Evaluation of Etest for susceptibility testing of multidrug-resistant isolates of Mycobacterium tuberculosis.

To prescribe effective treatment schemes for patients with tuberculosis, more-efficient susceptibility testing techniques for Mycobacterium tuberculosis are needed, especially in regions with multidrug resistance. Etest (AB BIODISK, Solna, Sweden) is a simple technique that provides quantitative drug susceptibility results for M. tuberculosis in 5 to 10 days from a culture grown at low cost. The performance of Etest was compared to that of the reference proportion method, using 95 M. tuberculosis clinical isolates of which 42.1% (40 of 95) were resistant to at least one antibiotic by the reference method. Overall agreement between Etest and the reference method was 98.9% (94 of 95) for detection of multidrug resistance; for resistance to individual drugs, agreement was 97.9% (93 of 95) for rifampin, 96.0% (92 of 95) for ethambutol, 94.7% (90 of 95) for isoniazid, and 85.3% (81 of 95) for streptomycin. This study supports the utility of Etest for timely detection of drug resistance in M. tuberculosis and for use in tuberculosis control programs.

Seroprevalence and seroincidence of Norwalk-like virus infection among Brazilian infants and children.

To determine the importance of Norwalk-like viruses (NLVs) as pediatric pathogens in a developing country, the seroprevalence and seroincidence of this group of viruses in a cohort of children less than 4 years of age in an urban shantytown in northeastern Brazil was examined. Serum samples were collected approximately every 6 months from 135 children who were surveyed three times each week for diarrhea and vomiting. NLV IgG was measured by an enzyme immunosorbent assay (EIA) with recombinant Norwalk virus capsid protein. Overall NLV seroprevalence was 71%, and the overall NLV seroconversion rate was 0.7 seroconversions per child-year. The highest age-specific NLV seroconversion rate (0.8 seroconversions per child-year) was observed in the 13-24-month age group. For all study children, the incidence of diarrhea and vomiting was significantly greater (P < 0.01) during time periods spanned by serum pairs that indicated NLV seroconversion compared with time periods without NLV seroconversion. However, NLV seroconversion was not associated with gastrointestinal symptoms during the first year of life.

Risk factors for horizontal transmission of hepatitis B virus in a rural district in Ghana.

Most hepatitis B virus (HBV) infections in sub-Saharan African infants and children are acquired through horizontal transmission, but the exact mechanisms of spread have not been documented. The authors conducted a study in rural Ghana which determined seroprevalence in a probability sample of 1,385 individuals of all ages, and evaluated risk factors for horizontal transmission of HBV in a subsample of 547 children aged 1-16 years who were not hepatitis B surface antigen (HBsAg) carriers. Most residents in this district live in compounds which typically contain 2-4 households each. Overall prevalence of HBV seropositives (any HBV marker) was 74.7% (95% confidence interval (CI) 72.5%-76.9%). Prevalence of HBsAg was 20.9% (95% CI 18.8%-23.1%). The data suggest a continuous nonuniform acquisition of HBV infection with advancing age predominantly through horizontal transmission in childhood, with the household, rather than the domestic compound, being the primary place for transmission. The behaviors most strongly associated with prevalence of HBV were sharing of bath towels (OR = 3.1, 95% CI 2.1-4.5), sharing of chewing gum or partially eaten candies (OR = 3.4, 95% CI 2.3-5.0), sharing of dental cleaning materials (OR = 2.5, 95% CI 1.3-4.6), and biting of fingernails in conjunction with scratching the backs of carriers (OR = 2.5, 95% CI 1.6-4.3).

PIP: Most hepatitis B virus (HBV) infections in sub-Saharan African infants and children are acquired through horizontal transmission. Findings are reported from a study conducted in rural Ghana to measure seroprevalence in a probability sample of 1385 people of all ages, and evaluate risk factors for the horizontal transmission of HBV in a subsample of 547 children aged 1-16 years who were not hepatitis B surface antigen (HBsAg) carriers. Most residents in the sample area live in compounds which typically contain 2-4 households each. The overall prevalence of HBV seropositives was 74.7% and the prevalence of HBsAg was 20.9%. These data suggest a continuous nonuniform acquisition of HBV infection with advancing age mainly through horizontal transmission in childhood, with the household, rather than the domestic compound, being the main place for transmission. The sharing of bath towels, sharing of chewing gum or partially eaten candies, sharing of dental cleaning materials, and biting of fingernails together with scratching the backs of carriers are the behaviors found to be most strongly associated with HBV prevalence.

Seroepidemiological survey of hepatitis B and C virus infections in Ghanaian children.

The seroprevalences of hepatitis B virus (HBV) and hepatitis C virus (HCV) markers were evaluated in a random sample of 803 children attending school in Ashanti-Akim North district in Ghana in order to gain a better understanding of transmission patterns of these viruses, particularly horizontal transmission of HBV. This rural district is typical of 70% of the Ghanaian population. The overall seroprevalence of at least one marker of HBV infection was 61.2%, with rates increasing from 48% to 80% between the ages of 6-18 years (P < 0.001). The overall HBsAg seroprevalence was 15.8%, with the proportion of HBsAg positives amongst those with anti-HBc increasing from 39.3% in 6-7-year-olds to 51.8% in 12-13-year-olds. It appears that horizontal transmission during this age period was accompanied by a high rate of HBsAg carriage. Among those infected but not carriers, i.e., those HBsAg negative and anti-HBc positive, > 50% lacked detectable levels of anti-HBs, an unusual pattern of convalescent immune response to HBV. The overall seroprevalence of anti-HCV was 5.4% and did not differ significantly by age or gender. Anti-HCV seroprevalence was not associated with the presence of any HBV marker. A better understanding of the unusually high prevalences of HBV and HCV infections demonstrated in this population is likely to influence vaccination and blood transfusion policies and to stimulate further evaluations of these infections and their vehicles of spread in highly endemic regions such as sub-Saharan Africa.

A case-control study examining risk factors for invasive Haemophilus influenzae type b disease in Victoria, Australia 1988-90.

OBJECTIVE: To determine whether day-care attendance was a risk factor for Haemophilus influenzae type b (Hib) disease, particularly for epiglottitis. METHODOLOGY: A case-control analysis of risk factors for invasive Hib disease was performed in Victoria, Australia between February 1988 and February 1990 prior to the introduction of immunization for Hib. A total of 210 cases and 367 day surgery hospital controls were enrolled prospectively. Data were collected by questionnaire at the time of admission. RESULTS: Logistic regression analysis showed that risk factors for meningitis were day-care attendance, household crowding and recent illness in a sibling. Risk factors for epiglottitis were day-care attendance and mother's birthplace in Australia or New Zealand. CONCLUSIONS: This study confirms that day-care attendance is a risk factor for Hib epiglottitis as well as meningitis. In addition, the mother's birthplace in Australia or New Zealand is a risk factor for epiglottitis in these data. The reason for this latter observation is unclear.

Epidemiology of cutaneous leishmaniasis in Colombia: a longitudinal study of the natural history, prevalence, and incidence of infection and clinical manifestations.

This prospective study measured the incidence of Leishmania infection, by Leishmanin skin test (LST) conversion, and leishmaniasis, by new acquisition of lesions, in a Leishmania braziliensis endemic area of Colombia, during 7243 person-years. The incidence rate of infection and leishmaniasis varied greatly by village, ranging from 2.8 to 23.0/100 person-years and 0.0 to 20.4/1000 person-years, respectively. Adult males experienced greater rates of both infection and leishmaniasis. Most primary infections (91%) were subclinical initially. Typical scars were predictive of subsequent leishmaniases both for persons initially LST-reactive (risk ratio = 11.3, P = .003) and for those initially nonreactive (risk ratio = 3.2, P = .02). Only one-third of the diagnosed leishmaniasis cases (24/77) were due to newly acquired infections in naive hosts. The relative contribution of existing lesions, recurrences, and new infections to the burden of disease should be considered in the planning of leishmaniasis control programs.

Epidemiology of cutaneous leishmaniasis in Colombia: environmental and behavioral risk factors for infection, clinical manifestations, and pathogenicity.

Through a longitudinal, active surveillance for Leishmania (Viannia) braziliensis and Leishmania (Viannia) panamensis infection and lesions on the Pacific Coast of Colombia, risk factors for infection (leishmanin skin test conversion), leishmanial lesions, and pathogenicity were examined. Risk factor information was obtained prior to and independently of case ascertainment. Similar factors were associated with acquisition of infection and of leishmaniasis, including male sex, age > 10 years, and farming occupation. The behaviors of entering the forest after sunset, hunting, and lumbering were most strongly associated with Leishmania infection independently of age, sex, and farming occupation. Environmental conditions associated with infection, including tall trees near the home, home located > 15 m from the nearest neighbor, and floor and roof made of open material, were less strong predictors of risk. Pathogenicity, the risk of lesion given a new infection, was reduced in those > 30 years of age and those entering the forest frequently.

Effect of fecal contamination on diarrheal illness rates in day-care centers.

Contact spread of enteropathogens in day-care centers is supported by the recovery (presence vs. absence) of fecal coliforms from hands and day-care center fomites. This prospective study was conducted to determine what, if any, quantitative measures of fecal coliforms predict the risk of diarrhea among day-care center attendees. Diarrheal illness without concomitant respiratory symptoms was monitored among 221 children aged < 3 years in 37 classrooms (24 day-care centers) through biweekly parental telephone interviews from October 1988 to May 1989 in Cumberland County, North Carolina. The risk of diarrhea was expressed as new episodes/classroom-fortnight. Contamination was expressed as the log10 fecal coliform count per unit of surface area, per toy, and per child and staff hands. Significant predictors of diarrheal risk were any hand contamination (p = 0.003) and the number of contaminated moist sites (hands, faucets, and sinks) (p = 0.006). After adjusting for the child/staff ratio using weighted multiple regression, the authors found that classrooms with either any hand contamination (p = 0.0015) or contamination on all moist sites (p = 0.015) had a significant twofold increased rate of diarrhea compared with classrooms without contamination. This was the first study to demonstrate an increased risk of diarrhea associated with fecal contamination and the frequent sink contamination in day-care centers.

A clinical prediction rule for American cutaneous leishmaniasis in Colombia.

Neither parasitological nor molecular diagnosis of leishmaniasis is widely available in clinical settings where American cutaneous leishmaniasis (ACL) is endemic. Therefore four clinical prediction rules for ACL were developed which incorporated physical examination findings (clinical rule), physical examination and leishmanin skin test (LST) (clinical-LST rule), physical examination and historical information (clinical-historical rule), or physical examination, historical information and LST (clinical-historical-LST rule). One hundred parasitologically diagnosed ACL cases and 38 cases of chronic skin lesions of other aetiologies comprised the derivation set. The validation set consisted of 124 ACL cases and 35 patients with lesions of other aetiologies. Components of each rule were selected by bivariate analysis, then step-wise logistic regression. Sensitivity, specificity and efficiency were calculated for each score threshold; the threshold achieving greatest efficiency was selected for each rule. When these rules were applied to the validity set the sensitivity, specificity and efficiency were respectively: clinical 93%, 31%, 79%; clinical-LST 90%, 73%, 85.9%; clinical-historical 97%, 51%, 87%; clinical-historical-LST 92%, 70%, 87%. Inclusion of LST skin test consistently improved the specificity of the rules. Should a given clinical setting warrant optimizing either sensitivity or specificity alone, the rule thresholds can be adjusted. These and other prediction rules, once evaluated in other settings, should be incorporated into leishmaniasis control programmes.

Leishmanin skin test standardization and evaluation of safety, dose, storage, longevity of reaction and sensitization.

Leishmanin skin test (LST) antigens prepared from Leishmania braziliensis panamensis were compared with respect to sensitivity, specificity, and side effects. Within the dose range 0.5-3.0 x 10(5) promastigotes of L. b. panamensis and 10 x 10(5) promastigotes of combined L. amazonensis and L. b. panamensis, specificity in healthy controls was nearly 100% for all antigens. Sensitivity increased minimally with increasing dose. Lot-to-lot differences were small. Side effects, such as vesiculation and ulceration at the site of LST application increased with antigen dose. Storage under harsh conditions decreased LST potency but not sensitivity while storage at 2-8 degrees C affected neither potency nor sensitivity. Eighty-five percent of parasitologically diagnosed, LST-positive cases of leishmaniasis remained LST-positive when retested six months to three years later. The LST did not sensitive 19 healthy controls who were skin tested twice or thrice.

Pertussis immunization in eight-month-old children in North Carolina.

Between 1984 and 1987 reported pertussis cases in North Carolina increased threefold. Pertussis immunization rates were examined for those years in three one-year cohorts drawn from a random selection of North Carolina birth records. The percentage of children immunized with three DTPs at eight months of age was 58.1, 58.6, and 56.7 for the three cohorts. Only 20.5 percent of 117 reported pertussis cases in children 9-36 months of age during the last 10 years were adequately immunized. The low pertussis immunization rate may have contributed to the recent increase in pertussis cases in North Carolina.

Effectiveness and cost benefit of a proposed live cytomegalovirus vaccine in the prevention of congenital disease.

Congenital infection by human cytomegalovirus (CMV) is presently the leading infectious cause of mental retardation and congenital deafness in the United States. Live CMV vaccines in healthy adults have been shown to be safe and to induce immune responses similar to those that occur with natural CMV infection. Yet, only recently has a live CMV vaccine been tested for its protective ability. To evaluate the cost benefit and effectiveness of the proposed live CMV vaccine, we compared the following strategies: routine immunization, selective immunization of those women screened and found to be seronegative, and no immunization. Our results show that, when direct costs alone are considered, routine immunization of healthy women aged 15-25 years is cost beneficial even in populations with CMV seroprevalence as high as 87%. In populations with lower seroprevalence (55%-70%), for every 100,000 women immunized, more than 24 cases of symptomatic congenital CMV infection at birth and a similar number of cases with late sequelae (mainly deafness) would be prevented yearly. Such immunization would result in a net annual saving of $2.5 million.

The relationship of Leishmania braziliensis subspecies and immune response to disease expression in New World leishmaniasis.

Multivariate analyses of clinical presentation, subspecies identity of the causal organism, and the Leishmania-specific immune response parameters (indirect fluorescent antibody test [IFAT], cutaneous delayed type hypersensitivity [DTH], and in vitro lymphocyte transformation [LT]) of 441 patients with tegumentary leishmaniasis were used to examine the human host-parasite interaction in L. braziliensis infection. Mucocutaneous disease (P less than .002) and L. braziliensis braziliensis infection (P less than .001) were independently associated with significantly higher IFAT titers and cutaneous DTH than were cutaneous disease or L. braziliensis panamensis infection. Lesion size was also correlated with IFAT titer (P. less than .001). Although time of lesion evolution was highly correlated with all parameters, differences associated with subspecies and disease form were independent of lesion duration (three-way analysis of variance). In contrast with the cutaneous DTH response, the in vitro lymphocyte proliferative response to Leishmania antigen did not correlate with disease form and only weakly with infecting subspecies when time of evolution and subspecies were controlled. The association of mucosal disease presentation with a particular subspecies and the independent correlation of both variables with heightened IFAT titers and cutaneous DTH to Leishmania antigen supports the possibility of immune mechanisms of pathogenesis in human tegumentary leishmaniasis.

Diagnosis of cutaneous and mucocutaneous leishmaniasis in Colombia: a comparison of seven methods.

Seven methods of diagnosing leishmaniasis were compared in 177 patients presenting with lesions of the skin (165) or mucosa (12) in Tumaco and Cali, Colombia. The three methods of visualizing amastigotes in tissue samples (histological staining of tissue sections, impression smears of punch biopsies, and smears of dermal scraping from slits in the lesion margins) were less sensitive than the four Leishmania isolation methods (aspiration of lesion border cultured in biphasic media, aspirate inoculated into hamster nasal tissue, culture of punch biopsy macerate, and hamster inoculation of macerate). The aspirate-culture and biopsy-hamster methods employed in this study proved most sensitive of the four methods for the recovery of parasites. The combined overall sensitivity of the 7 methods was 67% for all enrolled patients and 75% for Montenegro skin test-positive patients. The individual sensitivities for the methods for all patients and Montenegro-positive positive, patients, respectively, were: histopathology 14% and 16%, impression smear 19% and 21%, dermal scraping 22% and 26%, aspirate-culture 58% and 64%, aspirate-hamster 38% and 41%, biopsy-culture 50% and 55%, and biopsy-hamster 52% and 57%. All methods were less sensitive in lesions of greater than 6 months duration than in lesions of more recent onset. Mucosal lesions were best diagnosed by the culture or hamster inoculation of a macerated mucosal biopsy. The diagnosis by inoculation of hamsters was achieved within 2 to 12 weeks, a mean of 34.5 days. Promastigotes were seen on Senekjie's medium within 3-8 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Leishmania braziliensis from the Pacific coast region of Colombia: foci of transmission, clinical spectrum and isoenzyme phenotypes.

Tegumentary leishmaniasis is highly prevalent in the Pacific coast region of Colombia. We have identified 90 foci of transmission in this region based on 179 parasitologically diagnosed patients. Human transmission occurred in mangrove forests, secondary growth and intervened tropical rain forest. A parasitological diagnosis, that is, either isolation or visualization of Leishmania was made in 68.6% of suspected cases. Three phenotypically distinguishable groups of L. braziliensis were encountered based on isoenzymes: L. b. panamensis variants (82%), variants of L. b. braziliensis (14.5%), and stocks intermediate between L. b. panamensis and L. b. guyanensis reference strains (3.5%). The L. b. braziliensis variants produced cutaneous disease alone relatively infrequently (12% of classified cutaneous stocks) but were more frequently (38% of all mucosal stocks) isolated from mucosal lesions. Leishmania infection of the mucous membranes caused a wide spectrum of disease, severity being closely related to time of evolution. Both contiguous and metastatic spread to the mucous membranes was supported by the clinical course of 19 mucosal cases.