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PubMed1995

Demonstration of virus-specific CD8+ memory T cells in measles-seropositive individuals by in vitro peptide stimulation.

CD8+ cytotoxic T lymphocytes (CTL) in measles virus infection have been difficult to investigate due to the strong immunosuppressive effects exhibited by infectious measles virus in vitro. In order to circumvent immunosuppression we used predicted peptide epitopes to induce measles virus-specific CTL. This was done by screening the structural proteins of measles virus for HLA-A2.1 peptide-binding motifs with valine in position 2 and leucine in position 9. Synthetic peptides np210-218, np226-234, and np340-348 from the nucleoprotein, peptide hp29-37 from the haemagglutinin protein, and peptide pp 519-527 from the polymerase protein were synthesized and used to expand measles virus-specific CD8+ CTL in vitro. Induction of CTL with synthetic peptides was restricted to HLA-A2-positive peripheral blood mononuclear cells (PBMC) from measles-seropositive individuals. We conclude that this method is a useful tool to demonstrate memory CD8+ CTL in measles-seropositive adults and to evaluate the role of structural proteins in CTL responses against measles.

Adult↗
PubMed1975

Replication and persistence of measles virus in defined subpopulations of human leukocytes.

Replication of Edmonston strain measles virus was studied in several human lymphoblast lines, as well as in defined subpopulations of circulating human leukocytes. It was found that measles virus can productively infect T cells, B cells, and monocytes from human blood. These conclusions were derived from infectious center studies on segregated cell populations, as well as from ultrastructural analyses on cells labeled with specific markers. In contrast, mature polymorphonuclear cells failed to synthesize measles virus nucleocapsids even after infection at a relatively high multiplicity of infection. Measles virus replicated more efficiently in lymphocytes stimulated with mitogens than in unstimulated cells. However, both phytohemagglutinin and pokeweed mitogen had a negligible stimulatory effect on viral synthesis in purified populations of monocytes. In all instances the efficiency of measles virus replication by monocytes was appreciably less than that of mitogenically stimulated lymphocytes or of continuously culture lymphoblasts. Under standard conditions of infection, all of the surveyed lymphoblast lines produced equivalent amounts of measles virus regardless of the major histocompatibility (HL-A) haplotype. Hence, no evidence was found that the HL-A3,7 haplotype conferred either an advantage or disadvantage with respect to measles virus synthesis in an immunologically neutral environment. A persistent infection with measles virus could be established in both T and B lymphoblasts. The release of infectious virus from such persistently infected cells was stable over a period of several weeks and was approximately 100-fold less than peak viral titers obtained in each respective line after acute infection.

B-Lymphocytes↗
PubMed1990

Marmoset lymphoblastoid cells as a sensitive host for isolation of measles virus.

B95-8, an Epstein-Barr virus-transformed marmoset B-lymphoblastoid cell line, and its derivative B95a, capable of attachment to a substrate surface, were 10,000-fold more sensitive to measles virus present in clinical specimens than were Vero cells. B95-8 and B95a cells were thus thought to be useful host cells for the isolation of measles virus. Quantitation of measles virus present in clinical specimens showed that a large quantity of virus, exceeding 10(6) 50% tissue culture infective doses per ml of a nasal-swab eluate, is shed into secretions by patients with acute measles, consistent with the contagiousness of the disease. Measles viruses isolated in B95a cells differed in some biological properties from those adapted to Vero cells. First, the viruses isolated in B95a cells did replicate in Vero cells, but release into the fluid phase was less efficient than that of Vero cell-adapted viruses. Second, minor antigenic differences were found between virus strains isolated in B95a cells and those isolated in Vero cells from the same clinical specimens. Third, the viruses isolated and propagated in B95a cells caused clinical signs in experimentally infected monkeys resembling those of human measles. It was suspected that measles virus is subject to host cell-mediated selection and that the viruses grown in B95a cells are more representative of measles virus circulating among humans than are the viruses selected in Vero cells.

Animals↗
PubMed1998

A single amino acid change in the hemagglutinin protein of measles virus determines its ability to bind CD46 and reveals another receptor on marmoset B cells.

This paper provides evidence for a measles virus receptor other than CD46 on transformed marmoset and human B cells. We first showed that most tissues of marmosets are missing the SCR1 domain of CD46, which is essential for the binding of Edmonston measles virus, a laboratory strain that has been propagated in Vero monkey kidney cells. In spite of this deletion, the common marmoset was shown to be susceptible to infections by wild-type isolates of measles virus, although they did not support Edmonston measles virus production. As one would expect from these results, measles virus could not be propagated in owl monkey or marmoset kidney cell lines, but surprisingly, both a wild-type isolate (Montefiore 89) and the Edmonston laboratory strain of measles virus grew efficiently in B95-8 marmoset B cells. In addition, antibodies directed against CD46 had no effect on wild-type infections of marmoset B cells and only partially inhibited the replication of the Edmonston laboratory strain in the same cells. A direct binding assay with insect cells expressing the hemagglutinin (H) proteins of either the Edmonston or Montefiore 89 measles virus strains was used to probe the receptors on these B cells. Insect cells expressing Edmonston H but not the wild-type H bound to rodent cells with CD46 on their surface. On the other hand, both the Montefiore 89 H and Edmonston H proteins adhered to marmoset and human B cells. Most wild-type H proteins have asparagine residues at position 481 and can be converted to a CD46-binding phenotype by replacement of the residue with tyrosine. Similarly, the Edmonston H protein did not bind CD46 when its Tyr481 was converted to asparagine. However, this mutation did not affect the ability of Edmonston H to bind marmoset and human B cells. The preceding results provide evidence, through the use of a direct binding assay, that a second receptor for measles virus is present on primate B cells.

Amino Acid Sequence↗
PubMed2001

A chimeric human-bovine parainfluenza virus type 3 expressing measles virus hemagglutinin is attenuated for replication but is still immunogenic in rhesus monkeys.

The chimeric recombinant virus rHPIV3-N(B), a version of human parainfluenza virus type 3 (HPIV3) that is attenuated due to the presence of the bovine PIV3 nucleocapsid (N) protein open reading frame (ORF) in place of the HPIV3 ORF, was modified to encode the measles virus hemagglutinin (HA) inserted as an additional, supernumerary gene between the HPIV3 P and M genes. This recombinant, designated rHPIV3-N(B)HA, replicated like its attenuated rHPIV3-N(B) parent virus in vitro and in the upper and lower respiratory tracts of rhesus monkeys, indicating that the insertion of the measles virus HA did not further attenuate rHPIV3-N(B) in vitro or in vivo. Monkeys immunized with rHPIV3-N(B)HA developed a vigorous immune response to both measles virus and HPIV3, with serum antibody titers to both measles virus (neutralizing antibody) and HPIV3 (hemagglutination inhibiting antibody) of over 1:500. An attenuated HPIV3 expressing a major protective antigen of measles virus provides a method for immunization against measles by the intranasal route, a route that has been shown with HPIV3 and respiratory syncytial virus vaccines to be relatively refractory to the neutralizing and immunosuppressive effects of maternally derived virus-specific serum antibodies. It should now be possible to induce a protective immune response against measles virus in 6-month-old infants, an age group that in developing areas of the world is not responsive to the current measles virus vaccine.

Animals↗
PubMed2004

Characterization of nucleocapsid binding by the measles virus and mumps virus phosphoproteins.

We report an analysis of the interaction between the P protein and the RNA-associated N protein (N-RNA) for both measles and mumps viruses with proteins produced in a bacterial expression system. During this study, we verified that the C-terminal tail of the N protein is not required for nucleocapsid formation. For both measles and mumps virus N, truncated proteins encompassing amino acids 1 to 375 assemble into nucleocapsid-like particles within the bacterial cell. For measles virus N, the binding site for the P protein maps to residues 477 to 505 within the tail of the molecule, a sequence relatively conserved among the morbilliviruses. For mumps virus N, a binding site for the P protein maps to the assembly domain of N (residues 1 to 398), while no strong binding of the P protein to the tail of N was detected. These results suggest that the site of attachment for the polymerase varies among the paramyxoviruses. Pulldown experiments demonstrate that the last 50 amino acids of both measles virus and mumps virus P (measles virus P, 457 to 507; mumps virus P, 343 to 391) by themselves constitute the nucleocapsid-binding domain (NBD). Spectroscopic studies show that the NBD is predominantly alpha-helical in both viruses. However, only in measles virus P is the NBD stable and folded, having a lesser degree of tertiary organization in mumps virus P. With isothermal titration calorimetry, we demonstrate that the measles virus P NBD binds to residues 477 to 505 of measles virus N with 1:1 stoichiometry. The dissociation constant (K(d)) was determined to be 13 microM at 20 degrees C and 35 microM at 37 degrees C. Our data are consistent with a model in which an alpha-helical nucleocapsid binding domain, located at the C terminus of P, is responsible for tethering the viral polymerase to its template yet also suggest that, in detail, polymerase binding in morbilliviruses and rubulaviruses differs significantly.

Binding Sites↗
PubMed1996

Cell mediated immunity after measles in Guinea-Bissau: historical cohort study.

OBJECTIVE: To investigate whether children who have had measles have reduced general cell mediated immunity three years later compared with vaccinated children who have not had measles. DESIGN: Historical cohort study. SETTING: Bissau, Guinea-Bissau. SUBJECTS: 391 children aged 3-13 years who were living in Bissau during a measles epidemic in 1991 and still lived there. These included 131 primary cases and 139 secondary cases from the epidemic and 121 vaccinated controls with no history of measles. MAIN OUTCOME MEASURES: General cell mediated immunity assessed by measurement of delayed type hypersensitivity skin responses to seven recall antigens. Anergy was defined as a lack of response to all antigens. RESULTS: 82 out of 268 cases of measles (31%) were anergic compared with 20 of the 121 vaccinated controls (17%) (odds ratio adjusted for potential confounding variables 2.2 (95% confidence interval 1.2 to 4.0); P 0.009). The prevalence of anergy was higher in secondary cases (33% (46/138)) than in primary cases (28% (36/130)), although this difference was not significant. Anergy was more common in the rainy season (unadjusted prevalence 31% (91/291) than in the dry season (11% (11/98)) (adjusted odds ratio 4.8 (2.2 to 10.3)). This seasonal increase occurred predominantly in the case of measles. CONCLUSION: Reduced general cell mediated immunity may contribute to the higher long term mortality in children who have had measles compared with recipients of standard measles vaccine and to the higher child mortality in the rainy season in west Africa.

Adolescent↗
PubMed2006

The use of a tropism-modified measles virus in folate receptor-targeted virotherapy of ovarian cancer.

PURPOSE: Attenuated measles viruses are promising experimental anticancer agents currently being evaluated in a phase I dose escalation trial for ovarian cancer patients. Virus attachment, entry, and subsequent intercellular fusion between infected and uninfected neighboring cells are mediated via the two measles receptors (CD46 and SLAM). To minimize potential toxicity due to measles virus-associated immunosuppression and infection of nontarget tissues, we sought to develop an ovarian cancer exclusive fully retargeted measles virus. EXPERIMENTAL DESIGN AND RESULTS: Interactions of measles virus with its natural receptors were ablated, and a single-chain antibody (scFv) specific for alpha-folate receptor (FRalpha), a target overexpressed on 90% of nonmucinous ovarian cancer, was genetically engineered on the viral attachment protein (MV-alphaFR). Specificity of virus tropism was tested on tumor and normal cells. Biodistribution of measles virus infection was evaluated in measles-susceptible CD46 transgenic mice, whereas antitumor activity was monitored noninvasively by bioluminescence imaging in xenograft models. Tropism and fusogenic activity of MV-alphaFR was redirected exclusively to FRalpha without compromise to virus infectivity. In contrast to the parental virus, MV-alphaFR has no background infectivity on normal human cells. The antitumor activity of MV-alphaFR, as assessed by tumor volume reduction and overall survival increase, was equal to the parental virus in two models of human ovarian cancer (s.c. and i.p.). CONCLUSIONS: A FR-exclusive ovarian cancer targeted oncolytic virus was generated and shown to be therapeutically effective, thus introducing a new modality for FR targeting and a candidate measles virus for clinical testing.

Cancer Vaccines↗
PubMed1994

Acute measles infection in the hamster cochlea.

Measles virus has been implicated in sudden sensorineural hearing loss (SNHL) in adults as well as in children. Furthermore, sensorineural hearing loss following live measles virus vaccination has been reported. As of yet, however, there has been only few reports on human temporal bone pathology due to measles, and on experimental animal models of measles infection. This study was undertaken to examine acute measles infection in adult hamster cochlea morphologically and immunohistochemically for precise understanding of this viral infection. Atrophy of the stria vascularis, loss of the organ of Corti, "rolled-up" tectorial membrane, and cell infiltration with a positive immunofluorescent reaction primarily within the scale media indicating endolymphatic labyrinthitis were the principal findings. These results were generally consistent with previous ones on human temporal bone pathology not only due to measles but also to SNHL. We consider measles virus to be one of the possible pathogens, even if low in frequency, causing profound and irreversible hearing loss, including SNHL. Completion of measles vaccination without complication and selective or mass revaccination may be necessary to prevent such hearing loss.

Acute Disease↗
PubMed2003

Epidemiology of measles in the Central Region of Ghana: a five-year case review in three district hospitals.

OBJECTIVE: As part of a national accelerated campaign to eliminate measles, we conducted a study, to define the epidemiology of measles in the Central Region. DESIGN: A descriptive survey was carried out on retrospective cases of measles. SETTING: Patients were drawn from the three district hospitals (Assin, Asikuma and Winneba Hospitals) with the highest number of reported cases in the region. SUBJECTS: Records of outpatient and inpatient measles patients attending the selected health facilities between 1996 and 2000. Data on reported measles cases in all health facilities in the three study, districts were also analysed. MAIN OUTCOME MEASURES: The distribution of measles cases in person (age and sex), time (weekly, or monthly, trends) and place (residence), the relative frequency, of cases, and the outcome of treatment. RESULTS: There was an overall decline in reported cases of measles between 1996 and 2000 both in absolute terms and relative to other diseases. Females constituted 48%-52% of the reported 1508 cases in the hospitals. The median age of patients was 36 months. Eleven percent of cases were aged under nine months; 66% under five years and 96% under 15 years. With some minor variations between districts, the highest and lowest transmission occurred in March and September respectively. Within hospitals, there were sporadic outbreaks with up to 34 weekly cases. CONCLUSION: In Ghana, children aged nine months to 14 years could be appropriately targeted for supplementary, measles immunization campaigns. The best period for the campaigns is during the low transmission months of August to October. Retrospective surveillance can expediently inform decisions about the timing and target age groups for such campaigns.

Adolescent↗
PubMedDate not supplied

Outbreak of measles in the National Capital District, Papua New Guinea in 2001.

Documentation in the past has shown that measles outbreaks occurred in the National Capital District every 3-4 years, with the last outbreak in 1997. In 2001 another outbreak of measles occurred in the National Capital District. A total of 492 cases of measles were recorded during the 6 months (April-September) of a study conducted at the Children's Outpatients Department and the Paediatric Ward of the Port Moresby General Hospital (PMGH). The highest number was recorded in July. 44% of patients were infants less than 12 months of age. 9% of children with measles were under 6 months, the recommended age for vaccination. Only 35% of the children with measles had had their first inoculation and only 11% had received their second inoculation of measles vaccine. During this epidemic, 14.5% of the total attendance of 38,323 children received measles vaccine in the children's outpatients. 72% of children seen with measles at PMGH were admitted to the paediatric ward. Most were admitted because of complications, including severe pneumonia and/or diarrhoea. There were 19 deaths recorded during the 6 months study, a case fatality rate of 4%.

Child↗
PubMed1992

Severe measles in immunocompromised patients.

OBJECTIVE: To describe the severity of measles in immunocompromised hosts and to assess preventive and therapeutic modalities. DATA SOURCES: Patients admitted to two academic medical centers between September 1989 and December 1990 and English language references obtained by MEDLINE from 1963 to 1991. Bibliographies were used to identify reports prior to 1963. STUDY SELECTION: We identified nine immunocompromised patients with measles. Further analysis was based on 35 patients from two cohort studies of measles in oncology patients and 24 reported cases of measles in human immunodeficiency virus (HIV)-infected patients. DATA EXTRACTION: Clinical data are presented from the nine patients we treated. Information concerning measles complications, presence of rash, use of prophylactic immunoglobulin, and therapeutic measures was extracted from the literature. DATA SYNTHESIS: Of our nine patients, eight developed severe complications and two died. Two patients had no rash. In combining our patients with those from the literature, severe complications occurred in about 80%. The case fatality rate for severe measles was about 70% for oncology patients and about 40% for HIV-infected patients. Rash was absent in about 30%. The efficacy of prophylactic or therapeutic measures could not be assessed due to the small number of patients. However, we observed a rapid defervescence following administration of ribavirin. Vaccinated, HIV-infected patients had a lower mortality rate than those not previously vaccinated (P = .06). CONCLUSIONS: Measles is a severe illness in immunocompromised patients, and the absence of rash is frequent. While treatment is supportive, ribavirin requires further study. Measles vaccine may be efficacious in HIV-infected patients. Vaccination of oncology patients should be reassessed.

Adolescent↗
PubMed1992

Revaccination of children during school-based measles outbreaks: potential impact of a new policy recommendation.

OBJECTIVE: To evaluate the potential impact of revaccination on measles outbreak control during school-based epidemics. DESIGN: Retrospective cohort study. SETTING: Thirty-two public elementary and high schools in 14 communities on the west island of Montreal. PARTICIPANTS: All 19,439 children attending these schools during the 1989 measles epidemic in Quebec. INTERVENTION: After notification of a case children with provider-verified records of vaccination on or after their first birthday were identified; the remaining children were vaccinated or excluded from school. OUTCOME MEASURE: Clinical or confirmed measles cases not prevented by this intervention that could have been prevented had revaccination been included during the outbreak. RESULTS: Of the 88 measles cases (74 confirmed) proof of one adequate vaccination was present in 48 (55%). Intervention generally occurred within 5 school days after case notification. The nonpreventable cases involved 75 children who had measles onset before the intervention and 11 (7 vaccinated) who had onset within 8 days after the intervention. The two remaining cases occurred 20 and 25 days after the intervention among nonvaccinated students who refused to be vaccinated. Except for these two cases measles was eliminated at every school. Application of the new Canadian guidelines for measles outbreak control would have required the administration of at least 10,000 additional doses during the outbreak to students vaccinated before 1980; implementation of the new US guidelines would have required the administration of 16,629 additional doses to children previously vaccinated only once. Well-enforced provincial regulations ensuring vaccination of every student upon school entry might have prevented 38 (43%) of the cases. The US recommendation of two routine doses of vaccine before school entry might have prevented 86 (98%) of the cases. However, revaccination during the outbreak would not have prevented a single additional case. CONCLUSION: Revaccination of previously vaccinated students during a measles outbreak would have been costly and of little benefit.

Adolescent↗
PubMed2005

Import-associated measles outbreak--Indiana, May-June 2005.

On May 29, 2005, the Indiana State Department of Health (ISDH) was notified of suspected measles in a female Indiana resident aged 6 years who was hospitalized in Cincinnati, Ohio, where she had been visiting relatives. Serologic analyses performed by the Ohio State Department of Health Laboratory and a private reference laboratory confirmed the diagnosis of measles. The hospital in Cincinnati and the girl's parents told ISDH she had been at a church gathering in northwestern Indiana on May 15 where a fellow attendee had been ill. This fellow attendee was an adolescent girl aged 17 years, an Indiana resident who had not been vaccinated for measles and who had worked during May 4--14 as a missionary in an orphanage and hospital in Bucharest, Romania, where a large measles outbreak was subsequently reported. The teen had returned to the United States with prodromal fever, cough, conjunctivitis, and coryza, traveling on international and domestic commercial airliners on May 14. The next day the teen attended the church gathering along with others who had not been vaccinated because of nonmedical exemptions. Family members recalled that the teen had a rash on May 16; measles was diagnosed retrospectively, and the teen was identified as the index patient. An outbreak investigation was conducted by ISDH and CDC. This report summarizes 1) the results of that investigation, which identified 34 persons with measles, including three who required hospitalization, 2) the measures taken to control and prevent measles transmission, and 3) recommendations to prevent future cases of measles.

Adolescent↗
PubMed2006

Hospitalization rate due to measles in an area of the South East of Italy during an outbreak in the years 2002-2003.

AIM: Usually measles is not severe, but serious complications can occur and thus hospitalization is needed. The aim of this study was to assess the reasons of hospitalizations of the persons affected by measles and the severity of disease as a result of measles infection. METHODS: During an outbreak from 2002 to 2003 in the province of Taranto, 73 hospitalized persons affected by measles were evaluated. RESULTS: The age of the 73 hospitalized patients ranged between 1 and 42 years old (median age 14.5 years). An hospitalizations rate of 63% was reported in the first 4 months of 2003. Measles-related complications were observed in 35.6% of cases. In 14 cases (19%) we observed a pneumonia with a concomitant myocardititis and pancreatitis in 2 cases. Postmeasles encephalitis was diagnosed in 7 cases (9.5%). In 2 cases a concomitant myelitis occurred, with the presence of sequelae at the time of discharge but none permanent. Measles related appendicitis was observed in 5 males (6.8%) and appendectomy was performed in all cases. Data analysis showed that the patients with an age <15 years old had a higher risk of complications than patients with an age > or =15 years. None death was reported. CONCLUSIONS: At present, measles and its related complications continue to be a serious illness even in industrialized countries, only a complete immunization vaccine strategy could permit measles' eradication.

Adolescent↗
PubMedDate not supplied

Bronchopneumonia with measles in infants and children at the Department of Child Health School of Medicine, University of North Sumatera/Dr. Pirngadi Hospital Medan (January 1985-December 1989).

A retrospective study was done on patients with bronchopneumonia hospitalized at the Dr. Pirngadi Hospital, Medan/School of Medicine, University of North Sumatera, during January 1985 through December 1989. The purpose of this study is to assess the morbidity and mortality of bronchopneumonia with measles and the nutritional status of the patients. Out of the 14.082 patients admitted, 1310 children suffered from bronchopneumonia (10.7%). Ninetynine of them were also with measles (7.6%). Most of the patients with bronchopneumonia without measles were in the age group 0-1 year (58.7%). The mortality was 24.8% and the highest mortality rate was in the age group of 4-5 years (34.6%). Most of the patients with bronchopneumonia and measles were in the age group of 1-2 years (30.3%). The mortality rate of bronchopneumonia with measles was 22.2% and the highest mortality rate was in the age group of 3-4 years (35.7%). Bronchopneumonia with or without measles occurred more in malnourished patients rather than in well-nourished cases. All of the patients who had bronchopneumonia with measles in the present study had never been immunized against measles.

Bronchopneumonia↗
PubMed1991

Pediatric emergency room visits: a risk factor for acquiring measles.

In recent years, measles outbreaks have occurred among unimmunized children in inner cities in the United States. From May 1988 through June 1989, 1214 measles cases were reported in Los Angeles, and from October 1988 through June 1989, 1730 cases were reported in Houston. More than half of cases were in children younger than 5 years of age, most of whom were unvaccinated. Of cases of measles in preschool-aged children, nearly one fourth in Los Angeles and more than one third in Houston were reported by one inner-city emergency room. To evaluate whether emergency room visits were a risk factor for acquiring measles, in Los Angeles, 35 measles patients and 109 control patients with illnesses other than measles, and in Houston, 49 measles patients and 128 control patients, who visited these emergency rooms, were enrolled in case-control studies. Control patients were matched to case patients for ethnicity, age, and week of visit. Records were reviewed to determine whether case patients had visited the emergency room during the period of potential measles exposure, which was defined as 10 to 18 days before rash onset, and whether control patients had visited 10 to 18 days before their enrollment visit. In Los Angeles, 23% of case patients and 5% of control patients (odds ratio = 5.2, 95% confidence interval = 1.7, 15.9; P less than .01), and in Houston, 41% of case patients and 6% of control patients (odds ratio = 8.4, 95% confidence interval = 3.3, 21.2; P less than .01), visited the emergency room during these periods.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMedDate not supplied

Vitamin A levels of children with measles in Ankara, Turkey.

Recent studies show that vitamin A levels decrease during measles and that vitamin A therapy can improve measles outcome in children in the developing world. Vitamin A levels of children with measles have not been studied before in Turkey. Therefore we measured serum vitamin A levels in 21 children with measles and compared the results with "sick" and "healthy" control groups. The mean vitamin A levels in children with measles were markedly lower than in the "sick" and "healthy" control groups (p: 0.001). Vitamin A levels in children with measles ranged from 1.3 to 32 micrograms/dl; 11 (52%) were vitamin A deficient (< 10 micrograms/dl). This frequency among Turkish children supports evaluation of vitamin A status as a part of acute management of measles in Turkey. Clinicians may wish to consider vitamin A therapy for children with measles according to WHO recommendations.

Analysis of Variance↗