Invasive Haemophilus influenzae type b disease in Alaska: background epidemiology for a vaccine efficacy trial

In a previous study we demonstrated that Alaskan Eskimos had the highest endemic incidence of invasive Haemophilus influenzae type b (Hib) disease. In 1980 we established a prospective surveillance program for all invasive Hib disease throughout Alaska to characterize additional epidemiological features of disease in Native Alaskans to plan for a vaccine efficacy trial and define the epidemiology of Hib disease in all population groups in the state. For the three-year period, 1980-1982, 287 confirmed episodes of invasive Hib disease occurred. For children less than five years of age, the incidences for Eskimos, Indians, and non-Natives were 705, 401, and 129 cases per 100,000 population, respectively. The Native population represents only 16% of the population of Alaska but has 51% of all invasive Hib disease. Disease differed significantly among Eskimos, Indians, and non-Natives with regard to risk, age of onset, disease type, antibiotic susceptibility of strains, and regional incidence, but mortality and seasonal occurrence were similar. For Native Alaskans the cumulative Hib disease risk for the first two years of life was 4% (range, 1%-7% by region). This high endemic disease risk, concentrated in the first two years of life, provides a unique opportunity to prospectively evaluate the protective efficacy of a vaccine in a randomized, blinded, and placebo-controlled trial. Such a trial was initiated in December 1984.     

Invasive disease due to Streptococcus pneumoniae in an area with a high rate of relative penicillin resistance

During 1984 we conducted a population-based survey of culture-confirmed invasive disease due to Streptococcus pneumoniae among persons who lived in the Oklahoma City, Oklahoma, metropolitan area (population, 846,000) through the 20 clinical laboratories in the area. There were 139 residents identified with invasive pneumococcal disease (11 with meningitis and 128 with other bacteremic infections), for an infection rate of 16.4 per 100,000 population (meningitis, 1.3 cases per 100,000; other bacteremias, 15.1 cases per 100,000). Cases peaked in January-May and December (75% of cases). Rates were highest among infants less than 12 months old (97 cases per 100,000) and persons greater than or equal to 80 years old (87 cases per 100,000). Seventeen (12.2%) of the pneumococcal isolates were relatively penicillin resistant. These isolates were most prevalent among elderly persons greater than or equal to 70 years old (six [17.6%] of 34) and young children 0-4 years old (7 [15.9%] of 44) compared with persons 5-69 years old (four [6.6%] of 61).     

Invasive pneumococcal disease in Greenland

INTRODUCTION: The Inuit of Alaska and Canada have a higher incidence of invasive pneumococcal disease than non-inuit. The purpose of the present study was to evaluate incidence and outcome of these infections in Greenland with special reference to pneumococcal serotypes. Study Design: Retrospective study of invasive pneumococcal infections in Greenland in the period 1996-2002. METHODS: Cases were defined as patients with positive cultures of Streptococcus pneumoniae from blood and/or CSF samples received at the microbiological laboratory of Dronning Ingrids Hospital Nuuk. Isolates were sent to Statens Serum Institut in Copenhagen for serotyping. Medical charts were reviewed. RESULTS: Fifty one cases were identified. The incidence among Inuit was 54 and among non-inuit 17 per 100,000 per year. Twenty one patients were in the age group 35-49 years and 20 in the age group 50-64 years. Twenty patients had meningitis (incidence 6 per 100,000/year). Seventeen patients died (33%). The most common serotypes were 1 (6 cases) and 12F (8 cases). The mortality rate was significantly higher among patients with 12F than among others (p < 0.01). No patients with serotype 1 died. CONCLUSION: As in Canada and Alaska the incidence of invasive pneumococcal disease, especially meningitis, is high among the Inuit in Greenland. Young and middle aged adults were most frequently affected. Pneumococcal serotype seems to be an important determinant for the outcome of invasive pneumococcal disease.     

Epidemiology of paediatric invasive fungal infections and a case‐control study of risk factors in acute leukaemia or post stem cell transplant

Patients aged 0–18 years with confirmed or possible invasive fungal infection were identified by medical record and database searches. Cases with an underlying diagnosis of acute leukaemia or following stem cell transplantation were included in a case control study. Controls included all other children with acute leukaemia or stem cell transplant in the corresponding time period. Variables collected included demographics, underlying disease risk and status, organ impairment, admission to intensive care unit, fungal infection details and certain transplant variables. Risk factors for development of invasive fungal infection were examined using logistic regression. There were 106 cases of invasive fungal infection during the study. The incidence of invasive fungal infection was 21% in acute lymphoblastic leukaemia, 15% in acute myeloid leukaemia and 25% following stem cell transplantation. Sixty per cent were neutropenic at diagnosis and 39% had concomitant bacteremia. High risk acute lymphoblastic leukaemia, relapsed disease, intensive care admission and graft‐versus‐host disease were significantly associated with development of invasive fungal infection on multivariate analysis. These associations provide new information on paediatric invasive fungal infections and warrant further study; caution should be encouraged when extrapolating from adult studies.     

High incidence rates of invasive pneumococcal disease in the White Mountain Apache population.

OBJECTIVE--In this article we determine the incidence and clinical spectrum of invasive pneumococcal disease in the White Mountain Apache population, a group known to have a high incidence of invasive disease due to Haemophilus influenzae type b. DESIGN--Patients from whom cultures of normally sterile body sites yielded Streptococcus pneumoniae were identified retrospectively through review of hospital laboratory records from a 6.8-year period. Clinical data were reviewed and incidence rates were computed. SETTING--The Whiteriver Indian Health Service Hospital is located on the 1.7-million-acre White Mountain Apache Reservation in eastern Arizona. PATIENTS--Approximately 10,000 members of the White Mountain Apache Tribe reside on or near the reservation and receive health care through the Whiteriver Indian Health Service Hospital. OUTCOME MEASURES--The average annual incidence rates of invasive pneumococcal disease were calculated and clinical characteristics were reviewed. RESULTS--One hundred thirty-eight cases of invasive pneumococcal disease were identified. The average annual incidence rate was 207 per 100,000 population, and 156 per 100,000 population when adjusted for age by direct standardization to the 1988 US population. The incidence rate was highest in children between 1 and 2 years--2396 per 100,000. The overall case-fatality rate was 5%. Pneumococcal pneumonia was the diagnosis in 79% of the patients 5 years of age or older. Alcohol abuse, identified in 66% of the cases in adults, was the most common underlying medical condition. CONCLUSION--The incidence rates in White Mountain Apaches are the highest reported for any population. A vaccine effective in children would greatly benefit this population.     

Device-related infections in a pediatric intensive care unit: The Jordan University of Science and Technology experience

To estimate the prevalence of the most frequent infections related to device utilization and their antimicrobial sensitivity panel, and to investigate the overall incidence of device associated infection rates per 1000 device days, at the pediatric intensive care unit of the Jordan University of Science and Technology.This is a retrospective study from a single pediatric intensive care unit. Data were collected in relation to bloodstream infections associated with central venous catheters, pneumonia associated with ventilator endotracheal tubes, and urinary tract infections associated with Foley catheters, between January 2013 and December 2018, according to the center of disease control and prevention protocols.During the 5-year study, 3195 patients were admitted to the pediatric intensive care unit for a total of 16,487 days. Forty-six patients (1.4%) developed 55 infections, with a median incidence rate of 7.4, 3.7, and 0.7 per 1000 days for central line associated infections, ventilator associated pneumonia, and catheter associated infections, respectively. The commonest isolated microorganisms were gram-negative bacteria in 89.1% of cases, and fungi in 10.9% of cases. Among the resistant bacterial isolates, 59.2% were multidrug resistant, and 32.6% were extended spectrum beta lactamase producers Klebsiella pneumoniae and Eschericia coli. High infection rates were related to Acinetobacter baumannii and K pneumoniae, associated with high resistance to cephalosporins. Susceptibility was highest to tigecycline and imipenem at 42.9% and 32.7% respectively.Microbial isolates are commonly associated with healthcare device insertions in pediatric intensive care unit, invasive bacterial infections associated with critical morbidity and mortality. Further studies on device associated infections are recommended for regional profiling purposes.     

Invasive pneumococcal disease in children with cancer: Incidence density,risk factors and isolated serotypes

BackgroundPediatric oncology patients (POP) have a high risk of infections due to impaired immunity. Invasive pneumococcal disease (IPD) is an important cause of severe infection in these patients and it is associated with high mortality. This study aimed to evaluate the incidence and risk factors associated with IPD at a Pediatric Oncology Center in Brazil.MethodsThis was a retrospective case-control study. All IPD cases in children with cancer from 2005 through 2016 were reviewed. Each case of IPD was matched with two controls from a cohort of patients matched for year of IPD, age and disease in order to assess risk factors. The incidence density was calculated as the number of IPD per 100,000 patients-year.ResultsA total of 51 episodes of IPD in 49 patients was identified. All pneumococci were isolated from blood cultures. The median age was five years and 67% were male; mortality rate was 7.8%. The IPD incidence density rate in POP was 311.21 per 100,000 patients-year, significantly higher than the rate in the general pediatric population. Severe neutropenia was the only risk factor associated with IPD, after multivariate conditional logistic regression analysis.ConclusionAlthough pneumococcal disease decreased after the introduction of 10-valent pneumococcal vaccine in the Brazilian national immunization schedule in 2010, there was no decrease in the IPD incidence rate in our cohort. A higher coverage rate of pneumococcal vaccination in children in the general population might be necessary to reduce the incidence rate in this high-risk population.     

Nosocomial infections in adult patients undergoing extracorporeal membrane oxygenation.

The use of extracorporeal membrane oxygenation (ECMO) for adult patients has increased in recent years. A retrospective cohort study of adult patients undergoing ECMO was performed between 19 February 1985 and 10 October 1995 to evaluate nosocomial infections. Seventy-one evaluable patients underwent ECMO for a total of 799 days. Forty-six infections were identified in 32 (45%) of 71 patients. There were 15 bloodstream infections, 13 lower respiratory infections, 11 urinary tract infections, and 7 miscellaneous infections. The rates of bloodstream infection (18.8 cases per 1,000 ECMO days) and urinary tract infection (13.8 cases per 1,000 ECMO days) were significantly higher than those reported through the Centers for Disease Control and Prevention / National Nosocomial Infection Surveillance System (P < .0001 and P < .001, respectively). The rate of bloodstream infection increased with the duration of ECMO cannulation. This study highlights the increased risk for nosocomial infections in this patient population. Infection may not be apparent, and increased physician awareness of infection risk is imperative.     

Invasive Pseudomonas aeruginosa infections: high rate of recurrence and mortality after hematopoietic cell transplantation

Limited data exist regarding the incidence and factors associated with outcome of invasive Pseudomonal infections in hematopoietic cell transplant (HCT). A retrospective analysis of cases of invasive Pseudomonas aeruginosa infection and factors associated with outcome was performed. P. aeruginosa invasive infection occurred in 95 of 5772 patients (1.65%) a median of 63 days after HCT (range 5-1435). Only 28% of infections occurred during periods of neutropenia (absolute neutrophil count<500 cells/mm(3)). Infection-attributable mortality during the initial episode of infection was 35.8%. Factors associated with initial mortality included the presence of a copathogen and high-dose steroid use. Ten (16.4%) of those who survived the initial infection experienced a recurrence of P. aeruginosa infection at a median of 9 days (range 3-17) after stopping antibiotics and 60% of those died as a result of recurrent infection a median of 1 day (range 1-7) after onset of recurrence. Grade 3-4 graft-versus-host disease was associated with a higher risk of recurrent infection. The risk of recurrence was not influenced by the presence of copathogens. Thus, invasive P. aeruginosa infections are associated with high recurrence rates and mortality in this immunocompromised population. Aggressive attempts to reduce immunosuppression and to treat copathogens may help during the initial infection.     

Prevention of cryptococcosis in HIV-infected patients with limited access to highly active antiretroviral therapy: evidence for primary azole prophylaxis

Despite advances in the treatment of HIV disease, the incidence and mortality of invasive cryptococcal disease remain significant. A matched, case-control study was performed to examine the impact of highly active antiretroviral therapy (HAART) and azole use on the incidence of invasive cryptococcal disease in HIV-infected patients. The study was performed at a metropolitan hospital with a large indigent population and an incidence of seven cases of cryptococcal disease per 1000 persons with AIDS. Bivariate analysis, matched on CD4 count, revealed that both HAART use [odds ratio (OR) 0.43; 95% confidence interval (CI) 0.23-0.99] and azole use (OR 0.14; 95% CI 0.06-0.34) had a protective effect. Conditional logistic regression stratified on CD4 lymphocyte count revealed a protective role for azole use (OR 0.15; 95% CI 0.06-0.40) but not for HAART use (OR 0.47; 95% CI 0.18-1.26). Of note, the prevalence of HAART use was low in both cases and controls, with only 12% of cases and 23% of controls on HAART. The results of this study support previous evidence that azole use prevents invasive cryptococcal disease. Although current guidelines for the prophylaxis of opportunistic infections do not suggest routine prophylaxis for cryptococcal infection, this issue should be reconsidered, especially in populations that have a low prevalence of HAART use.     

Epidemiology of measles--a thirteen years prospective study in a village

A prospective study on measles was undertaken during 1974 to 1986 in Hiramanpur village, Varanasi having an initial population of 1538 which rose to 2101 in 1986 enabling to register a total of 23,221 (all population) person years of observation and a total of 9191 (0-14 years) person years of observation. The entire population was covered regularly through domicilliary visits by trained para-medical personnel under direct supervision of medical officers. All cases were verified by doctors. A total of 411 measles cases were detected, which gave average annual incidence rates of 17.7 and 44.7 per thousand population and per thousand children (0-14 yrs), respectively. The maximum number of cases occurred in Ist quarter of the year (69.7 per cent). The Kolmogorov-Smirnov Statistical method validated the seasonal character of the disease (Vn = 5.18, p less than 0.01). The maximum measles cases occurred in children 1-4 yrs (57.4 per cent). Males (54.9 per cent) were affected slightly more than females (45.1 per cent). A total of 246 (59.9 per cent) cases developed complications. The most frequent was respiratory infections (42.2 per cent) followed by infection of gastrointestinal system (32.2 per cent). The complication rates were found higher in infants and older children (greater than 5 yrs.) in both the sexes. Three-fourth of the cases did not get any treatment. The overall case-fatality rate was 2.2 per cent. Females had higher rate (3.3 per cent) than males (1.3 per cent) and the highest case fatality rate was observed in infants, particularly in females.     

Population-based study of the epidemiology of and the risk factors for invasive Staphylococcus aureus infections

A population-based active-surveillance study of the Calgary Health Region (population, 929,656) was conducted from May 1999 to April 2000, to define the epidemiology of invasive Staphylococcus aureus (ISA) infections. The annual incidence was 28.4 cases/100,000 population; 46% were classified as nosocomial. Infection was most common in people at the extremes of the age spectrum and in males. Several conditions were associated with acquisition of ISA infection, and the highest risk was observed in persons undergoing hemodialysis or peritoneal dialysis and in persons infected with human immunodeficiency virus. Forty-six patients (19%) died. Significant independent risk factors for mortality included positive blood-culture result, respiratory focus, empirical antibiotic therapy, and older age. A higher systolic blood pressure at presentation was associated with reduced case-fatality rate. ISA infections are common, with several definable groups of patients at increased risk for acquisition and death from these infections. This study provides important data on the burden of ISA disease and identifies risk groups that may potentially benefit from preventive efforts.     

Invasive pneumococcal infection in Baltimore, Md: implications for immunization policy

BACKGROUND: Streptococcus pneumoniae is a leading cause of infectious morbidity and mortality. Although blacks are known to have a higher incidence of invasive pneumococcal infection than whites, detailed analyses of these differences and their implications for vaccine prevention have not been reported. OBJECTIVE: To describe the epidemiological characteristics of invasive pneumococcal infection in Baltimore, Md, and its implications for immunization policy. METHODS: Analysis of active, laboratory-based surveillance during 1995 and 1996 among residents of the Baltimore metropolitan area. RESULTS: Of 1412 cases, 615 patients (43.6%) were classified as white and 766 (54.2%) as black. The annual incidence of invasive pneumococcal infection among white and black residents of the Baltimore metropolitan area was 17.8 and 59.2 per 100000 population, respectively (P<.01). Among patients aged 18 years and older, the median age of blacks with invasive pneumococcal infections was 27 years younger than that of whites (P<.01). Among males 40 to 49 years old, blacks had a 12-fold higher average incidence than whites (average incidence, 114.5 and 9.3, respectively; P<.01). By the age of 65 years, 83.8% of cases had occurred in black adults, as compared with 43.8% in white adults (P<.01). In a regression model, age, black race, male sex, low median family income, and county prevalence of acquired immunodeficiency syndrome were each independently associated with a higher incidence of pneumococcal infection. CONCLUSIONS: Young urban black adults in the Baltimore metropolitan area have a dramatically higher incidence of invasive pneumococcal infection than whites. The vast majority of cases of invasive pneumococcal infection in blacks occur before age 65 years. Current immunization efforts have not addressed the high incidence of pneumococcal infection in this population.     

Gender distribution in asymptomatic and invasive amebiasis

OBJECTIVE: The majority of individuals infected by the protozoan parasite Entamoeba histolytica experience subclinical infections. However, a small proportion of parasitized individuals develop severe invasive disease such as amebic dysentery or amebic liver abscess. Invasive amebiasis affects predominantly men; the usual explanation for this has been that men have a higher rate of asymptomatic infections and therefore experience a higher rate of invasive disease. To date, there is no convincing evidence of an increased rate of asymptomatic infection of men as compared with women. The purpose of this study was to evaluate the evidence supporting the hypothesis that men have higher rates of asymptomatic infection and thus an increased frequency of invasive amebiasis. METHODS: We reviewed published reports of invasive amebiasis and population-based parasitological studies from 1929-1997 to compare the gender ratio of asymptomatic and symptomatic E. histolytica infection. Infections with E. histolytica were differentiated from the nonpathogenic E. dispar whenever possible. RESULTS: The reports of invasive amebiasis (dysentery, liver abscess, colonic perforation, peritonitis, appendicitis, and ameboma) showed a higher proportion of men than women (ratio, male:female = 3.2:1, p < 0.05). This contrasts with the epidemiological surveys, where the rate of asymptomatic infection with E. histolytica was the same (1:1) for both genders (p > 0.05). CONCLUSIONS: Asymptomatic E. histolytica infection is equally distributed between the genders. The high proportion of men with invasive amebiasis may be due to a male-related susceptibility to invasive disease.     

Invasive pneumococcal disease in adult hematopoietic stem cell transplant recipients: a decade of prospective population-based surveillance

Prospective population-based surveillance to assess the epidemiology of invasive pneumococcal disease (IPD) in hematopoietic stem cell transplant (HSCT) patients is limited and a comparison to the general population is lacking. By using a population-based Invasive Bacterial Diseases Network surveillance program, we studied the incidence, clinical significance, serotypes and antimicrobial resistance of IPD in a large cohort of adult HSCT patients and the general population. Streptococcus pneumoniae isolates and patient data were collected prospectively from 1995 to 2004. We identified 14 cases of IPD (based on sterile site isolates) in our HSCT population over a 10-year period. This translated to an incidence rate of 347 infections per 100 000 persons per year. This compared to an incidence of 11.5 per 100 000 persons per year in the general population (regression ratio=30.2; 95% confidence interval (CI) 17.8-50.8, P<0.00001). If nonsterile site isolates (respiratory tract) were included, the incidence rate in transplant patients was 446 per 100 000 persons per year. Serotypes 23F and 6B were most common; 100 and 69.2% of isolates were a serotype included in the pneumococcal polysaccharide and conjugate vaccines, respectively. The antimicrobial resistance rates were high, especially for trimethoprim/sulfamethoxazole. HSCT recipients are at significantly greater risk for IPD than the general population. Preventative strategies are necessary.     

Infections after liver transplantation. An analysis of 101 consecutive cases

We studied infections in 101 consecutive patients who underwent liver transplantation between July 1984 and September 1985. The mean length of follow-up was 394 days. Eighty-three percent of population had 1 or more episodes of infection and 67% of the population had severe infections. The overall mortality was 26/101 (26%) and 23 of 26 deaths (88%) were associated with infection. Seventy percent of severe infections occurred in the first 2 months after transplantation. The most frequent severe infections were abdominal abscess, bacterial pneumonia, invasive candidiasis, Pneumocystis pneumonia, and symptomatic cytomegalovirus infection. Patients with more than 12 hours of cumulative surgical time had a higher rate of severe infections (P less than 0.001), particularly fungal (P less than 0.001) and bacterial (P less than 0.01) infections. Also, the use of choledocho-jejunostomy was associated with a higher rate of infection in patients who had more than 1 transplant operation (P less than 0.02). No increase in infection was found in patients who received azathioprine, or more than the median number of steroid boluses or "recycles"; but patients who received OKT3 therapy had a higher rate of protozoal infections (P less than 0.05). A result similar to that of our previous studies was a strong relation between the number of severe fungal infections and prolonged courses of antibiotics after transplant operation (P less than 0.001). Pretransplant manifestations of severe liver disease such as ascites, encephalopathy, and gastrointestinal bleeding were not associated with higher rates of infection after transplantation, but high serum levels of ALT were. Patients with lower ratios of T-helper to T-suppressor lymphocytes had more severe viral (P less than 0.02) and fungal (P less than 0.01) infections after transplantation.     

Emergence of serogroup C meningococcal disease associated with a high mortality rate in Hefei, China

ABSTRACT: BACKGROUND: Neisseria meningitidis serogroup C has emerged as a cause of epidemic disease in Hefei. The establishment of serogroup C as the predominant cause of endemic disease has not been described. METHODS: We conducted national laboratory-based surveillance for invasive meningococcal disease during 2000--2010. Isolates were characterized by pulsed-field gel electrophoresis and multilocus sequence typing. RESULTS: A total of 845 cases of invasive meningococcal disease were reported. The incidence increased from 1.25 cases per 100,000 population in 2000 to 3.14 cases per 100,000 in 2003 (p < 0.001), and peaked at 8.43 cases per 100,000 in 2005. The increase was mainly the result of an increase in the incidence of serogroup C disease. Serogroup C disease increased from 2/23 (9%) meningococcal cases and 0.11 cases per 100,000 in 2000 to 33/58 (57%) cases and 1.76 cases per 100,000 in 2003 (p < 0.01). Patients infected with serogroup C had serious complications more frequently than those infected with other serogroups. Specifically, 161/493 (32.7%) cases infected with serogroup C had at least one complication. The case-fatality rate of serogroup C meningitis was 11.4%, significantly higher than for serogroup A meningitis (5.3%, p = 0.021). Among patients with meningococcal disease, factors associated with death in univariate analysis were age of 15--24 years, infection with serogroup C, and meningococcemia. CONCLUSIONS: The incidence of meningococcal disease has substantially increased and serogroup C has become endemic in Hefei. The serogroup C strain has caused more severe disease than the previously predominant serogroup A strain.