Failure to detect infection by oral polio vaccine virus following natural exposure among inactivated polio vaccine recipients.

While oral polio vaccine (OPV) has been shown to be safe and effective, it has been observed that it can circulate within a susceptible population and revert to a virulent form. Inactivated polio vaccine (IPV) confers protection from paralytic disease, but provides limited protection against infection. It is possible, then, that an IPV-immunized population, when exposed to OPV, could sustain undetected circulation of vaccine-derived poliovirus. This study examines the possibility of polio vaccine virus circulating within the United States (highly IPV-immunized) population that borders Mexico (OPV-immunized). A total of 653 stool and 20 sewage samples collected on the US side of the border were tested for the presence of poliovirus. All samples were found to be negative. These results suggest that the risk of circulating vaccine-derived poliovirus is low in fully immunized IPV-using populations in developed countries that border OPV-using populations.

Contribution of second stool specimen to increased sensitivity of poliovirus detection in India, 1998-2000.

Acute flaccid paralysis (AFP) surveillance data from India were analysed to examine sensitivity of poliovirus isolation from stool specimens and the added sensitivity obtained from collection of a second stool specimen. Analysis was restricted to Indian AFP cases, 1998-2000, with two adequate stool specimens. The proportion of cases confirmed with wild poliovirus isolation by the second specimen only was calculated, regardless of specimen quality. Overall specimen sensitivity (1998-2000) was 81% using the first specimen, 78% using the second, and 96% using both. Sensitivity increased from 1998 to 2000, with slightly higher sensitivity each year for the first specimen. The second specimen increased sensitivity by 15% overall and contributed more when the first specimen was collected late or was in poor condition. As wild poliovirus disappears, increased sensitivity provided by a second stool specimen may reduce the risk of missing circulating virus.

Persistence of vaccine-derived poliovirus following a mass vaccination campaign in Cuba: implications for stopping polio vaccination after global eradication.

BACKGROUND: With substantial progress made toward polio eradication, developing the appropriate strategy for discontinuing global oral poliovirus vaccine (OPV) after global eradication becomes increasingly important. At issue is the theoretical risk of independent circulation of potentially virulent OPV-derived strains. Because Cuba uses OPV only in mass campaigns, it represents an ideal site to assess vaccine-derived poliovirus persistence. METHODS: Infants born after the 1997 biannual mass campaigns were evaluated for past (neutralizing antibody) or current (virus excretion) evidence of vaccine-derived poliovirus exposure. We obtained sera and/or stool specimens from 861 infants; a second serum from 218 infants. RESULTS: All stool specimens were poliovirus negative. Of 762 infants, 113 (14.8%) had initially detectable poliovirus type 1 antibody, 193 (25.3%) type 2, and 94 (12.3%) type 3. A precipitous antibody decline occurred in initially positive sera. CONCLUSIONS: Our results suggest that in a country with high population immunity, vaccine-derived virus is unlikely to establish ongoing circulation.

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.

Parainfluenza virus infection among adults hospitalized for lower respiratory tract infection.

To better define the contribution of human parainfluenza viruses (HPIVs) to lower respiratory tract infection in adults, we tested acute- and convalescent-phase serum specimens from hospitalized adults participating in a population-based prospective study of lower respiratory tract infection during 1991-1992. We tested all available specimens from the epidemic seasons for each virus and approximately 300 randomly selected specimens from the corresponding off-seasons for antibodies to HPIV-1, HPIV-2, or HPIV-3. During the respective epidemic season, HPIV-1 infection was detected in 18 (2.5%) of 721 and HPIV-3 infection in 22 (3.1%) of 705 patients with lower respiratory tract infection. Only 2 (0.2%) of 1,057 patients tested positive for HPIV-2 infection. No HPIV-1 infections and only 2 (0.7% of 281 patients tested) HPIV-3 infections were detected during the off-seasons. HPIV-1 and HPIV-3 were among the four most frequently identified infections associated with lower respiratory tract infection during their respective outbreak seasons.

Timing of development of measles-specific immunoglobulin M and G after primary measles vaccination.

A standard method for diagnosing measles is to detect measles-specific immunoglobulin M (IgM) in the serum of infected persons. Interpreting a positive IgM result from a person with suspected measles can be difficult if the person has recently received a measles vaccine. We have previously demonstrated that measles-specific IgM may persist for at least 8 weeks after primary vaccination, but it is unknown how quickly IgM appears. This study determined the timing of the rise of measles-specific IgM and IgG after primary measles vaccination with Schwartz vaccine. Two hundred eighty 9-month-old children from Ethiopia presenting for routine measles vaccination were enrolled. Sera were collected before and either 1, 2, 3, or 4 weeks after vaccination and tested for measles-specific antibodies by an IgM capture enzyme immunoassay (EIA) and by an indirect IgG EIA. A total of 209 of the 224 children who returned for the second visit had prevaccination sera that were both IgM and IgG negative. The postvaccination IgM positivity rates for these 209 children were 2% at 1 week, 61% at 2 weeks, 79% at 3 weeks, and 60% at 4 weeks. The postvaccination IgG positivity rates were 0% at 1 week, 14% at 2 weeks, 81% at 3 weeks, and 85% at 4 weeks. We conclude that an IgM-positive result obtained by this antibody capture EIA is difficult to interpret if serum is collected between 8 days and 8 weeks after vaccination; in this situation, the diagnosis of measles should be based on an epidemiologic linkage to a confirmed case or on the detection of wild-type measles virus.

Risk factors for West Nile virus infection and meningoencephalitis, Romania, 1996.

In 1996, an epidemic of 393 cases of laboratory-confirmed West Nile meningoencephalitis occurred in southeast Romania, with widespread subclinical human infection. Two case-control studies were performed to identify risk factors for acquiring infection and for developing clinical meningoencephalitis after infection. Mosquitoes in the home were associated with infection (reported by 37 [97%] of 38 asymptomatically seropositive persons compared with 36 [72%] of 50 seronegative controls, P<.01) and, among apartment dwellers, flooded basements were a risk factor (reported by 15 [63%] of 24 seropositive persons vs. 11 [30%] of 37 seronegative controls, P=.01). Meningoencephalitis was not associated with hypertension or other underlying medical conditions but was associated with spending more time outdoors (meningoencephalitis patients and asymptomatically seropositive persons spent 8.0 and 3.5 h [medians] outdoors daily, respectively, P<.01). Disease prevention efforts should focus on eliminating peridomestic mosquito breeding sites and reducing peridomestic mosquito exposure.

The effect of timing of sample collection on the detection of measles-specific IgM in serum and oral fluid samples after primary measles vaccination.

This study compares the timing of the rise and decline of measles-specific IgM in serum samples and in oral fluid samples. Two hundred and eighty 9-month-old infants presenting for routine measles vaccination in Addis Ababa, Ethiopia, were enrolled. Paired serum and oral fluid samples were collected before and 1, 2, 3 or 4 weeks after measles vaccination. Samples were tested by using a modified antibody-capture enzyme immunoassay. For the 321 IgM-negative pre- and post-vaccination serum samples, 317 (99 %) of their corresponding oral fluid samples were IgM-negative. Among the 130 IgM-positive serum samples, 75% of their paired oral fluid samples were IgM-positive, with the percentage rising to 87% after oral fluid samples collected > or =3.5 weeks after vaccination were excluded. Among the post-vaccination serum samples, the percent IgM-positive peaked in week 3 and declined to 79% in week 4. For post-vaccination oral fluid samples, the percent IgM-positive peaked in weeks 2 and 3, and then declined to 43% in week 4. This modified antibody-capture enzyme immunoassay appears to detect vaccine-induced measles-specific IgM in the first 3 weeks after vaccination.

Nonclassic measles infections in an immune population exposed to measles during a college bus trip.

This study investigated the frequency of mild or asymptomatic measles infections among 44 persons exposed to a student with measles during a 3-day bus trip using two buses. Questionnaires and serum samples were obtained 26-37 days after the trip. All participants had detectable measles-neutralizing antibodies, and none developed classic measles symptoms. Ten persons (23%) were IgM positive for measles, indicating recent infection. Among previously vaccinated IgM-negative persons, those who rode on bus A with the index case-patient had significantly higher microneutralization titers than those on bus B (P= .001), suggesting that some persons on bus A were infected but were IgM negative at the time of the study. Mild or asymptomatic measles infections are probably very common among measles-immune persons exposed to measles cases and may be the most common manifestation of measles during outbreaks in highly immune populations.

Decline of measles-specific immunoglobulin M antibodies after primary measles, mumps, and rubella vaccination.

Detection of measles-specific immunoglobulin M (IgM) has become the standard diagnostic method for laboratory confirmation of measles. In outbreaks, the interpretation of an IgM-positive result can be complicated when persons with suspected measles receive a dose of measles vaccine as part of outbreak control measures. This investigation evaluated the decay of measles-specific IgM antibodies 1 to 4 months after primary vaccination with measles, mumps, and rubella vaccine (MMRII). Serum samples were obtained from 536 infants vaccinated when they were 15 months old as part of a study to assess primary and secondary measles vaccine failure. Sixty serum specimens per week were selected from specimens collected between 4 and 9 weeks after MMRII vaccination; all 176 available serum specimens collected between 10 and > or = 16 weeks were included. Specimens were tested for the presence of measles-specific IgM by an antibody-capture enzyme immunoassay. The proportion of IgM-positive specimens dropped from 73% at 4 weeks after vaccination to 52% at 5 weeks after vaccination and then declined to 7% by 8 weeks after vaccination. Less than 10% of children remained IgM positive between 9 and 11 weeks. An IgM-negative result helps rule out the diagnosis of measles in a person with suspected infection and a history of recent vaccination. The interpretation of a positive IgM result from a person with a clinically suspected case of measles and a recent history of measles vaccination (especially within 8 weeks) is problematic, and the diagnosis of measles should be based on epidemiologic linkage to a confirmed case or on detection of wild-type measles virus.

A theoretical framework for evaluating the sensitivity of surveillance for detecting wild poliovirus: I. Factors affecting detection sensitivity in a person with acute flaccid paralysis.

Surveillance for cases of acute flaccid paralysis provides a means for detecting circulating wild poliovirus in a population and therefore is crucial to the global polio eradication effort. An initial step toward developing a more general framework for understanding the sensitivity of the acute flaccid paralysis surveillance system is presented by first specifying four categories of sensitivity involved: laboratory sensitivity, specimen sensitivity, person sensitivity, and population sensitivity. Using this framework, estimates for specimen sensitivity (the probability that virus will be detected in a specimen collected from an infected person) and the prevalence of infection are derived and applied to surveillance data from three regions. On the basis of the framework, our analysis indicates that a second specimen may significantly increase person sensitivity under some circumstances but provides little improvement under others.

A theoretical framework for evaluating the sensitivity of surveillance for detecting wild poliovirus: II. Factors affecting detection sensitivity in a population with circulating wild poliovirus.

A basic framework for describing sensitivity of surveillance to detect poliovirus is extended from individuals to general populations (population sensitivity). Using the mathematical formulations for population sensitivity, the theoretical behavior of surveillance sensitivity under various conditions is analyzed. As a region nears the elimination of poliovirus, population sensitivity falls to a value lower than the case-to-infection ratio, regardless of the system proficiency. Also, a second stool specimen makes a substantial contribution to population sensitivity only in regions with relatively low specimen sensitivity and then only over a narrow range of population infection incidence. Estimates of the mean numbers of infected and uninfected acute flaccid paralysis cases investigated in a season are derived. These may serve as additional indicators of system operation but require the collection of 2 specimens per case.

Duration of poliovirus excretion and its implications for acute flaccid paralysis surveillance: a review of the literature.

Timely investigation of children with acute flaccid paralysis, with collection of stool specimens for virus isolation, is the primary strategy used to detect wild poliovirus circulation. To determine the optimal timing of stool specimen collection, studies of wild and vaccine poliovirus excretion published between 1935 and 1995 were reviewed. Data were compiled from comparable studies, scatter plots of the data were created, and third-order regression lines were calculated. The data indicated that wild polioviruses were excreted by a majority of previously unvaccinated infants and young children for 3-4 weeks. The duration of viral shedding was reduced, however, among children who were previously vaccinated with inactivated poliovirus vaccine, who had preexisting antibodies to the infecting serotype, or who had previous intestinal infection with homologous poliovirus. These data suggest that the 14-day period after onset of paralysis is the interval with the highest probability of detecting wild poliovirus excretion in paralyzed children.

Comparison of a monoclonal antibody-based IgM capture ELISA with a neutralization assay for assessing response to trivalent oral poliovirus vaccine.

Monoclone-based IgM capture ELISAs were developed for each of the three poliovirus serotypes and compared with a neutralization assay for detecting response to trivalent oral poliovirus vaccine among 224 infants. The IgM-based response rates were significantly higher than the neutralizing antibody-based rates: 95% versus 83% to poliovirus type 1, 99% versus 94% to poliovirus type 2, and 89% versus 59% to poliovirus type 3. IgM responses to the first vaccine dose were significantly associated between serotypes, suggesting that some of the discordance may reflect a heterotypic IgM response. When the response rates in 4 vaccine formulation groups were compared, group differences using the two assays were similar for poliovirus types 1 and 2 but not for type 3. Therefore, IgM results using these assays may not be adequate substitutes for neutralizing antibody results when determining vaccine response.

Surveillance for chronic fatigue syndrome--four U.S. cities, September 1989 through August 1993.

PROBLEM/CONDITION: Although chronic fatigue syndrome (CFS) has been recognized as a cause of morbidity in the United States, the etiology of CFS is unknown. In addition, information is incomplete concerning the clinical spectrum and prevalence of CFS in the United States. REPORTING PERIOD COVERED: This report summarizes CFS surveillance data collected in four U.S. cities from September 1989 through August 1993. DESCRIPTION OF SYSTEM: A physician-based surveillance system for CFS was established in four U.S. metropolitan areas: Atlanta, Georgia; Wichita, Kansas; Grand Rapids, Michigan; and Reno, Nevada. The objectives of this surveillance system were to collect descriptive epidemiologic information from patients who had unexplained chronic fatigue, estimate the prevalence and incidence of CFS in defined populations, and describe the clinical course of CFS. Patients aged > or = 18 years who had had unexplained, debilitating fatigue or chronic unwellness for at least 6 months were referred by their physicians to a designated health professional(s) in their area. Those patients who participated in the surveillance system a) were interviewed by the health professional(s); b) completed a self-administered questionnaire that included their demographic information, medical history, and responses to the Beck Depression Inventory, the Diagnostic Interview Schedule, and the Sickness Impact Profile; c) submitted blood and urine samples for laboratory testing; and d) agreed to a review of their medical records. On the basis of this information, patients were assigned to one of four groups: those whose illnesses met the criteria of the 1988 CFS case definition (Group I); those whose fatigue or symptoms did not meet the criteria for CFS (Group II); those who had had an identifiable psychological disorder before onset of fatigue (Group III); and those who had evidence of other medical conditions that could have caused fatigue (Group IV). Patients assigned to Group III were further evaluated to determine the group to which they would have been assigned had psychological illness not been present, the epidemiologic characteristics of the illness and the frequency of symptoms among patients were evaluated, and the prevalence and incidence of CFS were estimated for each of the areas. RESULTS: Of the 648 patients referred to the CFS surveillance system, 565 (87%) agreed to participate. Of these, 130 (23%) were assigned to Group I; 99 (18%), Group II; 235 (42%), Group III; and 101 (18%), Group IV. Of the 130 CFS patients, 125 (96%) were white and 111 (85%) were women. The mean age of CFS patients at the onset of illness was 30 years, and the mean duration of illness at the time of the interview was 6.7 years. Most (96%) CFS patients had completed high school, and 38% had graduated from college. The median annual household income/for CFS patients was $40,000. In the four cities, the age-, sex-, and race-adjusted prevalences of CFS for the 4-year surveillance period ranged from 4.0 to 8.7 per 100,000 population. The age-adjusted 4-year prevalences of CFS among white women ranged from 8.8 to 19.5 per 100,000 population. INTERPRETATION: The results of this surveillance system were similar to those in previously published reports of CFS. Additional studies should be directed toward determining whether the data collected in this surveillance system were subject to selection bias (e.g., education and income levels might have influenced usage of the health-care system, and the populations of these four surveillance sites might not be representative of the U.S. population). ACTIONS TAKEN: In February 1997, CDC began a large-scale, cross-sectional study at one surveillance site (Wichita) to describe more completely the magnitude and epidemiology of unexplained chronic fatigue and CFS.

Characterization of T cell responses to herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) using a TNF-beta ELISpot cytokine assay.

We examined the suitability of a TNF-beta cytokine ELISpot assay for assessing various aspects of the T cell response to herpes simplex viruses. The number of T cells responding to HSV-1 or HSV-2 was measured by TNF-beta ELISpot assay. The number of T cells producing TNF-beta in response to HSV-1 was high, ranging from 76 to 222 per 10(5). HSV-1-specific TNF-beta-secreting responder cell frequencies fluctuated over time in individual donors. Comparable fluctuations were not observed in the T cell frequencies to phytohemaglutinin (PHA). Responder cell frequencies to glycoproteins gB and gD of HSV-2 accounted for a large number of the HSV-2-specific T cells as measured using the TNF-beta ELISpot assay. Type-specific and type-common components of the T cell response to HSV-1 and HSV-2 could be estimated with this assay. Type-common responder cells typically accounted for 25-30%. Finally, CD4+ and CD8+ TNF-beta-producing T cells were stimulated by HSV-1 at a CD4:CD8 ratio of 2:1, indicating that both major subsets of T lymphocytes are activated by HSV.

Immune responses associated with chronic fatigue syndrome: a case-control study.

An exploratory case-control study was conducted to assess whether the many reported differences in the immune function of chronic fatigue syndrome (CFS) patients are detectable in rigorously defined cases of CFS. Although many studies have reported differences between cases and controls in various measures of immune function, none of these differences were found in all studies. In this study, no differences were found in white blood cell numbers; immune complex, complement, or serum immunoglobulin levels; delayed type hypersensitivity and allergic responses; NK cell function; and proliferative responses to mitogens and antigens. Marginal differences were detected in cytokine responses and in cell surface markers in the total CFS population. However, when the patients were subgrouped by type of disease onset (gradual or sudden) or by how well they were feeling on the day of testing, more pronounced differences were seen.

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

BACKGROUND: High 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. METHODS: We 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. RESULTS: There 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. CONCLUSIONS: We 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.

Treatment of respiratory syncytial virus infection with vitamin A: a randomized, placebo-controlled trial in Santiago, Chile.

BACKGROUND: Treatment with high dose vitamin A reduces complications and duration of hospitalization for children with measles. In respiratory syncytial virus (RSV) infection, as with measles, low serum vitamin A concentrations correlate with increased severity of illness. METHODS: To determine whether high dose vitamin A treatment is also effective for treating RSV disease, we conducted a randomized, double blind, placebo-controlled trial among 180 RSV-infected children between 1 month and 6 years of age at three hospitals in Santiago, Chile. Children with nasal washes positive for RSV antigen were given oral vitamin A (50,000 to 200,000 IU of retinyl palmitate, doses according to age; n = 89) or placebo (n = 91) within 2 days of admission. RESULTS: There was no significant benefit from vitamin A treatment for the overall group in duration of hospitalization, need for supplemental oxygen or time to resolve hypoxemia. For the subgroup of children with significant hypoxemia on admission (room air oxygen saturation level < or = 90%), those given vitamin A had more rapid resolution of tachypnea (P = 0.01) and a shorter duration of hospitalization (5.5 vs. 9.3 days, P = 0.09). No toxicities were seen, including excess vomiting or bulging fontanel. CONCLUSIONS: If vitamin A has a beneficial effect on the course of RSV disease, it may be seen only in more severely ill children.

Respiratory syncytial virus is an important cause of community-acquired lower respiratory infection among hospitalized adults.

Respiratory syncytial virus (RSV), the most important cause of lower respiratory disease in infants and young children, is rarely considered among the causes for community-acquired lower respiratory infection in adults. All noninstitutionalized adults hospitalized with community-acquired pneumonia in two Ohio counties were evaluated between December 1990 and May 1992. Fifty-three (4.4%) of 1195 adults admitted during the RSV seasons and 4 (1.0%) of 390 in the off-season had serologic evidence of RSV infection, making RSV one of the four most common pathogens identified. RSV-infected patients had clinical features (e.g., wheezing and rhonchi) that distinguished them from all non-RSV-infected patients and other features (e.g., nonelevated white blood cell counts) that distinguished them from those infected with bacterial or atypical agents. However, RSV infection was not diagnosed during hospitalization for any of the 57 RSV-infected patients. RSV should be considered in the differential diagnosis for adults hospitalized between November and April with community-acquired lower respiratory infection.