Meningococcal Disease in California: Epidemiology and Management

Between 1969 and 1975 in California, 1,953 cases of meningococcal disease were reported. For cases reported in 1973, 1974 and 1975, detailed information about chemoprophylaxis of cases and contacts was obtained in addition to demographic and laboratory data. A review of data for the seven years showed a reduction in the case rate from 2.6 to 0.6 per 100,000 population, but this drop was due primarily to a very substantial decline in the military rate from 35.7 to 1.8 per 100,000 population. No reduction was apparent in the case fatality rate. Five groups of associated meningococcal disease cases were identified for a total of nine secondary or coprimary cases among 862 household contacts. Associated cases occurred in 10.4 per 1,000 household contacts—a rate several hundred times greater than that for the general population.The study findings indicate that many physicians are unaware of the following: (1) nonhousehold contacts are at little or no risk of contracting meningococcal disease; (2) prophylaxis should be offered only to household or intimate contacts immediately upon identification of an index case without waiting for test results for meningococcal carriage; (3) valid medical and epidemiologic indications exist for administering prophylaxis to household contacts who are culture negative as well as those who are culture positive; (4) the current drug of choice for prophylaxis is rifampin, but since no drug is completely effective, close medical observation remains the most important factor in the management of household or intimate contacts to meningococcal disease.     

Which contacts of patients with meningococcal disease carry the pathogenic strain of Neisseria meningitidis? A population based study

Objectives: To determine the prevalence of the pathogenic strain of Neisseria meningitidis in contacts of patients with meningococcal disease, and to determine which contact groups are likely to be carriers and warrant chemoprophylaxis. Design: Population based study. Setting: Norwegian county of Telemark. Subjects: 1535 primary contacts of 48 patients with meningococcal disease, and 78 secondary contacts. Interventions: Carriers of the pathogenic strain were treated with rifampicin. All household members and kissing contacts under 15 years of age were treated with oral penicillin. Contacts were taught to recognise the symptoms of meningococcal disease. Results: In 27 of 48 cases investigated, contacts carrying the pathogenic strain of N meningitidis were found. A total of 42 such contacts were identified. Contacts were stratified into three classes according to the assumed closeness of contact with patients. In class 1 (household members and kissing contacts) the prevalence of the pathogenic strain was 12.4% (95% confidence interval 5.5% to 19.3%). In classes 2 and 3 the prevalence was 1.9% (0.9% to 3.4%) and 1.6% (0.14% to 3.1%). Conclusions: There is a high rate of carriage of the pathogenic strain of N meningitidis in patients’ household members and kissing contacts, and this supports the practice of giving chemoprophylaxis to these contacts. The prevalence of carriage among other contacts is 2-3 times that found in the general population (0.7%); the benefits of chemoprophylaxis to these contacts may be marginal.

Key messages

• Contacts of patients with meningococcal disease have a 12.4% (95% confidence interval 5.5% to 19.3%) risk of carrying the pathogenic meningococcus if they are kissing contacts or household members
• The risk of carriage of the pathogenic strain for two groups of contacts less close than household members or kissing contacts is 1.9% (0.9% to 3.4%) and 1.6% (0.14% to 3.1%)

     

Secondary cases of meningococcal infection among close family and household contacts in England and Wales, 1984-7.

To determine the incidence of secondary meningococcal infection in close family and household contacts of index patients and to review the efficacy of chemoprophylaxis the records of 3256 cases occurring from 1984 through 1987 were examined. Seventeen secondary cases (0.5%) of infection were identified among these groups. The median interval between index and secondary cases was seven weeks. Fourteen secondary cases occurred more than one week after the disease was diagnosed in the index case. Three secondary cases had not received chemoprophylaxis and in another case the infecting strain had acquired resistance to rifampicin. Prophylaxis for the close contacts of 10 out of 11 of the remaining index patients failed to fulfil all the criteria of an optimal regimen. Even after optimal chemoprophylaxis the medical practitioner and the family should be aware of the increased and prolonged risk of secondary meningococcal infection among close contacts of patients with the disease.     

Prevention of secondary cases of meningococcal disease in household contacts by vaccination.

Household contacts of patients with group A meningococcal infection were vaccinated with either meningococcal vaccine or tetanus toxoid. Five of the 523 subjects who received tetanus toxoid developed meningococcal meningitis and another four probably had meningococcal disease. Only one possible case of meningococcal infection occurred among 520 contacts vaccinated with meningococcal vaccine. Vaccination had no effect on nasopharyngeal carriage of meningococci. Vaccination of household contacts of patients with group A meningococcal infections is an effective way of using limited supplies of meningococcal vaccine, though its value would be limited in an epidemic. Secondary cases of meningococcal infection often occur within a few days of the index case, and, although vaccine alone seemed to provide adequate prophylaxis in these Nigerian subjects, additional chemoprophylaxis may be needed to cover this critical period.     

Meningococcal infections in the Hamilton area during 1978.

During 1978 there was a marked increase in the number of patients with meningococcal infection in the Hamilton area. Of 21 patients admitted to St. Joseph''s Hospital, Hamilton, two thirds were under 5 years of age. Four patients died. All the isolates were sulfonamide-sensitive strains of serogroup B Neisseria meningitidis. Although no infections developed in contacts, several errors were made in the management of the hospital and household contacts of the infected patients: chemoprophylaxis was given to many contacts not considered to be at risk; ineffective antibiotics, particularly penicillin, were given for chemoprophylaxis; and chemoprophylaxis was often delayed while the results of cultures of nasopharyngeal and throat secretions were awaited. Circulation to local physicians of guidelines on proven prophylactic regimens was followed by a reduction in the frequency of these errors.     

Chemoprophylaxis in contacts of patients with cholera: systematic review and meta-analysis

Introduction

There is a pressing need for effective measures to prevent the spread of cholera. Our systematic review assesses the effects of chemoprophylaxis in preventing cholera among exposed contacts.

Methods and Findings

We considered published and unpublished reports of studies up to July 2011. For this we searched: PubMed (1966 to July, 2011), Embase (1980 to July 2011), Cochrane Central Register of Controlled Trials (6; 2011), LILACS (1982 to July, 2011), the International Clinical Trials Registry Platform (July 2011) and references of identified publications. We included controlled clinical trials (randomized and non-randomized) in which chemoprophylaxis was used to prevent cholera among patient contacts. The main outcome measures were hospitalization and laboratory diagnosis of cholera in contacts for cholera patients. We assessed the risk of bias. We identified 2638 references and these included 2 randomized trials and 5 controlled trials that added up to a total of 4,154 participants. The risk of bias scored high for most trials. The combined results from two trials found that chemoprophylaxis reduced hospitalization of contacts during the follow-up period by 8–12 days (2826 participants; RR 0.54 95% CI 0.40–0.74;I² 0%). A meta-analysis of five trials found a significant reduction in disease among contacts with at least one positive sample who received chemoprophylaxis during the overall follow-up (range 4–15 days) (1,414 participants; RR 0.35 95% CI 0.18–0.66;I² 74%). A significant reduction in the number of positive samples was also found with chemoprophylaxis (3 CCT; 6,918 samples; RR 0.39 95% CI 0.29–0.51;I² 0%).

Conclusion

Our findings suggest that chemoprophylaxis has a protective effect among household contacts of people with cholera but the results are based on studies with a high risk of bias. Hence, there is a need for adequate reliable research that allows balancing benefits and harms by evaluating the effects of chemoprophylaxis.     

Assessment of a two-step nucleic acid amplification assay for detection of Neisseria meningitidis followed by capsular genogrouping

Immediate prevention of meningococcal disease relies in part on the prompt treatment with antibiotics of household and other close contacts of cases; however intervention with effective vaccination relies on identification of serogroup-causing strains. Parenteral antibiotic for patient with suspected meningococcal disease before hospital admission is currently recommended. Laboratory standard methods are hindered by failure to detect bacteria by this medical approach to improve patient prognosis. We assessed two polymerase chain reaction (PCR) assays to detect (crgA) and define the serogroups (siaD, orf-2, and ctrA) of Neisseria meningitidis in 120 cerebrospinal fluid (CSF) samples from positive cases (culture or antigen detection or direct smear). The PCR sensitivity for the identification of N. meningitidis was 100% (95% confidence interval, CI, 96-100%) compared to a sensitivity of 46% for culture (95% CI 37-55%), 61% for latex agglutination test (95% CI 52-70%), and 68% for Gram stain (95% CI 59-76%); PCR specificity was 97% (95% CI 82-100%). PCR correctly identified the serogroups A, B, C, W135, Y, and X in CSF samples with a sensitivity of 88% (95% CI 80-93%); the primer sets were 100% specific. The introduction of PCR-based assays shall increase laboratory confirmed cases, consequently enhancing surveillance of meningococcal disease.     

An Intercity Outbreak of Meningococcal Meningitis in Adults

An intercity outbreak of meningococcal meningitis occurred in five adults, with the acute onset of symptoms developing in two of the patients after they returned to Los Angeles from the San Francisco Bay area. The secondary attack rate was 36.4 percent in this entirely adult household. The authors review reports of secondary cases in civilian epidemics, as well as recommendations for chemoprophylaxis in household contacts.     

Early treatment with parenteral penicillin in meningococcal disease.

OBJECTIVE--To measure the effect of parenteral antibiotics given before admission to hospital on mortality and on bacteriological investigations in meningococcal disease. DESIGN--Retrospective review of hospital notes and laboratory and public health medicine department records. SETTING--Three health districts in south west England. SUBJECTS--Patients with meningococcal disease in Gloucester district presenting between 1 January 1982 and 31 December 1991 (n = 190); patients with meningococcal disease in Plymouth (n = 118) and Bath (n = 73) districts presenting between 1 January 1988 and 31 December 1991 (total = 381). MAIN OUTCOME MEASURE--Number of deaths from meningococcal disease. RESULTS--Parenteral antibiotic given by general practitioners was associated with a substantial reduction in mortality (from 9% to 5%; relative risk 0.6, 95% confidence interval 0.2 to 1.5); patients with a rash were more likely to be given parenteral antibiotics, and mortality was further reduced (from 12% to 5%; 0.5, 0.2 to 1.4). In a district where such treatment was regularly encouraged its use increased from 5% to 40% of cases over 10 years (p = 0.00001). Treatment with parenteral antibiotics before admission made isolation of meningococci from blood and cerebrospinal fluid less likely but did not affect nasopharyngeal cultures. CONCLUSIONS--General practitioners should carry benzylpenicillin in their emergency bags at all times and should administer it promptly, preferably intravenously, whenever meningococcal disease is suspected, unless the patient has had an anaphylactic reaction to penicillin. Specimens for culture should include a nasopharyngeal swab.     

Transmission of Multidrug-Resistant and Drug-Susceptible Tuberculosis within Households: A Prospective Cohort Study

Background

The “fitness” of an infectious pathogen is defined as the ability of the pathogen to survive, reproduce, be transmitted, and cause disease. The fitness of multidrug-resistant tuberculosis (MDRTB) relative to drug-susceptible tuberculosis is cited as one of the most important determinants of MDRTB spread and epidemic size. To estimate the relative fitness of drug-resistant tuberculosis cases, we compared the incidence of tuberculosis disease among the household contacts of MDRTB index patients to that among the contacts of drug-susceptible index patients.

Methods and Findings

This 3-y (2010–2013) prospective cohort household follow-up study in South Lima and Callao, Peru, measured the incidence of tuberculosis disease among 1,055 household contacts of 213 MDRTB index cases and 2,362 household contacts of 487 drug-susceptible index cases.A total of 35/1,055 (3.3%) household contacts of 213 MDRTB index cases developed tuberculosis disease, while 114/2,362 (4.8%) household contacts of 487 drug-susceptible index patients developed tuberculosis disease. The total follow-up time for drug-susceptible tuberculosis contacts was 2,620 person-years, while the total follow-up time for MDRTB contacts was 1,425 person-years. Using multivariate Cox regression to adjust for confounding variables including contact HIV status, contact age, socio-economic status, and index case sputum smear grade, the hazard ratio for tuberculosis disease among MDRTB household contacts was found to be half that for drug-susceptible contacts (hazard ratio 0.56, 95% CI 0.34–0.90, p = 0.017). The inference of transmission in this study was limited by the lack of genotyping data for household contacts. Capturing incident disease only among household contacts may also limit the extrapolation of these findings to the community setting.

Conclusions

The low relative fitness of MDRTB estimated by this study improves the chances of controlling drug-resistant tuberculosis. However, fitter multidrug-resistant strains that emerge over time may make this increasingly difficult.     

Incidence,Carriage and Case-Carrier Ratios for Meningococcal Meningitis in the African Meningitis Belt: A Systematic Review and Meta-Analysis

BackgroundTo facilitate the interpretation of meningococcal meningitis epidemiology in the “African meningitis belt”, we aimed at obtaining serogroup-specific pooled estimates of incidence, carriage and case-carrier ratios for meningococcal meningitis in the African meningitis belt and describe their variations across the endemic, hyperendemic and epidemic context.MethodsWe conducted a systematic review and meta-analysis of studies reporting serogroup-specific meningococcal meningitis monthly incidence and carriage in the same population and time period. Epidemiological contexts were defined as endemic (wet season, no epidemic), hyperendemic (dry season, no epidemic), and epidemic (dry season, epidemic).FindingsEight studies reporting a total of eighty pairs of serogroup-specific meningococcal meningitis incidence and carriage estimates were included in this review. For serogroup A, changes associated with the transition from endemic to hyperendemic incidence and from hyperendemic to epidemic incidence were 15-fold and 120-fold respectively. Changes in carriage prevalence associated with both transitions were 1-fold and 30-fold respectively.
For serogroup W and X, the transition from endemic to hyperendemic incidence involved a 4-fold and 1•1-fold increase respectively. Increases in carriage prevalence for the later transition were 7-fold and 1•7-fold respectively. No data were available for the hyperendemic-epidemic transition for these serogroups. Our findings suggested that the regular seasonal variation in serogroup A meningococcal meningitis incidence between the rainy and the dry season could be mainly driven by seasonal change in the ratio of clinical cases to subclinical infections. In contrast appearance of epidemic incidences is related to a substantial increase in transmission and colonisation and to lesser extent with changes in the case-carrier ratio.ConclusionSeasonal change in the rate of progression to disease given carriage together with variations in frequency of carriage transmission should be considered in models attempting to capture the epidemiology of meningococcal meningitis and mainly to predict meningitis epidemics in the African meningitis belt.     

Leprosy reactions: the effect of gender and household contacts

Various host-related factors have been reported as relevant risk factors for leprosy reactions. To support a new hypothesis that an antigenic load in local tissues that is sufficient to trigger the immune response may come from an external supply of Mycobacterium leprae organisms, the prevalence of reactional leprosy was assessed against the number of household contacts. The number of contacts was ascertained at diagnosis in leprosy patients coming from an endemic area of Brazil. The prevalence of reactions (patients with reactions/total patients) was fitted by binomial regression and the risk difference (RD) was estimated with a semi-robust estimation of variance as a measure of effect. Five regression models were fitted. Model 1 included only the main exposure variable "number of household contacts"; model 2 included all four explanatory variables ("contacts", "fertile age", "number of skin lesions" and "bacillary index") that were found to be associated with the outcome upon univariate analysis; models 3-5 contained various combinations of three predictors. Male and female patients were analyzed separately. In females, household contacts were a significant predictor for leprosy reactions in model 1 [crude RD = 0.06; 95% confidence interval (CI) = 0.01; 0.12] and model 5 (RD = 0.05; CI = 0.02; 0.09), which included contacts, bacillary index and skin lesions as predictors. Other models were unsatisfactory because the joint presence of fertile age and bacillary index was a likely source of multicollinearity. No significant results were obtained for males. The likely interpretation of our findings might suggest that in female patients, leprosy reactions may be triggered by an external spreading of M. leprae by healthy carrier family members. The small number of observations is an obvious limitation of our study which requires larger confirmatory studies.     

Haemophilus influenzae type B meningitis: a contagious disease of children.

The families of 126 consecutive patients with Haemophilus influenzae type B meningitis were surveyed for secondary invasive H influenzae disease among household contacts. A total of 120 of the families were contacted. In six cases no contact was possible and the medical record was reviewed. Some 555 household contacts were found; 31% (171) were under 5 years of age. A secondary case was defined as a household contact with H influenzae type B isolated from blood or cerebrospinal fluid more than 24 hours, but less than 30 days, after admission to hospital of the index case. Four secondary cases were identified, all in children aged under 5 years. The secondary attack rate in children under 5 years or less in the month after exposure to an index case was thus 2.3%, 800 times the endemic attack rate for H influenzae meningitis. This is a conservative estimate since five additional contact cases were documented, but not included in the secondary attack rate. Young contacts of a child with H influenzae meningitis are thus at significant risk of life-threatening secondary disease.     

Estimating the contribution of HIV-infected adults to household pneumococcal transmission in South Africa, 2016–2018: A hidden Markov modelling study

Human immunodeficiency virus (HIV) infected adults are at a higher risk of pneumococcal colonisation and disease, even while receiving antiretroviral therapy (ART). To help evaluate potential indirect effects of vaccination of HIV-infected adults, we assessed whether HIV-infected adults disproportionately contribute to household transmission of pneumococci. We constructed a hidden Markov model to capture the dynamics of pneumococcal carriage acquisition and clearance observed during a longitudinal household-based nasopharyngeal swabbing study, while accounting for sample misclassifications. Households were followed-up twice weekly for approximately 10 months each year during a three-year study period for nasopharyngeal carriage detection via real-time PCR. We estimated the effect of participant’s age, HIV status, presence of a HIV-infected adult within the household and other covariates on pneumococcal acquisition and clearance probabilities. Of 1,684 individuals enrolled, 279 (16.6%) were younger children (<5 years-old) of whom 4 (1.5%) were HIV-infected and 726 (43.1%) were adults (≥18 years-old) of whom 214 (30.4%) were HIV-infected, most (173, 81.2%) with high CD4+ count. The observed range of pneumococcal carriage prevalence across visits was substantially higher in younger children (56.9–80.5%) than older children (5–17 years-old) (31.7–50.0%) or adults (11.5–23.5%). We estimate that 14.4% (95% Confidence Interval [CI]: 13.7–15.0) of pneumococcal-negative swabs were false negatives. Daily carriage acquisition probabilities among HIV-uninfected younger children were similar in households with and without HIV-infected adults (hazard ratio: 0.95, 95%CI: 0.91–1.01). Longer average carriage duration (11.4 days, 95%CI: 10.2–12.8 vs 6.0 days, 95%CI: 5.6–6.3) and higher median carriage density (622 genome equivalents per millilitre, 95%CI: 507–714 vs 389, 95%CI: 311.1–435.5) were estimated in HIV-infected vs HIV-uninfected adults. The use of ART and antibiotics substantially reduced carriage duration in all age groups, and acquisition rates increased with household size. Although South African HIV-infected adults on ART have longer carriage duration and density than their HIV-uninfected counterparts, they show similar patterns of pneumococcal acquisition and onward transmission.     

Lessons from meningococcal carriage studies

Neisseria meningitidis, an obligate commensal of humans, normally colonizes the mucosa of the upper respiratory tract without affecting the host, a phenomenon known as carriage. In Europe, as much as 35% of young adults are carriers at a given time. Recent studies using molecular methods for clone identification have demonstrated the extensive genetic diversity of the strains isolated from carriers, in comparison with a limited number of hypervirulent strains associated with invasive disease. Published studies and new data generated through the framework of the EU-MenNet clearly indicated significant differences in pathogenicity between meningococcal clones and in the distribution of multilocus sequence types among isolates from asymptomatic carriers among European countries; simultaneous carriage of more than one meningococcal strain in the throat is rare, but occasionally occurs; and the commensal association of particular clones with a host is a long-term relationship, often lasting several months. Further investigations of the carrier state are warranted to improve our understanding of the epidemiology and pathogenesis of meningococcal disease, as well as to support the introduction and to measure the impact of mass vaccination.     

Integrated Source Case Investigation for Tuberculosis (TB) and HIV in the Caregivers and Household Contacts of Hospitalised Young Children Diagnosed with TB in South Africa: An Observational Study

Background

Contact tracing, to identify source cases with untreated tuberculosis (TB), is rarely performed in high disease burden settings when the index case is a young child with TB. As TB is strongly associated with HIV infection in these settings, we used source case investigation to determine the prevalence of undiagnosed TB and HIV in the caregivers and household contacts of hospitalised young children diagnosed with TB in South Africa.

Methods

Caregivers and household contacts of 576 young children (age ≤7 years) with TB diagnosed between May 2010 and August 2012 were screened for TB and HIV. The primary outcome was the detection of laboratory-confirmed, newly-diagnosed TB disease and/or HIV-infection in close contacts.

Results

Of 576 caregivers, 301 (52·3%) self-reported HIV-positivity. Newly-diagnosed HIV infection was detected in 63 (22·9%) of the remaining 275 caregivers who self-reported an unknown or negative HIV status. Screening identified 133 (23·1%) caregivers eligible for immediate anti-retroviral therapy (ART). Newly-diagnosed TB disease was detected in 23 (4·0%) caregivers. In non-caregiver household contacts (n = 1341), the prevalence of newly-diagnosed HIV infection and TB disease was 10·0% and 3·2% respectively. On average, screening contacts of every nine children with TB resulted in the identification of one case of newly-diagnosed TB disease, three cases of newly diagnosed HIV-infection, and three HIV-infected persons eligible for ART.

Conclusion

In high burden countries, source case investigation yields high rates of previously undiagnosed HIV and TB infection in the close contacts of hospitalised young children diagnosed with TB. Furthermore, integrated screening identifies many individuals who are eligible for immediate ART. Similar studies, with costing analyses, should be undertaken in other high burden settings–integrated source case investigation for TB and HIV should be routinely undertaken if our findings are confirmed.     

Characterization of Carriage Isolates of Neisseria meningitidis in the Adolescents and Young Adults Population of Bogota (Colombia)

Background

Meningococcal carriage studies are important to improve our understanding of the epidemiology of meningococcal disease. The aim of this study was to determine the prevalence of meningococcal carriage and the phenotypic and genotypic characteristics of isolates collected from a sample of students in the city of Bogotá, Colombia.

Materials and Methods

A total of 1459 oropharyngeal samples were collected from students aged 15–21 years attending secondary schools and universities. Swabs were plated on a Thayer Martin agar and N. meningitidis was identified by standard microbiology methods and PCR.

Results

The overall carriage prevalence was 6.85%. Carriage was associated with cohabitation with smokers, and oral sex practices. Non-groupable and serogroup Y isolates were the most common capsule types found. Isolates presented a high genetic diversity, and circulation of the hypervirulent clonal complexes ST-23, ST-32 and ST-41/44 were detected.

Conclusion

The meningococcal carriage rate was lower than those reported in Europe and Africa, but higher than in other Latin American countries. Our data also revealed antigenic and genetic diversity of the isolates and the circulation of strains belonging to clonal complexes commonly associated with meningococcal disease.     

Factors Associated with Household Transmission of Pandemic (H1N1) 2009 among Self-Quarantined Patients in Beijing,China

As the pandemic (H1N1) 2009 progressed, the Ministry of Health of China advised cases with mild symptoms to remain home for isolation and observation, which may have increased the risk for infection among other household members. Describing the transmission characteristics of this novel virus is indispensable to effectively controlling the spread of disease; thus, the aim of this study was to assess risk factors associated with household transmission of pandemic H1N1 from self-quarantined patients in Beijing, the capital city of China. A 1:2 case-control study with 54 case households and 108 control households was conducted between August 1 and September 30, 2009 in Beijing. Cases were households with a self-quarantined index patient and a secondary case, while controls were households with a self-quarantined index patient and a close contact. Controls were also matched to cases for sex and age of index case-patient. A structured interview guide was used to collect the data. Conditional logistical models were employed to estimate Odds Ratios (OR) with 95% confidence intervals (95% CI). Results indicated that higher education level (OR 0.42; 95% CI 0.22-0.83), sharing room with an index case-patient (OR 3.29; 95%CI 1.23-8.78), daily room ventilation (OR 0.28; 95%CI 0.08-0.93), and hand washing ≥3/d (OR 0.71; 95%CI 0.48-0.94) were related to the household transmission of pandemic H1N1 from self-quarantined patients. These results highlight that health education, as well as the quarantine of the index case-patient immediately after infection, frequent hand hygiene, and ventilation are critical to mitigating household spread of pandemic H1N1 virus and minimizing its impact. Household contacts should be educated to promote these in-home practices to contain transmission, particularly when household members are quarantined at home.     

Carriage of Neisseria meningitidis and Neisseria lactamica among ethnic Greek school children from Russian immigrant families in Athens

During February and March 1995, a survey of meningococcal carriage in 625 school children was carried out in a suburb of Athens in which there was a large number of ethnic Greeks who had immigrated from Russia beginning in the early 1990s. The objectives of the study were: (1) to determine if factors associated with carriage of meningococci observed in a previous study of Greek school children were similar for the immigrant population; (2) to compare phenotypic characteristics of meningococci from the immigrant population with those isolated from children in Athens. Overall isolation rate for meningococci was 82/625 (13.1%), significantly higher than that found for school children in Athens (5.8%) during the winter of 1990 1991 (5.8%) (chi=25.98, P=0.0000003). By univariate analysis, carriage was not associated with sex, number of individuals per household, blood group, secretor status, socioeconomic level or maternal smoking; however, it was associated with fathers' smoking. The high proportion of men who smoked compared with the low proportion of women smokers might contribute to this finding. The main serogroup of meningococci isolated from this population was A (28%). While serogroup A appears to be more prevalent among Russian and Kurdish immigrants (14%) than among Greek school children or military recruits (4%), there has not been an increase in group A meningococcal disease in Greece. The isolation rate for N. lactamica was high 105/625 (17.3%). A few of these strains bound some of the monoclonal antibodies used for meningococcal serotyping and subtyping, and they are being examined in greater detail.     

PCR-Based Techniques for Leprosy Diagnosis: From the Laboratory to the Clinic

In leprosy, classic diagnostic tools based on bacillary counts and histopathology have been facing hurdles, especially in distinguishing latent infection from active disease and diagnosing paucibacillary clinical forms. Serological tests and IFN-gamma releasing assays (IGRA) that employ humoral and cellular immune parameters, respectively, are also being used, but recent results indicate that quantitative PCR (qPCR) is a key technique due to its higher sensitivity and specificity. In fact, advances concerning the structure and function of the Mycobacterium leprae genome led to the development of specific PCR-based gene amplification assays for leprosy diagnosis and monitoring of household contacts. Also, based on the validation of point-of-care technologies for M. tuberculosis DNA detection, it is clear that the same advantages of rapid DNA detection could be observed in respect to leprosy. So far, PCR has proven useful in the determination of transmission routes, M. leprae viability, and drug resistance in leprosy. However, PCR has been ascertained to be especially valuable in diagnosing difficult cases like pure neural leprosy (PNL), paucibacillary (PB), and patients with atypical clinical presentation and histopathological features compatible with leprosy. Also, the detection of M. leprae DNA in different samples of the household contacts of leprosy patients is very promising. Although a positive PCR result is not sufficient to establish a causal relationship with disease outcome, quantitation provided by qPCR is clearly capable of indicating increased risk of developing the disease and could alert clinicians to follow these contacts more closely or even define rules for chemoprophylaxis.