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.     

Cellular immunity in patients with malignant melanoma and their household contacts

Summary Immune reactivity was measured in control subjects and in 86 patients with malignant melanoma using four tests of cellular immunity. In addition, cellular immune reactivity to melanoma extract was studied in 13 household contacts of patients with melanoma. Thirty percent (4/13) of the household contacts showed reactivity to melanoma extract as determined by lymphocyte stimulation as compared to 20% of patients and 5% of controls. Seventy-two percent (8/11) household contacts showed reactivity as measured by the indirect MIF test, compared to 38% of patients and 23% of normal controls. As determined by the leukocyte migration inhibition test, 71% (5/7) of household contacts showed reactivity to melanoma extract versus 20% of patients and 22% of controls. The number of household contacts studied was low; however, it was observed that these subjects showed responses to melanoma extract with considerably greater frequency than did normal control subjects, and the frequency of positive responses in patients with melanoma was intermediate between that of the household contacts and the normal controls.This work was supported in part by grants AI-10495, AI CA-10686, and CA 13671 from the U.S. Public Health Service. Dr. Spitler is supported by a National Institutes of Health Career Development Award (AI-43012).     

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.     

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.     

Immunoglobulin G response against 10-kDa and 65-kDa heat-shock proteins in leprosy patients and their household contacts

Abstract We measured antibody responses to recombinant Mycobacterium leprae 65-kDa (rML65) and 10-kDa (rML10) by indirect ELISA in sera from leprosy patients, household contacts and healthy controls in a leprosy-endemic area in the north east of Argentina. Serum antibody levels to those antigens were correlated with IgM anti-phenolic glycolipid I (PGL-I) levels, with bacterial index and the period of time under chemotherapy. Bacterial index positive (BI⁺) patients showed higher mean values when compared with BI negatives (BI⁻). Among lepromatous patients a positive correlation was observed between IgG antibody responses to both recombinant antigens and IgM antibody response to PGL-I. Anti-rML10 test detected a higher percentage of positive/total than anti-rML65 in all leprosy groups and healthy contacts. Bacterial load, leprosy clinical form and the time under chemotherapy were factors which could influence levels of the antibody response. The contribution of these antibody studies for a precise and early diagnosis in leprosy is discussed.     

Actin-associated proteins related to focal and close cell-substrate contacts in murine fibroblasts

Based on the premise that cell-surface proteins involved in focal or close cell-to-substrate contact will be linked across the membrane, either directly or indirectly to F-actin of the cytoskeleton, we have used a modification of the myosin affinity technique (Leonardi, C L & Rubin, R W, Anal biochem 118 (1981) 58) to precipitate F-actin filaments and associated proteins from Nonidet P-40 solubilized cells. BALB/c 3T3 fibroblasts, which have close and focal contacts, and their adhesion-defective mutant, AD6, which has only close contacts were compared. Clarified cell homogenates were incubated with rabbit muscle myosin thick filaments and were pelleted. Supernatants obtained from successive washes of the pellets, before and after release of actin and associated proteins by adenosine triphosphate, were analysed by gel electrophoresis under reducing conditions. The metabolic origin of the actin-associated proteins was determined by [35S]methionine labelling of BALB/c 3T3 cells. By these methods, 38 and 57 kD proteins were found to be actin-associated in BALB/c 3T3 but not in AD6. Biochemically reverting AD6 to the BALB/c 3T3 phenotype restored focal contacts and the association of the 38 and 57 kD proteins to actin, further implying roles for the proteins in the focal contact. Proteins of 48 and 145 kD were actin-associated in all three cell types indicating a potential role for these proteins in the close contact.     

Survey to identify Mycobacterium leprae-infected household contacts of patients from prevalent regions of leprosy in Colombia

Leprosy in Colombia is in the post-elimination phase; nevertheless, there are regions of this country where the incidence is still around 3-4/100,000. Early detection of leprosy patients is a priority for achieving control and elimination of leprosy; however, the clinical exam is not very sensitive and thus, the majority of patients are diagnosed only when they demonstrate lesions, and damage to the nerves and skin has already occurred. The goal of the present study was to identify Mycobacterium leprae infection and immune responses in household contacts (HHC) of leprosy patients from three prevalent regions of Colombia. Clinical examination, the Mitsuda test, evaluation of IgM anti-PGL-I in the serum, the bacillar index (BI), and polymerase chain reaction (PCR) from nasal swabs (NS) were performed for 402 HHC of 104 leprosy patients during a cross-sectional survey. Positive titers for IgM anti-PGL1 were found for 54 HHC, and PCR-positive NS for 22. The Mitsuda reaction was negative for 38 HHC, although three were positive for IgM anti-PGL-1 titers. The data document that leprosy transmission among HHC is still occurring in a non-endemic country.     

Curiosities of the methicillin-resistant Staphylococcus aureus survey - possibility of pseudo-outbreak and transmission to household contacts

Methicillin-resistant Staphylococcus aureus (MRSA) is currently one of the most prevalent antibiotic-resistant pathogens in hospitals, but it is also emerging as a community-acquired pathogen. We analysed the clinical and microbiological data of the patients in a county teaching hospital regarding MRSA. During the examination period (1996-2010), four outbreaks and one pseudo-outbreak occurred. It also became evident that health care workers and their families are possibly at risk of becoming carriers of MRSA. The importance of the molecular epidemiological investigation (pulsed-field gel-electrophoresis (PFGE)) typing and hygienic measures in order to detect and control MRSA outbreaks must be emphasised. Following infection control guidelines seems to be cost-effective method of controlling the nosocomial transmission of MRSA.     

Susceptibility to Vibrio cholerae infection in a cohort of household contacts of patients with cholera in Bangladesh

Background

Despite recent progress in understanding the molecular basis of Vibrio cholerae pathogenesis, there is relatively little knowledge of the factors that determine the variability in human susceptibility to V. cholerae infection.

Methods and Findings

We performed an observational study of a cohort of household contacts of cholera patients in Bangladesh, and compared the baseline characteristics of household members who went on to develop culture-positive V. cholerae infection with individuals who did not develop infection. Although the vibriocidal antibody is the only previously described immunologic marker associated with protection from V. cholerae infection, we found that levels of serum IgA specific to three V. cholerae antigens—the B subunit of cholera toxin, lipopolysaccharide, and TcpA, the major component of the toxin–co-regulated pilus—also predicted protection in household contacts of patients infected with V. cholerae O1, the current predominant cause of cholera. Circulating IgA antibodies to TcpA were also associated with protection from V. cholerae O139 infection. In contrast, there was no association between serum IgG antibodies specific to these three antigens and protection from infection with either serogroup. We also found evidence that host genetic characteristics and serum retinol levels modify susceptibility to V. cholerae infection.

Conclusions

Our observation that levels of serum IgA (but not serum IgG) directed at certain V. cholerae antigens are associated with protection from infection underscores the need to better understand anti–V. cholerae immunity at the mucosal surface. Furthermore, our data suggest that susceptibility to V. cholerae infection is determined by a combination of immunologic, nutritional, and genetic characteristics; additional factors that influence susceptibility to cholera remain unidentified.     

Whole blood interferon-gamma responses to mycobacterium tuberculosis antigens in young household contacts of persons with tuberculosis in Uganda

Background

Due to immunologic immaturity, IFN-γ-producing T cell responses may be decreased in young children compared to adults, thus we hypothesized that IFN-γ responses to mycobacterial antigens in household contacts exposed to Mycobacterium tuberculosis (Mtb) would be impaired in young children relative to adults. The objective of this study was to compare whole blood IFN-γ production in response to mycobacterial antigens between children and adults in Uganda.

Methodology/Principal Findings

We studied household contacts of persons with culture-positive pulmonary tuberculosis (TB) enrolled in a cohort study conducted in Kampala, Uganda. Whole blood IFN-γ production in response to Mtb culture-filtrate antigens was measured by ELISA and compared between infants (<2 years old, n = 80), young children (2 <5 years old, n = 216), older children (5 <15 years old, n = 443) and adults (≥15 years old, n = 528). We evaluated the relationship between IFN-γ responses and the tuberculin skin test (TST), and between IFN-γ responses and epidemiologic factors that reflect exposure to Mtb, and the effect of prior BCG vaccination on IFN-γ responses. Young household contacts demonstrated robust IFN-γ responses comparable to those of adults that were associated with TST and known risk factors for infection. There was no effect of prior BCG immunization on the IFN-γ response.

Conclusions/Significance

Young children in a TB endemic setting can mount robust IFN-γ responses generally comparable to those of adults, and as in adults, these responses correlated with the TST and known epidemiologic risk factors for Mtb infection.