Measles.

Measles is a highly contagious, potentially fatal, but vaccine-preventable disease caused by measles virus. Symptoms include fever, maculopapular rash, and at least one of cough, coryza, or conjunctivitis, although vaccinated individuals can have milder or even no symptoms. Laboratory diagnosis relies largely on the detection of specific IgM antibodies in serum, dried blood spots, or oral fluid, or the detection of viral RNA in throat or nasopharyngeal swabs, urine, or oral fluid. Complications can affect many organs and often include otitis media, laryngotracheobronchitis, pneumonia, stomatitis, and diarrhoea. Neurological complications are uncommon but serious, and can occur during or soon after the acute disease (eg, acute disseminated encephalomyelitis) or months or even years later (eg, measles inclusion body encephalitis and subacute sclerosing panencephalitis). Patient management mainly involves supportive therapy, such as vitamin A supplementation, monitoring for and treatment of secondary bacterial infections with antibiotics, and rehydration in the case of severe diarrhoea. There is no specific antiviral therapy for the treatment of measles, and disease control largely depends on prevention. However, despite the availability of a safe and effective vaccine, measles is still endemic in many countries and causes considerable morbidity and mortality, especially among children in resource-poor settings. The low case numbers reported in 2020, after a worldwide resurgence of measles between 2017 and 2019, have to be interpreted cautiously, owing to the effect of the COVID-19 pandemic on disease surveillance. Disrupted vaccination activities during the pandemic increase the potential for another resurgence of measles in the near future, and effective, timely catch-up vaccination campaigns, strong commitment and leadership, and sufficient resources will be required to mitigate this threat.

The Resurgence of Measles Infection and its Associated Complications in Early Childhood at a Tertiary Care Hospital in Peshawar, Pakistan.

Measles infection is of substantial interest to immunologists due to its paradoxical interaction with the immune system. After the acquisition of the measles infection, secondary infection plays a pivotal role in measles-related deaths. A cross-sectional study conducted between December 2018 and July 2019 is presented here. A total of one hundred children of both genders presented with measles complications were included following WHO criteria. Measles confirmation was done by quantitative determination of anti-measles antibodies (IgM) in patients' sera while patient-related demographic data, vaccination status, and other clinical information were obtained on a separate form. The number of female patients (52%) slightly exceeded the number of males (48%). 43% of patients' parents were illiterate, and half of the patients (50%) were from a poor background. The majority of children (76%) who presented with the complications did not receive a measles vaccine. 56% of children were breastfed while 58% received vitamin A supplements but developed complications. The elevated levels of anti-measles IgM were observed in 77% of cases. In both genders, the major complications were pneumonia, lower respiratory tract infection (LRTI), acute diarrhea, diarrhea and LRTI, pneumonia and diarrhea, otitis media and pneumonia, myocarditis and LRTI, and pneumothorax. The majority of the infected children (n = 48) under 12 months of age had associated complications. It has been observed that the measles virus strikes early age children in the northwestern region of Pakistan, which is an alarming situation and is associated with the aforementioned complications, especially in unvaccinated children. Anti-measles IgM is an important serological parameter for early diagnosis of measles infection.Measles infection is of substantial interest to immunologists due to its paradoxical interaction with the immune system. After the acquisition of the measles infection, secondary infection plays a pivotal role in measles-related deaths. A cross-sectional study conducted between December 2018 and July 2019 is presented here. A total of one hundred children of both genders presented with measles complications were included following WHO criteria. Measles confirmation was done by quantitative determination of anti-measles antibodies (IgM) in patients' sera while patient-related demographic data, vaccination status, and other clinical information were obtained on a separate form. The number of female patients (52%) slightly exceeded the number of males (48%). 43% of patients' parents were illiterate, and half of the patients (50%) were from a poor background. The majority of children (76%) who presented with the complications did not receive a measles vaccine. 56% of children were breastfed while 58% received vitamin A supplements but developed complications. The elevated levels of anti-measles IgM were observed in 77% of cases. In both genders, the major complications were pneumonia, lower respiratory tract infection (LRTI), acute diarrhea, diarrhea and LRTI, pneumonia and diarrhea, otitis media and pneumonia, myocarditis and LRTI, and pneumothorax. The majority of the infected children (n = 48) under 12 months of age had associated complications. It has been observed that the measles virus strikes early age children in the northwestern region of Pakistan, which is an alarming situation and is associated with the aforementioned complications, especially in unvaccinated children. Anti-measles IgM is an important serological parameter for early diagnosis of measles infection.

Preventative Care in the Patient with Inflammatory Bowel Disease: What Is New?

Patients with inflammatory bowel disease (IBD) do not receive routine preventative care at the same rate as general medical patients. This patient population is at increased risk of vaccine preventable illness such as influenza and pneumococcal pneumonia. This review will discuss health maintenance needs and preventative care issues in patients with IBD.

The effects of vitamin A supplementation with measles vaccine on leucocyte counts and in vitro cytokine production.

As WHO recommends vitamin A supplementation (VAS) at vaccination contacts after age 6 months, many children receive VAS together with measles vaccine (MV). We aimed to investigate the immunological effect of VAS given with MV. Within a randomised placebo-controlled trial investigating the effect on overall mortality of providing VAS with vaccines in Guinea-Bissau, we conducted an immunological sub-study of VAS v. placebo with MV, analysing leucocyte counts, whole blood in vitro cytokine production, vitamin A status and concentration of C-reactive protein (CRP). VAS compared with placebo was associated with an increased frequency of CRP ≥ 5 mg/l (28 v. 12%; P=0·005). Six weeks after supplementation, VAS had significant sex-differential effects on leucocyte, lymphocyte, monocyte and basophil cell counts, decreasing them in males but increasing them in females. Mainly in females, the effect of VAS on cytokine responses differed by previous VAS: in previous VAS recipients, VAS increased the pro-inflammatory and T helper cell type 1 (Th1) cytokine responses, whereas VAS decreased these responses in previously unsupplemented children. In previous VAS recipients, VAS was associated with increased IFN-γ responses to phytohaemagglutinin in females (geometric mean ratio (GMR): 3·97; 95% CI 1·44, 10·90) but not in males (GMR 0·44; 95% CI 0·14, 1·42); the opposite was observed in previously unsupplemented children. Our results corroborate that VAS provided with MV has immunological effects, which may depend on sex and previous VAS. VAS may increase the number of leucocytes, but also repress both the innate and lymphocyte-derived cytokine responses in females, whereas this repression may be opposite if the females have previously received VAS.

Diarrhoea in slum children: observation from a large diarrhoeal disease hospital in Dhaka, Bangladesh.

OBJECTIVES: To determine and compare socio-demographic, nutritional and clinical characteristics of children under five with diarrhoea living in slums with those of children who do not live in slums of Dhaka, Bangladesh. METHODS: From 1993 to 2012, a total of 28 948 under fives children with diarrhoea attended the Dhaka Hospital of icddr,b. Data were extracted from the hospital-based Diarrhoea Disease Surveillance System, which comprised 17 548 under fives children from slum and non-slum areas of the city. RESULTS: Maternal illiteracy [aOR = 1.57; 95% confidence interval (1.36, 1.81), P-value <0.001], paternal illiteracy [1.37 (1.21, 1.56) <0.001], mother's employment [1.59 (1.37, 1.85) <0.001], consumption of untreated water [2.73 (2.26, 3.30) <0.001], use of non-sanitary toilets [3.48 (3.09, 3.93) <0.001], 1st wealth quintile background [3.32 (2.88, 3.84) <0.001], presence of fever [1.14 (1.00, 1.29) 0.047], some or severe dehydration [1.21 (1.06, 1.40) 0.007], stunting [1.14 (1.01, 1.29) 0.030] and infection with Vibrio cholerae [1.21 (1.01, 1.45) 0.039] were significantly associated with slum-dwelling children after controlling for co-variates. Measles immunisation [0.52 (0.47, 0.59) P < 0.001] and vitamin A supplementation rates [0.36 (0.31, 0.41) P < 0.001] amongst children 12-59 months were lower for slum dwellers than other children in univarate analysis only. CONCLUSIONS: Slum-dwelling children are more malnourished, have lower immunisation rates (measles vaccination and vitamin A supplementation) and higher rates of measles, are more susceptible to diarrhoeal illness due to V. cholerae and suffer from severe dehydration more often than children from non-slum areas. Improved health and nutrition strategies should give priority to children living in urban slums.

A randomized trial of an early measles vaccine at 4½ months of age in Guinea-Bissau: sex-differential immunological effects.

BACKGROUND: After measles vaccine (MV), all-cause mortality is reduced more than can be explained by the prevention of measles, especially in females. OBJECTIVE: We aimed to study the biological mechanisms underlying the observed non-specific and sex-differential effects of MV on mortality. METHODS: Within a large randomised trial of MV at 4.5 months of age blood samples were obtained before and six weeks after randomisation to early MV or no early MV. We measured concentrations of cytokines and soluble receptors from plasma (interleukin-1 receptor agonist (IL-1Ra), IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, monocyte chemoattractant protein (MCP)-1, soluble urokinase-type plasminogen activator receptor), and secreted cytokines (interferon-γ, TNF-α, IL-5, IL-10, IL-13, IL-17) after in vitro challenge with innate agonists and recall antigens. We analysed the effect of MV in multiple imputation regression, overall and stratified by sex. The majority of the infants had previously been enrolled in a randomised trial of neonatal vitamin A. Post hoc we explored the potential effect modification by neonatal vitamin A. RESULTS: Overall, MV versus no MV was associated with higher plasma MCP-1 levels, but the effect was only significant among females. Additionally, MV was associated with increased plasma IL-1Ra. MV had significantly positive effects on plasma IL-1Ra and IL-8 levels in females, but not in males. These effects were strongest in vitamin A supplemented infants. Vitamin A shifted the effect of MV in a pro-inflammatory direction. CONCLUSIONS: In this explorative study we found indications of sex-differential effects of MV on several of the plasma biomarkers investigated; in particular MV increased levels in females, most strongly in vitamin A recipients. The findings support that sex and micronutrient supplementation should be taken into account when analysing vaccine effects. TRIAL REGISTRATION: clinicaltrials.gov number NCT 00168545.

[Enhancement of measles-mumps divaccine using myelopeptide 2 in experiment].

Combined application of mumps and measles vaccine strains in equal doses results in significant decrease of immune response to the former component in humans. It is possible that this phenomenon is related with well-known immunodepressive effect of measles virus, which was demonstrated both in vivo and in vitro. It was previously shown that myelopeptide-2 (MP-2) partially neutralizes suppressive effect of measles vaccine on blast transformation of activated human lymphocytes in vitro. Partial supression of immune response to mumps vaccine by live measles vaccine was reproduced in laboratory animals. It was shown that in experiment MP-2 partially neutralized suppressive effect of measles vaccine.

Aerosol measles vaccination in macaques: preclinical studies of immune responses and safety.

The comparative efficacy and safety of measles vaccination via the aerosol route versus subcutaneous injection has not been fully resolved. We vaccinated cynomolgus monkeys (Macaca fascicularis) with the live-attenuated Edmonston-Zagreb measles virus (MV) vaccine and compared different routes of administration in the immunocompetent and the immunocompromised host. Immunogenicity and protective efficacy of aerosol vaccination using devices similar to those previously used in humans were comparable to those in animals vaccinated by injection. No evidence for a safety hazard associated with the route of vaccination was detected. The results of this study support further clinical evaluation of aerosol vaccination for measles.

Characterization of immune responses induced by intramuscular vaccination with DNA vaccines encoding measles virus hemagglutinin and/or fusion proteins.

Measles virus (MV) hemagglutinin (MV-H) and fusion (MV-F) proteins induce plaque reduction neutralizing (PRN) antibodies and cell-mediated immune responses that protect against clinical measles. DNA vaccines that encode MV-H and MV-F are being investigated as a new generation of measles vaccine to protect infants too young to receive currently licensed attenuated measles vaccines. However, it is unclear whether DNA vaccines encoding both MV-H and MV-F act synergistically to induce stronger immunity than immunization with plasmids encoding MV-H or MV-F alone. To address this question, we generated Sindbis virus-based pSINCP DNA vaccines that encode either MV-H or MV-F alone or bicistronic or fusion system vectors that encode both MV-H and MV-F (to mimic MV infection where both MV-H and MV-F proteins are expressed by the same mammalian cell). Mice immunized with DNA vaccine encoding MV-H alone developed significantly greater PRN titers than mice immunized with bicistronic constructs. Interestingly, the presence of MV-F in the bicistronic constructs stimulated serum MV-specific immunoglobulin G of reduced avidity. By contrast, mice immunized with bicistronic constructs induced equivalent or higher levels of MV-specific gamma interferon responses than mice immunized with DNA vaccine encoding MV-H alone. These data will help guide the design of DNA-based MV vaccines to be used early in life in a heterologous prime-boost strategy.

[Effect of myelopeptide 2 on the immunization of guinea pigs with live measles vaccine]. / Vliianie mielopeptida 2 na rezul'taty immunizatsii morskikh svinok zhivoi korevoi vaktsinoi.

A model is suggested to study the effects the myelopeptide 2 (MP2) immunomodulator on the results of live measles rash immunized by vaccine. Guinea pigs were found to respond to live measles vaccine L-16 the way man does, i.e. the antibodies' level in their sera was increasing until days 28-56 after a single intramuscular vaccine injection. An intramuscular injection of the MP2 immunomodular, made alongside with vaccination, was demonstrated to enhance the immune response to the measles vaccine and to induce its action. Finally, it was for the first time, that the possibility was proven to enhance the action of the live measles vaccine by an immunomodulator.

Neutralising immunogenicity of a polyepitope antigen expressed in a transgenic food plant: a novel antigen to protect against measles.

Transgenic carrot plants were developed expressing a designer polyepitope combining tandem repeats of a protective loop-forming B cell epitope (H386-400) of the measles virus hemagglutinin protein with a human promiscuous, measles-unrelated T cell epitope (tt830-844). Despite the sensitivity of the loop conformation to its molecular environment, proper folding was confirmed by conformation-dependent monoclonal antibodies. The antibodies also reacted with the boiled antigen in Western blot. Immunisation of mice peritoneally with carrot plant extracts induced high titers of antibodies that crossreacted strongly with the virus. Furthermore, the sera neutralised field isolates of different geographic origins and genotypes in a modified plaque reduction neutralisation assay performed on CD150-transfected Vero cells. These results demonstrate that transgenic carrot plants can serve as an efficient expression system to produce highly immunogenic, randomly assembled polyepitope antigens. The combined features of the selected epitopes and the potential of the plant expression system may pave the way towards new vaccines against measles.

Evaluation of the national immunisation programme in the Netherlands: immunity to diphtheria, tetanus, poliomyelitis, measles, mumps, rubella and Haemophilus influenzae type b.

The immunity to vaccine-preventable diseases included in the Dutch immunisation programme in the general population and among orthodox reformed individuals who refuse vaccination was assessed. The programme induces good protection. However, a large proportion of adults lacks diphtheria and tetanus immunity. Measles, mumps and rubella seroprevalence was somewhat lower among vaccinated compared to unvaccinated cohorts. The prevalence of HibPS antibodies declined during 2.5 years after the fourth vaccination. However, protection occurs also by memory immunity. Herd immunity is sufficient among the general population, but not among orthodox reformed individuals. Immunosurveillance is an efficient way to evaluate the effects of immunisation programmes and identify risk groups for infection.

Effect of vitamin A supplementation on measles-specific antibody levels in Guinea-Bissau.

We have previously reported that vitamin A supplementation with measles vaccine at age 9 months increases measles-specific antibody concentrations in children at age 18 months compared with placebo. We examined these children when they reached age 6-8 years. Fewer vitamin A-supplemented children had non-protective antibody concentrations (p=0.0095); among children with protective antibody levels, vitamin A-supplemented children tended to have higher geometric mean antibody titres (p=0.09). Thus, simultaneous administration of vitamin A and measles vaccine at age 9 months had a long-term effect on measles-specific antibody levels and may contribute to improved measles control in less-developed countries.

Complement and IL-12: yin and yang.

Interleukin 12 (IL-12) is central to the orchestration of cell-mediated immune responses in the innate as well as the adaptive immune system. Recent studies of the pathogenesis of diseases as disparate as measles and asthma have suggested that the complement system, itself at the interface of innate and adaptive immunity, is a biologically relevant regulator of IL-12 production. These data are reviewed here.

Measles HI-antibody levels in Lagos children, Nigeria: a follow-up study to resurgence of measles in Lagos metropolis.

A total of 138 children aged between 0-36 months were bled and screened for measles haemagglutination inhibiting (HI)-antibody. Twenty seven children were from age group (0-4) months with 16 (59.3%) seropositive while, 67 and 44 were bled in the group (5-9) and > or = 12 months with 29 (43.3%) and 31 (70.5%) sero positive sera respectively. The distribution of the antibody titre pattern among various age groups suggest vaccination against measles should be at age 9 month. The antibody titres pattern of seroconverted vaccinees also showed that the vaccine administered at our study centre were potent enough to elicit good and protective immune response in vaccinees when given at age 9 month. Our study agrees with the current policy of vaccinating children against measles at age 9 months in Nigeria and should therefore be continued. Based on observations in this study, we suggest; continued administration of the Edmonston-Zagreb strain of measle vaccine currently-in-use in Nigeria, mother's breast-feeding of children for a longer period before the apporpriate age for vaccination, and the possible administration of Vitamin A-a potent immune enhancer, as a supplement during immunization programmes in Nigeria. The introduction of a booster dose of measles vaccine at elementary school age in order to care for the residual unvaccinated children may be a good strategy for measles eradication necessary to be considered in Nigeria and might probably forestall instances of measles outbreaks in children during their second year in school.

Vitamin A and immunity to viral, bacterial and protozoan infections.

Studies in animal models and cell lines show that vitamin A and related retinoids play a major role in immunity, including expression of mucins and keratins, lymphopoiesis, apoptosis, cytokine expression, production of antibody, and the function of neutrophils, natural killer cells, monocytes or macrophages, T lymphocytes and B lymphocytes. Recent clinical trials suggest that vitamin A supplementation reduces morbidity and mortality in different infectious diseases, such as measles, diarrhoeal disease, measles-related pneumonia, human immunodeficiency virus infection and malaria. Immune responses vary considerably during different infections, and the available data suggest that the modulation of immune function by vitamin A may also vary widely, depending on the type of infection and immune responses involved.

Vitamin A administered with measles vaccine to nine-month-old infants does not reduce vaccine immunogenicity.

After a report of reduced seroconversion to measles in infants, aged 6 mo, given vitamin A with their measles vaccination, serious concerns were raised regarding the safety of the WHO's recommendation that infants be supplemented with vitamin A at the time of measles immunization. To determine the impact of coadministered vitamin A on the antibody response to measles vaccine given to infants aged 9 mo, the more common age for immunization in developing countries, we conducted a randomized, double-blind, placebo-controlled trial in an urban slum community in Delhi. Infants (618) were randomly allocated to receive 30 mg vitamin A or a placebo with the measles immunization. Antibodies to measles were measured by ELISA in serum samples obtained at before (baseline) and 12 wk after immunization. Overall, the seroconversion rates did not differ between vitamin A (89.5%) and placebo (87.6%) groups. There were no significant differences in the geometric mean titers in the two groups (ratio of geometric means, 1.19; 95% confidence interval, 0.97-1.46). Among malnourished infants, the geometric mean titer was significantly greater in the vitamin A group compared to the placebo group (ratio of geometric means, 1.57; 95% confidence interval, 1. 18-2.0), but seroconversion rates did not differ. There were no differences in seroconversion rates and geometric mean titers in the two study groups among the well-nourished children. These results indicate that 30 mg vitamin A does not reduce the immune response to the coadministered vaccine and, therefore, can be continued to be given safely in public health programs.

Effect of vitamin A supplementation on measles vaccination in nine-month-old infants.

OBJECTIVE: Childhood immunization programs have been suggested as an infrastructure to deliver vitamin A supplements to children in developing countries. The effects of giving vitamin A, a potent immune enhancer, with measles immunization to nine-month-old infants is unknown. METHODS: A randomized, double-masked, placebo-controlled clinical trial of vitamin A, 100,000 IU at the time of standard titer Schwarz measles immunization was conducted with nine-month-old infants in Bogor District, West Java, Indonesia. Antibody titers to measles were measured at baseline and one and six months following immunization. RESULTS: 394 infants received measles immunization, and 37 infants (9.4%) had baseline antibody titers > 1:120, which is consistent with previous natural measles infection. Of the remaining infants, 98.8% seroconverted to measles, and 99.3% had titers consistent with protection against measles six months postimmunization. Seroconversion rates were similar in vitamin A and placebo treatment groups. CONCLUSION: High dose vitamin A supplementation can be given without reducing seroconversion to standard titer Schwatz measles immunization in nine-month-old infants.

PIP: The feasibility of combining vitamin A supplementation and measles immunization was investigated in a double-masked, placebo-controlled clinical trial involving 394 9-months-old infants in Bogor district, West Java, Indonesia. Vitamin A, a potent immune enhancer, has been shown to reduce child mortality by 20-50% in developing countries and is among the most cost-effective child survival interventions. 130 infants received a placebo; 132 were given 25,000 IU of vitamin A at 6, 10, and 14 weeks and 100,000 IU at 9 months; and the final 132 were given 50,000 IU of vitamin A at 6, 10, and 14 weeks and 100,000 IU at 9 months. 37 (9.4%) of the study infants had pre-immunization measles titers greater than 1:120 at 9 months of age, indicative of a previous history of natural measles infection. 98.8% of the remaining infants had seroconverted to measles 1 month after immunization, regardless of whether they received vitamin A or placebo; after 6 months, 99.3% had titers consistent with protection against measles. Geometric mean titers were 1:1772 and 1:2298 at 1 month post-immunization and 1:1164 and 1:1900 at 6 months post-immunization in infants receiving vitamin A and placebo, respectively. Since vitamin A supplementation does not interfere with seroconversion to standard titer Schwarz measles immunization, its inclusion in Expanded Program on Immunization campaigns is recommended.

Reduced seroconversion to measles in infants given vitamin A with measles vaccination.

Administration of 100,000 IU vitamin A at the time of measles immunisation is currently recommended for infants in developing countries. However, the safety and value of giving vitamin A, a potent immune enhancer, with live measles virus vaccines are unknown. We conducted a randomised, double-blind, placebo-controlled clinical trial in Indonesia to evaluate the effect of simultaneous vitamin A supplementation on the immune response to measles immunisation at six months of age. 336 infants received either vitamin A (100,000 IU) or placebo when immunised with standard-titre Schwarz measles vaccine. 82% of infants seroconverted to measles. In a multiple logistic regression model adjusting for maternal antibody titres, vitamin A supplementation was associated with a lower likelihood of seroconversion to measles (odds ratio 0.40, 95% CI 0.19-0.88), and girls were less likely to seroconvert than boys (0.34, 0.15-0.76). Immunisation with standard-titre Schwarz vaccine at six months of age in this study population is characterised by high seroconversion rates. However, simultaneous high-dose vitamin A may interfere with seroconversion to live measles vaccine in infants with maternal antibody.

PIP: In 19 villages in the Bogor District of West Java, Indonesia, between December 1992 and March 1993, pediatricians immunized 336 infants 6 months old with 0.5 ml of the standard-titer Schwarz measles vaccine and administered either 100,000 IU vitamin A (169 infants) or a placebo (167 infants) at the same time. The researchers wanted to determine the effect of vitamin A administration on antibody responses to the measles vaccination. 82% of 306 infants seroconverted to measles. About 33% of the 336 infants had no detectable maternal antibodies to measles, indicating that they were very vulnerable to measles infection. The multiple logistic regression model controlling for maternal antibody titers found that vitamin A administration reduced the likelihood of seroconversion to measles (odds ratio [OR] = 0.4). Females were less likely to seroconvert than males (OR = 0.34). At 1 and 6 months after immunization, infants who were administered vitamin A had a 25% lower geometric mean than those who were administered the placebo (p = 0.05 and 0.09, respectively). They were also less likely than the placebo group to develop a generalized rash (8.7% vs. 15.9%; p 0.05), suggesting that vitamin A may limit replication of vaccine-strain measles vaccine. These results suggest that simultaneous high- dose vitamin A may thwart seroconversion to live measles vaccine in infants with maternal antibodies. More research is needed.