Persistence of vaccine-induced measles antibody beyond age 12 months: a comparison of response to one and two doses of Edmonston-Zagreb measles vaccine among HIV-infected and uninfected children in Malawi.

BACKGROUND: Previously, we demonstrated that measles antibody prevalence was lower at age 12 months among children infected with human immunodeficiency virus (HIV) than uninfected children following measles vaccination (MV) at ages 6 and 9 months. Among HIV-uninfected children, measles antibody prevalence was lower among 1- than 2-dose MV recipients. Here, we report results through age 24 months. METHODS: Children born to HIV-infected mothers received MV at 6 and 9 months, and children of HIV-uninfected mothers were randomized to MV at 6 and 9 months or MV at 9 months. We followed children through age 24 months. The child's HIV status was determined and measles immunoglobulin G (IgG) level was measured by enzyme immunoassay (EIA) and by plaque reduction neutralization (PRN) on a subset. RESULTS: Among HIV-uninfected children, the difference in measles antibody prevalence at age 12 months between one- and two-dose recipients reported previously by EIA was shown to be smaller by PRN. By age 24 months, 84% and 87% of HIV-uninfected children receiving 1 or 2 doses, respectively, were seroprotected. Only 41% of 22 HIV-infected children were measles seroprotected at age 20 months. DISCUSSION: Measles seroprotection persisted through age 24 months among HIV-uninfected children who received 1 or 2 doses of MV. HIV-infected children demonstrated seroprotection through age 12 months, but this was not sustained.

Transmission of lymphocytic choriomeningitis virus by organ transplantation.

BACKGROUND: In December 2003 and April 2005, signs and symptoms suggestive of infection developed in two groups of recipients of solid-organ transplants. Each cluster was investigated because diagnostic evaluations were unrevealing, and in each a common donor was recognized. METHODS: We examined clinical specimens from the two donors and eight recipients, using viral culture, electron microscopy, serologic testing, molecular analysis, and histopathological examination with immunohistochemical staining to identify a cause. Epidemiologic investigations, including interviews, environmental assessments, and medical-record reviews, were performed to characterize clinical courses and to determine the cause of the illnesses. RESULTS: Laboratory testing revealed lymphocytic choriomeningitis virus (LCMV) in all the recipients, with a single, unique strain of LCMV identified in each cluster. In both investigations, LCMV could not be detected in the organ donor. In the 2005 cluster, the donor had had contact in her home with a pet hamster infected with an LCMV strain identical to that detected in the organ recipients; no source of LCMV infection was found in the 2003 cluster. The transplant recipients had abdominal pain, altered mental status, thrombocytopenia, elevated aminotransferase levels, coagulopathy, graft dysfunction, and either fever or leukocytosis within three weeks after transplantation. Diarrhea, peri-incisional rash, renal failure, and seizures were variably present. Seven of the eight recipients died, 9 to 76 days after transplantation. One recipient, who received ribavirin and reduced levels of immunosuppressive therapy, survived. CONCLUSIONS: We document two clusters of LCMV infection transmitted through organ transplantation.

Confirmation of rubella within 4 days of rash onset: comparison of rubella virus RNA detection in oral fluid with immunoglobulin M detection in serum or oral fluid.

Rubella virus infection is typically diagnosed by the identification of rubella virus-specific immunoglobulin M (IgM) antibodies in serum, but approximately 50% of serum samples from rubella cases collected on the day of rash onset are negative for rubella virus-specific IgM. The ability to detect IgM in sera and oral fluids was compared with the ability to detect rubella virus RNA in oral fluids by reverse transcription-PCR (RT-PCR) by using paired samples taken within the first 4 days after rash onset from suspected rubella cases during an outbreak in Perú. Sera were tested for IgM by both indirect and capture enzyme immunoassays (EIAs), and oral fluids were tested for IgM by a capture EIA. Tests for IgM in serum were more sensitive for the confirmation of rubella than the test for IgM in oral fluid during the 4 days after rash onset. RT-PCR confirmed more suspected cases than serum IgM tests on days 1 and 2 after rash onset. The methods confirmed approximately the same number of cases on days 3 and 4 after rash onset. However, a few cases were detected by serum IgM tests but not by RT-PCR even on the day of rash onset. Nine RT-PCR-positive oral fluid specimens were shown to contain rubella virus sequences of genotype 1C. In summary, RT-PCR testing of oral fluid confirmed more rubella cases than IgM testing of either serum or oral fluid samples collected in the first 2 days after rash onset; the maximum number of confirmations of rubella cases was obtained by combining RT-PCR and serology testing.

Supplemental measles vaccine antibody response among HIV-infected and -uninfected children in Malawi after 1- and 2-dose primary measles vaccination schedules.

BACKGROUND: The long-term antibody response to measles vaccine (MV) administered at age 6 months with or without subsequent doses is not well documented. METHODS: Measles serum antibody responses were evaluated after a supplemental dose of measles vaccine (sMV) administered at a median age of 20 months among Malawian children who had previously received 2 doses of measles vaccine (MV) at ages 6 and 9 months (HIV-infected and random sample of HIV-uninfected) or 1 dose at age 9 months (random sample of HIV-uninfected). We compared measles antibody seropositivity between groups by enzyme linked immunoassay and seroprotection by plaque reduction neutralization geometric mean concentrations. RESULTS: Of 1756 children enrolled, 887 (50.5%) received a sMV dose following MV at 9 months of age and had specimens available after sMV receipt, including 401 HIV-uninfected children who received one MV dose at 9 months, 464 HIV-uninfected and 22 HIV-infected children who received two doses of MV at ages 6 and 9 months. Among HIV-uninfected children, protective levels of antibody were found post sMV in 90-99% through ages 24-36 months and were not affected by MV schedule. Geometric mean concentration levels of measles antibody were significantly increased post-sMV among those HIV-uninfected children previously non-responsive to vaccination. Among HIV-infected children, the proportion seroprotected increased initially but by 9 months post-sMV was no higher than pre-sMV. CONCLUSIONS: Our findings support early 2-dose MV to provide measles immunity for young infants without risk of interference with antibody responses to subsequent MV doses administered as part of SIAs.

Evaluation of the immune response to a 2-dose measles vaccination schedule administered at 6 and 9 months of age to HIV-infected and HIV-uninfected children in Malawi.

BACKGROUND: The World Health Organization recommends that infants at high risk for developing measles before 9 months of age, including human immunodeficiency virus (HIV)-infected infants, receive measles vaccination (MV) at 6 and 9 months of age. METHODS: Children born to HIV-infected mothers received MV at 6 and 9 months, and children of HIV-uninfected mothers were randomized to receive MV at 6 and 9 months, MV at 9 months, or routine MV without follow-up. Blood samples were obtained before and 3 months after each MV. Data were collected on adverse events for 21 days after each MV, at all clinic visits, on any hospitalization, and for subjects who died. HIV-infection status was determined by antibody assays and polymerase chain reaction; the presence of measles IgG was determined by EIA. RESULTS: Twenty-two hundred mother-infant pairs were enrolled. After the first and second doses of measles vaccine, respectively, the percentages of children who were measles seropositive were 59% (36 of 61) and 64% (29 of 45) among HIV-infected children, 68% (152 of 223) and 94% (189 of 202) among HIV-exposed but uninfected children, and 62% (288 of 467) and 92% (385 of 417) among HIV-unexposed children. Of 521 HIV-unexposed children vaccinated only at 9 months, 398 (76%) were measles seropositive at 12 months. No serious vaccine-related adverse events were identified. CONCLUSIONS: An early, 2-dose MV schedule was immunogenic, but a higher proportion of HIV-infected children remained susceptible to measles, compared with HIV-uninfected children (whether HIV exposed or HIV unexposed).

Dried blood spots versus sera for detection of rubella virus-specific immunoglobulin M (IgM) and IgG in samples collected during a rubella outbreak in Peru.

Most persons with rubella virus-specific immunoglobulin M (IgM)- or IgG-positive sera tested positive (98% [n = 178] and 99% [n = 221], respectively) using paired filter paper dried blood spot (DBS) samples, provided that DBS indeterminate results were called positive. For persons with IgM- or IgG-negative sera, 97% and 98%, respectively, were negative using DBS.

Evaluating the impact of the HIV pandemic on measles control and elimination.

OBJECTIVE: To estimate the impact of the HIV pandemic on vaccine-acquired population immunity to measles virus because high levels of population immunity are required to eliminate transmission of measles virus in large geographical areas, and HIV infection can reduce the efficacy of measles vaccination. METHODS: A literature review was conducted to estimate key parameters relating to the potential impact of HIV infection on the epidemiology of measles in sub-Saharan Africa; parameters included the prevalence of HIV, child mortality, perinatal HIV transmission rates and protective immune responses to measles vaccination. These parameter estimates were incorporated into a simple model, applicable to regions that have a high prevalence of HIV, to estimate the potential impact of HIV infection on population immunity against measles. FINDINGS: The model suggests that the HIV pandemic should not introduce an insurmountable barrier to measles control and elimination, in part because higher rates of primary and secondary vaccine failure among HIV-infected children are counteracted by their high mortality rate. The HIV pandemic could result in a 2-3% increase in the proportion of the birth cohort susceptible to measles, and more frequent supplemental immunization activities (SIAs) may be necessary to control or eliminate measles. In the model the optimal interval between SIAs was most influenced by the coverage rate for routine measles vaccination. The absence of a second opportunity for vaccination resulted in the greatest increase in the number of susceptible children. CONCLUSION: These results help explain the initial success of measles elimination efforts in southern Africa, where measles control has been achieved in a setting of high HIV prevalence.

The challenges and strategies for laboratory diagnosis of measles in an international setting.

Serum-based measles-specific IgM EIAs are the recommended laboratory assays for diagnosis of acute measles infections and appear to be sufficient for measles control programs. However, serum samples are not ideal for molecular characterization of measles virus. Although neither laboratory nor field-based diagnostic tests that rival the EIAs have been developed, laboratory surveillance could be improved if specimen collection were simplified. Ideally the collection method should be noninvasive, have no requirement for a cold chain, and/or have no requirement for technically sophisticated equipment. Two alternative specimen collection technologies appear promising and can be used for both diagnostics and for collecting pertinent genotyping information: oral fluid and filter paper collection methods. These methods are compared along with their respective utilities in supporting measles diagnosis and strain surveillance.

Immunogenicity of measles and rubella vaccines in Oman: a prospective clinical trial.

A prospective immunogenicity trial of measles and rubella vaccines was conducted in Oman. Children received measles vaccine at age 9 months and measles-rubella vaccine at age 15 months. Serum specimens were tested for measles-specific IgG and rubella-specific IgG. Of 1025 eligible infants, 881 (86.0%) returned for all five visits and had adequate serum samples for testing. Seroconversion to measles after vaccination at 9 months was 98.1%. At 15 months, 47 (5.3%) of the 881 children were seronegative for measles; of these, 44 (93.6%) seroconverted. At 16 months, 99% of the children seronegative at age 9 months seroconverted after receiving two doses of measles vaccine. At age 15 months, 684 (77.6%) children were seronegative for rubella. Of these, 676 (98.8%) seroconverted by age 16 months. One dose of measles vaccine at age 9 months was highly immunogenic. One dose of measles-rubella vaccine at age 15 months closed the remaining measles immunogenicity gap and resulted in a high rate of rubella seroconversion.

Lack of evidence of measles virus shedding in people with inapparent measles virus infections.

Serological evidence of measles virus infection has been detected among people exposed to measles who do not exhibit classical clinical symptoms. Throat swabs, lymphocytes, and serum and urine samples were collected from contacts of individuals with confirmed measles 12-16 days after exposure, during measles outbreaks occurring in 1998. Follow-up serum samples were drawn 2 weeks later. Samples were tested for measles IgM antibody by enzyme immunoassays and plaque reduction neutralization testing. Virus isolation and reverse transcriptase-polymerase chain reaction testing was attempted for all samples. None of the 133 contacts developed classical measles disease; 11 (8%) had serological evidence of infection. Duration of exposure of >or=3 h was the only significant risk factor for developing serological response (24% vs. 4% among contacts exposed for 1-2 h; relative risk, 6.0; 95% confidence interval, 1.9-19.2). None of the 133 contacts had virological evidence of infection by culture or polymerase chain reaction. We found no evidence that persons with inapparent measles virus infections shed measles virus.