Day care center attendance and diarrheal morbidity in Colombia.

This study was designed to determine whether day care center attendance was associated with increased risk of diarrheal disease among poor children in an urban, developing country setting. From July 17 to December 18, 1988, mothers of 493 Colombian children less than 5 years old (241 attendees and 252 nonattendees) were interviewed weekly about diarrheal events during the previous week. The incidence of diarrhea was greater for day care center attendees than for nonattendees (3.2 vs 2.0 episodes per child-year, P < .0005). For children less than 2 years of age, attendees experienced 7.2 episodes/child-year vs 3.5 episodes per child-year for nonattendees (P < .0005). Analyses controlling for water source and availability, excreta disposal, socioeconomic status, and duration of follow-up showed that the increased diarrheal risk was limited to children younger than 3 years of age spending more than 30 hours per week in the centers. In addition, although the risk among attendees of suffering diarrheal episodes of longer duration was fairly constant across levels of socioeconomic status, this risk was inversely proportional to socioeconomic status for nonattendees. In summary, the increase in risk of diarrhea among young, full-time day care attendees was modest, yet important, because diarrhea continues to be a major cause of morbidity and mortality in Colombian children.

Environmental chemical exposures and risk of herpes zoster.

This study investigated whether residence in Aberdeen, North Carolina, the location of the Aberdeen pesticides dumps site (a national priority list Superfund site containing organochlorine pesticides, volatile organic compounds, and metals), is associated with immune suppression as indicated by a higher incidence of herpes zoster and recent occurrences of other common infectious diseases. Study participants included 1,642 residents, 18-64 years of age, who responded to a telephone survey concerning potential occupational and recreational exposures to pesticides and other chemicals, lifetime history of herpes zoster (shingles), and the recent occurrence of other common infectious diseases. Stratified and logistic regression analyses were used to compare the cumulative incidence of herpes zoster among Aberdeen residents and residents of nearby communities. There was little evidence of an overall increased risk of herpes zoster among Aberdeen residents during the period 1951-1994 [relative risk (RR), 1.3; 95% confidence interval (CI), 0.8-2.1]. However, an elevated risk of herpes zoster was noted consistently among Aberdeen residents of younger ages as compared to residents of the nearby communities. The RR was 2.0 (CI, 1.0-4.0) among those 18-40 years of age and was not affected by controlling for potential confounders. The RR of herpes zoster was also consistently elevated in all age groups for the period before 1985. No differences were noted between residents of Aberdeen and those of the nearby communities with respect to the recent occurrence of other common infectious diseases. These results support the plausibility of an association between exposure to the Aberdeen pesticides dumps site and immune suppression and the potential use of herpes zoster as a marker of immune suppression in studies of environmental chemical exposures.

Effects on the immune system associated with living near a pesticide dump site.

In this paper, we report results of the second phase of a larger study designed to evaluate the effects on the immune system of living near a Superfund site containing organochlorine pesticides, volatile organic compounds, and metals. Phase II was conducted to determine whether living near the site, consisting of six locations in Aberdeen, North Carolina, is associated with higher plasma organochlorine levels, immune suppression, or DNA damage. Each of 302 residents of Aberdeen and neighboring communities provided a blood specimen, underwent a skin test, and answered a questionnaire. Blood specimens were analyzed for organochlorine pesticides, immune markers, and micronuclei. Of 20 organochlorines tested, only DDE was detected in the blood of participants (except for one individual). Age-adjusted mean plasma DDE levels were 4.05 ppb for Aberdeen residents and 2.95 ppb (p = 0.01) for residents of neighboring communities. Residents of 40-59 years of age who lived within a mile of any site, but particularly the Farm Chemicals site, had higher plasma DDE levels than residents who lived farther away. Residents who lived near the Farm Chemicals site before versus after 1985 also had higher plasma DDE levels. Overall, there were few differences in immune markers between residents of Aberdeen and the neighboring communities. However, residents who lived closer to the dump sites had statistically significantly lower mitogen-induced lymphoproliferative activity than residents who lived farther away (p < 0.05). Residential location was not consistently associated with frequency of micronuclei or skin test responses. Although some statistically significant differences in immune markers were noted in association with residential location, the magnitude of effects are of uncertain clinical importance.

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.

Age-related changes in mitogen-induced lymphocyte function from birth to old age.

This study examines the relationship between age and mitogen-induced lymphocyte blastogenesis. Lymphocytes were stimulated with PHA; Concanavalin A (Con A), and PWM in 156 normal, healthy subjects ranging in age from birth to 75 years. The findings indicate a gradual but significant decrease in PHA- and Con A-induced blastogenesis with increasing age. The decrease in Con A and PHA induced in vitro lymphocyte function begins in early childhood and young adulthood, respectively, and continues throughout the age range studied. In addition, there appears to be a decreased range of lymphocyte functional capacity among the 50-75-year-old subjects. The clinical and laboratory implications of these observations are discussed.

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.

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.

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)

Age-related changes in T- and B-lymphocyte subpopulations in the peripheral blood.

Quantitation of T and B lymphocytes in infants and children is an important test in the diagnosis of a suspected immuno-deficiency. Previous studies indicated that the absolute and relative numbers of lymphocyte subpopulations vary with age, but these data in the pediatric age group are incomplete and often contradictory. We reviewed the literature and investigated the relationship between age and lymphocyte subpopulations in healthy infants and children using common methods and recent methodologic improvements. We found that absolute numbers of T and B cells followed the same trend as the total lymphocyte count, which was elevated at birth, increased in the first six months, and then gradually decreased to adult levels at approximately 13 years of age. Compared with adult values, the percentage of B cells also was higher at birth and continued to increase for six months, followed by a gradual decrease to adult levels by late childhood or early adolescence. The percentage of T cells gradually increased to adult levels by the same age range.

Common expression of varicella-zoster viral glycoprotein antigens in vitro and in chickenpox and zoster vesicles.

Human cells infected with varicella-zoster virus (VZV) produce at least three major virus-specific, immunogenic glycoproteins: gp118, gp98, and gp62. Since glycoproteins gp98 and gp62 were found to be prominent constituents of the infected cell membrane, a murine monoclonal antibody (clone 3B3) that reacted avidly with this glycoprotein complex was selected as a probe for detection of VZV replication in laboratory and clinical settings. Cultured cells of human, simian, and caviid origin, when infected with wild-type isolates as well as laboratory and vaccine strains of VZV all expressed these viral glycoproteins. The monoclonal antibody immunostained the basal and malpighian epithelial layers of a zoster vesicle biopsy specimen and also reacted with all specimens of vesicular cells obtained from epidemiologically unrelated patients with chickenpox and zoster. Thus, these studies demonstrate that the VZV-specific glycoprotein complex gp98/gp62 is highly conserved, abundantly expressed, and easily detected with a monoclonal antibody probe.

Molecular dissection of the humoral immune response to individual varicella-zoster viral proteins during chickenpox, quiescence, reinfection, and reactivation.

The sequence of antibody formation to molecularly defined varicella-zoster virus (VZV) proteins was examined during the course of chickenpox, quiescence, and subsequent VZV reactivation and reinfection. The first antibodies produced after primary VZV infection were to two virion envelope glycoproteins, gp66 and gp118 , and the nucleocapsid protein p155 . Within one to two months, antibodies to a greater array of viral proteins and glycoproteins were observed. Antibodies to the immunodominant viral proteins ( gp66 , gp118 , and p155 ) persisted for years after varicella and were, therefore, excellent markers of prior VZV infection. Subclinical VZV reinfection also was associated with transient rises in levels of the same polypeptide-specific antibodies as during primary disease. The immunoglobulin response to zoster appeared more rapidly than that to chickenpox or reinfection and was to the broadest complement of viral proteins, including the distinctive VZV polypeptide p32. These radioimmune-precipitation profiles could be subdivided into six different patterns characteristic of the following clinical states: acute- and convalescent-phase chickenpox, quiescence, acute- and convalescent-phase zoster, and postzoster quiescence.

[Evaluation of immunoglobin isotype specific to Leishmania in tegumentary American leishmaniasis]. / Evaluación de la respuesta de isotipos de inmunoglobulina específica a Leishmania en leishmaniasis tegumentaria Americana.

Leishmania-specific immunoglobulin subclass response was evaluated in 133 patients infected with Leishmania braziliensis. The indirect immunofluorescent antibody test (IFAT) was employed with amastigotes of L. mexicana amazonensis as antigen. Among the 133 sera obtained at consultation for diagnosis of active lesions, IgM was detected in 54 following absorption with Staphylococcus aureus Cowan strain I, and in 5 sera prior to absorption. IgM reactive with Leishmania antigen was only found in sera from patients whose lesions had evolved over the past two months or less. Leishmania-specific IgG was detected in all sera prior to absorption. Sera obtained at the time of recurrence or after complete healing of lesions presented only specific IgG. The combined use of the Montenegro skin test and specific IgM increased the sensitivity of immunodiagnostic methods in patients with lesions of less than 2 months duration. Normal control volunteers were negative for specific IgM and unreactive to Montenegro skin testing. Among 16 patients with non-leishmanial lesions, 3 with sporotrichosis showed IgG reactive with Leishmania; none, including 4 with lesions of less than two months duration, showed specific IgM. We conclude that in patients infected with L. braziliensis the presence of specific IgG and IgM is associated with the time of lesion evolution and the primary or recurrent nature of the lesions. In addition, the combined use of IgM titer and Montenegro reactivity is of potential utility in the diagnosis of early lesions.

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.

Gender differences in response to the multitest CMI skin test in the general population.

BACKGROUND: Previous studies of gender differences in response to the Multitest CMI skin test have produced conflicting results. OBJECTIVE: To determine whether gender is associated with response to the Multitest CMI skin test. METHODS: Two-hundred ninety-seven adults, aged 18 to 64 years, recruited originally for a study of the immune effects associated with living near a hazardous waste site containing primarily organochlorine pesticides, underwent a skin test using the Multitest CMI skin test. Six of seven antigens were tested: tetanus toxoid, diphtheria toxoid, Candida, Tricophyton, Streptococcus, and Proteus. The tuberculin antigen was excluded. Lymphocyte function was also evaluated in vitro using standardized methods of mitogen stimulation with phytohemaglutinin (PHA), concanavalin A (CON-A), and pokeweed mitogen. RESULTS: The frequency of positive responses to the skin tests was significantly (P < .001) higher among males (80.4%) than among females (55.7%). Males were more likely than females to respond to all six antigens tested (P < .05). The mean diameter of positive skin test measurements for males statistically significantly (P < .05) exceeded female responses for tetanus and diphtheria. Although not statistically significant, male response size exceeded that of females for all other antigens except Trycophyton. Controlling for age, race, smoking, income, and plasma DDE levels did not change these results. Skin test positivity was not associated with mitogen stimulation assay results overall or within gender groups. CONCLUSION: Significant gender differences in response to the Multitest CMI skin test could limit its use as a marker of anergy in general population studies.

Enzyme-linked immunosorbent assay for evaluation of immunity to measles virus.

An enzyme-linked immunosorbent assay for the determination of immunity to measles virus was developed and standardized; it was compared to the hemagglutination inhibition and plaque reduction neutralization methods for sensitivity and specificity. The conditions of the enzyme-linked immunosorbent assay were adjusted such that groups of susceptible and immune individuals were clearly separable on the basis of the reactivity of a single (1:100) dilution of their sera to viral and control antigens. The range of values corresponding to susceptibility and immunity was defined by using the distribution of values observed from testing sera obtained from susceptible and immune control groups. The enzyme-linked immunosorbent assay was then applied in a study of measles vaccinees and found to be more sensitive than the hemagglutination inhibition method and equal in sensitivity to the plaque reduction neutralization method. The three methods were equal in specificity. Thus, the measles virus enzyme-linked immunosorbent assay is a rapid, reproducible, sensitive, and specific method for screening for the presence of measles antibody.