Inga Lind

Dynamics of the meningococcal carrier state and characteristics of the carrier strains: a longitudinal study within three cohorts of military recruits

Three cohorts of Danish male military recruits (n = 1069) were studied for pharyngeal meningococcal carriage during 3 months at different seasons: 39-47% of entrants were meningococcal carriers and the carriage rate remained constant over time and season. However, individual changes in the carrier state occurred frequently, and after 3 months 34% had changed carrier state on one or more occasions. Initially, a loss of carriage predominated; on the other hand almost 20% of non-carriers had acquisition of meningococci within the first month. The serological phenotypes of the 670 carrier strains were compared with those of 261 invasive strains recovered concurrently from patients with meningococcal disease country-wide. Both carrier strains and invasive strains were phenotypically heterogeneous. Almost 60% of the invasive strains belonged to three phenotypes: B:15:P1.7, 16, C:2a:P1.2, 5 and C:2b:P1.2, 5. In contrast, these phenotypes only amounted to 3.2% of the carrier strains, among which no phenotype was found with a prevalence above 4.9%. However, 30% of the carrier strains had serological phenotypes identical to those of 80% of the invasive strains. Our results indicated that the transmission rate of potential pathogenic carrier strains did not differ from that of other carrier strains.

Performance of Three Microimmunofluorescence Assays for Detection of Chlamydia pneumoniae Immunoglobulin M, G, and A Antibodies

ABSTRACT The microimmunofluorescence (MIF) test is considered the “gold standard” for laboratory diagnosis of acute and chronic Chlamydia pneumoniae infection. The performance of a MIF test based on C. pneumoniae antigen from Washington Research Foundation (WRF) was compared with those of assays from Labsystems (LAB) and MRL Diagnostics (MRL) by investigation of sera from three groups of patients: group I, 83 sera from 28 patients with atypical pneumonia; group II, 37 sera from 16 patients with acute C. pneumoniae or Chlamydia psittaci respiratory tract infection confirmed by PCR or culture; group III, 100 sera from 100 persons enrolled in the Copenhagen City Heart Study. The accordance among the results of the WRF assay and the two commercial assays was excellent for the immunoglobulin M (IgM) antibody detection rate (98%). The accordance in detection rates for IgG and IgA antibodies in sera from patients with acute infections was acceptable (87 and 88%), and in sera from group III, it was excellent (95 and 97%). The determinations of endpoint titers were reproducible with <1 dilution step difference for all three methods, except that the mean IgM antibody titer found by the LAB assay was almost 2 dilution steps higher than that found by the other two methods. Although the three assays use different C. pneumoniae strains as antigens, the detection rates and IgG and IgA endpoint titers were similar. The difference in endpoint titers of IgM antibodies is of no major concern, as the diagnosis of acute C. pneumoniae infection rests on the presence of IgM antibodies, not on their level.

Pharyngeal carriage of Neisseria meningitidis before and after treatment of meningococcal disease

The aim of the study was to determine whether patients with meningococcal disease carry meningococci in the throat both before and after treatment for the disease. During the 7 months of the study 106 patients with confirmed meningococcal disease were admitted to Danish hospitals, of whom 77 (73%) had a throat swab examined at least once and were included in the study. Sixty-two patients were examined on admission and 52 were examined on discharge; 37 were examined on both occasions. On admission, meningococci were isolated from 18 (49%) of 37 throat specimens examined selectively for pathogenic Neisseria spp. Meningococci were not isolated from any throat specimen taken on discharge from hospital; 47 (90%) of 52 of these specimens had been examined adequately. From an observed carriage rate of 0 out of 47 it can be judged that the carrier rate does not exceed 6.4% (95% confidence limit). From these results we conclude that it is unlikely that patients who have been treated for meningococcal disease according to the regimens used in Denmark can be the source of infection for secondary cases.

Surveillance of cases of meningococcal disease associated with military recruits studied for meningococcal carriage.

Through a 14-months extended surveillance of meningococcal disease in Denmark, all 322 notified cases were investigated for possible connection with a military camp where 3 cohorts of recruits (n = 1069) were studied prospectively for meningococcal carriage. One case occurred in a recruit who was a constant non-carrier during the preceding 3 months. The invasive Neisseria meningitidis B:1:P1.1,7 strain was isolated from the pharynx only in 3 out of 17 room-mates (18%); the strains were identical as assessed by genotyping (PFGE and ribotyping). Two civilian cases outside the camp had direct contact with 2 recruits, but neither these 2 nor other recruits in the relevant divisions carried the invasive strains on any occasion. Six civilian cases had marginal relationship with the camp, but no contact with the recruits. In conclusion, pheno- and genotyping concordantly demonstrated a high carriage rate of the invasive strain among the room-mates to a recruit with meningococcal disease. Transmission to the patient most likely occurred shortly before onset of illness. The extended surveillance did, however, not identify any unexpected epidemiological links and restriction of antibiotic chemoprophylaxis to household/sleeping/kissing contacts in sporadic cases of meningococcal disease seems appropriate and relevant.Through a 14-months extended surveillance of meningococcal disease in Denmark, all 322 notified cases were investigated for possible connection with a military camp where 3 cohorts of recruits (n 1069) were studied prospectively for meningococcal carriage. One case occurred in a recruit who was a constant non-carrier during the preceding 3 months. The invasive Neisseria meningitidis B:1:P1.1,7 strain was isolated from the pharynx only in 3 out of 17 room-mates (18%); the strains were identical as assessed by genotyping (PFGE and ribotyping). Two civilian cases outside the camp had direct contact with 2 recruits, but neither these 2 nor other recruits in the relevant divisions carried the invasive strains on any occasion. Six civilian cases had marginal relationship with the camp, but no contact with the recruits. In conclusion, pheno- and genotyping concordantly demonstrated a high carriage rate of the invasive strain among the room-mates to a recruit with meningococcal disease. Transmission to the patient most likely occurred shortly before onset of illness. The extended surveillance did, however, not identify any unexpected epidemiological links and restriction of antibiotic chemoprophylaxis to household/sleeping/kissing contacts in sporadic cases of meningococcal disease seems appropriate and relevant.

Laboratory surveillance of urogenital Chlamydia trachomatis infections in Denmark 1988 – 2007

In 1994 laboratory reporting of urogenital chlamydia was integrated in the countrywide notification system for infectious diseases. Previously (1988–1993), laboratory confirmed cases had been reported on a voluntary basis. The applied laboratory technologies changed significantly: in 1988, 48% of cases were diagnosed by culture; in 1994, 88% by enzyme immunoassays; and since 2004 more than 99% by nucleic acid amplification tests. The proportions of chlamydia-positive men diagnosed by testing urine were <1% in 1994, 10% in 2001 and 75% in 2007. From 1994 to 2002 the annual incidence rates of chlamydia per 100,000 population among women were around 350–400 and then increased to 586 in 2007. Among men the incidence rate rose from 125 in 1994 to 358 in 2007. In conclusion, the annual incidence rates of urogenital chlamydia remained high and possibly increasing during a 14-y period (1994–2007), with a high testing activity, improving technologies and countrywide information campaigns. The observed increase is likely to be associated with the introduction of more sensitive diagnostic methods and with increasing testing of men. A possible change in target groups from low- to high-prevalence could not be assessed due to lack of information about persons being tested.

Epidemiological markers in Neisseria meningitidis : An estimate of the performance of genotyping vs phenotyping

In order to estimate the performance of genotypic vs phenotypic characterization of Neisseria meningitidis, 2 methods, DNA fingerprinting and multilocus enzyme electrophoresis (MEE), were assessed as regards applicability, reproducibility and discriminating capacity. 50 serogroup B and 52 serogroup C Neisseria meningitidis strains from 96 patients with meningococcal disease and 22 serogroup C strains from healthy carriers were investigated. Both methods were 100% applicable to meningococcal strains and results of DNA fingerprinting as well as of MEE were reproducible. The number of types defined by DNA fingerprinting and MEE as compared to that defined by phenotypic characteristics (serogroup, serotype, serosubtype and sulphonamide resistance) was as follows: for serogroup B strains from patients, 11 and 12 vs 8; for serogroup C strains from patients, 10 and 15 vs 8; and for serogroup C carrier strains, 12 and 19 genotypes vs 10 phenotypes were defined. By use of both DNA fingerprinting and MEE the number of genotypes defined for the 3 groups of strains was 14, 17 and 19, respectively. DNA fingerprinting and MEE showed a discriminating capacity superior to that of phenotyping, and as applied in the study MEE was superior to DNA fingerprinting. Clusters of invasive strains were reliably identified by phenotyping alone, whereas determination of identity of carrier strains and an invasive strain required genotyping.