- Historical Review: Does Falciparum Malaria Destroy Isolated Tribal Populations? [REVIEW, JOURNAL ARTICLE]
- Travel Med Infect Dis 2016 Aug 20.
Many isolated populations of tribal peoples were nearly destroyed when they first contacted infectious diseases particularly respiratory pathogens such as measles and smallpox. Surviving groups have often been found to have declining populations in the face of multiple social and infectious threats. Malaria, especially Plasmodium falciparum, was thought to be a major cause of depopulation in some tribal peoples isolated in tropical jungles. The dynamics of such host parasite interactions is unclear especially since most such populations would have had long histories of exposure to malaria. Three groups are individually reviewed: Meruts of Borneo, Yanomami of Amazonia, Jarawas of the Andaman Islands. The purpose of this review is to examine the role of falciparum malaria in the depopulation of some isolated tribal groups in order to understand what measures, if any, would be likely to prevent such losses.
- Statistical Methods for Testing Genetic Pleiotropy. [JOURNAL ARTICLE]
- Genetics 2016 Aug 15.
Genetic pleiotropy is when a single gene influences more than one trait. Detecting pleiotropy and understanding its causes can improve the biological understanding of a gene in multiple ways, yet current multivariate methods to evaluate pleiotropy test the null hypothesis that none of the traits are associated with a variant; departures from the null could be driven by just one associated trait. A formal test of pleiotropy should assume a null hypothesis that one or fewer traits are associated with a genetic variant. For the special case of two traits, one can construct this null hypothesis based on the intersection-union test (IU) [Silvapulle and Sen 2004], which rejects the null hypothesis only if the null hypotheses of no association for both traits are rejected. To allow for more than two traits, we developed a new likelihood ratio test for pleiotropy. We then extended the testing framework to a sequential approach to test the null hypothesis that k + 1 traits are associated, given that the null of k traits are associated was rejected. This provides a formal testing framework to determine the number of traits associated with a genetic variant, while accounting for correlations among the traits. By simulations, we illustrate the Type-I error rate and power of our new methods, describe how they are influenced by sample size, the number of traits, and the trait correlations, and apply the new methods to multivariate immune phenotypes in response to smallpox vaccination. Our new approach provides a quantitative assessment of pleiotropy, enhancing current analytic practice.
- "Gharikon"/"Agharikon" a Valuable Medicinal Mushroom in Iranian Traditional Medicine. [Journal Article]
- Iran J Med Sci 2016 May; 41(3):S34.
Gharikon is a well-known medicinal mushroom in Iranian traditional medicine and mentioned several times in different kinds of authentic literature. Considering both traditional and modern literature, the aim of this study is to present a review of its biological activities.Using online databases (e.g. PubMed, Scopus, and Google Scholar) as well as reviewing traditional medicinal literature (e.g. Makhzan-ul-Adwiah, Al-Qanun fi al-Tibb); we reviewed the published literature on the pharmacological effects of Laricifomes officinalis (the most common species considered as "Gharikon").Laricifomes officinalis (Polyporus officinalis) is a wood-rotting fungus that grows on different hosts such as conifers. The mushroom is native to Europe, Asia, and North America. According to the judgment of traditional medicine, its temperament is warm and dry. It has been used since the ancient times to treat sciatica, weakness of muscles, bronchitis, constipation, stomach and uterus pain, jaundice, fever and insect bites. It also has diuretic and emmenagogue effects. In recent decades, several research studies have been performed on L. officinalis. The results showed that the biological effects of L. officinalis are anti-viral (especially against smallpox, H5N1 influenza, and hepatitis C virus), anti-tuberculosis, boosting the immune system, treating dysmenorrhea, hemorrhoids, cough, rheumatoid arthritis and anticoagulant activity. A survey revealed that L. officinalis is a well-known medicinal mushroom with some formulations as dietary supplements on the market.Considering traditional literature and recent findings on biological activities that in most cases corroborate each other, it seems that Laricifomes officinalis needs more attention in new investigations, including more pharmacologic assays and clinical trials, which may lead to the development of new natural products.
- The Integration of Epistasis Network and Functional Interactions in a GWAS Implicates RXR Pathway Genes in the Immune Response to Smallpox Vaccine. [Journal Article]
- PLoS One 2016; 11(8):e0158016.
Although many diseases and traits show large heritability, few genetic variants have been found to strongly separate phenotype groups by genotype. Complex regulatory networks of variants and expression of multiple genes lead to small individual-variant effects and difficulty replicating the effect of any single variant in an affected pathway. Interaction network modeling of GWAS identifies effects ignored by univariate models, but population differences may still cause specific genes to not replicate. Integrative network models may help detect indirect effects of variants in the underlying biological pathway. In this study, we used gene-level functional interaction information from the Integrative Multi-species Prediction (IMP) tool to reveal important genes associated with a complex phenotype through evidence from epistasis networks and pathway enrichment. We test this method for augmenting variant-based network analyses with functional interactions by applying it to a smallpox vaccine immune response GWAS. The integrative analysis spotlights the role of genes related to retinoid X receptor alpha (RXRA), which has been implicated in a previous epistasis network analysis of smallpox vaccine.
- Revaccination with Live Attenuated Vaccines Confer Additional Beneficial Nonspecific Effects on Overall Survival: A Review. [JOURNAL ARTICLE]
- EBioMedicine 2016 Jul 15.
Live vaccines against measles (MV), tuberculosis (BCG), polio (OPV) and smallpox reduce mortality more than explained by target-disease prevention. The beneficial nonspecific effects (NSEs) of MV are strongest when MV is given in presence of maternal antibodies. We therefore hypothesised that revaccination in presence of prior immunity enhances beneficial NSEs.Literature search for studies of revaccination and mortality.In two randomised trials (RCTs), two doses versus one dose of MV reduced all-cause mortality by 63% (95% CI: 23-83%) from 9 to 18months of age. In a quasi-experimental study two doses before and after 9months compared with one dose of MV after 9months of age reduced mortality by 59% (25-81%). BCG-revaccination significantly enhanced BCG's effect against overall child mortality in two RCTs. In a natural experiment study of OPV campaigns over a 13-year-period in Guinea-Bissau, each additional dose of OPV was associated with a 13% (4-21%) reduction in mortality rate. The beneficial NSEs of smallpox vaccination for survival increased significantly with the number of smallpox vaccination scars.Revaccination with live vaccines led to substantial reductions in overall mortality. These findings challenge current understanding of vaccines and may explain the beneficial effects of campaigns with live vaccines.
- Acute Disseminated Encephalomyelitis following Vaccination against Hepatitis B in a Child: A Case Report and Literature Review. [Journal Article]
- Case Rep Neurol Med 2016.:2401809.
Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disease of the central nervous system, which has been associated with several vaccines such as rabies, diphtheria-tetanus-polio, smallpox, measles, mumps, rubella, Japanese B encephalitis, pertussis, influenza, and the Hog vaccine. Here, we presented a case of 12-year-old child who suffered from ADEM three weeks after hepatitis B vaccination. He was admitted to our hospital with symptoms of weakness of limbs, high fever, and alteration of consciousness. Some abnormalities were also found in CSF. Treatment with high-dose corticosteroids and intravenous immunoglobulin had significant effect, with marked improvement of the clinical symptoms and the results of CSF. The findings of MRI also detected some abnormal lesions located in both brain and spinal cord. The clinical features, the findings of CSF and MRI, and therapeutic effect may contribute to such diagnosis of ADEM.
- Species-specific differentiation of variola, monkeypox, and varicella-zoster viruses by multiplex real-time PCR assay. [JOURNAL ARTICLE]
- J Virol Methods 2016 Jul 28.:215-220.
A method of one-stage rapid detection and differentiation of epidemiologically important variola virus (VARV), monkeypox virus (MPXV), and varicella-zoster virus (VZV) utilizing multiplex real-time TaqMan PCR assay was developed. Four hybridization probes with various fluorescent dyes and the corresponding fluorescence quenchers were simultaneously used for the assay. The hybridization probes specific for the VARV sequence contained FAM/BHQ1 as a dye/quencher pair; MPXV-specific, JOE/BHQ1; VZV-specific, TAMRA/BHQ2; and internal control-specific, Cy5/BHQ3. The specificity and sensitivity of the developed method were assessed by analyzing DNA of 32 strains belonging to orthopoxvirus and herpesvirus species.
- Ectromelia Virus Disease Characterization in the BALB/c Mouse: A Surrogate Model for Assessment of Smallpox Medical Countermeasures. [Journal Article]
- Viruses 2016; 8(7)
In 2007, the United States- Food and Drug Administration (FDA) issued guidance concerning animal models for testing the efficacy of medical countermeasures against variola virus (VARV), the etiologic agent for smallpox. Ectromelia virus (ECTV) is naturally-occurring and responsible for severe mortality and morbidity as a result of mousepox disease in the murine model, displaying similarities to variola infection in humans. Due to the increased need of acceptable surrogate animal models for poxvirus disease, we have characterized ECTV infection in the BALB/c mouse. Mice were inoculated intranasally with a high lethal dose (125 PFU) of ECTV, resulting in complete mortality 10 days after infection. Decreases in weight and temperature from baseline were observed eight to nine days following infection. Viral titers via quantitative polymerase chain reaction (qPCR) and plaque assay were first observed in the blood at 4.5 days post-infection and in tissue (spleen and liver) at 3.5 days post-infection. Adverse clinical signs of disease were first observed four and five days post-infection, with severe signs occurring on day 7. Pathological changes consistent with ECTV infection were first observed five days after infection. Examination of data obtained from these parameters suggests the ECTV BALB/c model is suitable for potential use in medical countermeasures (MCMs) development and efficacy testing.
- Vacca pox to pexa vec: John Hunter's and Edward Jenner's contribution to oncolytic virotherapy. [Journal Article, Review]
- J Surg Res 2016 Jul; 204(1):228-31.
- [THE USE OF THE MODEL MOUSE ICR--VARIOLA VIRUS FOR EVALUATION OF ANTIVIRAL DRUG EFFICACY]. [English Abstract, Journal Article, Research Support, Non-U.S. Gov't]
- Vopr Virusol 2016; 61(2):79-84.
Mice of the ICR outbred population were infected intranasally (i/n) with the variola virus (VARV, strain Ind-3a). Clinical signs of the disease did not appear even at the maximum possible dose of the virus 5.2 lg PFU/head (plaque-forming units per head). In this case, 50% infective dose (ID50) of VARV estimated by the presence or absence of the virus in the lungs three days after infection (p.i.) was equal to 2.7 ± 0.4 lg PFU/head. Taking into account the 10% application of the virus in the lungs during the intranasal infection of the mice, it was adequate to 1.7 lg PFU/lungs. This indicates a high infectivity of the VARV for mice comparable to its infectivity for humans. After the i/n infection of mice with the VARV at a dose 30 ID50/ head the highest concentration of the virus detected in the lungs (4.9 ± 0.0 lg PFU/ml of homogenate) and in nasal cavity tissues (4.8 ± 0.0 lg PFU/ml) were observed. The pathomorphological changes in the respiratory organs of the mice infected with the VARV appeared at 3-5 days p.i., and the VARV reproduction noted in the epithelial cells and macrophages were noticed. When the preparations ST-246 and NIOCH-14 were administered orally at a dose of 60 μg/g of mouse weight up to one day before infection, after 2 hours, 1 and 2 days p.i., the VARV reproduction in the lungs after 3 days p.i. decreased by an order of magnitude. Thus, outbred ICR mice infected with the VARV can be used as a laboratory model of the smallpox when evaluating the therapeutic and prophylactic efficacy of the antismallpox drugs.