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PubMed1999

IL-12, IFN-gamma, and T cell proliferation to measles in immunized infants.

Measles infection in infants is associated with severe complications, and secondary infections are attributed to generalized immunosuppression. Measles binding to its monocyte receptor down-regulates IL-12 which is expected to diminish Th1-like cytokine responses, including IFN-gamma. Whether young infants can be immunized effectively against measles is an important public health issue. We evaluated Ag-specific IL-12, IFN-gamma, and T cell responses of infants at 6 (n = 60), 9 (n = 46), or 12 mo (n = 56) of age and 29 vaccinated adults. IL-12 and IFN-gamma release by PBMC stimulated with measles Ag increased significantly after measles immunization in infants. IL-12 and IFN-gamma concentrations were equivalent in younger and older infants, but IL-12 concentrations were significantly lower in infants than in adults (p = 0.04). IL-12 production by monocytes was down-regulated by measles; the addition of recombinant human IL-12 enhanced IFN-gamma production by PBMC stimulated with measles Ag, but infant T cells released significantly less IFN-gamma than adult T cells under this condition. Of particular interest, the presence of passive Abs to measles had no effect on the specific T cell proliferation or IFN-gamma production after measles stimulation. Cellular immunity to measles infection and vaccination may be limited in infants compared with adults as a result of less effective IFN-gamma and IL-12 production in response to measles Ags. These effects were not exaggerated in younger infants compared with effects in infants who were immunized at 12 mo. In summary, infant T cells were primed with measles Ag despite the presence of passive Abs, but their adaptive immune responses were limited compared with those of adults.

Adult↗
PubMedDate not supplied

Measles reporting completeness during a community-wide epidemic in inner-city Los Angeles.

A study was undertaken to determine the extent of measles underreporting among preschool-age children. In two community surveys conducted in inner-city Los Angeles during 1990 and 1991, respondents were asked whether preschool-age children in their households had ever been ill with measles. Information about measles episodes was obtained and medical records were reviewed, when available. A probable measles case was defined as having 3 or more days of rash with fever of 38.3 degrees centigrade or greater, and either cough, coryza, or conjunctivitis. To determine the proportion of cases reported, probable measles cases identified were matched with measles cases reported to the Los Angeles County Department of Health Services. Of the 947 children ages 6 weeks through 59 months included in the surveys, 35 children had experienced an illness episode which met the probable measles case definition. Ten (29 percent) of the 35 probable measles cases were reported to the health department. Hospitals reported 9 (69 percent) of 13 probable measles cases evaluated while private physicians' offices reported 0 (0 percent) of 12 evaluated (Fisher's exact test, P < 0.001), although 5 children were seen by private physicians before rash onset. Reporting was more complete for cases occurring during 1990 and 1991 (33 percent) than from 1987 through 1989 (18 percent). The hospitalization rate for preschool-age children with probable measles cases in the catchment area was estimated to be 8 percent (95 percent confidence interval = 0 to 18 percent). Although measles is a serious communicable disease which is almost completely preventable, cases of it among preschool-age children in this high incidence area were substantially underreported,especially by private physicians. Due to reporting bias, reported measles cases were representative of more severe cases than all the cases that occurred.

Child, Preschool↗
PubMed1976

Is multiple sclerosis an age-dependent host response to measles?

Several lines of evidence support the possibility that multiple sclerosis (M.S.) may be an age-dependent host response to measles. In animals, measles evokes different responses depending upon age at inoculation. In man, measles is already known to produce at least two age-dependent responses: risk of subacute sclerosing panencephalitis is increased among those who have had measles before 2 years of age and risk of measles encephalitis increases with age, at least during adolescence. Studies of immigrant populations indicate that an event at or before adolescence but not infancy affects risk of M.S. In the tropics where M.S. is rare, measles tends to be acquired very early in life, usually before the age of 3, whereas in temperate areas, measles tends to be acquired later, after the age of 5. A retrospective study has shown that M.S. patients tend to have had measles later than controls. Mechanisms which might underlie an age-dependent host response to measles include maturation of an immune system (k.g., number of available B cells) or change in the metabolic state of a target cell (e.g., oligocytes which change from laying down myelin to maintaining it). If the hypothesis that M.S. is a host response to later measles infection is valid, then mass measles vaccination programmes should produce a decline in the rate of M.S., but the effect may not be discernible before 1980.

Adolescent↗
PubMed1999

Measles virus infection causes transient depletion of activated T cells from peripheral circulation.

BACKGROUND: Natural measles virus infection as well as vaccination with attenuated measles virus induce temporary immunosuppression, which is responsible for part of the morbidity and mortality associated with measles. The underlying molecular mechanisms are not known. Recently, in vitro studies have revealed a marked increase of LFA-1 expression of lymphocytes in the presence of infectious measles virus. OBJECTIVES: In order to further investigate immune dysfunction in measles we analyzed the expression of leukocyte function-associated antigen 1 (LFA-1) on ex vivo derived circulating human T cells. STUDY DESIGN: Expression of LFA-1 was measured by flow cytometry using monoclonal antibodies directed against CD11a and CD18. LFA-1 expression was followed in the course of infection in four adult seronegative vaccinees and in four patients with natural measles. RESULTS: There was a remarkable loss of LFA-1-bright cells during natural measles and after measles vaccination. The number of LFA-1-bright cells reached a minimum on day 7-14 after vaccination, and at the onset of rash during natural measles infection, and approached normal levels within 3-5 weeks. CONCLUSION: It is suggested that measles virus infection interferes with lymphocyte trafficking and reallocation. Disruption of recirculation and random homing of lymphocytes might contribute to the immunosuppression, which is characteristic for measles virus infection.

Adult↗
PubMed1992

Seroepidemiology and evaluation of passive surveillance during 1988-1989 measles outbreak in Taiwan.

A seroepidemiological study was carried out to explore the risk factors of a measles outbreak that occurred among school children at a rural village (Li-Tse) in Taiwan. Among the 1166 participants, the percentage susceptible before the outbreak was 10.5% (122/1158) which was estimated as the sum of measles IgG-negative (29/1158) and IgM-positive (93/1166) individuals. Among 340 vaccinated children, 16 (4.7%) were measles IgM-positive and 10 (2.9%) were measles IgG-negative; therefore the vaccine failure rate was estimated to be 7.6% (26/340) and vaccine efficacy was 79.7% (95% confidence interval [CI] : 65.0-88.5). The most important risk factors for acquiring measles infection were the presence of other measles cases in the family (Odds Ratio [OR] = 32.5, P = 0.002) and the presence of more than two cases in a class (OR = 29.1, P = 0.003). The physician reporting rate was 6.1% (4/66), and the sensitivity of passive measles surveillance was only 4.3% (4/93) by active serosurvey. A concomitant rubella epidemic also amplified the inaccuracy of a passive reporting system based only on clinical diagnosis. Five children developed measles IgM but did not experience any symptoms, indicating that asymptomatic measles infection can occur. Our experience has highlighted three important areas for future measles elimination: (1) the need for serological evaluation of vaccinees, particularly those who were born during the introduction of mass immunization; (2) improvement in measles vaccine efficacy; and (3) further investigations on the role of asymptomatic transmission and susceptibles who remain after mass immunization.

Adolescent↗
PubMed1996

Antibody persistence after primary measles-mumps-rubella vaccine and response to a second dose given at four to six vs. eleven to thirteen years.

BACKGROUND: Since 1989 the American Academy of Pediatrics and the ACIP have recommended a second dose of measles-mumps-rubella vaccine (M-M-R-II) at either school entry or age 11 to 13 years. Unfortunately few studies are available to compare responses to vaccine at the two ages. We performed a prospective trial to determine the persistence of antibody to measles, mumps and rubella vaccination in two age groups and the response to a second dose given at either 4 to 6 or 11 to 13 years. METHODS: Thirty-eight children 4 to 6 years old and 57 children 11 to 13 years old were given a second dose of M-M-R-II as they presented for yearly examinations. All had received the first dose at > or = 15 months of age. Measles and rubella antibody were measured by enzyme-linked immunosorbent assay (ELISA) and neutralizing antibody (NT) assay, and mumps antibody was measured by an ELISA method only. An IgM-ELISA antibody assay for measles was used in selected children. Prevaccination and 3- to 4-week post-vaccination sera were obtained. Measles ELISA, measles-neutralizing antibody (NT) and rubella-neutralizing antibody (NT) assays were performed in all children. Seventy-nine of the 95 children had sufficient sera for repeat measles tests, as well as mumps and rubella ELISA determinations. RESULTS: Before the second dose ELISA seropositivity rates for measles and mumps were not significantly different between the two groups. Rubella ELISA seropositivity was 67% in 11- to 13-year-olds, compared with 90% in 4- to 6-year-olds (P < 0.01), suggestive of waning immunity. Rubella NT seropositivity was also lower in 11- to 13-year-olds than in 4- to 6-year-olds (63% vs. 100%, P < 0.01). After revaccination, 100% of the children become seropositive for all 3 antibodies. We performed measles IgM-ELISA testing on all 17 measles-seronegative children, as well as 15 seropositive children and 19 children who were 1 month postvaccination with the first M-M-R-II at 15 months. The purpose was to determine whether the seronegative children were primary or secondary failures. Five of the 17 children with undetectable pre-second dose antibody made IgM measles antibody after revaccination, suggesting that they were primary vaccine failures. CONCLUSIONS: Because all children became seropositive after revaccination, the age of administration can be based on the convenience of vaccine scheduling. However, in view of the apparent decline in rubella antibodies at 11 to 13 years, future studies of rubella vaccination should address the issue of whether earlier boosting leads to greater susceptibility at the time of reproductive age.

Adolescent↗
PubMed2001

Predicting and comparing long-term measles antibody profiles of different immunization policies.

OBJECTIVE: Measles outbreaks are infrequent and localized in areas with high coverage of measles vaccine. The need is to assess long-term effectiveness of coverage. Since 1991, no measles epidemic affecting the whole island has occurred in Taiwan, China. Epidemiological models are developed to predict the long-term measles antibody profiles and compare the merits of different immunization policies on the island. METHODS: The current measles immunization policy in Taiwan, China, is 1 dose of measles vaccine at 9 months of age and 1 dose of measles, mumps and rubella (MMR) vaccine at 15 months of age, plus a 'mop-up' of MMR-unvaccinated schoolchildren at 6 years of age. Refinements involve a change to a two-dose strategy. Five scenarios based on different vaccination strategies are compared. The models are analysed using Microsoft Excel. FINDINGS: First, making the assumption that measles vaccine-induced immunity will not wane, the predicted measles IgG seroprevalences in preschool children range from 81% (lower bound) to 94% (upper bound) and in schoolchildren reach 97-98% in all strategy scenarios. Results are dependent on the association of vaccine coverage between the first and second dose of vaccine. Second, if it is assumed that vaccine-induced antibody titres decay, the long-term measles seroprevalence will depend on the initial titres post vaccination, decay rates of antibody titres and cut-off of seropositivity. CONCLUSION: If MMR coverage at 12 months of age can reach > 90%, it would be worth changing the current policy to 2 doses at 12 months and 6 years of age to induce higher antibody titres. These epidemiological models could be applied wherever a similar stage of measles elimination has been reached.

Adolescent↗
PubMed2001

[The study of countermeasures on measles control in infants].

OBJECTIVE: To understand: a) measles antibody levels in purpura and their newborns, and the relation between them, b) maternal transferred measles antibody level of different age group infants, c) immunization rates of success in 6 and 8 month old infants, d) to study measles control countermeasures on infants. METHOD: To test measles IgG antibody levels of infant's blood using ELISA method. RESULTS: Antibody levels of measles in 58 pairs of mother and their newborns, 51 pairs were the same, while 7 pairs were different. Measles antibody levels in newborns was not high and reduced to 50% in 3 months, 20% in 6 months, and 15% in 8 months. The antibody levels in 6 and 8 month olds were low, nearly no protection to children. It was found that rates of immunization success and the antibody distribution were not statistically different between 6 and 8 months olds after measles vaccination. CONCLUSION: It was found that the measles antibody level in most matured women was low. Since mother's measles antibody level has close relation to their newborns, it seems that the newborn's antibody level can be improved by vaccination to matured women. In order to reduce morbidity of infant measles, the age of first vaccination of measles vaccine should be changed from 8 months old to 6 months old in some regions.

Age Factors↗
PubMed1997

In situ immune responses in Crohn's disease: a comparison with acute and persistent measles virus infection.

The implied aetiological association of measles virus with Crohn's disease would be supported by detection of an immune response to infected cells in affected tissues. This study sought to detect and characterise in situ immune responses to measles virus in both acutely and persistently infected tissues, and in particular, Crohn's granulomata. Tissue sections from patients with Crohn's disease (n = 17), tuberculosis (n = 9), acute intestinal ischaemia (n = 5), acute measles pneumonitis (n = 2), acute measles appendicitis (n = 1), subacute sclerosing panencephalitis (SSPE; n = 1), and measles inclusion body encephalitis (MIBE; n = 1), were examined. Single and double immunohistochemical labelling was performed to identify both cytotoxic lymphocytes (CD8, TIA, perforin, Leu 7, CD45RO, CD45RA) and macrophages (KP1). The relationship of these cells to measles infected cells was examined by double immunolabelling with antimeasles virus nucleoprotein antibody. In both acute measles appendicitis and SSPE, CD8+/TIA cytotoxic lymphocytes (CTL) targeted infected cells. In the cases of Crohn's disease (13/17), MIBE, fatal pneumonitis, and one tuberculous granuloma, that were positive for measles virus, infected cells appeared to be targeted by macrophages rather than CTL. CTL in both tuberculous and Crohn's granulomata were similar in their peripheral distribution, number, and phenotype. The data suggest that measles-specific CTL responses may be attenuated in Crohn's disease compared with acute measles appendicitis and SSPE, and secondly, that an abnormal macrophage response to persistent measles virus infection of the intestine may result in granulomatous inflammation.

Acute Disease↗
PubMed2000

Protective titres of measles neutralising antibody.

A nation-wide measles outbreak occurred in 1988 in Taiwan. A retrospective cohort study was conducted to define the protective titre of measles neutralising (NT) antibody. Paired sera collected in 1987 and 1988 were available from 190 individuals born in 1984 who had participated in an annual hepatitis B immunisation follow-up from 1986 to 1991. Measles NT titres were quantified using a standardised neutralisation enzyme immunoassay. Measles infection was defined as a >/=4-fold rise in NT titre or seroconversion between paired sera. Symptomatic measles infection was ascribed to individuals who had measles infection and who reported measles-like symptoms between 1987 and 1988. Results demonstrated a dose-response relationship between pre-exposure NT titres and protection against measles infection. 47 of 48 individuals with measles infection in 1988 had pre-exposure NT titres </=1,017 mIU/ml; all 12 symptomatic cases had pre-exposure NT titres </=434 mIU/ml. Eleven vaccinees had pre-exposure NT titres <50 mIU/ml, of whom nine developed asymptomatic infection. The study suggests that measles NT titres >1, 000 mIU/ml may prevent measles infection and NT titres >500 mIU/ml may prevent symptomatic infection but vaccinees with undetectable or low NT titres may not necessarily be susceptible to symptomatic infection.

Antibodies, Viral↗
PubMed2006

Immune activation at effector and gene expression levels after measles vaccination in healthy individuals: a pilot study.

Cellular immunity to measles vaccination is not fully understood at the effector response and gene expression levels. We enrolled 15 healthy individuals (15-25 years old) previously vaccinated with two doses of measles-mumps-rubella-II vaccine to characterize their cellular immunity. We detected a spectrum of lymphoproliferative response (median stimulation indices of 3.4), low precursor frequencies of interferon-gamma (median 0.11%) and interleukin-4 (median 0.05%) by Elispot, and cosecretion of Th1 and Th2 cytokines after measles virus stimulation. Further, global gene expression was examined in five subjects from this cohort after vaccination with an additional dose of measles vaccine (Attenuax, Merck) to identify the genes involved in measles immunity. Linear mixed effect models were used to identify genes significantly up or downregulated in vivo between baseline and Days 7 and 14 after measles vaccination. Measles vaccination induced upregulation of a set of 80 genes, which play a role in measles immunity, signal transduction, apoptosis, cell proliferation, and metabolic pathways. Among the 34 genes that were downregulated, only interferon-alpha is known to have a direct role in measles immunity. This study suggests that measles vaccination leads to activation of multiple cellular mechanisms that can override the immunosuppressant effects of the measles virus and induce immunity.

Adolescent↗
PubMed1991

Nosocomial measles infection in a pediatric hospital during a community-wide epidemic.

From Jan. 1, 1988, through Dec. 31, 1988, a total of 89 cases of measles were observed at Childrens Hospital of Los Angeles, and 37 patients were admitted to the hospital. Of the 37 patients, six were not initially thought to have measles, which resulted in exposure of 107 patients and 24 personnel. Of the exposed patients, measles developed in four. One nosocomially infected infant died of pneumonia. Another exposed patient was subsequently admitted to another hospital with unrecognized measles, which led to exposure of an additional eight patients. Of seven employees in whom measles developed, two required hospitalization because of pneumonia. Two hundred eleven employee days were lost because of measles exposure or infection. Infection control interventions included prophylaxis of exposed patients, employee education, and measles immunization for susceptible personnel. Of 1103 hospital personnel considered susceptible to measles, 800 received monovalent measles vaccine. No secondary cases of measles occurred in hospital personnel who received appropriate prophylaxis. We conclude that infection control programs aimed at mandating measles immunity in hospital employees at risk should be instituted.

Age Factors↗
PubMed2004

Measles immunity after allogeneic stem cell transplantation; influence of donor type, graft type, intensity of conditioning, and graft-versus host disease.

During follow-up after allogeneic stem cell transplantation (SCT), patients frequently lose their immunity to infectious agents such as measles. The aim of this study was to analyze the influence of different factors on measles immunity. In total, 395 patients with a disease-free survival of at least 1 year were included. Measles vaccination was given at 2 years after SCT to children and young adults without chronic GVHD or ongoing immunosuppression. In all, 264 patients had matched sibling donors and 131 either mismatched family or unrelated donors. Totally, 318 patients received bone marrow and 77 peripheral blood stem cells. Overall, 375 patients had undergone myeloablative and 20 nonmyeloablative conditioning. Out of 395 patients, 133 (34%) were seronegative to measles. In multivariate models, younger age or being vaccinated to measles, rather than previous measles disease, before transplantation were risk factors both for becoming seronegative and to have doubtfully protective immunity to measles. Acute GVHD grade II-IV was a risk factor for seronegativity and blood stem cells a risk factor for doubtfully protective immunity. Children and young adults previously immunized to measles have a high risk for becoming vulnerable to a measles infection. Since measles is again circulating in many countries and measles is a serious infection after SCT, vaccination should be considered.

Adolescent↗
PubMed2000

Serological survey of measles and rubella immunity in Sydney preschool children.

OBJECTIVES: To estimate the prevalence of serological evidence of immunity to measles and rubella in preschool children in central and southern Sydney (NSW, Australia) and the prevalence of immunity in children with either documented or parentally reported immunization. METHODS: Geographical cluster random sampling was used to select children aged between 18 and 60 months to participate in the present study. Standardized interviews obtained information on each child's reported (by parents) immunization status and documentary evidence of immunization was recorded from the Personal Health Record. Venous blood was collected, serum was separated and stored frozen until tested. Measles and rubella antibodies were measured using ELISA, with either immunofluorescence or haemagglutination inhibition being used to clarify equivocal results. The study was conducted from 1992 to 1994 in conjunction with surveys of blood lead concentrations, iron status and micronutrient status. RESULTS: Parents of 726 of 953 children identified between 9 and 60 months of age agreed to participate in the lead, immunization, iron status and micronutrient studies. Sufficient blood for antibody testing was obtained from 580 children, aged 18 to 62 months at the time of collection. Parents reported that 94.7% (95% confidence interval (CI) 92.7-96.5%) of children had received a measles-mumps or measles-mumps-rubella (MMR) immunization. General practitioners administered 72.8% of these immunizations. The prevalence of serological evidence of immunity to measles and rubella was 88.8% (95% CI 86.2-91.4%) and 91.9% (95% CI 89.6-94.2%). respectively. There was documented evidence of measles and rubella immunization for 88.4% (95% CI 85.7-91.2%) and 86.4% (95% CI 83.4-89.3%) of children, respectively. Of children with documented measles immunization, 91.6% (95% CI 89.2-94.0%) had detectable measles antibody. Of children with documented rubella immunization 97.2% (95% CI 95.8-98.6%) had detectable rubella antibody. CONCLUSIONS: Measles and rubella immunization rates in central and southern Sydney are relatively high and most of these immunizations are provided by the private sector. Immunity to rubella in children with documented rubella immunization is at the level that would be expected from seroconversion studies. Immunity to measles in children with documented measles immunization is slightly lower than expected from seroconversion studies, highlighting the need for the second MMR immunization in preschool children, as well as making near universal immunization imperative if this disease is to be eradicated.

Antibodies, Viral↗
PubMed2004

Defining and assessing measles elimination goals.

Although 3 of 6 World Health Organization regions have established measles elimination targets, measles elimination goals are not well defined. In general, disease elimination has been defined as the reduction of incidence in a population to zero. However, measles is so contagious that zero incidence is difficult to achieve and sustain because the risk of imported measles remains while measles is endemic in any country. Also, imported cases will occasionally result in short chains of indigenous transmission unless a country achieves 100% immunity. Therefore, the United States currently uses the absence of endemic measles (i.e., no indigenous chains of transmission persisting for >or=1 year) as the programmatic goal for measles elimination. To document the absence of endemic measles in the United States, we compiled information on the epidemiology of measles, genotype distribution, population immunity, and adequacy of measles surveillance. A panel of experts, convened in March 2000 to review the data, concluded that measles is no longer endemic in the United States.

Disease Notification↗
PubMed2005

Case-fatality rate during a measles outbreak in eastern Niger in 2003.

BACKGROUND: The World Health Organization (WHO) estimates that the case-fatality rate (CFR) for measles in West Africa is 4%-6%. In Niger, 50,138 measles cases and 201 deaths (CFR, 0.4%) were reported in 2003. We conducted an investigation to determine the epidemiology and the true CFR of measles in the Mirriah district in Niger. METHODS: Twenty-two villages from the Mirriah district that reported measles cases in 2003 were included in the investigation. A comprehensive household search for measles cases and deaths was conducted, and serum samples from 12 villages were collected for laboratory confirmation. A measles case was defined as illness characterized by fever, rash, and either cough, coryza, or conjunctivitis, with rash onset during the period from 1 January 2003 to 15 April 2003. Deaths occurring within 30 days after rash onset were attributed to measles unless they were obviously due to other causes. RESULTS: Measles was confirmed serologically in all villages from which samples were collected. Of 945 case patients identified, 900 (95.2%) were aged <15 years, 114 (12.3%) were vaccinated, and 789 (83.5%) sought treatment at a health care facility. A total of 92 deaths were attributed to measles (CFR, 9.7%; 95% confidence interval, 7.9%-11.5%). The CFR was highest in infants aged <1 year (15.6%). Households with >or=2 case patients had a higher CFR (10.8%) than that of households with only 1 case patient (6.0%). Households consisting of >or=8 members had a CFR of 12.8%, whereas the CFR of smaller households was 7.1%. CONCLUSIONS: This investigation suggests that the measles CFR in the Mirriah district may be 2-fold higher than the WHO regional estimate and 20-fold higher than the estimate derived from routine surveillance. Reducing measles mortality in Niger will require wide-age-range vaccination campaigns, improvement in routine immunization services, and periodic "follow-up" campaigns.

Adolescent↗
PubMed1999

Seroconversions in unvaccinated infants: further evidence for subclinical measles from vaccine trials in Niakhar, Senegal.

BACKGROUND: Increases in measles antibodies without rash-illnesses have been documented in previously vaccinated children exposed to measles cases. The phenomenon has been incompletely evaluated in young unvaccinated infants with immunity of maternal origin. METHODS: Monthly cohorts of newborns were prospectively randomized to vaccine and placebo control groups during a trial of high-titre vaccines in Niakhar, Senegal. Measles antibodies were assayed in blood samples of enrolled children collected at 5 months old, when controls received a placebo injection, and at 10 months, when the placebo group was given measles vaccine. Intensive prospective surveillance for measles was conducted throughout the trial. RESULTS: One-fifth (n = 53) of the placebo controls seroconverted, with known exposure to a measles case in only three of them. None of the seroconverters developed a measles-like rash. Sixteen-fold or greater increases in titres were noted in about one-quarter of them. Compared with placebo controls who did not seroconvert, seroconverters were more likely to have had exposure to a measles case and to travel, more likely to be boys than girls, and had significantly lower baseline antibody titres. Measles was endemic in the study area throughout the trial. Seroconversions did not adversely effect subsequent nutritional indices or mortality. CONCLUSIONS: Although laboratory errors and inadvertent injection of vaccine rather than placebo may have played some role, they do not fully explain the above observations, which are consistent with subclinical measles in the seroconverters. The possible role of subclinical measles in occult transmission, its potential effect on the type and duration of subsequent immunity, and its impact on response to primary vaccination need to be determined.

Analysis of Variance↗
PubMed1999

Early two-dose measles vaccination schedule in Guinea-Bissau: good protection and coverage in infancy.

BACKGROUND: Previous studies from Africa have suggested that there is little benefit to be gained from early two-dose measles vaccination schedules. Two-dose schedules have been associated with no improvement in coverage due to immunization of the same individuals on both occasions, low return rate, high refusal rate, low vaccine efficacy, and fear of blunting of the antibody response. Because of the poor results achieved previously with two-dose measles vaccination schedules, we studied patterns of participation, reasons for non-participation, vaccination coverage and relative efficacy of a one-dose versus a two-dose schedule in connection with the implementation of an early two-dose trial in Guinea-Bissau. METHODS: Children born from September 1994 to January 1996 were randomized into two groups receiving either two doses of measles vaccine at 6 and 9 months or one dose of inactivated polio vaccine (IPV) at 6 months and measles vaccine at 9 months. RESULTS: At 6 months of age 86% (1869/2181) of the children participated, and at 9 months of age participation was 87% (1775/2035). The return rate for obtaining a second dose of vaccine was 93% (1647/1773). The main reason for not participating was travelling (78%). Around 50% of those who did not take part in one vaccination took part in the other. When only children participating the first time they were called for a measles vaccination were included, the measles vaccination coverage in the one-dose group was 59% versus 80% in the two-dose group, i.e. a 50% reduction in the risk of not being vaccinated (relative risk [RR] 0.50; confidence interval [CI]: 0.43-0.57). Few measles cases have occurred in the study area since the implementation of the trial making precise estimation of the relative efficacy of the two vaccine strategies difficult, but all seven clinically diagnosed measles cases occurred in the one-dose group making the relative efficacy for the two-dose group compared with the one-dose group 100% (95% CI: 35%-100%; two-tailed P = 0.016). When including maternal reports, the relative efficacy was 90% (95% exact confidence interval; two-tailed P = 25%-97%, P = 0.022). CONCLUSION: In this study of a two-dose measles immunization schedule at 6 and 9 months of age there was no sign of low participation or poor return rates. The risk of not being vaccinated was lower in the two-dose group than in the one-dose group, and the relative efficacy of a two-dose versus a one-dose schedule was high. Although our results were obtained within a trial where dedicated personnel informed every participant personally about the study, we believe our results indicate that with thorough information about the population it may be possible to achieve a higher coverage with a two-dose measles vaccination schedule than a one-dose schedule. A two-dose schedule may be a feasible way to resolve the problems of low coverage and severe measles infection among infants.

Confidence Intervals↗