Howard E. Gary

Case-control study of risk factors for human infection with a new zoonotic paramyxovirus, Nipah virus, during a 1998-1999 outbreak of severe encephalitis in Malaysia.

An outbreak of encephalitis affecting 265 patients (105 fatally) occurred during 1998-1999 in Malaysia and was linked to a new paramyxovirus, Nipah, that infected pigs, humans, dogs, and cats. Most patients were pig farmers. Clinically undetected Nipah infection was noted in 10 (6%) of 166 community-farm controls (persons from farms without reported encephalitis patients) and 20 (11%) of 178 case-farm controls (persons from farms with encephalitis patients). Case patients (persons with Nipah infection) were more likely than community-farm controls to report increased numbers of sick/dying pigs on the farm (59% vs. 24%, P=.001) and were more likely than case-farm controls to perform activities requiring direct contact with pigs (86% vs. 50%, P=.005). Only 8% of case patients reported no contact with pigs. The outbreak stopped after pigs in the affected areas were slaughtered and buried. Direct, close contact with pigs was the primary source of human Nipah infection, but other sources, such as infected dogs and cats, cannot be excluded.

Vitamin A therapy for children with respiratory syncytial virus infection : a multicenter trial in the United States

BACKGROUNDnHigh dose vitamin A therapy is effective in reducing morbidity and mortality associated with measles infection. Children with acute respiratory syncytial virus (RSV) infection have low serum vitamin A concentrations.nnnMETHODSnWe performed a multicenter, randomized, placebo-controlled trial of high dose vitamin A therapy among 239 children 1 month to 6 years of age to determine whether high dose vitamin A therapy would reduce morbidity associated with RSV infection.nnnRESULTSnThere were no differences between the vitamin A and placebo recipients for most clinical outcomes; however, vitamin A recipients had-longer hospital stays than placebo recipients (5.0 days vs. 4.4 days, P = 0.01) after enrollment. This effect was significant for children who were older than 1 year (who also had received the highest doses of vitamin A), particularly among those at low risk for complications of RSV infection and those enrolled during the second study season. Serum retinol levels at enrollment were inversely correlated with severity of illness.nnnCONCLUSIONSnWe found no evidence of a beneficial effect of vitamin A for the treatment of RSV infection in children in the United States. There may be groups of children for which vitamin A has an adverse effect, resulting in longer hospital stays.

Growth properties of human herpesvirus-6 strain Z29

Experiments performed to optimize the growth conditions of HHV-6(Z29) revealed that the virus grows best in phytohemagglutinin-stimulated umbilical cord blood lymphocytes (CBL) cultured in media containing 32 units/ml interleukin-2 and 0.01 mg/ml hydrocortisone. The titer of maternal antibody in the plasma of the cord blood cells does not affect the ability of the cells to support virus growth. DEAE-dextran and polybrene do not increase virus growth in umbilical cord blood lymphocytes. Phorbol myristate acetate abolishes virus growth. The HHV-6(Z29) growth cycle in CBL was approximately 5 days; capsids were not seen before day 3, and mature virions were not seen before day 5.

Assessment of a retrovirus sequence and other possible risk factors for the chronic fatigue syndrome in adults

Several infectious agents, including Epstein-Barr virus, cytomegalovirus, enteroviruses, human herpesvirus-6, and Candida species, have been reported to be associated with the chronic fatigue syndrome (CFS) only to be rejected as causes [1-9]. Recently, DeFreitas and colleagues [10], using molecular assays to detect specific segments of the retroviral genome, reported a human T-lymphotropic virus type 2 (HTLV-II) gag gene sequence in 10 of 12 adults with CFS, 13 of 18 children with CFS, 7 of 20 contacts of these patients, but in no noncontact controls. Sequences for other retroviral genetic regions, such as the HTLV-I gag gene and HTLV-II tax gene, were not detectable in blood specimens from patients or controls. The investigators also reported HTLV-I antibodies in 6 of 12 adults and 11 of 18 children with CFS. These data were interpreted as evidence for an HTLV-II-like virus infection in a major subset of persons with CFS and some of their contacts. Suggested roles for this virus in CFS included a cause or a benign secondary infection. We investigated the prevalence of this retrovirus marker in persons with CFS who were identified through the Centers for Disease Control and Prevention (CDC) CFS surveillance system in Atlanta, Georgia. Because the presence of this marker had been interpreted to imply retroviral infection, we also evaluated other possible risk factors, with emphasis on those for known retroviral infection. Methods Participants and Study Design Two parallel matched casecontrol studies were conducted: one to compare the presence of retroviral markers in blood samples and the other to investigate other potential risk factors. Case-patients were identified in the Atlanta metropolitan area through the CDC CFS surveillance system [11], in which sentinel physicians identify patients with at least 6 months of unexplained fatigue or unwellness. After the referred patients provide extensive clinical and psychological histories and their medical records are reviewed, they are classified into four groups by a panel of physicians on the basis of standard criteria. To be classified as a CFS case, a person must have reported at least 6 months of unexplained fatigue with 50% or greater reduction in either energy or activity level and must have met all other criteria of the published CFS case definition [12]. Between September 1989 and August 1991, 26 CFS case-patients were identified, 21 of whom agreed to participate in the studies. For the retroviral marker study, each patient with CFS was matched with a healthy CDC employee for age ( 5 years), gender, and race (CDC control). Persons reporting a chronic fatigue-like illness or who were employed in a retrovirology laboratory were excluded from consideration. Each CDC control was paid

Psychosocial correlates of hemoglobin A1c in young adults with type I diabetes

5 for participating in the study. For the risk-factor study, each patient with CFS was matched with two controls for age (5 years), gender, and race using a random-digit dialing system within the patients telephone prefix (neighborhood controls). Each neighborhood control was paid

Early priming with inactivated poliovirus vaccine (IPV) and intradermal fractional dose IPV administered by a microneedle device: A randomized controlled trial

50. Retroviral Studies Blood samples were drawn from patients with CFS and their matched CDC controls within 1 day of each other. Each heparinized specimen was given a numeric label and sent to the laboratory within 6 hours of venipuncture. All specimens were assayed for retroviral proviral DNA. A random subset of nine patients with CFS and nine matched controls was tested for serum antibodies against HTLV-I/II by Western blot and synthetic peptide enzyme-linked immunosorbent assay (ELISA) [13, 14]. Preparation of Genomic DNA Peripheral blood lymphocytes were prepared from Ficoll-Hypaque gradients of heparinized blood samples and lysed with proteinase K [15]. Total leukocytes from the same blood samples were also separated by lysing twice with 3 volumes of ammonium chloride solution (0.85% NH4Cl, 1 mM TRIS; pH 7.2) with two subsequent washes with phosphate-buffered saline. The leukocyte suspensions were lysed in a similar fashion. Cells from Mo-T (HTLV-II infected) and Hut-78 (uninfected) cell lines lysed similarly were used as positive and negative controls, respectively. The DNA was then phenol/chloroform extracted from lysate aliquots and ethanol precipitated [16]. The template competence of all DNA-lysate preparations was verified by polymerase chain reaction amplification, using primers from the myeloperoxidase gene [17]. Polymerase Chain Reaction Assays Aliquots of 2 g of DNA (or 50 L of lysate) from peripheral blood lymphocytes and leukocytes of patients and controls were amplified for the HTLV-II gag gene fragment under conditions optimized for minimal sensitivity of 30 Mo-T cells (or 200-pg of Mo-T DNA): 1.25 mM Mg++, and 40 cycles of 1 minute denaturation (94 C), annealing (55 C except for the first 6 cycles at 45 C), and 1 minute extension (72 C), with an additional ramping time of 30 seconds separating the annealing and extension steps [15, 18]. Only experiments that showed optimal signals with the sensitivity control and no signal with the negative control or the amplification cocktail control (all reagents except DNA template) were considered acceptable. An HTLV-I specificity control (MT-2, an HTLV-I-infected cell line) was included. The amplified products were subjected to electrophoresis on 1.5% agarose gels, were hybridized by the Southern blot method to a Phosphorus-32-labeled-probe, and were then exposed for 1 to 7 days [10]. Measurement of Risk Factors To investigate potential risk factors, patients and neighborhood controls were first interviewed using a questionnaire to elicit basic demographic information, clinical data related to case definition, possible exposures to retroviruses, and other possible risk factors for CFS (Table 1). They were then asked to complete a self-administered questionnaire concerning sexual practices (Table 2). Controls were interviewed approximately 2 to 3 months after patients were interviewed. Table 1. Prevalence of Potential Risk Factors before Illness Onset for the Chronic Fatigue Syndrome in Patients and Controls Table 2. Sexual Behaviors before Onset of Illness in Patients with the Chronic Fatigue Syndrome and in Controls Statistics P values, odds ratios, and exact 95% CIs were calculated for stratified binomial data [19-21]. Ordered data were analyzed using the stratified exact Wilcoxon rank-sum test as indicated [22]. All P values are twice the one-tailed value unless otherwise specified and are calculated based on matched analyses. The exact tests for stratified binomial data and the exact Wilcoxon rank-sum test were computed using StatXact software (Metha and Patel, Cytel Software Corporation, Cambridge, Massachusetts). Results The 21 patients had onset of CFS between 1979 and 1990, with most (12 of 21) experiencing onset between 1986 and 1990. The median age at onset of CFS was 34 years (mean, 33 years; range, 16 to 51 years); the median interval from onset of CFS to interview for this study was 4.5 years (range, 1 to 12 years). Patients were all white, non-Hispanic, and native-born U.S. citizens; 18 were women. Retroviral Studies All samples from DNA and lysate preparations of both peripheral blood lymphocytes and leukocytes obtained from the 21 patients and 21 CDC controls failed to amplify with the HTLV-II gag gene-specific primers under conditions optimized for minimal sensitivity of 30 Mo-T cells (or 200-pg of Mo-T DNA). A representative autoradiograph from these studies is shown in Figure 1. The 18 serum samples (9 from patients and 9 from controls) tested for HTLV-I/II antibodies by Western blot and peptide ELISA were also negative. Figure 1. A representative polymerase chain reaction analysis of the human T-lymphotropic virus type 2 (HTLV-II) gag gene sequence. Other Possible Risk Factors Before becoming ill, the patients median household income was

Isolation and Characterization of Circulating Type 1 Vaccine-Derived Poliovirus from Sewage and Stream Waters in Hispaniola

40 000 to

Limited duration of vaccine poliovirus and other enterovirus excretion among human immunodeficiency virus infected children in Kenya

50 000, and half had completed at least 2 years of college. No statistically significant differences in these demographic variables were demonstrable between patients and controls at either the time of interview or at the time of illness onset. Patients were less likely to be living with children than were controls, both at the time of the interview (5 of 21 patients [24%] compared with 26 of 42 controls [62%]; P < 0.01) and before illness onset (6 of 21 patients [29%] compared with 24 of 42 controls [57%]; P = 0.01). The mean household size was smaller for patients than for controls at the time of interview (2.3 compared with 3.3 household members, respectively; Wilcoxon ranked-sum test, P = 0.002). Consistent with these data, women with CFS were more likely to be nulliparous at the time of interview than were women without CFS (9 of 18 female patients [50%] compared with 9 of 36 female controls [25%]; P = 0.05). Risk factors for retroviral infection, including sexual behaviors, were not significantly different between case-patients and controls (see Tables 1 and 2). These factors included a history of sexually transmitted diseases, which may be considered a surrogate marker for the frequency of sexual behaviors conducive to retroviral transmission. Patients were more likely than controls to report having a household member or a first-degree relative ill with a chronic fatiguing illness that reduced their activity by 50% or more for a period of at least 6 months (5 of 21 patients [24%] compared with 0 of 42 controls [0%]; P < 0.01). Seven such ill persons were reported by five case-patients. However, direct telephone questioning of the five living adult relatives indicated that only the illness of two could be confirmed as being associated with a 50% or greater reduction of activity for at least a 6-month period. The first reported having recovered from documented monospot-positive mononucleosis as a teenager, a condition that reduced his activity for a 6-month period; the onset of his illness was 7 years after the onset of CFS in the associated patient. The second reported

Effectiveness of a Third Dose of MMR Vaccine for Mumps Outbreak Control

To determine whether psychosocial variables are related to long-term glycemic control; trait anxiety, depression, loneliness and life stress were assessed in 48 Type I diabetic patients. Hemoglobin A1c (HbA1c), an indicator of long-term glycemic utilization, was assayed from blood samples drawn shortly before the self-report instruments were administered. Of the psychosocial variables, anxiety was significantly related to current values of HbA1c. The association between anxiety and current HbA1c remained after statistically controlling for potentially confounding variables, including the previous value of HbA1c. Despite the stability of HbA1c values over time, anxiety scores were not significantly correlated with follow-up HbA1c. The implications of the significant relationships between psychological constructs and glycemic control are discussed.

Epidemic Keratoconjunctivitis in a Chronic Care Facility: Risk Factors and Measures for Control

INTRODUCTIONnInactivated poliovirus vaccine (IPV) introduction and phased oral poliovirus vaccine (OPV) cessation are essential for eradication of polio.nnnMETHODSnHealthy 6-week old infants in Bangladesh were randomized to one of five study arms: receipt of trivalent OPV (tOPV) or bivalent OPV (bOPV) at ages 6, 10 and 14 weeks, intramuscular IPV or intradermal one-fifth fractional dose IPV (f-IPV) at ages 6 and 14 weeks, or f-IPV at ages 6 and 14 weeks with bOPV at age 10 weeks (f-IPV/bOPV). All participants received tOPV at age 18 weeks.nnnRESULTSnOf 975 infants randomized, 95% (922) completed follow-up. Type 1 seroconversion after 3 doses at 6, 10 and 14 weeks was higher with bOPV compared with tOPV (99% vs 94%, p=0.019). Seroconversions to types 1 and 3 after 2 IPV doses at ages 6 and 14 weeks were no different than after 3 doses of tOPV or bOPV at ages 6, 10 and 14 weeks. A priming response, seroconversion 1 week after IPV at 14 weeks among those who did not seroconvert after IPV at 6 weeks, was observed against poliovirus types 1, 2 and 3 in 91%, 84% and 97%, respectively. Compared with IPV, f-IPV failed non-inferiority tests for seroconversion with 1 or 2 doses and priming after 1 dose.nnnDISCUSSIONnThe findings demonstrate considerable priming with IPV at age 6 weeks, comparable immunogenicity of tOPV and bOPV, and inferior immunogenicity of one-fifth f-IPV compared with IPV. If IPV induced priming at age 6 weeks is similar to that at age 14 weeks, IPV could be administered at a younger age and possibly with a higher coverage.