Rubella seropositivity in the United States, 1988-1994.

Data obtained in the third National Health and Nutrition Examination Survey (NHANES III), conducted during 1988-1994, were analyzed to determine the epidemiology of rubella seropositivity in the United States, including risk factors for low rubella seropositivity. Serological samples obtained from NHANES III study participants > or =6 years of age were tested for rubella IgG antibodies. "Rubella seropositivity" was defined as serum rubella IgG antibody level > or =10 IU by enzyme immunoassay. Overall, rubella seropositivity rates in the United States were 92% in persons aged 6-11 years, 83% in persons aged 12-19 years, 85% in persons aged 20-29 years, 89% in persons aged 30-39 years, and >or =93% in persons aged > or =40 years. The lowest rate (78%) of any United States birth cohort of the 20th century occurred among persons born from 1970-1974. Eliminating rubella and chronic rubella syndrome in the United States will require international efforts, including vaccination of preschool- and school-age children and all susceptible young adults.

[Critical review of anti-influenza drugs]. / Griepremmers in kritisch perspectief.

Neuraminidase inhibitors such as zanamivir and oseltamivir belong to a new class of antiviral drugs for the treatment and prevention of influenza. As yet however, the therapeutic efficacy of these drugs (shortening of recovery time by approximately one day) has only been demonstrated in healthy adults affected by influenza A, but not in risk groups and in influenza B disease, whereas studies of prophylactic efficacy are still going on. Neither do these drugs impact on viral spread, a public health risk against which the economic advantages of early work resumption have to be weighed. Since flu symptoms can be caused by other germs than the influenza A or B virus, caution in prescribing these drugs seems warranted, also to prevent the development of drug resistance. In addition, when designing therapeutic efficacy trials in risk groups, selecting the rate of secondary complications and death may be more adequate as clinical endpoint than (economically important) duration of illness.

Sociodemographic, hygienic and nutritional correlates of Helicobacter pylori infection of young Bangladeshi children.

BACKGROUND: By the age of 10 years most children in developing countries have been infected by Helicobacter pylori Identification of clues to modes of transmission of this organism to children, as well as evaluation of the sequelae of childhood infections, constitute important research priorities for developing countries. OBJECTIVES: To evaluate demographic, socioeconomic and hygienic factors associated with acquisition of infection by H. pylori early in childhood among Bangladeshi children ages 2 to 5 years and to assess whether infection by H. pylori was associated with poor nutritional status in these children and in an older group ages 6 to 9 years. METHODS: A random population-based survey of 257 rural Bangladeshi children ages 2 to 5 years and 312 children ages 6 to 9 years. Seropositivity for H. pylori, as manifested by the presence of serum IgG anti-H. pylori antibodies, was correlated with nutritional status of the sampled children and with sociodemographic features and access to clean water and latrine facilities among families of the children. RESULTS: Among children ages 2 to 5 years, the 123 (48%) who were infected by H. pylori were similar to the 134 noninfected children with respect to socioeconomic level, family access to tube well water and family ownership of a latrine. However, families of infected children had more persons per sleeping room in the home (3.8 vs. 3.2, P < 0.05) and were more likely to be Hindu (20% vs. 10%, P < 0.05). Infected children did not differ significantly from noninfected children in Z scores for weight-for-age (-2.66 vs. -2.78), weight-for-height (-1.17 vs. -1.28) or height-for-age (-3.58 vs. -3.56). Analysis of survey children ages 6 to 9 years also revealed similar nutritional indexes among infected vs. noninfected children. CONCLUSIONS: Household crowding and behaviors that differ between Hindus and Muslims, but not lack of access to clean water and latrines, may enhance the transmission of H. pylori to rural Bangladeshi children. Although confirming the high frequency of infections in young Bangladeshi children, our findings do not support the notion that H. pylori is responsible for the high prevalence of malnutrition in this setting.

The effect of L-glutamine on salt and water absorption: a jejunal perfusion study in cholera in humans.

OBJECTIVES: To assess the efficacy of an L-glutamine solution on jejunal salt and water absorption in cholera patients. DESIGN: A randomized double-blind jejunal perfusion study. SETTING: International Centre for Diarrhoeal Disease Research, Bangladesh. PATIENTS: Nineteen adults with acute cholera. INTERVENTIONS: Perfusion of balanced salt solutions alternated with defined glucose salt solution and glutamine glucose salt or alanine glucose salt solutions. MAIN OUTCOME MEASURES: Net jejunal water and sodium secretion. RESULTS: Perfusion of glutamine in the presence of glucose significantly reduced net water secretion (JnetH2O = -2.6 +/- 1.3 ml/h/cm) and also reduced net sodium secretion (JnetNa = -213 +/- 153 mumol/h/cm). Similar results were observed during the perfusion of solutions that contained alanine in addition to glucose (JnetH2O = -4.2 +/- 1.1 ml/h/cm and JnetNa = -444 U +/- 142 mumol/h/cm, respectively) or glucose alone (JnetH2O = -4.3 +/- 1.7 ml/h/cm and JnetNa = -452 +/- 212 mumol/h/cm, respectively). In addition, a higher basal secretion was associated with a greater stimulation of water absorption (F = 17, P < 0.001). CONCLUSION: Glutamine in the presence of glucose significantly reduces net water secretion and also reduces sodium secretion; higher basal secretion is associated with greater water absorption. As glutamine is able to stimulate water absorption to the same degree as glucose and alanine, and because it has the theoretical advantage of providing fuel for the mucosa, the inclusion of glutamine as the sole substrate in oral rehydration solution warrants further study.

Field trial of inactivated oral cholera vaccines in Bangladesh: results from 5 years of follow-up.

To determine the protective efficacy (PE) of three doses of oral B subunit-killed whole cell (BS-WC) or killed whole cell-only (WC) vaccines against cholera, a clinical trial was conducted among 62285 children over 2 years and adult women in rural Bangladesh. During 5 years of follow-up, there were 144 cases of cholera in the BS-WC group (PE = 49%; P < 0.001), 150 in the WC group (PE = 47%; P < 0.001), and 283 in the K12 group. Protection by each vaccine was evident only during the first three years of follow-up; long-term protection of young children was observed only against classical but not El Tor cholera; 3-year protection against both cholera biotypes occurred among older persons, but at a higher level against classical cholera.

Mumps surveillance--United States, 1988-1993.

PROBLEM/CONDITION: CDC monitors the incidence of mumps in the United States through the passive reporting of cases to its National Notifiable Disease Surveillance System (NNDSS). REPORTING PERIOD COVERED: 1988-1993. DESCRIPTION OF SYSTEM: Weekly reports to the NNDSS from 48 states and the District of Columbia were used to calculate incidence rates for mumps. State immunization requirements were obtained from the U.S. Department of Health and Human Services. RESULTS: After the licensure of mumps vaccine in the United States in December 1967 and the subsequent introduction of state immunization laws in an increasing number of states, the reported incidence of mumps decreased substantially. The 1,692 cases of mumps reported for 1993 represent the lowest number of cases ever reported to NNDSS and a 99% decrease from the 152,209 cases reported for 1968. During 1988-1993, most cases occurred in children 5-14 years of age (52%) and in persons > or = 15 years of age (36%). Although the incidence decreased in all age groups, the largest decreases (> 50% reduction in incidence rate per 100,000 population) occurred in persons > or = 10 years of age. Overall, the incidence of mumps was lowest in states that had comprehensive school immunization laws requiring mumps vaccination and highest in states that did not have such requirements. INTERPRETATION: Because of the extensive use of mumps vaccine and the increased number of states that had enacted mumps immunization laws, the number of reported mumps cases decreased further since the marked decline that began during the early 1970s. The earlier shift in incidence from children of school ages to older persons that was noted during 1985-1988 continued until 1992, when the proportion of cases occurring in children of school ages increased and exceeded the proportions occurring in other age groups. ACTIONS TAKEN: All health-care providers are encouraged to a) report mumps cases to their local and state health departments for transmission to NNDSS and b) enact school immunization laws requiring mumps vaccination.

Impact of infection by Helicobacter pylori on the risk and severity of endemic cholera.

To evaluate the relationship between Helicobacter pylori infection and the subsequent risk and severity of endemic Vibrio cholerae O1 diarrhea among rural Bangladeshis, 285 children and adults with cholera (cases) and 881 contemporaneously selected community controls were studied. Cases and controls were contrasted for H. pylori infection, as manifested by serum IgG anti-H. pylori antibodies. Although the overall risk of cholera was not significantly increased among H. pylori-infected subjects, the risk of cholera of life-threatening severity was significantly elevated (relative risk [RR] = 1.61; 95% confidence interval [CI] = 1.07-2.42). A significant increase in the risk of severe cholera was seen in subjects who lacked natural serum vibriocidal antibodies (RR = 2.88; 95% CI = 1.28-6.48) but not in those with such antibodies. Thus, H. pylori infection was associated with a significant increase in the risk of life-threatening cholera, but only among persons lacking natural vibriocidal immunity.

The design and analysis of cholera vaccine trials: recent lessons from Bangladesh.

The recent spread of cholera to Latin America, together with the persistent burden of this disease in Asia and Africa, have stimulated efforts to evaluate new cholera vaccines in field settings. Although the standard experimental paradigm for vaccine field trials is well established, the success of these trials will also depend on suitable consideration of the epidemiology of cholera and of cholera vaccination in the setting under study. Epidemiological studies done in Bangladesh emphasize the importance of appreciating the poorly predictable, multifocal occurrence of cholera in estimating a probable incidence of cholera for a field trial. They also underscore how the filtering effect of enrolling subjects into a prospective trial can dramatically reduce the available population for study, and can yield a study sample whose expected risk of cholera differs markedly from that for the source population. Finally, the data highlight the subtle effects that the mode of surveillance and the choice of an outcome definition can have upon protective efficacy, and emphasize the need for subgroup analyses that address the distinctive variations in vaccine protection that may occur in subjects differing in age and in ABO blood groups, and in subjects exposed to classical versus El Tor cholera.

PIP: It is important to predict cholera incidence for clinical trials, but it is hard to do so, even in areas where there is a regular endemic pattern. In Matlab, Bangladesh, cholera tends to occur seasonally, right before and after the summer monsoon. Various host facts affect cholera incidence, e.g., insufficient natural immunity and exposure to infected persons. Passive surveillance data in Matlab demonstrate that cholera occurs in a temporo-spatially clustered, multifocal pattern within a community. Ineligibility, refusal to participate, and absenteeism have a strong filtering effect on the population in a field trial. For example, in a field trial of killed oral cholera vaccines in Bangladesh, only 62.285 of the original 124,035 people completed the trial. As a result of nonparticipation, the expected incidence for nonvaccinees was overestimated. The definition of cholera used also determines incidence. For example, if a trial in endemic areas uses the classical definition (watery diarrhea with excretion of cholera vibrios but no copathogens), it would miss those cases with atypical symptoms (e.g., 21% of treated cholera episodes in the oral vaccine trial were clinically atypical or microbiologically mixed). Age related distinctions, ABO blood group, and biotype of the infecting organisms all influence vaccine efficacy. The above issues were considered when designing field trails of killed oral cholera vaccines in Colombia and Peru, but most people in these countries lack preexisting natural immunity, these areas have only E1 for cholera, and it will be very difficult to predict incidence among nonvaccines. This review of epidemiological studies of cholera in Bangladesh, including a large-scale field trial of killed oral cholera vaccines, describes the significance of these considerations.

Immunogenicity of a supplemental dose of oral versus inactivated poliovirus vaccine.

In many developing countries, the immunogenicity of three doses of live, attenuated, oral poliovirus vaccine (OPV) is lower than that in industrialised countries. We evaluated serum neutralising antibody responses in 368 children aged 6 months and 346 children aged 9 months in Côte d'Ivoire who had previously received three doses of OPV at 2, 3, and 4 months of age, and who were then randomised to receive a supplemental dose of OPV or enhanced-potency inactivated poliovirus vaccine (IPV) at the time of measles vaccination. Although both vaccines increased seroconversion to all three poliovirus types, antibody responses were greater in the IPV group. Among children with no detectable antibody at baseline, IPV was 2 to 14 times more likely than OPV to induce seroconversion (type 1, 80% vs 40% at 6 months [p < 0.001] and 81% vs 14% at 9 months [p < 0.001]; type 3, 76% vs 22% at 6 months [p < 0.001], and 67% vs 5% at 9 months [p < 0.001]. Among children with detectable antibody at baseline, IPV was 1.4 to 7 times more likely than OPV to elicit 4-fold or more rises in antibody titre (p < 0.01). Geometric mean titres (GMTs) to all three poliovirus types were also consistently higher among IPV recipients than in OPV recipients when measured 4-6 weeks and 13-17 months after vaccination. Administration of a supplemental dose of IPV or OPV, which requires no additional visits or changes in the existing immunisation schedule, might improve protection against paralytic poliomyelitis in communities with suboptimum seroconversion rates after three doses of OPV.

Cholera: developments in prevention and cure.

The current pandemic of cholera coincides with a flurry of research activities in cholera prevention and cure. This article highlights important developments in cholera research, including key findings of a large-scale oral cholera vaccine trial, new insights in cholera epidemiology and risk factors, and recent directions in rehydration therapy and medical treatment of cholera.

Evidence that protection against rotavirus diarrhea after natural infection is not dependent on serotype-specific neutralizing antibody.

This case-control study sought to determine whether protection against clinically significant rotavirus diarrhea in children aged 4-35 months correlated with titers of serum neutralizing antibody and, if so, whether this protection was serotype-specific. Titers of acute-phase sera from 156 cases of treated rotavirus diarrhea in rural Bangladesh were contrasted with titers from 312 contemporaneously selected, age-matched controls. Analyses of the culture-adapted rotaviruses from the cases revealed that 24%, 15%, 43%, and 17% belonged to serotypes 1-4, respectively. Titers of both homologous and heterologous neutralizing antibody in acute blood specimens of cases were significantly lower than those of matched controls. However, multivariate logistic regression models demonstrated that only antibody titers to heterotypic rotaviruses were independently associated with protection against rotavirus disease. These data, which indicate that the correlation of protection with neutralizing antibody titers is not serotype-specific, suggest that immunity to rotavirus disease may be mediated by other factors.

Evidence that inactivated oral cholera vaccines both prevent and mitigate Vibrio cholerae O1 infections in a cholera-endemic area.

In a randomized, placebo-controlled field trial of B subunit-killed whole cell (BS-WC) and killed whole cell only (WC) inactivated oral cholera vaccines in rural Bangladesh, active surveillance of selected neighborhoods during the first year after vaccination identified 127 Vibrio cholerae O1 infections among 3285 three-dose recipients. For each vaccine, protective efficacy was greater against symptomatic (57%, P < .05 for BS-WC; 58%, P < .05 for WC) than against asymptomatic infections (46%, P < .05 for BS-WC; 32%, P = .09 for WC), and protection against each grade of infection was demonstrable for both the classical and El Tor biotypes. Although vaccine protection against symptomatic infections was evident in both young children and older persons, only persons vaccinated at age > 5 years were protected against asymptomatic infections. These results suggest that the inactivated oral vaccines acted both to protect against intestinal colonization by V. cholerae O1 and to interrupt the pathogenic sequence of established infections.

Perfusion studies in cholera: methods and procedures.

This paper reviews the characteristics of perfusion techniques in the study of intestinal functions by specifically examining the methods and procedures of perfusion in patients with diarrhoea due to infection with V. cholerae 01. Because of abundant jejunal secretion of water and electrolytes in cholera, perfusion studies require special approaches with regard to patient preparation, use of tubing material, selection of markers, and rate of perfusion. A discussion on specific problems involved in marker perfusion techniques in cholera and on the interpretation of the results is followed by practical recommendations.

Indomethacin decreases jejunal fluid secretion in addition to luminal release of prostaglandin E2 in patients with acute cholera.

Human cholera is associated with an increased luminal release of prostaglandin E2 (PGE2), but whether inhibition of increased PGE2 synthesis will reduce or control intestinal secretion is uncertain. 'Steady state' perfusions (10 ml/minute) in 12 patients with acute cholera, and repeat perfusions in nine of these patients during the convalescent phase were therefore performed using the triple lumen technique. The proximal jejunum was perfused with isotonic saline containing sodium-sulphobromophthalein as a non-absorbable marker. After intravenous administration of indomethacin (1.0 mg/kg) the jejunal net transfer of fluid and the jejunal flow rate of PGE2 were determined in 30 minute periods for 120 minutes after a 120 minute control period. Indomethacin decreased net fluid secretion (2.1 (0.3-4.2) v 4.5 (2.5-8.4) ml/hour x cm; medians, Q50 ranges, p less than 0.01) and the jejunal flow rate of PGE2 (1.5 (1.2-2.7) v 2.2 (1.4-4.9) ng/minute, p less than 0.05). The results of similar perfusion studies in 22 patients with acute cholera, used to establish the spontaneous time related change in fluid secretion, showed no significant change in net fluid transfer (3.5 (2.2-6.2) to 3.5 (2.6-11.6) ml/hour x cm, p greater than 0.25) over 240 minutes. These data provide further evidence in favour of the hypothesis that prostaglandins have a role in the cholera toxin induced intestinal fluid secretion in man.

Seroepidemiologic evaluation of antibodies to rotavirus as correlates of the risk of clinically significant rotavirus diarrhea in rural Bangladesh.

A case-control study was conducted among children and adult women in rural Bangladesh to evaluate whether serologic immunity to rotavirus was associated with a lower risk of rotavirus diarrhea of sufficient severity to cause patients to seek medical care. Acute-phase sera from 219 cases of rotavirus diarrhea, detected among patients treated in three diarrheal treatment centers, were compared with sera from 477 contemporaneously selected community controls. Overall, serum IgG antirotavirus antibody titers were nearly one-fourth as high in cases as in controls (107 vs. 417 units/ml; P less than .001). Among persons aged greater than or equal to 8 months, in whom titers of maternal antirotavirus antibodies should have been negligible, even the lowest range of detectable titers (100-200 units/ml) was associated with a substantial (75%, P less than .05) reduction of the risk of rotavirus diarrhea. We conclude that titers of serum IgG antirotavirus antibodies induced by earlier infection were inversely related to the risk of clinically significant rotavirus diarrhea.

Rotavirus-associated diarrhea in rural Bangladesh: two-year study of incidence and serotype distribution.

Stools were evaluated from 5,811 patient visits for treatment of diarrhea in Matlab, Bangladesh, between June 1987 and May 1989. The stools were analyzed to determine the distribution of serotypes of group A rotaviruses (RV). A total of 898 stool samples (15.5%) contained RV, as determined by using an enzyme-linked immunosorbent assay. RV isolates from 855 of these samples were serotyped by using serotype-specific synthetic oligonucleotide probes. A total of 558 (65.3%) could be assigned to specific serotypes: 166 (19.4%), 228 (26.7%), 39 (4.6%), and 125 (14.6%) belonged to serotypes 1 through 4, respectively; 12 (1.4%) hybridized with more than one serotype; and 285 (33.3%) failed to hybridize. RV diarrhea was evident throughout the year, with peaks in the dry winter months and in September 1988, coinciding with a major flood. RV was isolated from 46.6% of patients between 7 and 12 months old. Among children under 24 months of age with RV diarrhea, 1.2% (10 of 828) died. The corresponding percentage for children with diarrhea from all causes is 0.9% (29 of 3,301).

ABO blood groups and the risk of diarrhea due to enterotoxigenic Escherichia coli.

To determine whether blood group O persons are at higher risk for enterotoxigenic Escherichia coli (ETEC) diarrhea, a case-control study was done for 17 months among rural Bangladeshis who were under systematic surveillance for diarrhea. Cases were children less than 3 years old who presented between 1 January 1985 and 1 June 1986 for care of heat labile (LT) or heat stabile toxin-producing ETEC diarrhea. Controls were of similar ages and were randomly selected from three community-based serosurveys between July 1985 and May 1986. No association between blood group O and ETEC diarrhea was found for the 510 cases and 641 controls, nor was an association evident for cases of each toxin phenotype. Further refinement of the case definition to include only patients with LT-ETEC diarrhea, without enteric copathogens, also failed to reveal a substantial association with blood group O. These data suggest that a strong association with ABO groups, analogous to that for cholera, does not exist for ETEC diarrhea.