PMID: 

Vaccine. 2018 02 1 ;36(6):818-826. Epub 2018 Jan 6. PMID: 29317117

Abstract Title: 

Measles, mumps, and rubella antibody patterns of persistence and rate of decline following the second dose of the MMR vaccine.

Abstract: 

BACKGROUND: Antibodies to measles, mumps, and rubella decline 3% per year on average, and have a high degree of individual variation. Yet, individual variations and differences across antigens are not well understood. To better understand potential implications on individual and population susceptibility, we reanalyzed longitudinal data to identify patterns of seropositivity and persistence.METHODS: Children vaccinated with the second dose of measles, mumps, rubella vaccine (MMR2) at 4-6 years of age were followed up to 12 years post-vaccination. The rates of antibody decline were assessed using regression models, accounting for differences between and within subjects.RESULTS: Most of the 302 participants were seropositive throughout follow-up (96% measles, 88% mumps, 79% rubella). The rate of antibody decline was associated with MMR2 response and baseline titer for measles and age at first dose of MMR (MMR1) for rubella. No demographic or clinical factors were associated with mumps rate of decline. One month post-MMR2, geometric mean titer (GMT) to measles was high (3892 mIU/mL), but declined on average 9.7% per year among those with the same baseline titer and15 months, respectively. GMT to mumps one month post-MMR2 was 151, declining 9.2% per year. Only 14% of subjects had the same persistence trends for all antigens.CONCLUSIONS: The rate of antibody decay varied substantially among individuals and the 3 antigen groups. A fast rate of decline coupled with high variation was observed for mumps, yet no predictors were identified. Future research should focus on better understanding waning titers to mumps and its impacts on community protection and individual susceptibility, in light of recent outbreaks in vaccinated populations.

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PMID: 

Pediatrics. 1987 Jun ;79(6):858-63. PMID: 3588140

Abstract Title: 

National patterns of aspirin use and Reye syndrome reporting, United States, 1980 to 1985.

Abstract: 

The number of cases of Reye syndrome reported annually to the Centers for Disease Control declined markedly between 1980 and 1985. In this article, we present pharmaceutical marketing research data that suggest sharp decreases in the use and purchase of children's aspirin between 1980 and 1985. These trends appear to correspond to the decrease in reporting of Reye syndrome cases. Additionally, analysis of physician mentions of aspiring and acetaminophen for treating flu and chickenpox showed statistically significant trends toward decreasing recommendations for the use of aspirin and significant trends toward increasing recommendations for use of acetaminophen. Trends in wholesale purchases of aspirin and acetaminophen by drug stores from 1979 through 1985 demonstrated a significant decline for the 81-mg children's aspirin tablet and an increase in purchases of children's acetaminophen products. Many factors may influence physician and parents' choice of analgesic/antipyretic medication, including information about Reye syndrome. Data suggest that a continuing decline in the use of aspirin for children may be accompanied by a continuing decline in the reported number of Reye syndrome cases.

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PMID: 

Inflammopharmacology. 2018 Aug ;26(4):951-961. Epub 2018 Jan 11. PMID: 29327281

Abstract Title: 

Effect of early natal supplementation of paracetamol on attenuation of exotoxin/endotoxin induced pyrexia and precipitation of autistic like features in albino rats.

Abstract: 

The present study was aimed to test the hypothesis that paracetamol (PCM) can precipitate autistic like features when used to counteract vaccine-induced fever using experimental rat pups. The pups were treated with measles mumps rubella (MMR) vaccine, diphtheria tetanus and pertussis (DPT) vaccines and lipopolysaccharide (LPS) with subsequent PCM treatment. The pups were evaluated for postnatal growth (weight gain, eye opening) and behavior alterations (swimming performance, olfactory discrimination, negative geotaxis, nociception, and locomotor activity) by performing battery of neurobehavioral test. Significant correlation was observed between social behavioral domains (nociception, anxiety and motor coordination) and pro-inflammatory load in the pups when treated with MMR/LPS along with PCM. A significant change in pro and anti-inflammatory (IL-4, IL-6, IL-10) markers were observed in rats treated with PCM, MMR, LPS, DPS alone or in combination with MMR, LPS and DPT (5128.6 ± 0.000, 15,488 ± 0.000, 9661.1 ± 157.29, 15,312 ± 249.29, 10,471 ± 0.00, 16,789 ± 273.34and 12,882 ± 0.00). Pups were also scrutinized for the markers of oxidative stress, inflammation and histopathologically. All the treatment groups showed significant alteration in the behavioral changes, oxidative markers (TBARS-in control-4.33 ± 0.02, PCM-9.42 ± 0.18, MMR-5.27 ± 0.15, MMR + PCM-8.57 ± 0.18, LPS-6.84 ± 0.10, LPS + PCM-4.51 ± 0.30, DPT-5.68 ± 0.12, DPT + PCM-7.26 ± 0.18) and inflammatory markers without following any specific treatment. These observation could be accorded to variable phenotypes of autistic spectrum disorders (ASDs).

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PMID: 

BMJ. 2005 Nov 19 ;331(7526):1177. Epub 2005 Nov 10. PMID: 16282378

Abstract Title: 

Cost effectiveness analysis of strategies for child health in developing countries.

Abstract: 

OBJECTIVE: To determine the costs and effectiveness of selected child health interventions-namely, case management of pneumonia, oral rehydration therapy, supplementation or fortification of staple foods with vitamin A or zinc, provision of supplementary food with counselling on nutrition, and immunisation against measles.DESIGN: Cost effectiveness analysis.DATA SOURCES: Efficacy data came from published systematic reviews and before and after evaluations of programmes. For resource inputs, quantities came from literature and expert opinion, and prices from the World Health Organization Choosing Interventions that are Cost Effective (WHO-CHOICE) database,RESULTS: Cost effectiveness ratios clustered in three groups, with fortification with zinc or vitamin A as the most cost effective intervention, and provision of supplementary food and counselling on nutrition as the least cost effective. Between these were oral rehydration therapy, case management of pneumonia, vitamin A or zinc supplementation, and measles immunisation.CONCLUSIONS: On the grounds of cost effectiveness, micronutrients and measles immunisation should be provided routinely to all children, in addition to oral rehydration therapy and case management of pneumonia for those who are sick. The challenge of malnutrition is not well addressed by existing interventions.

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PMID: 

JAMA. 1999 Jan 6 ;281(1):61-6. PMID: 9892452

Abstract Title: 

Trends in infectious disease mortality in the United States during the 20th century.

Abstract: 

CONTEXT: Recent increases in infectious disease mortality and concern about emerging infections warrant an examination of longer-term trends.OBJECTIVE: To describe trends in infectious disease mortality in the United States during the 20th century.DESIGN AND SETTING: Descriptive study of infectious disease mortality in the United States. Deaths due to infectious diseases from 1900 to 1996 were tallied by using mortality tables. Trends in age-specific infectious disease mortality were examined by using age-specific death rates for 9 common infectious causes of death.SUBJECTS: Persons who died in the United States between 1900 and 1996.MAIN OUTCOME MEASURES: Crude and age-adjusted mortality rates.RESULTS: Infectious disease mortality declined during the first 8 decades of the 20th century from 797 deaths per 100000 in 1900 to 36 deaths per 100000 in 1980. From 1981 to 1995, the mortality rate increased to a peak of 63 deaths per 100000 in 1995 and declined to 59 deaths per 100000 in 1996. The decline was interrupted by a sharp spike in mortality caused by the 1918 influenza epidemic. From 1938 to 1952, the decline was particularly rapid, with mortality decreasing 8.2% per year. Pneumonia and influenza were responsible for the largest number of infectious disease deaths throughout the century. Tuberculosis caused almost as many deaths as pneumonia and influenza early in the century, but tuberculosis mortality dropped off sharply after 1945. Infectious disease mortality increased in the 1980s and early 1990s in persons aged 25 years and older and was mainly due to the emergence of the acquired immunodeficiency syndrome (AIDS) in 25- to 64-year-olds and, to a lesser degree, to increases in pneumonia and influenza deaths among persons aged 65 years and older. There was considerable year-to-year variability in infectious disease mortality, especially for the youngest and oldest age groups.CONCLUSIONS: Although most of the 20th century has been marked by declining infectious disease mortality, substantial year-to-year variation as well as recent increases emphasize the dynamic nature of infectious diseases and the need for preparedness to address them.

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PMID: 

Lancet. 1998 02 28 ;351(9103):637-41. PMID: 9500320

Abstract Title: 

Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children.

Abstract: 

BACKGROUND: We investigated a consecutive series of children with chronic enterocolitis and regressive developmental disorder.METHODS: 12 children (mean age 6 years [range 3-10], 11 boys) were referred to a paediatric gastroenterology unit with a history of normal development followed by loss of acquired skills, including language, together with diarrhoea and abdominal pain. Children underwent gastroenterological, neurological, and developmental assessment and review of developmental records. Ileocolonoscopy and biopsy sampling, magnetic-resonance imaging (MRI), electroencephalography (EEG), and lumbar puncture were done under sedation. Barium follow-through radiography was done where possible. Biochemical, haematological, and immunological profiles were examined.FINDINGS: Onset of behavioural symptoms was associated, by the parents, with measles, mumps, and rubella vaccination in eight of the 12 children, with measles infection in one child, and otitis media in another. All 12 children had intestinal abnormalities, ranging from lymphoid nodular hyperplasia to aphthoid ulceration. Histology showed patchy chronic inflammation in the colon in 11 children and reactive ileal lymphoid hyperplasia in seven, but no granulomas. Behavioural disorders included autism (nine), disintegrative psychosis (one), and possible postviral or vaccinal encephalitis (two). There were no focal neurological abnormalities and MRI and EEG tests were normal. Abnormal laboratory results were significantly raised urinary methylmalonic acid compared with age-matched controls (p=0.003), low haemoglobin in four children, and a low serum IgA in four children.INTERPRETATION: We identified associated gastrointestinal disease and developmental regression in a group of previously normal children, which was generally associated in time with possible environmental triggers.

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PMID: 

J Child Neurol. 1999 Jun ;14(6):388-94. PMID: 10385847

Abstract Title: 

Familial clustering of autoimmune disorders and evaluation of medical risk factors in autism.

Abstract: 

Autism is an age-dependent neurologic disorder that is often associated with autoimmune disorders in the patients' relatives. To evaluate the frequency of autoimmune disorders, as well as various prenatal and postnatal events in autism, we surveyed the families of 61 autistic patients and 46 healthy controls using questionnaires. The mean number of autoimmune disorders was greater in families with autism; 46% had two or more members with autoimmune disorders. As the number of family members with autoimmune disorders increased from one to three, the risk of autism was greater, with an odds ratio that increased from 1.9 to 5.5, respectively. In mothers and first-degree relatives of autistic children, there were more autoimmune disorders (16% and 21%) as compared to controls (2% and 4%), with odds ratios of 8.8 and 6.0, respectively. The most common autoimmune disorders in both groups were type 1 diabetes, adult rheumatoid arthritis, hypothyroidism, and systemic lupus erythematosus. Forty-six percent of the autism group reported having relatives with rheumatoid diseases, as compared to 26% of the controls. Prenatal maternal urinary tract, upper respiratory, and vaginal infections; asphyxia; prematurity, and seizures were more common in the autistic group, although the differences were not significant. Thirty-nine percent of the controls, but only 11% of the autistic, group, reported allergies. An increased number of autoimmune disorders suggests that in some families with autism, immune dysfunction could interact with various environmental factors to play a role in autism pathogenesis.

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PMID: 

Epidemiology. 2010 Nov ;21(6):805-8. PMID: 20798635

Abstract Title: 

Parental autoimmune diseases associated with autism spectrum disorders in offspring.

Abstract: 

BACKGROUND: Autism spectrum disorders are often idiopathic. Studies have suggested associations between immune response and these disorders. We explored associations between parental autoimmune disorders and children's diagnosis of autism by linking Swedish registries.METHODS: Data for each participant were linked across 3 Swedish registries. The study includes 1227 cases and 25 matched controls for each case (30,693 controls with parental linkage). Parental diagnoses comprised 19 autoimmune disorders. We estimated odds ratios (ORs) using multivariable conditional logistic regression.RESULTS: Parental autoimmune disorder was weakly associated with autism spectrum disorders in offspring (maternal OR = 1.6 [95% confidence interval = 1.1-2.2]; paternal OR = 1.4 [1.0-2.0]). Several maternal autoimmune diseases were correlated with autism. For both parents, rheumatic fever was associated with autism spectrum disorders.CONCLUSIONS: These data support previously reported associations between parental autoimmune disorders and autism spectrum disorders. Parental autoimmune disorders may represent a critical pathway that warrants more detailed investigation.

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PMID: 

Neurosci Biobehav Rev. 2015 Aug ;55:322-32. Epub 2015 May 15. PMID: 25981892

Abstract Title: 

Family history of autoimmune diseases is associated with an increased risk of autism in children: A systematic review and meta-analysis.

Abstract: 

BACKGROUND: We conducted a systematic review and meta-analysis to summarize the current evidence on the relationship between family history of autoimmune diseases (ADs) and risk of autism in children, as current evidence suggests inconsistent results.METHODS: We identified relevant studies by searching PubMed, EmBase, and Web of Science databases up to Dec 2014. Risk estimates from individual studies were pooled using random-effects models. Sub-groups analyses were conducted by some study-level factors. Publication bias was assessed by funnel plots, Egger's regression test and Begg-Mazumdar test.RESULTS: A total of 11 articles were included in the meta-analysis, including 3 cohort studies, 6 case-control studies, and 2 cross-sectional studies. The meta-analysis showed that family history of all ADs combined was associated with a 28% (95% CI: 12-48%) higher risk of autism in children. For some specific ADs, evidence synthesis for risk of autism in children showed a statistically significant association with family history of hypothyroidism (OR=1.64, 95% CI: 1.07-2.50), type 1 diabetes (OR=1.49, 95% CI: 1.23-1.81), rheumatoid arthritis (OR=1.51, 95% CI: 1.19-1.91), and psoriasis (OR=1.59, 95% CI: 1.28-1.97). The results varied in some subgroups.CONCLUSION: An overall increased risk of autism in children with family history of ADs was identified. More mechanistic studies are needed to further explain the association between family history of ADs and increased risk of autism in children.

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PMID: 

CNS Neurol Disord Drug Targets. 2016 ;15(4):448-63. PMID: 26996174

Abstract Title: 

Neuro-Inflammatory Mechanisms in Developmental Disorders Associated with Intellectual Disability and Autism Spectrum Disorder: A Neuro- Immune Perspective.

Abstract: 

Intellectual disability (ID) and autism are present in several neurodevelopmental disorders and are often associated in genetic syndromes, such as Fragile X and Rett syndromes. While most evidence indicates that a genetic component plays an important role in the aetiology of both autism and ID, a number of studies suggest that immunological dysfunctions may participate in the pathophysiology of these disorders. Brain-specific autoantibodies have been detected in the sera of many autistic children and autoimmune disorders are increased in families of children with autism. Furthermore, cytokine imbalance has been reported in children with autism. These results may reflect an inappropriate immune response to environmental factors, such as infectious or toxic exposure. The role of microglia as sensors of pre- and post-natal environmental stimuli and its involvement in the regulation of synaptic connectivity, maturation of brain circuitry and neurogenesis has recently emerged. An abnormal immune response during critical windows of development and consequent abnormal production of neuro-inflammatory mediators may have an impact on the function and structure of brain and can play a role in the pathogenesis of non syndromic autism. Recent evidence suggests an involvement of neuro-inflammation also in syndromic forms of autism and ID. Immune dysregulation has been found in children with Fragile X syndrome and an intrinsic microglia dysfunction has been recently reported in Rett syndrome. The present review summarizes the current literature suggesting that neuro-inflammatory mechanisms may contribute to the pathogenesis of different ID- and autism-associated disorders, thus representing common pathophysiological pathways and potential therapeutic targets.

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