Meningococcal Disease in Patients With Human Immunodeficiency Virus Infection: A Review of Cases Reported Through Active Surveillance in the United States, 2000-2008.

BackgroundAlthough human immunodeficiency virus (HIV) infection is an established risk factor for several bacterial infections, the association between HIV infection and meningococcal disease remains unclear.MethodsExpanded chart reviews were completed on persons with meningococcal disease and HIV infection reported from 2000 through 2008 from 9 US sites participating in an active population-based surveillance system for meningococcal disease. The incidence of meningococcal disease among patients meeting Centers for Disease Control and Prevention acquired immune deficiency syndrome (AIDS) surveillance criteria was estimated using data from the National HIV Surveillance System for the participating sites.ResultsThirty-three cases of meningococcal disease in individuals with HIV infection were reported from participating sites, representing 2.0% of all reported meningococcal disease cases. Most (75.8%) persons with HIV infection were adult males aged 25 to 64 years old. Among all meningococcal disease cases aged 25 to 64 years old, case fatality ratios were similar among HIV-infected and HIV-uninfected persons (13.3% vs 10.6%; P = .6). The cumulative, mean incidence of meningococcal disease among patients aged 25 to 64 years old with HIV infection ever classified as AIDS was 3.5 cases per 100000 person years (95% confidence interval [CI], 2.1-5.6), compared with 0.3 cases per 100000 person years (95% CI, 0.3-0.3) for persons of the same age group not reported to have AIDS (relative risk = 12.9; 95% CI, 7.9-20.9).ConclusionsIndividuals with HIV infection meeting the AIDS surveillance case definition have a higher incidence of meningococcal disease compared with the general adult population

Sentinel Surveillance: A Reliable Way To Track Antibiotic Resistance in Communities?

We used population-based data to evaluate how often groups of randomly selected clinical laboratories accurately estimated the prevalence of resistant pneumococci and captured trends in resistance over time. Surveillance for invasive pneumococcal disease was conducted in eight states from 1996 to 1998. Within each surveillance area, we evaluated the proportion of all groups of three, four, and five laboratories that estimated the prevalence of penicillin-nonsusceptible pneumococci (%PNSP) and the change in %PNSP over time. We assessed whether sentinel groups detected emerging fluoroquinolone resistance. Groups of five performed best. Sentinel groups accurately predicted %PNSP in five states; states where they performed poorly had high between-laboratory variation in %PNSP. Sentinel groups detected large changes in prevalence of nonsusceptibility over time but rarely detected emerging fluoroquinolone resistance. Characteristics of hospital-affiliated laboratories were not useful predictors of a laboratory’s %PNSP. Sentinel surveillance for resistant pneumococci can detect important trends over time but rarely detects newly emerging resistance profiles

Eff ectiveness of the 13-valent pneumococcal conjugate vaccine against invasive pneumococcal disease in South African children: a case-control study

Background The 13-valent pneumococcal conjugate vaccine (PCV13) was designed to include disease-causing serotypes that are important in low-income and middle-income countries. Vaccine eff ectiveness estimates are scarce in these settings. South Africa replaced PCV7 with PCV13 in 2011 using a 2 + 1 schedule. We aimed to assess the eff ectiveness of two or more doses of PCV13 against invasive pneumococcal disease in children with HIV infection and in those not infected with HIV. Methods Cases of invasive pneumococcal disease in children aged 5 years or younger were identifi ed through national laboratory-based surveillance. Isolates were serotyped with the Quellung reaction or PCR. We sought in-hospital controls for every case, matched for age, HIV status, and study site. We aimed to enrol four controls for every case not infected with HIV and six controls for every case with HIV infection (case-control sets). With conditional logistic regression, we calculated vaccine eff ectiveness as a percentage, with the equation 1 – [adjusted odds ratio for vaccination] × 100. We included data from an earlier investigation of PCV7 to assess vaccine eff ectiveness in children exposed to but not infected with HIV and in malnourished children not infected with HIV. Findings Between January, 2012, and December, 2014, we enrolled children aged 16 weeks or older to our study: 240 were cases not infected with HIV, 75 were cases with HIV infection, 1118 were controls not infected with HIV, and 283 were controls with HIV infection. The eff ectiveness of two or more doses of PCV13 against PCV13-serotype invasive pneumococcal disease was 85% (95% CI 37 to 96) among 11 case-control sets of children not infected with HIV and 91% (–35 to 100) among three case-control sets of children with HIV infection. PCV13 eff ectiveness among 26 case-control sets of children not infected with HIV was 52% (95% CI –12 to 79) against all-serotype invasive pneumococcal disease and 94% (44 to 100) for serotype 19A. Vaccine eff ectiveness against PCV7-serotype invasive pneumococcal disease was 87% (95% CI 38 to 97) in children exposed to HIV but uninfected and 90% (53 to 98) in malnourished children not infected with HIV. Interpretation Our results indicate that PCV13 in a 2 + 1 schedule is eff ective for preventing vaccine-type pneumococcal infections in young children not infected with HIV, including those who are malnourished or who have been exposed to HIV. Although the point estimate for PCV13 vaccine eff ectiveness in children infected with HIV was high, it did not reach signifi cance, possibly because of the small sample size. These fi ndings support recommendations for widespread use of pneumococcal conjugate vaccine in low-income and middle-income countries

Aggregated Antibiograms and Monitoring of Drug-Resistant Streptococcus pneumoniae

Community-specific antimicrobial susceptibility data may help monitor trends among drug-resistant Streptococcus pneumoniae and guide empiric therapy. Because active, population-based surveillance for invasive pneumococcal disease is accurate but resource intensive, we compared the proportion of penicillin-nonsusceptible isolates obtained from existing antibiograms, a less expensive system, to that obtained from 1 year of active surveillance for Georgia, Tennessee, California, Minnesota, Oregon, Maryland, Connecticut, and New York. For all sites, proportions of penicillin-nonsusceptible isolates from antibiograms were within 10 percentage points (median 3.65) of those from invasive-only isolates obtained through active surveillance. Only 23% of antibiograms distinguished between isolates intermediate and resistant to penicillin; 63% and 57% included susceptibility results for erythromycin and extended-spectrum cephalosporins, respectively. Aggregating existing hospital antibiograms is a simple and relatively accurate way to estimate local prevalence of penicillin-nonsusceptible pneumococcus; however, antibiograms offer limited data on isolates with intermediate and high-level penicillin resistance and isolates resistant to other agents

Antimicrobial Postexposure Prophylaxis for Anthrax: Adverse Events and Adherence

We collected data during postexposure antimicrobial prophylaxis campaigns and from a prophylaxis program evaluation 60 days after start of antimicrobial prophylaxis involving persons from six U.S. sites where Bacillus anthracis exposures occurred. Adverse events associated with antimicrobial prophylaxis to prevent anthrax were commonly reported, but hospitalizations and serious adverse events as defined by Food and Drug Administration criteria were rare. Overall adherence during 60 days of antimicrobial prophylaxis was poor (44%), ranging from 21% of persons exposed in the Morgan postal facility in New York City to 64% of persons exposed at the Brentwood postal facility in Washington, D.C. Adherence was highest among participants in an investigational new drug protocol to receive additional antibiotics with or without anthrax vaccine—a likely surrogate for anthrax risk perception. Adherence of <60 days was not consistently associated with adverse events

Consumer Attitudes and Use of Antibiotics

Recent antibiotic use is a risk factor for infection or colonization with resistant bacterial pathogens. Demand for antibiotics can be affected by consumers’ knowledge, attitudes, and practices. In 1998–1999, the Foodborne Diseases Active Surveillance Network (FoodNet) conducted a population-based, random-digit dialing telephone survey, including questions regarding respondents’ knowledge, attitudes, and practices of antibiotic use. Twelve percent had recently taken antibiotics; 27% believed that taking antibiotics when they had a cold made them better more quickly, 32% believed that taking antibiotics when they had a cold prevented more serious illness, and 48% expected a prescription for antibiotics when they were ill enough from a cold to seek medical attention. These misguided beliefs and expectations were associated with a lack of awareness of the dangers of antibiotic use; 58% of patients were not aware of the possible health dangers. National educational efforts are needed to address these issues if patient demand for antibiotics is to be reduced

Case-control vaccine effectiveness studies: Preparation, design, and enrollment of cases and controls.

Case-control studies are commonly used to evaluate effectiveness of licensed vaccines after deployment in public health programs. Such studies can provide policy-relevant data on vaccine performance under 'real world' conditions, contributing to the evidence base to support and sustain introduction of new vaccines. However, case-control studies do not measure the impact of vaccine introduction on disease at a population level, and are subject to bias and confounding, which may lead to inaccurate results that can misinform policy decisions. In 2012, a group of experts met to review recent experience with case-control studies evaluating the effectiveness of several vaccines; here we summarize the recommendations of that group regarding best practices for planning, design and enrollment of cases and controls. Rigorous planning and preparation should focus on understanding the study context including healthcare-seeking and vaccination practices. Case-control vaccine effectiveness studies are best carried out soon after vaccine introduction because high coverage creates strong potential for confounding. Endpoints specific to the vaccine target are preferable to non-specific clinical syndromes since the proportion of non-specific outcomes preventable through vaccination may vary over time and place, leading to potentially confusing results. Controls should be representative of the source population from which cases arise, and are generally recruited from the community or health facilities where cases are enrolled. Matching of controls to cases for potential confounding factors is commonly used, although should be reserved for a limited number of key variables believed to be linked to both vaccination and disease. Case-control vaccine effectiveness studies can provide information useful to guide policy decisions and vaccine development, however rigorous preparation and design is essential

Case-control vaccine effectiveness studies: Data collection, analysis and reporting results.

The case-control methodology is frequently used to evaluate vaccine effectiveness post-licensure. The results of such studies provide important insight into the level of protection afforded by vaccines in a 'real world' context, and are commonly used to guide vaccine policy decisions. However, the potential for bias and confounding are important limitations to this method, and the results of a poorly conducted or incorrectly interpreted case-control study can mislead policies. In 2012, a group of experts met to review recent experience with case-control studies evaluating vaccine effectiveness; we summarize the recommendations of that group regarding best practices for data collection, analysis, and presentation of the results of case-control vaccine effectiveness studies. Vaccination status is the primary exposure of interest, but can be challenging to assess accurately and with minimal bias. Investigators should understand factors associated with vaccination as well as the availability of documented vaccination status in the study context; case-control studies may not be a valid method for evaluating vaccine effectiveness in settings where many children lack a documented immunization history. To avoid bias, it is essential to use the same methods and effort gathering vaccination data from cases and controls. Variables that may confound the association between illness and vaccination are also important to capture as completely as possible, and where relevant, adjust for in the analysis according to the analytic plan. In presenting results from case-control vaccine effectiveness studies, investigators should describe enrollment among eligible cases and controls as well as the proportion with no documented vaccine history. Emphasis should be placed on confidence intervals, rather than point estimates, of vaccine effectiveness. Case-control studies are a useful approach for evaluating vaccine effectiveness; however careful attention must be paid to the collection, analysis and presentation of the data in order to best inform evidence-based vaccine policies

Dealing with noncompliance and missing outcomes in a randomized trial using Bayesian technology: Prevention of perinatal sepsis clinical trial, Soweto, South Africa

The success of interventions designed to address important issues in social and medical science is best addressed by randomized experiments. With human beings there are often complications, however, such as noncompliance and missing data. Such complications are often addressed by statistically invalid methods of analysis, in particular, intention-to-treat and per-protocol analyses. Here we address these two complications using a statistically valid approach based on principal stratification with a fully Bayesian analysis. This analysis is applied to a randomized trial of a potentially important intervention designed to reduce the transmission of bacterial colonization between mothers and their infants through vaginal delivery in South Africa : the Prevention of Perinatal Sepsis (PoPs).Statistic