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The Global Polio Eradication Initiative continues to make progress toward the eradication target. Indigenous wild poliovirus (WPV) type 2 was last detected in 1999, WPV type 3 was last detected in 2012, and over the past 2 years WPV type 1 has been detected only in parts of 2 countries (Afghanistan and Pakistan). Once the eradication of poliomyelitis is achieved, infectious and potentially infectious poliovirus materials retained in laboratories, vaccine production sites, and other storage facilities will continue to pose a risk for poliovirus reintroduction into communities. The recent breach in containment of WPV type 2 in an inactivated poliovirus vaccine manufacturing site in the Netherlands prompted this review, which summarizes information on facility-associated release of polioviruses into communities reported over >8 decades. Successful polio eradication requires the management of poliovirus containment posteradication to prevent the consequences of the reestablishment of poliovirus transmission.

Three selective enrichment procedures-the U.S. Food and Drug Administration (FDA) method, the U.S. Department of Agriculture (USDA) method, and the Netherlands Government Food Inspection Service (NGFIS) method-were compared for isolating Listeria monocytogenes from contaminated foods. The foods were obtained from the refrigerators of patients with culture-proven listeriosis who were identified through multistate active surveillance in a U.S. population of 19 million. The study was designed to identify foods that may be important in transmission of L. monocytogenes in sporadic cases of human listeriosis. Of 899 foods analyzed by all three methods, 121 were positive for L. monocytogenes by at least one method. The three enrichment methods detected L. monocytogenes in 65% (FDA), 74% (USDA), and 74% (NGFIS) of the foods shown to contain L. monocytogenes . The differences among the three methods were not statistically significant. However, the recovery of L. monocytogenes by a combination of any two methods (USDA-FDA 88%, USDA-NGFIS 91%, FDA-NGFIS 87%) was significantly better than that by one method alone (p < 0.02). The differences among the combinations of methods were not statistically significant. These results suggest that at least two enrichment methods must be used in combination to recover L. monocytogenes from contaminated foods with a success rate near 90%. Correlations were observed between negative results and low (

Before introduction of Haemophilus influenzae type b (Hib) vaccines, rates of Hib disease in Alaska's indigenous people were among the highest in the world. Vaccination reduced rates dramatically; however, invasive H. influenzae type a (Hia) disease has emerged. Cases of invasive disease were identified through Alaska statewide surveillance during 1983-2011. Of 866 isolates analyzed for serotype, 32 (4%) were Hia. No Hia disease was identified before 2002; 32 cases occurred during 2002-2011 (p

Outbreaks of invasive pneumococcal disease (IPD) caused by Streptococcus pneumoniae serotype 12F were observed in two neighboring regions of rural Alaska in 2003 to 2006 and 2006 to 2008. IPD surveillance data from 1986 to 2009 and carriage survey data from 1998 to 2004 and 2008 to 2009 were reviewed to identify patterns of serotype 12F transmission. Pulsed-field gel electrophoresis was performed on all available isolates, and selected isolates were characterized by additional genetic subtyping methods. Serotype 12F IPD occurred in two waves in Alaska between 1986 and 2008. While cases of disease occurred nearly every year in Anchorage, in rural regions, 12F IPD occurred with rates 10- to 20-fold higher than those in Anchorage, often with many years between disease peaks and generally caused by a single predominant genetic clone. Carriage occurred predominantly in adults, except early in the rural outbreaks, when most carriage was in persons

BACKGROUND American Indians and Alaska Natives (AI/ANs) have had documented outbreaks of methicillin-resistant Staphylococcus aureus (MRSA) infection but, to our knowledge, no studies have examined MRSA infection among this population nationally. We describe MRSA-associated hospitalizations among the approximately 1.6 million AI/ANs who receive care at Indian Health Service health care facilities nationwide. METHODS We used hospital discharge data from the Indian Health Service National Patient Information Reporting System to determine the rate of MRSA-associated hospitalizations among AI/ANs who used Indian Health Service health care in 1996-2005 and in the comparison periods 1996-1998 and 2003-2005. Hospitalization rates among AI/ANs were examined by year, age group, sex, and region. MRSA-associated diagnoses were also examined. Rate comparisons were performed using Poisson regression analysis. Comparison of rates to those of the general United States population was made for 2003-2005 by means of the Nationwide Inpatient Sample. RESULTS Between comparison periods, the rate of MRSA-associated hospitalization increased from 4.6 to 50.6 hospitalizations per 100,000 AI/ANs (P

OBJECTIVES: The purpose of this study was to evaluate the effectiveness of Haemophilus influenzae type b (Hib) conjugate vaccines among children aged 2 to 18 months and to determine risk factors for invasive Hib disease during a period of declining incidence (1991-1994). METHODS: A prospective population-based case-control study was conducted in a multistate US population of 15.5 million. A laboratory-based active surveillance system was used for case detection. RESULTS: In a multivariate analysis, having a single-parent mother (odds ratio [OR] = 4.3, 95% confidence interval [CI] = 1.2, 14.8) and household crowding (OR = 3.5, 95% CI = 1.03, 11.7) were risk factors for Hib disease independent of vaccination status. After adjustment for these risk factors, the protective efficacy of 2 or more Hib vaccine doses was 86% (95% CI = 16%, 98%). Among undervaccinated subjects, living with a smoker (P = .02) and several indicators of lower socioeconomic status were risk factors for Hib disease. CONCLUSIONS: Hib disease still occurs at low levels in the United States, predominantly in socioeconomically disadvantaged populations. Low immunization coverage may facilitate continuing transmission of Hib. Special efforts to achieve complete and timely immunization in disadvantaged populations are needed.

Haemophilus influenzae type b (Hib) was the major cause of invasive bacterial disease in the United States and Canada before the introduction of Hib conjugate vaccines. Between 10000 and 20000 cases of Hib meningitis and other serious diseases occurred each year, leading to death in at least 3% of all patients and long term neurologic problems in up to 25% of survivors of meningitis. Introduction of Hib conjugate vaccines in Canada and the United States, first in children 18 months and older and later as a routine infant immunization, dramatically decreased the incidence of disease. By 1995 Hib disease levels had declined by more than 95% below preimmunization levels. The remarkably rapid reduction in disease incidence was partly because of the ability of the vaccine to reduce nasopharyngeal carriage of the organism, leading, when given widely, to reduced rates of exposure and infection even in those not immunized. Complete elimination of Hib disease in North America, however, will require achievement of relatively high coverage rates, especially in hard to reach populations where much of the remaining disease is occurring.

Understanding the basis of sporadic (endemic) meningococcal disease may be critical to prevention of meningococcal epidemic outbreaks and to understanding fluctuations in incidence. Active, prospective, population-based surveillance and molecular epidemiologic techniques were used to study sporadic serogroup C meningococcal disease in a population of 2.34 million persons (Atlanta area). During 1988-1994, in which no outbreaks or case clusters were reported, 71 patients developed sporadic serogroup C meningococcal disease (annual incidence, 0.51/100,000). Eighty-three percent of patients were >2 years old. By multilocus enzyme electrophoresis, pulsed-field gel electrophoresis, and serotyping, 84% (52/62) of the isolates available for study were identical or closely related members of the electrophoretic type 37 (ET 37) complex responsible for multiple serogroup C outbreaks in the United States in the 1990s. Sporadic disease caused by 9 clonal strains occurred over periods up to 4 years and accounted for 45% (28/62) of cases. Sporadic serogroup C meningococcal disease was most often due to a limited number of related strains that appear to slowly circulate in the population.

Background Before the introduction of the conjugate vaccines, Haemophilus influenzae type b was the major cause of bacterial meningitis in the United States, and meningitis was primarily a disease of infants and young children. We describe the epidemiologic features of bacterial meningitis five years after the H. influenzae type b conjugate vaccines were licensed for routine immunization of infants. Methods Data were collected from active, population-based surveillance for culture-confirmed meningitis and other invasive bacterial disease during 1995 in laboratories serving all the acute care hospitals in 22 counties of four states (total population, more than 10 million). The rates were compared with those for 1986 obtained by similar surveillance. Results On the basis of 248 cases of bacterial meningitis in the surveillance areas, the rates of meningitis (per 100,000) for the major pathogens in 1995 were Streptococcus pneumoniae, 1.1; Neisseria meningitidis, 0.6; group B streptococcus, 0.3; Listeria mono...

Background. Since 1992 the US Pacific Northwest has experienced a substantial increase in the incidence of serogroup B meningococcal disease. The current meningococcal polysaccharide vaccine is poorly immunogenic in young children and does not protect against N. meningitidis serogroup B. Defining alternative approaches to the prevention and control of meningococcal disease is of considerable public health importance. Methods. We performed a case-control study comparing 129 patients in Oregon and southwest Washington with 274 age- and area-matched controls. We used conditional logistic regression analysis to determine which exposures remained associated with disease after adjusting for other risk factors and confounders and calculated the proportion of disease attributable to modifiable exposures. Results. After adjustment for all other significant exposures identified, having a mother who smokes was the strongest independent risk factor for invasive meningococcal disease in children

Background . American Indian/Alaska Native (AI/AN) people suffer substantially higher rates of invasive pneumococcal disease (IPD) than the general US population. We evaluated antimicrobial prescribing data and their association with non-susceptibility in Streptococcus pneumoniae causing IPD in AI/AN people between 1992 and 2009. Methods . Antimicrobial use data were gathered from the electronic patient management system and included all prescriptions dispensed to Alaska Native patients aged 5 years and older from outpatient pharmacies at the Alaska Native Medical Center (ANMC). Antimicrobial susceptibility data were gathered from pneumococcal isolates causing IPD among Anchorage Service Unit AI/AN residents aged 5 years and older. Data were restricted to serotypes not contained in the pneumococcal vaccine (PCV7). Results . Over the study period, overall antimicrobial prescribing increased 59% (285/1,000 persons/year in 1992 to 454/1,000 persons per year in 2009, p

BACKGROUND In 2010, a 13-valent pneumococcal conjugate vaccine (PCV13) replaced a 7-valent vaccine (PCV7) that contained all PCV7 serotypes plus 6 additional serotypes (PCV6+). We conducted annual surveys from 2008 to 2012 to determine the effect of PCV13 on colonization by pneumococcal serotypes. METHODS We obtained nasopharyngeal swabs for pneumococcal identification and serotyping from residents of all ages at 8 rural villages and children age

From January through March 1993, there were 54 cases of meningococcal disease in Los Angeles County, California, of which 9 occurred among men incarcerated in the county's jail system, which was 40 percent above capacity at the time. Several of the 45 patients from the community had had contact with men recently released from a county jail.We interviewed patients from the community (n=42) and neighborhood controls matched with the patients for age, race, and ethnic group (n=84) about potential exposures. We collected and cultured pharyngeal swabs for Neisseria meningitidis from men entering the central jail (n=162), men leaving the central jail (n=379), members of the jail staff (n=121), and patients at a community health center (n=214). Meningococcal isolates were identified by serotyping and multilocus enzyme electrophoresis.The presence of community-acquired meningococcal disease was strongly associated with exposure to a person who had been in or worked at one of the county jails (multivariate matched odds ratio, 18.5; 95 percent confidence interval, 3.8 to 90.8; P0.001). Pharyngeal carriage of meningococcus was significantly more frequent among men released from jail (19 percent) or entering jail (17 percent) than among workers at the jails (3 percent) or community residents seen at the clinic (1 percent). Among men entering jail, those who had previously been incarcerated were more often carriers than those who had not (21 percent vs. 7 percent, P=0.03). Of the isolates from nine community residents with serogroup C meningococcal disease, eight were the same strain as that isolated from the eight inmates with serogroup C disease.In this outbreak of meningococcal disease in Los Angeles County, nearly half of community residents with the disease had contact with persons who had been in a county jail. The high rates of carriage among recidivists and released inmates suggests that the men became meningococcal carriers while in jail.

With the decline in the rate of infections caused by Haemophilus influenzae serotype b, H. influenzae serotype f (Hif) is becoming a relatively important cause of invasive disease due to H. influenzae. We identified 91 cases of invasive Hif infections in a multistate area over a 6-year period. The incidence of invasive Hif disease was 0.5 case per 1,000,000 population in 1989 and 1.9 cases per 1,000,000 population in 1994. The proportion of all invasive H. influenzae disease caused by Hif rose from 1% in 1989 to 17% in 1994. Seventy-two percent of cases occurred in adults, and 26% of cases occurred in children younger than 5 years of age. Respiratory tract infections accounted for 82% of adult cases, and most adults had significant underlying diseases. In children, pneumonia and meningitis each accounted for 40% of cases, respectively. Overall mortality was 30% among adults, and 21% among children. Molecular typing demonstrated limited overall diversity in Hif isolates. Continued surveillance is warranted to evaluate the trend toward the increasing incidence of Hif disease that was noted in this study.

To estimate the prevalence of Neisseria meningitidis relatively resistant to penicillin in the United States, antimicrobial susceptibility testing was performed on all US meningococcal isolates submitted to the Centers for Disease Control and Prevention in 1991, including isolates identified through population-based surveillance for invasive meningococcal disease in selected areas of the United States. Three of the 100 isolates tested had MICs of penicillin of 0.125 microgram/mL. All were serogroup B, beta-lactamase-negative, and unique by multilocus enzyme electrophoresis subtyping. None of the 3 patients had been treated solely with penicillin; all recovered completely. About 4% of the isolates obtained from the population-based surveillance system were relatively penicillin-resistant. Given the low prevalence and uncertain clinical significance of infection with these organisms, routine susceptibility testing of meningococcal isolates is not indicated at this time; however, continued surveillance is necessary to monitor trends in antimicrobial susceptibility of meningococci in the United States.

We evaluated nasopharyngeal carriage of Streptococcus pneumoniae (pneumococci) in nine Alaskan communities and used an algorithm combining microbiologic, serologic, and sequential multiplex PCR (MP-PCR) techniques to serotype the isolates. After microbiological identification as pneumococci, isolates ( n = 1,135) were serotyped using latex agglutination and Quellung tests (LA/Q) as well as a series of six sequential MP-PCR assays. Results from the two methods agreed for 94% (1,064/1,135) of samples. Eighty-six percent (61/71) of the discordant results were resolved. Discordant results occurred because (i) the MP-PCR gel was misread (31/61 [51%]), (ii) the LA/Q agglutination was misinterpreted (13/61 [21%]), (iii) two serotypes or sets of serotypes were identified by MP-PCR and only one of the two was identified by LA/Q (9/61 [15%]), (iv) different serotypes or sets of serotypes were identified by LA/Q and MP-PCR and both were correct (7/61 [11%]), and (v) the capsular polysaccharide locus ( cps ) did not amplify during the initial MP-PCR but was present upon retesting (1/61 [2%]). Overall, isolation of pneumococci followed by MP-PCR quickly and accurately identified pneumococcal serotypes in >97% of samples and made available isolates for additional tests such as antimicrobial susceptibility. Misinterpretation of the MP-PCR gel was identified as the main source of discordance. Increasing the number of MP-PCRs from six to seven and reducing the number of serotypes in each reaction may reduce this error. This method may be of use to laboratories characterizing large numbers of S. pneumoniae samples, especially when antimicrobial susceptibility data are needed.

Rates of invasive Haemophilus influenzae type b (Hib) disease in children decreased very rapidly after licensure of Hib conjugate vaccines. A role for a vaccine-related reduction in nasopharyngeal carriage of Hib has been suggested. We studied oropharyngeal carriage of Hib and vaccination rates in a population of 2- to 5-year-old children in metropolitan Atlanta. Among 584 children 75% were vaccinated with an Hib conjugate vaccine, 17% had not been vaccinated and 8% had no vaccination records available. Forty-one percent of the children were colonized with H. influenzae. One child was colonized with Hib. Hib carriage (0.17%; upper 95% confidence interval boundary, 0.97%) was substantially lower than the estimates of Hib carriage from prior studies of children who had not received Hib conjugate vaccines. Our data are consistent with a decline in Hib carriage induced by widespread use of conjugate Hib vaccines, which may have contributed to the decline of Hib disease in United States children.

BACKGROUND Mucosal immunity induced by oral poliovirus vaccine (OPV) is imperfect and potentially allows immunized individuals to participate in asymptomatic wild-type poliovirus transmission in settings with efficient fecal-oral transmission of infection. METHODS We examined the extent of asymptomatic wild-type poliovirus transmission in India by measuring the prevalence of virus in stool samples obtained from 14,005 healthy children who were in contact with 2761 individuals with suspected poliomyelitis reported during the period 2003-2008. RESULTS Wild-type poliovirus serotypes 1 and 3 were isolated from the stool samples of 103 (0.74%) and 104 (0.74%) healthy contacts, respectively. Among contacts of individuals with laboratory-confirmed poliomyelitis, 27 (12.7%) of 213 and 29 (13.9%) of 209 had serotypes 1 and 3, respectively, isolated from their stool samples. The odds ratio of excreting serotype 1 wild-type poliovirus was 0.13 (95% confidence interval, 0.02-0.87) among healthy children reporting 6 doses of OPV, compared with children reporting 0-2 doses. However, two-thirds of healthy children who excreted this virus reported >or=6 doses, and the prevalence of this virus did not decrease with age over the sampled range. CONCLUSIONS Although OPV is protective against infection with poliovirus, the majority of healthy contacts who excreted wild-type poliovirus were well vaccinated. This is consistent with a potential role for OPV-vaccinated children in continued wild-type poliovirus transmission and requires further study.

Persistent conjunctival carriage of the Haemophilus influenzae biogroup aegyptius (Hae) strain (BPF clone) responsible for Brazilian purpuric fever (BPF) has been documented. Topical chloramphenicol is routinely used to treat conjunctivitis in areas affected by BPF in Brazil. Although the BPF clone is susceptible to chloramphenicol, we observed a number of children treated with topical chloramphenicol for conjunctivitis who still developed BPF. During an investigation of an outbreak of BPF in Mato Grosso State, Brazil, we compared oral rifampin (20 mg/kg/day for 4 days) with topical chloramphenicol for eradication of conjunctival carriage of H. influenzae biogroup aegyptius among children with presumed BPF clone conjunctivitis. Conjunctival samples were taken for culture on the day treatment was initiated and a mean of 8 and 21 days later. At 8 days the eradication rates for oral rifampin and topical chloramphenicol were 100 and 44%, respectively (P = 0.003); at 21 days they were 100 and 50% (P = 0.01). Oral rifampin was more effective than topical chloramphenicol for eradication of the BPF clone and may be useful in prevention of BPF.

Alaska Native (AN) children, especially those in the Yukon-Kuskokwim region (YK-AN children), suffer some of the highest rates of invasive pneumococcal disease (IPD) in the world. Rates of IPD declined after statewide introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in 2001, but increased in subsequent years.Population-based laboratory surveillance data (1986-2007) for invasive Streptococcus pneumoniae infection in Alaskan children5 years old were used to evaluate the association of IPD rates and serotype distribution with immunization, socioeconomic status, and in-home water service.Introduction of PCV7 vaccine resulted in elimination of IPD caused by vaccine serotypes, but was followed by increasing rates of IPD caused by nonvaccine serotypes. Among YK-AN children IPD rates dropped by 60%, but then rose due to non-PCV7 serotypes to levels 5- to 10-fold higher than rates in non-YK-AN children and non-AN children. IPD rates in YK-AN children were twice as high in villages where10% of houses had in-home piped water compared with villages where more than 80% of houses had in-home piped water (390 cases/100,000 vs. 146 cases/100,000, P = 0.008).High IPD rates in Alaska are associated with lack of in-home piped water (controlling for household crowding and per capita income). The effect of in-home piped water is most likely mediated through reduced water supply leading to limitations on handwashing.

Background. Persistent wild-poliovirus transmission, particularly in India, has raised questions about the degree of mucosal immunity induced by oral poliovirus vaccine (OPV) in tropical countries. Methods. Excretion of vaccine poliovirus after challenge with OPV was measured in stool samples collected from children identified by the acute flaccid paralysis surveillance program in India during 2005-2007. The effectiveness of trivalent and monovalent OPV against excretion of each poliovirus type was estimated. Results. Vaccine poliovirus was isolated from 4994 (5.2%) of 96,641 children with 2 stool samples. The relative odds of excreting challenge poliovirus among children with ≥5 reported previous doses of trivalent OPV compared with 0 previous doses was 0.24 (95% confidence interval [CI], 0.12-0.45), 0.08 (95% CI, 0.04-0.14), and 0.40 (95% CI, 0.19-0.85) for serotypes 1, 2, and 3, respectively, but the relative odds increased to 0.62 (95% CI, 0.44-0.88), 0.44 (95% CI, 0.20-0.99), and 0.66 (95% CI, 0.41-1.06), respectively, in the northern states of Uttar Pradesh and Bihar. In these 2 states, the relative odds of excretion of serotype 1 was 0.32 (95% CI, 0.26-0.41) after ≥5 doses of type 1 monovalent OPV. Conclusions. The mucosal immunity induced by OPV in India varies by location, serotype, and vaccine formulation. These findings have implications for global eradication and the potential role played by inactivated vaccine in this setting.

We compared the cold enrichment (CE) and U.S. Department of Agriculture (USDA) methods for isolating Listeria monocytogenes by examining 402 food samples. The food samples were collected from refrigerators of listeriosis patients as part of a multistate active surveillance project to determine the role of foods in sporadic listeriosis in the United States. L. monocytogenes was isolated from 51 food samples (13%). The USDA method was significantly better (P less than 0.001) than the CE method. The isolation efficiencies of the USDA and CE methods were 96 and 59%, respectively. Quantitation of L. monocytogenes in the food samples revealed that many food samples containing less than 0.3 CFU/g were negative as determined by the CE method but positive as determined by the USDA method.

A facility which produced turkey franks that had been microbiologically linked to a case of human listeriosis was evaluated to establish prevalence of contamination and identify potential points for intervention. Listeria monocytogenes was isolated from only two of 41 environmental samples obtained in the plant. Among production line product samples analyzed by the Centers for Disease Control, 0 to 8% of samples from the production stages before the peeler-conveyor belt apparatus were positive for the case strain of L. monocytogenes , whereas 12 of 14 (86%) samples collected from this apparatus were positive (p0.001). The most probable number (MPN) of L. monocytogenes in finished product purchased from a retail outlet was less than 0.3 per gram; however, the opened package of franks from the case patient's refrigerator had an MPN of1100 per gram. These data suggest that systematic culturing and analysis of products and production facilities may help identify appropriate interventions to reduce L. monocytogenes contamination in food processing plants and contribute to control of L. monocytogenes in ready-to-eat meat products.

A prospective, laboratory-based surveillance project obtained accurate data on meningitis in a population of 34 million people during 1986. Haemophilus influenzae was the most common cause of bacterial meningitis (45%), followed by Streptococcus pneumoniae (18%), and Neisseria meningitidis (14%). Rates of H. influenzae meningitis varied significantly by region, from 1.9/100,000 in New Jersey to 4.0/100,000 in Washington state. The overall case fatality rates for meningitis were lower than those reported in several studies from the early 1970s, suggesting that improvements in early detection and antibiotic treatment may have occurred since that time. Concurrent surveillance was also performed for all invasive disease due to the five most common causes of bacterial meningitis. Serotypes of group B streptococcus other than type III caused more than half of neonatal group B streptococcal disease and mortality, suggesting that an optimal vaccine preparation must be multivalent. Of the organisms evaluated, group B streptococcus was the second most common cause of invasive disease in persons greater than 5 years old.

To identify characteristics of day care facilities associated with H. influenzae disease, we compared 92 licensed facilities in which a case of H. influenzae disease had occurred with randomly selected facilities at which no cases occurred. Matched univariate analysis showed that personnel at facilities where H. influenzae disease occurred were more likely than those at control facilities to use towels or handkerchiefs to wipe children's noses, admit children who were not toilet trained or had diarrhea ("liberal fecal policy"), had a narrower age range, were more likely than control facilities to be for-profit and less likely to use volunteers. In a multivariate model that adjusted for age range, profit status and liberal fecal policy, towel or handkerchief use (OR 5.5, 95% CI: 1.1, 30) was the only variable independently associated with case facilities. This is the first association of a specific day care practice with H. influenzae disease.

Summary Background A high-potency monovalent oral type 1 poliovirus vaccine (mOPV1) was developed in 2005 to tackle persistent poliovirus transmission in the last remaining infected countries. Our aim was to assess the efficacy of this vaccine in India. Methods We estimated the efficacy of mOPV1 used in supplementary immunisation activities from 2076 matched case-control pairs of confirmed cases of poliomyelitis caused by type 1 wild poliovirus and cases of non-polio acute flaccid paralysis in India. The effect of the introduction of mOPV1 on population immunity was calculated on the basis of estimates of vaccination coverage from data for non-polio acute flaccid paralysis. Findings In areas of persistent poliovirus transmission in Uttar Pradesh, the protective efficacy of mOPV1 was estimated to be 30% (95% CI 19–41) per dose against type 1 paralytic disease, compared with 11% (7–14) for the trivalent oral vaccine. 76–82% of children aged 0–23 months were estimated to be protected by vaccination against type 1 poliovirus at the end of 2006, compared with 59% at the end of 2004, before the introduction of mOPV1. Interpretation Under conditions where the efficacy of live-attenuated oral poliovirus vaccines is compromised by a high prevalence of diarrhoea and other infections, a dose of high-potency mOPV1 is almost three times more effective against type 1 poliomyelitis disease than is trivalent vaccine. Achieving high coverage with this new vaccine in areas of persistent poliovirus transmission should substantially improve the probability of rapidly eliminating transmission of the disease.

The feasibility of global polio eradication is being questioned as a result of continued transmission in a few localities that act as sources for outbreaks elsewhere. Perhaps the greatest challenge is in India, where transmission has persisted in Uttar Pradesh and Bihar despite high coverage with multiple doses of vaccine. We estimate key parameters governing the seasonal epidemics in these areas and show that high population density and poor sanitation cause persistence by not only facilitating transmission of poliovirus but also severely compromising the efficacy of the trivalent vaccine. We analyze strategies to counteract this and show that switching to monovalent vaccine may finally interrupt virus transmission.

A total of 250 Corynebacterium diphtheriae isolates from clinical cases and carriers in Russia were assayed by PCR directed at the A subunit of the diphtheria toxin gene to distinguish toxigenic from nontoxigenic strains; 170 strains were positive as indicated by the presence of the 248-bp amplicon. The results of this PCR assay were in complete concordance with those of the standard immunoprecipitation assay (Elek), and the PCR assay is a useful tool for rapid identification in clinical laboratories.

Aims: To estimate Haemophilus influenzae type b (Hib) disease burden in Fiji in children under the age of 5 years (under-5s) prior to vaccine introduction. To compare estimates from WHO’s Hib rapid assessment tool (RAT), with that from decline in disease after vaccine introduction. Methods: Laboratory data (meningitis), hospitalization and mortality data (pneumonia and meningitis) before and after Hib vaccine introduction were collected. The RAT protocol provides two independent estimates of pre-vaccine disease burden (one based on meningitis incidence laboratory data and the other based on mortality statistics). A third estimate uses the decline in disease following vaccine introduction. Results: The decline in meningitis hospitalizations implies a pre-vaccine Hib meningitis incidence of 66 per 100,000 in under-5s. This compares with a pre-vaccine RAT estimate of Hib meningitis incidence of 84 per 100,000 (for 1992–1993). The RAT estimated the total annual pre-vaccine Hib burden (meningitis plus pneumonia) at 476 cases and 36 deaths per year (“meningitis incidence method”) and 70 cases and 5 deaths (“child mortality method”). Hib vaccine led to declines of 32% (95% confidence interval (CI)=11–48%), and 78% (95% CI=22–94%) for all under-5s meningitis hospitalizations and deaths, respectively. There was no similar consistent decline in pneumonia hospitalizations or deaths after vaccine introduction, except for a statistically significant reduction in pneumonia mortality in children aged under 1 year. Conclusions: Hib disease constitutes an important burden on the health of Pacific children that can be rapidly reduced with Hib vaccine. In this setting, routine morbidity statistics (comparing pre-and post-vaccine) provided an estimate of Hib meningitis burden which is broadly similar to that of the Hib RAT, suggesting that both might be valid ways to estimate Hib meningitis incidence. However, Hib pneumonia burden could not be estimated from routine statistics.

Background. Although the meningococcal polysaccharide vaccine has contributed to the control of Group A meningitis in the meningitis belt of Africa, recurrent large outbreaks have led to questions regarding vaccination strategy. We evaluated current and hypothetical vaccination strategies for the region. Methods. A model was formulated to analyze the effectiveness and costs of vaccine campaigns in response to outbreaks based on 7 years of weekly incidence data from Burkina Faso. Additional models analyzed the potential impact and costs of either a 1- or 4-dose routine scheduled delivery of meningococcal polysaccharide vaccine based on data reported to the World Health Organization from 16 countries during 1948 through 1996. Vaccine efficacy, vaccination coverage and economic data from literature reviews provided model assumptions. Results. For Burkina Faso neither 1- nor 4-dose vaccination schedules would prevent >30% of meningitis cases compared with the 42% prevented through an outbreak response program of vaccinating districts, which reach an incidence of 15 per 100 000 persons for 2 weeks. For the entire meningitis belt, routine coverage with the 1- or 4-dose schedule meningococcal vaccine would require 4.9 and 19.6 million doses annually, respectively, for an annual net cost of $4.4 to $12.3 million and prevent an average 10 300 to 12 600 cases (23 to 28%), assuming a long term vaccine efficacy of 50%. In addition an initial catch-up campaign costing up to $72 million to vaccinate the population from 1 to 30 years of age would be required before achieving that level of effectiveness. Conclusion. Given the relatively poor routine vaccination coverage in this region, current strategies of vaccination campaigns that achieve higher coverage would generally be more effective and less costly than the modeled routine scheduled programs, assuming that campaigns can be rapidly implemented. Until a better vaccine is available, countries in this region would be more efficient in improving the response times to outbreaks, perhaps through improved surveillance, and in bolstering existing vaccination infrastructures rather than embarking on strategies of questionable effectiveness.

Jacob Puliyel and colleagues highlight the importance of ensuring appropriate ethical standards are adhered to in the course of scientific studies. In our study of the field efficacy of monovalent oral type 1 poliovirus vaccine (mOPV1) we analysed existing surveillance data from acute flaccid paralysis (AFP) cases collected since 1997. The vaccines assessed were licensed for administration in India by the national regulatory authority the Drugs Controller General of India. The mOPV1 formulation assessed in our study has been used since mid-2005 by the Government of India and now in over 20 countries around the world. The absence of interference from types 2 and 3 particularly type 2 seems to be the reason for the three-fold greater efficacy per dose of mOPV1 against paralysis from type 1 wild poliovirus compared with trivalent vaccine in northern India. To clarify the background to the increase in cases of AFP in recent years noted by Puliyel and colleagues this is the result of a deliberate effort that began in 2004 to intensify surveillance and reporting as India pushes to eradicate polio. The increase in AFP cases began before mOPV1 was introduced and occurred across India including states where mOPV1 has not been used. The introduction of mOPV1 is not therefore the cause of the increase in cases of AFP. The National Polio Surveillance Project continues to monitor cases of vaccine-associated paralytic poliomyelitis (VAPP) which typically occur at a rate of two to four cases per million birth cohort immunised with trivalent oral poliovirus vaccine. The postmarketing surveillance of mOPV1 that was implemented as part of its licensing has not detected any increase in the proportion of AFP cases with VAPP in areas where this vaccine has been used. (excerpt)

Serum bactericidal activity (SBA) and ELISA antibody levels elicited by two efficacious serogroup B meningococcal vaccines were measured in a controlled trial involving 408 15- to 20-year-olds. Subjects were given two doses at a 6-week interval of a serogroup B or control vaccine. Response was defined as > or = 4-fold rise in antibody level. After two doses of the Finlay Institute (Havana) vaccine at 12 months, the proportions of SBA and ELISA responders were not different from those of the control group (15% and 17% [vaccine] vs. 13% and 9% [control], P > .05). After two doses of the National Institute of Public Health (Oslo) vaccine, there were more SBA and ELISA responders than in the control group (47% and 34% [vaccine] vs. 10% and 1% [control]) or the Finlay Institute vaccine group (P < .05 for both). SBA and ELISA may be insensitive correlates for protective efficacy for some outer membrane protein-based serogroup B meningococcal vaccines.

Between February 1991 and April 1992, eight undergraduates at a US residential university and one at a nearby 2-year college contracted serogroup C meningococcal disease. A case-control investigation with 20 controls per case, oropharyngeal carriage surveys, and multilocus enzyme electrophoresis (MEE) of serogroup C isolates were used to identify factors contributing to the outbreak. All eight sterile-site isolates from cases were closely related by MEE and were similar (though not identical) to the strain associated with the 1991-1992 epidemic of meningococcal disease in eastern Canada. Disease was associated with cigarette smoking (p = 0.012), recent patronage of campus-area bars (p = 0.034), estimated amount of time spent in campus-area bars (p = 0.0003), and, especially, recent patronage of one specific bar, bar A (p = 0.0006 ; odds ratio = 23.1, 95% confidence interval 3.0-571.5). In carriage surveys, 1,528 throat cultures taken from (primarily student) noncases yielded only five (0.3%) strains that were identical by MEE to those from cases. Two of these were found among 22 cultures obtained from bar A employees in spring 1992. Some cases in this outbreak may have followed transmission of the epidemic strain in bar A. Campus bar environments may facilitate the spread of meningococcal disease among teenagers and young adults.

Bacillary angiomatosis (BA) presents most commonly as a cutaneous disease and is caused by two organisms. Bartonella (Rochalimaea) henselae and Bartonella (Rochalimaea) quintana. Biopsy confirmation of cutaneous BA is essential because lesions can mimic nodular Kaposi's sarcoma in appearance. Although the vast majority of human immunodeficiency virus (HIV)-infected patients with BA have CD4 lymphocyte counts of less than 100 cells per mm3, the disease responds well to antimicrobial therapy. Staphylococcus aureus is the most common bacterial skin pathogen affecting HIV-infected patients. The prevalence of skin disease due to S. aureus may be explained by high nasal carriage rates for the organism ( > or = 50%) and altered immune function in conjunction with an impaired cutaneous barrier. Herpes simplex virus causes mucocutaneous disease early in the course HIV infection and ulcerative lesions at any site in advanced HIV infection. Herpes zoster is common early in the course of HIV infection; recurrent and disseminated herpes zoster infections are characteristic of patients with advanced HIV disease. Acyclovir resistance is usually seen in patients with large, untreated, ulcerative lesions of herpes simplex virus and in patients with chronic, verrucous lesions of varicella-zoster virus. Cutaneous cryptococcosis, histoplasmosis, and coccidiomycosis are markers of disseminated disease and require biopsy confirmation. Scabies is easily diagnosed but may be atypical in presentation and difficult to eradicate in advanced HIV disease.

The long-term kinetics of the immunologic response after vaccination of adults with Neisseria meningitidis polysaccharide vaccine is unknown. Total meningococcal anti-capsular antibody response (measured by ELISA) and serum bactericidal activity after routine vaccination with quadrivalent meningococcal vaccine were evaluated in US Air Force personnel. In a retrospective cross-sectional study, blood samples were obtained from approximately 40 personnel before vaccination, at 1 and 4-6 months, and at 2, 3, 4, 6, 8, and 10 years after vaccination. Total anti-group A and -group C capsular antibody levels and bactericidal activity peaked 1 month after vaccination and declined substantially by 2 years. At each interval, significantly higher levels of total antibody and bactericidal activity were detected than before vaccination. Anti-capsular antibodies and bactericidal activity persisted for up to 10 years after immunization. These and further studies on the serologic measure of protection against meningococcal disease are important for evaluation of candidate vaccines and development of recommendations for immunization.

The incidence, demographics, and clinical outcome of infections due to Listeria monocytogenes in individuals infected with the human immunodeficiency virus (HIV) were evaluated by prospective population-based surveillance. During a 2-year study period, 37 cases of invasive listeriosis occurred in metropolitan Atlanta (annual incidence, 0.8 case per 100,000 population). Seven of these cases occurred in known HIV-infected individuals (19% of all cases); five had an AIDS-defining illness, and the other two had CD4 lymphocyte cell counts of < 200/microL. The estimated incidence of listeriosis among HIV-infected patients in metropolitan Atlanta was 52 cases per 100,000 patients per year, and among patients with AIDS it was 115 cases per 100,000 patients per year, rates 65-145 times higher than those among the general population. HIV-associated cases occurred in adults who were 29-62 years of age and in postnatal infants who were 2 and 6 months of age. Mortality among the HIV-infected group was 29%. L. monocytogenes serotypes 1/2a, 1/2b, and 4b were isolated from the HIV-infected patients. L. monocytogenes is an important opportunistic pathogen in HIV-infected patients.

Serogroup B Neisseria meningitidis is the most common cause of epidemic meningococcal disease in developed countries. Until recently no vaccine has been available for prevention of infection with this organism. In an attempt to control epidemic serogroup B meningococcal disease in greater Sao Paulo, Brazil, during 1989 and 1990, a Cuban-produced outer-membrane-protein-based serogroup B meningococcal vaccine was given to about 2.4 million children aged from 3 months to 6 years. We have done a case-control study to estimate the efficacy of the vaccine in greater Sao Paulo. Microbiologically confirmed cases of serogroup B meningococcal disease were identified through hospital-based surveillance. Controls were matched by neighbourhood and age. Vaccination status was confirmed by inspection of vaccination cards. Between June, 1990, and June, 1991, 112 patients and 409 matched controls with confirmed vaccine status were enrolled. Estimated vaccine efficacy varied by age: 48 months or older = 74% (95% Cl 16 to 92%), 24 to 47 months = 47% (-72 to 84%), and less than 24 months = -37% (-100 to 73%). Our results suggest that the Cuban-produced vaccine may be effective for prevention of serogroup B meningococcal disease in older children and adults.In 1990, researchers compared data on 112 3 month-6 year old children who received a Cuban produced, outer-membrane-protein-based serogroup B meningococcal vaccine (cases) and lived in greater Sao Paulo, Brazil with data on 409 age and neighborhood matched controls to determine the protective efficacy of the vaccine against serogroup B meningococcal disease (Neisseria meningitidis). Health workers began administering the vaccine in 1989 to control an epidemic of serogroup B meningococcal disease in the area. In fact, in mid-1989 and early 1990, the rates of serogroup B meningococcal disease in 1-6 year old children in Sao Paulo were 2.07/100,000 and 2.3/100,000, respectively. Even though only 44% of serogroup B meningococcal isolates corresponded with the vaccine type strain (B:4:P1:15), many isolates had man of the same serotype or subtype antigens as the vaccine type strain. Thus the vaccine was able to protect against some other serogroup B meningococcal strains other than the vaccine type strain. Vaccine efficacy for 4-year old children was 74%, but was much lower for 24-47 month old children (47%) and 24-month old children (-37%). The change in the log odds ratio for vaccination by age was linear and significant (p=.057). The researchers suggested that poor vaccine efficacy among younger children may reflect a need for more boosting to achieve protective levels of immunity. The results showed that the Cuban-produced vaccine could contribute to control of outbreaks of serogroup B meningococcal disease by protecting older children and adults from the disease. Researchers need to conduct additional studies of the vaccine and other possible serogroup B meningococcal vaccines.

We have developed a simple test that differentiates between virulent and avirulent Listeria species as defined by the mouse 50% lethal doses (LD50S). The assay is based on trypan blue-revealed cytopathogenic effects that are produced during the infection of the human enterocytelike cell line Caco-2. These effects were elicited only by Listeria strains that had an intraperitoneal mouse LD50 less than 10(8) and were not produced by nonhemolytic, avirulent strains of Listeria monocytogenes generated spontaneously or by Tn916 mutagenesis or by avirulent Listeria species. A negative test was also obtained with hemolysin-producing, avirulent L. monocyotogenes NCTC5105 and Listeria ivanovii KC1786. The test was negative with avirulent L. monocytogenes strains which are strong inducers of opacity in egg yolk agar. However, a strain which has a low LD50, such as 10(4), may show less severe cytopathogenic effects than a strain having a higher LD50, such as 10(6). The test has been effectively used to screen for virulent listerial isolates, spontaneous mutants, and transposon-induced mutants.

A nonisotopic ribosomal DNA fingerprinting technique was developed for the characterization of Listeria monocytogenes. Plasmid pKK3535 (a pBR322-derived plasmid containing rrnB ribosomal RNA operon of Escherichia coli) was labeled with digoxigenin-II-dUTP by random priming and used to probe EcoRI fragments of L. monocytogenes chromosomal DNA on nylon filters. The method was successfully applied to the characterization of two sets of patient and food isolates of L. monocytogenes.

When data were stratified by age, subtype 1 accounted for 73% (29/40) of isolates from those ^2 months but 86% (127/ 147) of isolates from those > 12 months of age. This difference was almost statistically significant (x2 , P = .06). This suggests that children 12 months of age. Takala et al. [6] reported a similar finding in Finland. The biotype prevelance of Hib subtypes was similar to that reported previously from the United States and Europe. Biotypes I, II, IV, and V accounted for 8996, 7%, 3ft, and \7c of isolates, respectively. There was no clustering of biotypes by disease manifestation.

To define the incidence, demographics, clinical features, and risk factors for sporadic meningococcal disease in adults (or = 18 years) residing in metropolitan Atlanta.Prospective, population-based surveillance, with retrospective review of clinical and laboratory records.Eight-county metropolitan Atlanta area.All adult patients in whom Neisseria meningitidis was isolated from normally sterile sites (blood, cerebrospinal fluid) during the period 1 December 1988 to 30 November 1993.Incidence, relative risk, clinical and laboratory parameters, and serogroup of meningococcal isolates.For the 5-year period, 44 (33%) of 132 cases of meningococcal disease in Atlanta occurred in adults (annual incidence, 0.50/100,000 adults per year). Twenty-three (52%) of the 44 adults presented without rash or meningitis, the two most obvious signs of meningococcal disease. Pneumonia, sinusitis, or purulent tracheobronchitis, but without rash, were the likely sources of meningococcal bacteremia in 15 (34%) of the 44 adults. Twelve of the 15 patients with meningococcal respiratory infection were older than 50 years of age or were immunocompromised (or both), and three fourths of the 15 patients had disease caused by serogroups B, Y, and W-135. Overall, two thirds of adults older than 24 years of age with meningococcal disease had one or more immunocompromising conditions (for example, low complement 50 level [CH50], corticosteroid use, congestive heart failure, multiple myeloma, human immunodeficiency virus infection). Meningococcemia or meningococcal meningitis, often caused by serogroup C, were the presentations in 14 of 15 adults 18 to 24 years old; only 2 had an identified underlying condition.In this 5-year population-based study, one third of all cases of sporadic meningococcal disease occurred in adults. Over half of the adults presented without rash or meningitis. Pneumonia, sinusitis, and tracheobronchitis are important sources of bacteremic meningococcal disease, especially in immunocompromised patients and elderly persons.

Objective. —Multiple outbreaks of serogroup C Neisseria meningitidis have recently been reported from diverse areas of the United States. To better define the characteristics of this increasingly important problem, we reviewed data on all known serogroup C outbreaks in the United States from January 1980 through June 1993. Data Sources. —MEDLINE searches, Centers for Disease Control and Prevention records, state health department officials, infectious disease experts, and the meningococcal vaccine manufacturer. Definition of an Outbreak. —Three or more cases of serogroup C meningococcal disease within a 3-month period, either among members of a community or persons attending a single school or other institution, for which those cases represented an attack rate of at least five per 100 000 population. Results. —Twenty-one outbreaks of serogroup C meningococcal disease were identified; eight occurred since 1991. In 1992 and the first half of 1993, approximately 180 000 doses of vaccine were administered for outbreak control, compared with approximately 34000 doses from 1980 to 1991. Approximately 50% of community-outbreak cases were between the ages of 5 and 24 years, compared with only 19% of sporadic serogroup C cases ( P Conclusions. —Serogroup C outbreaks are occurring more frequently in the United States. The effectiveness of preventive measures depends on early recognition; therefore, physicians should promptly report all cases of suspected meningococcal disease, and the causative serogroup should be established for every case. ( JAMA . 1995;273:383-389)

Objective To define the incidence of and possible risk factors for invasive Haemophilus influenzae disease in adults. Design Prospective, population-based surveillance of hospital and referral bacteriology laboratories. Setting Metropolitan Atlanta, Georgia community. Patients All patients with H. influenzae isolated from normally sterile sites (blood, cerebrospinal fluid, joint, pleura) from 1 December 1988 through 31 May 1990. Measurements Isolates of H. influenzae were analyzed for serotype and biotype status, outer membrane proteins, lipooligosaccharide phenotypes, ribotyping patterns and beta-lactamase production. Results A total of 194 cases of invasive H. influenzae occurred (annual incidence of 5.6 cases/100,000 population), of which 47 (24%) were in adults 18 years old or older (annual incidence 1.7 cases/100,000 adults). Adults with invasive H. influenzae ranged from 18 to 96 years; 79% were women. Bacteremic pneumonia accounted for 70% of the adult cases. Other sources for invasive H. influenzae in adults were obstetric infections, epiglottitis, and tracheobronchitis; one patient had meningitis. Underlying conditions were noted in 92% of the patients. Chronic lung disease was the most common risk factor, but pregnancy (annual incidence, 4.9/100,000 pregnant women), HIV infection (annual incidence, 41/100,000 known HIV-infected adults), and malignancy were also important. Overall mortality was 28% in adults, and over half of pregnancy-related infections resulted in fetal death. Fifty percent of the 40 isolates available for testing were serotype b; 47.5%, nontypable; and 2.5%, serotype f. Sixteen of the 45 isolates (36%) were ampicillin-resistant. Based on biotypes, outer membrane protein profiles, lipooligosaccharide phenotypes, and ribotyping patterns, the type b isolates showed less heterogeneity than the nontypable isolates but were distinguishable from one another. Conclusions Adult cases currently represent one quarter of all cases of invasive H. influenzae disease. Half of the reported adult cases were caused by type b H. influenzae, and the rate of ampicillin resistance in H. influenzae isolates from adults was higher than previously reported. Haemophilus influenzae is an important cause of bacteremia in compromised adults.

Over a 12-year period, 16 human strains of a gram-negative, catalase-positive, halophilic, aerobic, nonmotile, small coccoid bacterium were received for identification. On the bases of biochemical characteristics and cellular fatty acid profiles, 14 of these strains were similar to the "Philomiragia" bacterium (Yersinia philomiragia, species incertae sedis). Additional characteristics were growth on Thayer-Martin agar but no growth or sparse, delayed growth on MacConkey agar; oxidase positive; acid production, often weak and delayed, from D-glucose, sucrose, and maltose; urease negative; no reduction of nitrates; and H2S produced but often delayed in triple sugar iron agar. Both the human isolates and the "Philomiragia" bacterium contained C10:0, C14:0, C16:0, C18:1 omega 9c, C18:0, 3-OH C18:0, C22:0, and C24:1 as major cellular fatty acids and ubiquinone eight (Q8) as the major isoprenoid quinone. These cellular acids in these relative amounts have been found previously only in Francisella tularensis and Francisella novicida, suggesting a relationship between the "Philomiragia" bacterium and Francisella species. Of the 14 human "Philomiragia"-like isolates, 9 were from blood, 3 were from lung biopsies or pleural fluid, and one each was from peritoneal fluid and cerebrospinal fluid. DNA relatedness studies (hydroxyapatite method, 50 and 65 degrees C) showed that these 14 strains were a single group that was the same species as the "Philomiragia" bacterium. Two other human strains were oxidase negative and H2S negative. They formed a single DNA relatedness group that was indistinguishable from the type strains of both F. tularensis and F. novicida. DNA relatedness of "Philomiragia" bacterium type and other strains to strains of F. novicida and F. tularensis, including the type strains, was 35 to 46%. One of the two F. novicida- and F. tularensis-like strains was isolated from blood, and the other was isolated from a cervical lymph node. On the basis of these findings, we propose transferring Y. philomiragia from the genus Yersinia to the genus Francisella as Francisella philomiragia comb. nov. Having confirmed that F novicida and F. tularensis are the same species and having shown that F. novicida is pathogenic for humans, we further propose eliminating the species F. novicida and demoting it to a biogroup of F. tularensis.

To assess the efficacy of the Haemophilus b polysaccharide vaccine following licensure and to evaluate the risk of Haemophilus influenzae type b (Hib) disease in the week following vaccination, we conducted a day care—based case-control efficacy study using cases of invasive Hib disease ascertained through active surveillance in areas with a total population of 34 million. For each patient 18 to 59 months old, up to three 18- to 59-month-old controls were chosen from the same day care classroom. Using conditional logistic regression, the vaccine efficacy was estimated to be 45% (95% confidence interval = -1% to 70%) and did not change significantly after accounting for potential biases. In addition, three (3%) of 104 patients vs five (2%) of 207 controls were vaccinated within seven days before the patients' dates of admission (odds ratio = 1.8,95% confidence interval = 0.3 to 10.2), which does not suggest an increased risk of Hib disease in the week following immunization. This study suggests that the efficacy of the currently used HBPV is less than expected from previous studies and points out the usefulness of case-control studies for monitoring vaccine efficacy following licensure. ( JAMA 1988;260:1413-1418)