PubMed Health⌕ Search

Biomedical subjects

Marc Lipsitch

Publications and source records attributed to Marc Lipsitch.

43 records · Page 3Linked to original sources
PubMed2003

Construction of otherwise isogenic serotype 6B, 7F, 14, and 19F capsular variants of Streptococcus pneumoniae strain TIGR4.

The polysaccharide capsule is the primary virulence factor in Streptococcus pneumoniae. There are at least 90 serotypes of S. pneumoniae, identified based on the immunogenicity of different capsular sugars. The aim of this study was to construct pneumococcal strains that are isogenic except for capsular type. Serotype 4 strain TIGR4 was rendered unencapsulated by recombinational replacement of the capsular polysaccharide synthesis (cps) locus with the bicistronic Janus cassette (C. K. Sung, J. P. Claverys, and D. A. Morrison, Appl. Environ. Microbiol. 67:5190-5196, 2001). In subsequent transformation with chromosomal DNA, the cassette was replaced by the cps locus derived from a strain of a different serotype, either 6B, 7F, 14, or 19F. To minimize the risk of uncontrolled recombinational replacements in loci other than cps, the TIGRcps::Janus strain was "backcross" transformed three times with chromosomal DNA of subsequently constructed capsular type transformants. Capsular serotypes were confirmed in all new capsule variants by the Quellung reaction. Restriction fragment length polymorphism (RFLP) analysis of the cps locus confirmed the integrity of the cps region transformed into the TIGR strain, and RFLP of the flanking regions confirmed their identities with the corresponding regions of the recipient. Transformants had in vitro growth rates greater than or equal to that of TIGR4. All four strains were able to colonize C57BL/6 mice (female, 6 weeks old) for at least 7 days when mice were intranasally inoculated with 6 x 10(6) to 8 x 10(6) CFU. The constructed capsular variants of TIGR4 are suitable for use in studies on the role of S. pneumoniae capsular polysaccharide in immunity, colonization, and pathogenesis.

Animals↗
PubMed2002

Control-group selection importance in studies of antimicrobial resistance: examples applied to Pseudomonas aeruginosa, Enterococci, and Escherichia coli.

We aimed to illustrate the importance of control-group selection on the results of risk factor analysis for (1) imipenem-resistant Pseudomonas aeruginosa, (2) vancomycin-resistant enterococci (VRE), and (3) ampicillin-sulbactam-resistant Escherichia coli. Case patients were compared with 2 different control groups: patients with the susceptible form of the organism (type 1), and control patients among whom the case patients arose during the same period as the case patients (type 2). Comparison of case patients who had imipenem-resistant P. aeruginosa with type-1 control patients identified use of imipenem (odds ratio [OR], 27.1) and quinolones (OR, 3.25) as a risk factor for selection of antimicrobial resistance, and comparison of the same case patients with type-2 control patients identified imipenem (OR, 6.34). When case patients with VRE were compared with type-1 and with type-2 control patients, use of vancomycin was identified as a risk factor (OR, 4.38 and 2.77, respectively). Comparison of case patients who had ampicillin-sulbactam-resistant E. coli compared with type-1 control patients identified ampicillin-sulbactam (OR, 2.71) and quinolones (OR, 2.72), and comparison with type-2 control patients identified ampicillin-sulbactam (OR, 1.68). The selection of control patients from the potentially suboptimal control type 1 can falsely identify certain antibiotics and overestimate the OR of the resistance-defining antibiotic.

Anti-Bacterial Agents↗
PubMed2002

Historical intensity of natural selection for resistance to tuberculosis.

Infections have long been thought to exert natural selection on humans. Infectious disease resistance is frequently invoked as a mechanism shaping human genetic diversity, but such hypotheses have rarely been quantitatively evaluated with direct measures of disease-related mortality. Enhancement of genetically determined resistance to tuberculosis by natural selection has been proposed as a factor explaining the decline of tuberculosis in Europe and North America in the period 1830-1950 (before the advent of antimicrobial chemotherapy) and the apparently reduced susceptibility of Europeans and their descendants to tuberculosis infection and/or disease. We used Swedish vital statistics from 1891 to 1900 to estimate that individuals who escaped mortality from pulmonary tuberculosis (PTB) during the European tuberculosis epidemic would have enjoyed a fitness advantage of 7-15% per generation compared to individuals who were susceptible to PTB mortality; individuals with 50% protection would have had a selection coefficient of 4-7%/generation. Selection during the peak of the European TB epidemic could have substantially reduced the frequency of already rare alleles conferring increased susceptibility to PTB mortality, but only if the phenotypic effects of these alleles were very large. However, if resistant alleles were rare at the beginning of this period, 300 years would not have been long enough for such selection to increase their frequency to epidemiologically significant levels. Reductions in the frequency of rare susceptibility alleles could have played at most a small part in the decline of the epidemic in the century preceding 1950. Natural selection by PTB deaths during the European TB epidemic alone cannot account for the presently low level of TB disease observed among Europeans and their descendants just prior to the appearance of antibiotic treatment.

Female↗
PubMed2002

Potential benefits of a serodiagnostic test for herpes simplex virus type 1 (HSV-1) to prevent neonatal HSV-1 infection.

BACKGROUND: Changes in sexual practices have led to an increase in the incidence of genital herpes simplex virus type 1 (HSV-1) infections. Such infections affect an estimated 400 newborns each year, with serious consequences. GOAL: To evaluate the use of a serodiagnostic test for HSV-1 to be used by pregnant women, and possibly their sexual partners, in preventing neonatal HSV-1 infections by identifying seronegative (at-risk) women. STUDY DESIGN: The number of cases of neonatal HSV-1 prevented by a test of a given sensitivity and specificity is estimated using two simple models parameterized with data from published sources. RESULTS: Used by women only, a 90%-specific test for HSV-1 could avert 71%-90% of the expected cases of infection among women using the test, requiring about 14,000 tests per case averted. This result depends linearly on the specificity of the test and does not depend on the sensitivity. Use by women and their partners results in more tests for the same benefit (about 24,000 tests per case averted if the test is 90% sensitive and 90% specific), because the only additional information provided by testing the partner of an at-risk woman is to determine that her partner may not be HSV-1 positive. CONCLUSIONS: The key feature of such a diagnostic test is its specificity; its use to identify at-risk women could provide public health benefits if the specificity exceeds 70%, but these benefits would increase dramatically for higher specificities. Use of such a test for couples is likely to be more costly and less effective than testing women only.

Adult↗
PubMed2002

Projection of the future dimensions and costs of the genital herpes simplex type 2 epidemic in the United States.

BACKGROUND: Infection with herpes simplex virus type 2 (HSV-2) currently affects approximately 22% of adult Americans and increased markedly in prevalence between the late 1970s and early 1990s. Although some estimates of the costs of prevalent disease due to HSV-2 are available, selection of interventions to prevent HSV-2 infection, as well as evaluation of their potential cost-effectiveness, should take into account projected future costs that will result if the epidemic is left unchecked. GOAL: The goal was to estimate the future health and economic consequences attributable to the HSV-2 epidemic in the absence of interventions to slow the epidemic. STUDY DESIGN: A mathematical model was constructed to project future increases in HSV-2 seroprevalence in the United States. The probability of heterosexual transmission of HSV-2 was estimated from cross-sectional estimates of infection prevalence reported by the National Health and Nutrition Examination Survey (NHANES). Per-infection expected costs were calculated on the basis of data obtained from the published medical literature. RESULTS Without intervention, the prevalence of HSV-2 infection among individuals aged 15 to 39 years was projected to increase to 39% among men and 49% among women by 2025. Annual incidence was projected to increase steadily between 2000 and 2025, from 9 to 26 infections per 1,000 men and from 12 to 32 infections per 1,000 women in this age group. The cost of incident infections in the year 2000 were estimated to be $1.8 billion; the cost of incident infections was predicted to rise to $2.5 billion by 2015 and $2.7 billion by 2025. The projected cumulative cost of incident HSV-2 infections occurring over the next 25 years was estimated to be $61 billion; at a 3% discount rate, this sum has a present value of $43 billion. CONCLUSION: The costs of incident HSV-2 infection in the United States are substantial and can be expected to increase as both the incidence and prevalence of this disease increase in the first half of the century. The level of resource allocation for HSV-2 prevention strategies should reflect the economic benefits that would result from control of this epidemic.

Adolescent↗
PubMed2002

Antimicrobial use and antimicrobial resistance: a population perspective.

The need to stem the growing problem of antimicrobial resistance has prompted multiple, sometimes conflicting, calls for changes in the use of antimicrobial agents. One source of disagreement concerns the major mechanisms by which antibiotics select resistant strains. For infections like tuberculosis, in which resistance can emerge in treated hosts through mutation, prevention of antimicrobial resistance in individual hosts is a primary method of preventing the spread of resistant organisms in the community. By contrast, for many other important resistant pathogens, such as penicillin-resistant Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant Enterococcus faecium resistance is mediated by the acquisition of genes or gene fragments by horizontal transfer; resistance in the treated host is a relatively rare event. For these organisms, indirect, population-level mechanisms of selection account for the increase in the prevalence of resistance. These mechanisms can operate even when treatment has a modest, or even negative, effect on an individual host's colonization with resistant organisms.

Anti-Bacterial Agents↗