned, while for the remaining 100 patients the protocol was to continue until remission or dropout. The median treatment period was 13 months (range 3 days-8.5 yrs). Patients were assessed every 2 months for 2 years for efficacy, side effects, growth and need for glucocorticoids, and outcome evaluated in late 1996., Results: Remission without drugs was attained in 19 patients (15%); in addition, temporary remission in patients continuing treatment was attained in 18 cases (14%). Treatment was discontinued due to side effects in 18 cases (14%); in two-thirds of these cases side effects occurred during the first 2 months. Of the total number of patients, 49 (38%) completed 2 years of treatment, with significant improvement in both clinical and laboratory indices of disease activity. Treatment had no noticeable effect on iridocyclitis. One patient died of cytomegalovirus infection during azathioprine treatment., Conclusion: Azathioprine is a useful drug in severe JCA, with a sustained effect and acceptable side effects. Even in cases of incomplete remission, its glucocorticoid sparing effect was noteworthy.

According to the WHO (World Health Organization), 12 million children die annually before reaching the age of five. Seventy per cent of the deaths are related to one or more of five common diseases: acute respiratory tract infection, diarrhoea, measles, malaria and malnutrition. Consequently, drawing on international experience and expertise, the WHO and UNICEF (United Nations International Children's Emergency Fund) have compiled and developed guidelines for the primary care of Third World children. This programme, entitled Integrated management of childhood illness (IMCI), is expected to improve the care of children in areas and situations resources are limited.

To evaluate the use of extracorporeal membrane oxygenation (ECMO) in patients with Gram-negative or viral sepsis, a survey of ECMO centres comprising the Extracorporeal Life Support Organization was conducted. Data collected from neonatal and paediatric intensive care units included patient demographics, indicators of infection, presence of cardiac instability and respiratory criteria for ECMO. One-hundred-and-seven patients with documented sepsis were divided into survivors and nonsurvivors. Prior to ECMO, the patients with a persistent metabolic acidosis (p < 0.008) and/or hypotension requiring more than two inotropic agents (p < 0.02) to support blood pressure were less likely to survive. Also, patients with Gram-positive infections (77%) were more likely to survive their ECMO course than those with Gram-negative (60%) or viral infections (40%). Although survival is less in septic infants than in infants with traditional respiratory failure placed on ECMO, sepsis should not be a contraindication to the use of ECMO. The parents should be informed of the chances of survival with each type of sepsis or respiratory infection (if known), so that a truly informed decision can be made by the parents. We feel that the additional information regarding Gram-negative and viral sepsis should assist the clinician in this goal.

Objective: To determine risk factors for serious infection during treatment with cyclophosphamide (CYC) and high-dose corticosteroids in systemic lupus erythematosus (SLE)., Methods: Records of 100 SLE patients who had received CYC were examined for documentation of serious infections that occurred during CYC therapy and the subsequent 3 months., Results: Infection occurred in 45 of 100 patients during CYC therapy. Patients with infection were more likely to have multiple organ disease (49% versus 29%; P = 0.04), a lower nadir in the white blood cell (WBC) count (2,818 versus 3,558 cells/microliter; P = 0.02), and a higher maximum corticosteroid dose (195 versus 73 mg; P < or = 0.01) than patients without infection. Infection occurred with equal prevalence in those who received intravenous (IV) (39%) or oral (40%) CYC, but was more common with use of sequential IV and oral therapy (68%). By multivariate analysis, the strongest association with infection was a WBC nadir < or = 3,000 cells/microliter (odds ratio [OR] 2.8, 95% confidence interval [95% Cl] 1.4-5.5) and use of sequential IV and oral CYC (OR 2.3, 95% Cl 1.2-4.3). Infection occurred in more CYC-treated patients taking concomitant steroids than in those treated with high-dose steroids alone (45% versus 12%; P = 0.001). Fatal and opportunistic infections during CYC therapy were associated with a low WBC nadir and a high maximum corticosteroid dose., Conclusion: The risk of serious infection in patients with SLE is influenced by the inclusion of CYC in the treatment regimen. The likelihood of infection in this setting is enhanced by CYC-induced reductions in the total WBC count < 3,000 cells/microliter and by sequential IV and oral therapy. Both of these factors may be indicators of aggressive cytotoxic treatment, underscoring the need for close observation during treatment to minimize the risk of serious infection.

The clinical characteristics of 15 adult patients with virus-associated haemophagocytic syndrome (VAHS) were studied. The patients were 3 males and 12 females with a mean age of 39.5 years (range 20 to 67 years). Seven patients (mean age 48.6 years) were immunosuppressed by drugs or as a result of having malignant or autoimmune disease. Eight patients (mean age 31.6 years) had no underlying diseases. The prognosis of the patients with immunosuppression was poor, as previously reported, and 3 of them died. In younger adult patients with this syndrome who had no underlying immunosuppressive diseases, the prognosis was good even without therapy. The sera from the patients in both groups contained extremely high levels of macrophage colony-stimulating factor (M-CSF) and slightly elevated levels of tumour necrosis factor-alpha (TNF-alpha). These findings suggested that VAHS, can occur in presumably healthy adults and that VAHS can be a more benign condition than previously believed. M-CSF and TNF-alpha may play an important role in the development of the syndrome in both groups.

Acute infectious myocarditis in childhood has a very poor initial outcome, but the long-term outlook is relatively good for the survivors. This retrospective study was based on cases of acute myocarditis admitted to two hospital departments with different modes of recruitment. Firstly, a polyvalent paediatric intensive care unit where 12 children (mean age 12 months) were admitted during the acute phase of myocarditis. The initial symptoms were non-specific and misleading, the diagnosis being established at autopsy in 9 cases. Only 4 children presented with typical cardiac failure. The clinical signs were hepatomegaly, sinus tachycardia, cardiomegaly, ECG ST-T wave changes and biological signs of multiple organ failure. Left ventricular function was very poor with a fractional shortening of only 17%. The causal agent was usually viral. The clinical course was marked by a high early mortality (11/26, 42%) within 23 hours of hospital admission. Secondly, a paediatric cardiology unit where 81 children (mean age 15 months) were followed up after acute infectious myocarditis. Thirteen cases were taken from our first series and were included for long-term follow-up; 76.5% had premonitory signs of infection and 71% were in cardiac failure, Classes III or IV, during the hospital admission. The causal agent was identified in 30 cases (37%) and was usually a virus (22 cases). Treatment was classical (association of digitalis, diuretics, angiotensin converting enzyme inhibitors, anticoagulants and beta-sympathomimetics when necessary).(ABSTRACT TRUNCATED AT 250 WORDS)

Fulminant hepatic failure without liver transplantation is associated with a high mortality rate (80-100 per cent). Some 254 liver transplantations were performed on 202 patients between April 1986 and February 1992. Of these, 26 patients had fulminant hepatic failure. The median age was 31.5 (range 3-60) years. Reduced-size grafts were used in seven patients. The preoperative mortality rate was six of 26 patients, and five patients died during follow-up. Ten patients underwent retransplantation and two a second retransplant. The overall mortality rate was 16 of 26 and actuarial survival rate was 62.7 per cent at 12 months and 48.7 per cent at 36 months. The preoperative mortality rate is relatively high but liver transplantation is currently recommended as a last-resort treatment for patients with fulminant hepatic failure in the absence of response to medical treatment.

Antibody-dependent enhancement of infection (ADE) is an in vitro serological phenomenon--or a group of phenomena--in which viral infection of susceptible cells is modified by the addition of virus-reactive antibody. Evidence suggests that ADE reflects immunologic processes that occur in vivo. Various severe and even fatal viral conditions of humans and animals, including dengue shock syndrome, the "early-death phenomenon" in experimental infections of immune animals, and other vaccine- and immunoglobulin-modified conditions, have been attributed to ADE by some researchers. ADE has caused great concern in relation to the development of vaccines against dengue virus and human immunodeficiency virus. More data are urgently needed on the mechanisms and determinants of ADE and on its alleged role in disease pathogenesis and in vaccine-associated phenomena.

Based on the results of seven ICTH-controlled PUP studies only the virus-inactivating procedures by pasteurization (60 degrees C for 10 h), tri-n-butyl-phosphate/detergent treatment, and vapor heating (60 degrees C for 10 h and 1,200 mbar) have prevented the haemophilic patients from infections with hepatitis B, C and HIV. After the disaster of the HIV infection in haemophilic patients at the beginning of the 80's the factor concentrates given today seem to be safe for virus infections during substitution therapy. To prove this high therapeutical standard there is a need for a prospective long-term pharmaco-vigilance study under the auspices of an independent body such as the Medical Advising Committee of the National Haemophilia Society or other scientific organisations.