Transcript THE ROLE OF INFECTIONS IN THE EMERGENCE OF NON

THE ROLE OF INFECTIONS IN THE
EMERGENCE OF NON –
COMMUNICABLE DISEASES (NCDs):
Compelling needs for novel strategies.
By
PROF. G. C. ONYEMELUKWE (MON)
FORMER CHAIRMAN FEDERAL MINISTRY
OF HEALTH EXPERT COMMITTEE ON NCDs
NON COMMUNICABLE DISEASES AND RISK FACTORS
INTRAUTERINE INFECTIONS AND FOETAL IMPRINTING
BAKER’S HYPOTHESIS
I. Foetal malnutrition and stress(infection)
II. Foetal programming, Immune programming
III. Intrauterine growth retardation(low birth weight)
A. INSULIN RESISTANCE, NIDDM, HYPERTENSION, STROKE,
CORONARY HEART DISEASE IN ADULT LIFE. UTI,
TOXOPLASMA, RUBELLA, CMV, HERPES. FORRESTAL T.
HISTORIC EARLY LIFE ORIGINS OF HYPERTENSION IN AFRICA.
J. Nutr.2004:134:211-6.
B. PSYCHOLOGICAL; SCHIZOPHRENIA - CYTOKINE INDUCED
PROBLEM DURING FOETAL NEURODEVELOPMENT BY
RUBELLA, INFLUENZA, TOXOPLASMOSIS
BROWN. A. PRENATAL INFECTIONS AS RISK FOR
SCHIZOPHRENIA. SCHIZOPHRENIA BULL 2006;32(2); 200202.DOGRA S. V. INTRAUTERINE GROWTH.
C. MALARIA SCHISTOMIASIS IN MOTHER MAKES
TH2 RESPONSE ˃ TH1 RESPONSE IN CHILDHOOD.
CLASSIFICATIONS OF INFECTIONS
INTRACELLULAR AND EXTRACELLULAR
1.BACTERIA
2.VIRUSES
3.CHLAMYDIA
4.PARASITES
5.PRIONS
INNATE SYSTEM WORKS WITH ADAPTIVE IMMUNE SYSTEM
Cell mediated
MECHANISMS
TOXINS
ENDOTOXIN
MIMICRY
Rheumatic fever/
Rheumatic disease
AGGRESSINS
INDUCE
AUTOIMMUNE
TYPE I - IV
PRION/CALCIFICATION
HOST/IMMUNE –
PARASITE/INFECTION INTERACTION
IMMUNO
SUPPRESSION
ONCOGENE
±CO-CARCINOGEN
SUPPRESSION OF
AUTOIMMUNITY (Plasmodium
knowelsi on NZB mice)
GENE PRESSURE
(MALARIA)
1. Sickle gene
2. Thalasemia
3. G6PD
CYTOKINE
CHEMOKINES
PERSISTENCE/ TRANSFORMATION
CHRONIC INFLAMMATION
HYPERSENSITIVITY
(TYPE I – V)
CELLULAR DIFFERENTIATION
(Ad – 36 virus – Adipocyte)
MODULATION OF
TH1/TH2/T(REG)
BALANCE
INFECTIONS AND STRESS
IL-6
HEART DISEASE ARTHRITIS
ANXIETY DEPRESSION
CHRONIC
STRESS
CRIME/VIOLENCE
STRESS
PSYCHONEUROIMMUNOLOGY
STRESS
INDUCED
MEMORY
DYSFUNCTION
NEUROENDOCRINEIMMUNE AXIS
INFECTIONS
A
OBESITY OF INFECTIOUS ORIGIN
Nikhil V. Dhurandhar, PhD; Richard L. Atkinson,MD; Aftab
Ahmed,PhD. GGH JOURNAL.COM 2004:20(3)
FAT CELL IN ENERGY HOMEOSTASIS, INFLAMATION, IMMUNITY
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
RESISTIN
LEPTIN
ADIPONECTIN
INSULIN RESISTANCE
VISFATIN
APELIN
TUMOUR NECROSIS FACTOR (TNF)
RETINOL BINDING PROTEIN
MONOCYTE CHEMOTACTIC PROTEIN1 (MCP-1)
PLASMINOGEN ACTIVATOR INHIBITOR 1 (PAI-1)
INTERLEUKIN 6
ABDOMINAL FAT CELL IS ACTIVE
PATHOGENS RESPONSIBLE FOR OBESITY
PATHOGEN
ANIMAL MODEL
POSSIBLE
(REFERENCE)
MECHANISM(S)
*Human adenovirus
(11,15,16)
Chickens, mice, nonhuman
primates
Up-regulation of preadipocyte
differentiation
Human adenovirus(33)
Chickens
Unknown
SMAM-1 adenovirus (8,9)
Chickens
Unknown
Borna-disease virus (10,50,51)
Rats
Hypothalamic damage
Chlamydia pneumoniae(68)
Unknown
Scrapie agent (76-79)
No animal model,
associated with weight
gain in humans
Mice
Canine Distemper virus (5)
Mice
Rous-Associated virus-7 (6,7)
Chickens
Hypothalamic damage,
reduced hypothalamic
leptin receptor expression
Reduced thyroid hormone
levels
* Human pathogens, and/or associated with human obesity.
Hypothalamic-pituitaryadrenal
axis damage
ADIPOGENIC PATHOGENS AND THE POTENTIAL MECHANISMS LEADING TO OBESITY
Canine distemper
virus (CDV)
1. Reduced
catecholamine
Levels
2. Hypothalamic
damage
3. Reduced expression
of hypothalamic
leptin receptor
4. Down-regulation of
Melanin- concentrating
hormone
precursor mRNA
Adenovirus
Ad-36:
Up-regulation
of fat cell
differentiation,
reduced leptin
secretion.
Borna-disease virus
(BDV)
Hypothalamic
damage
Hypothalamus
Adipose
tissue
Scrapie agent
Hypothalamicpituitaryadrenal
axis damage
GLUT-1 Alterations
Rous virus-7
RAV-7: Reduced
thyroid
hormone levels
Chlamydia
pneumonia
Immunomodulators
(?)
METABOLIC SYNDROME AND ALTERED
GUT MICROBIOTA IN MICE LACKING
TOLL-LIKE RECEPTORS Matam VijayKumar, Jesse D. Aitken, Frederic A. Carvalho, Tyler
C. Cullender, Simon Mwangi, Shanthi Srinivasan,
Shanthi V. Sitaraman, Rob Knight, Ruth E. Ley,
Andrew T. Gewirtz. Sci 2010, Apr;328 (9): 5975,228231 DOI: 10.1126/sci.1179721
TLR-5 DEFICIENT MICE cannot recognize
PAMP(pathogen associated molecular
pattern of bacteria
METABOLIC SYNDROME AND ALTERED GUT MICROBIOTA IN MICE LACKING TOLL-LIKE RECEPTOR
doi: 10.1126/science.1179721 Science 9 April 2010: vol. 328 no. 5975 228-231
1. Study found that mice without a protein known as Toll-like receptor 5 (TLR5) of innate
immunity in their gut had hyperphagia, gain excessive weight and develop full-blown
diabetes and fatty liver disease when fed a high-fat diet.
2. Other studies have shown that the composition of the gut flora differs in people who are obese and
diabetic, and people who are normal weight with no metabolic irregularities.
3. Other studies have shown that changes in the gut flora can increase the rate at which we absorb fatty
acids and carbohydrates, and increase the storage of calories as fat.
4. Dysregulated gut flora has been linked to diseases ranging from autism and depression to autoimmune
conditions like Hashimoto’s, inflammatory bowel disease and type 1 diabetes.
Metabolic adaptation of C57Bl/6J and SWR/J mice to infection with H. polygyrus. A) Body
weights of naïve mice compared to those infected with H. polygyrus for 21 days, Mean ±
SEM, N=5–8 in each group; B) Average food intake per 24 hours in naïve vs. 21 day H.
polygyrus infected mice, Mean ± SEM, N=5–8 mice per group, *p=0.001; C) A comparison
of energy expenditure in naïve vs. H. polygyrus infected SWR/J mice over 24 hours
measured by indirect calorimetry, arrows indicate dark cycle period, N=4 mice per group;
D) Total ambulatory activity in naïve vs. H. polygyrus infected SWR/J mice over 24 hours,
arrows indicate dark cycle period, N=4 mice per group.
B
CANCER AND INFECTIONS
TOTAL INFECTION-ATTRIBUTABLE CANCERS WORLDWIDE
Agent
H. Pylori
Cancer
Stomach
Lymphoma
# cases
592,000
11,500
% all Ca.
5.5
HPV
Cervix
Anogenital
492,800
53,880
5.2
Oropharynx
14,500
Liver
Nasopharynx
Hodgkin L.
535,000
78,100
28,600
Burkitt L.
6,700
Kaposi sarcoma
Non-Hod. L.
66,200
36,100
0.9
10,600
0.1
3,300
2,500
1,932,800
0.03
0.02
17.8
HBV, HCV
EBV
HIV/HHV8
Schistosomes
Bladder
HTLV-1
Liver flukes
Total
ATL
Bile duct
4.9
1.0
I-A Ca in Developing and Developed Countries
Developed Countries
Developing Countries
Site
Liver
Agent
HBV,HCV
Flukes
# cases
48,000
0
% all Ca
1.0
# cases
475,000
2,500
% all Ca.
8.2
Cervix
Stomach
Kaposi
NHL
HPV
H. pylori
HHV8
HIV/EBV
EBV (BL)
83,400
192,000
3,700
9,300
100
1.7
3.8
0.1
0.2
409,400
400,000
62,500
26,800
6,600
7.0
6.9
1.1
0.7
H.pylori
5,600
5,900
HTLV-1
550
2,790
HPV
EBV
22,450
6,500
0.4
0.1
31,430
71,600
0.5
1.2
5,600
11,500
0
389,000
0.1
0.2
0.0
7.7
8,800
17,100
10,600
1,527,000
0.2
0.3
0.2
26.3
Anogenital
Nasopharyn
x
Oropharynx HPV
Hodgkin L. EBV
Bladder
Schistos
Total
COULD INFECTIONS CAUSE PROSTRATE CANCER?
IS A VIRUS INVOLVED?
1. Robert Schlaberg in 2006 found a virus called Xenotropic
murine-like retrovirus, or XMRV, in the cell samples from
prostate cancer patients. RNaseL gene, XMRV is one of
the retroviruses.
IS A PARASITE INVOLVED?
1. Parasites called Trichomonas vaginalis (T. vaginalis)
Casey, G et al.(2002),32 (4), 581-583
doi:10.1038/ng1021; Urisman, A et al.(2006) RNASEL
Variant PLoS; Pathogens, 2 (3) doi:10.1371 Stark, J. et
al.(2009),JNCI .doi:10.1093.
PRINCIPLES OF ONCOLOGY
• Uncontrolled proliferation induces apoptosis
Noxa, Puma
p53
Noxa, Puma
BclxL, Mcl1
Bak,Bax
BclxL,Mc1
Cyt C
Mule
caspases
Bak/Bax
NATURAL HISTORY OF CERVICAL HPV INFECTIONS
Atypia/ASCUS/
CIN1-2/LSIL
CIN2-3/CIS/HSIL
STRATEGIES FOR HPV VACCINATION
Eliminate Residual Disease
Prevent Infection
Mediate Regression
HBV and HCV in the etiology of Hepatocellular Carcinoma
• Prevalence of HCC is correlated with endemic chronic infection with
HBV and HCV
• Chronic HBV and HCV infections result in cirrhosis in ~ 15% of
subjects in 25-30 years, with HCC arising in ~1% of subjects with
cirrhosis.
• Non-viral cirrhosis is also a risk factor for HCC.
HCC only arises in the context of cirrhosis.
Hepatitis viruses are very diverse
• Hepatitis C virus (HCV) is a positive strand RNA
Flavivirus.
HCV core induces signalling pathways
E2 interferes with interferon signalling
EBV is associated with multiple cancers
• Burkitt’s lymphoma
• Post transplant lymphomas
• Hodgkin’s lymphoma
• Nasopharyngeal carcinoma
• Gastric cancer
EBV is associated with multiple cancers
• EBV infection occurs in > 90% of the population;
cancer is very rare.
• Most EBV associated cancers are associated with
immunosuppression - transplantation
(drugs);
HIV; malaria;
• EBV causes cancer in both B cells, where the virus
is latent and productive, and in epithelial
cells that do not support viral latency.
EBV associated cancers
Other
B
cells
Naïve
B
cell
PTLD
EBNAs1-3, LMPs1-2b
Hodgkin’s
EBNA1, LMP1,2A
Germinal
Center
Memory
B
cell
Burkitt’s
EBNA1 only
EBV associated cancers
Epithelial
cell
Nasopharyngeal
Carcinoma
EBNA1, LMP1, 2a
Plasma
cells
Memory
B
cell
HHV-8 (KSHV) and Cancer
• Kaposi’s sarcoma - spindle cell (endothelial origin)
• Pulmonary Effusion Lymphoma
• Multicentric Castleman’s Disease - B cell (noncancer)
Viral genome encodes homologues for cellular
genes that block innate and adaptive immunity,
block apoptosis, induce proliferation.
STAGES IN DEVELOPMENT OF CANCER
1. Protooncogenes (c-onc genes) are the cellular counterparts of v-onc genes. Their functions
are cellular growth and development. The activation of c-onc genes with mutation leads to
uncontrolled cell growth.
a. Growth factors
b. Growth factor receptors
c. Signal transducers
d. Transcription factors
2. Antioncogenes (tumor suppressor genes). When these genes lose their suppressive
effects, unpreventable growth occurs.
a. Retinoblastoma gene (Rb)
b. p53
c. Wilms tumor gene (WTI)
d. VHL gene in Von-Hippel Lindau syndrome
e. NF1 and NF2 genes in neurofi bromatosis
f. APC and DCC genes in familial adenomatous polyposis
HUMAN ONCOGENIC DNA VIRUSES
TAXONOMIC GROUPING
EXAMPLES
TUMOR TYPES
Adenoviridae
Adenovirus types 9, 12, 18, 31
Various solid tumors in rodents
Hepadnaviridae
Herpesviridae
HBV
EBV
Hepatocellular carcinoma
Burkitt’s lymphoma
Nasopharyngeal carcinoma
KSHV (HHV-8)
B-cell lymphoma
Hodgkin’s lymphoma
Kaposi’s sarcoma
Primary eff usion lymphoma
Papillomaviridae
HPV types 6, 11, 16, 18, 31, 45
Multicentric Castleman’s
disease
Oral, cervical, and anal cancer
Polyomaviridae
Poxviridae
Merkel cell polyomavirus
BK virus, JC virus
MCV
Merkel cell carcinoma
Solid tumors in rodents
Various solid tumors
HBV: Hepatitis B virus, EBV: Epstein-Barr virus, KSHV: Kaposi’s sarcoma-associated herpesvirus, HHV: Human
herpes virus, HPV:Human papillomavirus, MCV: Molluscum contagiosum virus
HUMAN ONCOGENIC RNA VIRUSES.
Taxonomic
grouping
Examples
Tumor types
Retroviridae
HTLV type 1
Adult T-cell
leukemia
Flaviviridae
Hepatitis C virus
Hepatocellular
carcinoma
HTLV: Human T-cell leukemia virus.
C
NUTRITION AND INFECTION
SPIRAL OF MALNUTRITION AND INFECTION
HYPERMETABOLISM
IL-1,IL-6,TNF, FEVER
INADEQUATE DIETARY
INTAKE
APPETITE LOSS
NUTRIENT LOSS
MALABSORPTION
ALTERED METABOLISM
PROTEIN
LOOSING
ENTEROPATHY
WEIGHT LOSS
GROWTH FATTERING
LOWERED IMMUNITY
MUCOSAL DAMAGE
DISEASE:
INCIDENCE DURATION
SEVERITY
AFLATOXINS FROM FUNGI –
ASPERGILLUS FLAVUS
Onyemelukwe GC, Ogoina D, Ibiam G E, GH Ogbadu. Aflatoxins in body fluids and food of
Nigerian children with protein- energy malnutrition. Afri. J. of Food, Agriculture, Nutrition
and development, 12: (5 )2012 , ISSN 1684 5374 (KWASHIOKOR,MARASMUS,STUNTING.)
UNDERNUTRITION
DECREASED
IMMUNE FUNCTION
-INNATE
-ACQUIRED
INFECTION
IMPAIRED ABSORPTION
. ALTERED GUT LUMEN
. MUCOSAL INJURY
D
CARDIOVASCULAR - ATHEROSCLEROSIS
ATHEROSCLEROSIS IS ASSOCIATED WITH MULTIPLE PATHOGENIC
MECHANISMS IN HIV-INFECTED ANTIRETROVIRAL-NAÏVE OR TREATED
INDIVIDUALS.
Piconi, Stefania;Parisotto, Serena; Rizzardini, Guiliano; Passerini, Simone; Meraviglia,
Paola; Schiavini, Monica; Niero, Fosca; Biasin, Mara; Bonfanti, Paolo; Ricci, Elena Delfina;
Trabattoni, Daria; Clerici, Mario. AIDS 2013,27:381-389.
1. HIV- infected patients have a greater burden of sub-clinical and
clinical atherosclerotic disease compared to the general population.
2. A complex pathogenesis drives atherogenesis in HIV infection. Thus,
whereas inflammation could be responsible for this process in ARTnaïve individuals.
3. ABCA-1, an ATP-binding transporter cassette protein involved in
cholesterol efflux, which is inhibited by Nef, is up-regulated in ARTtreated individuals.
1. CHRONIC HEPATITIS C VIRUS INFECTION IS ASSOCIATED
WITH EARLY ATHEROSCLEROSIS. Mostafa et al Gut June 28, 2010.
2. Bacterial persistence in phagocyte cells by Dr. Emil Kozarov in
Columbia University: J. Atherosclerosis Thrombosis Bacillus
Enterobacter hormaechei chronic infection.
Periodontal bacteria in carotid artery.
3. Autoimmunity to heat shock proteins(HSP 60) from bacteria with
autoantibodies in the lesion. Zhu et al 2001. Am.Coll.Cardiol.Florida
850.
4. Individual pathogens CMV, Hepatitis A, Herpes simplex 1 (HSV1),
Herpes simplex 2 (HSV2), C.pneumoniae, Helicobacter pylori.
5. Pathogen burden. Zhu J. et al; Am. J. Cardiol.2000, 85: 140-146 of
multiple infections with intracellular organisms in (4 )above
asociated with elevated C-reactive proteins.
INFLUENZA AND CARDIOVASCULAR DISEASE
Mohammad Madjid, MD; Ibrahim Aboshady, MD; Imran Awan, MD; Silvio Litovsky, MD;
S.Ward Casscells, MD. Tex Heart Inst J 2004; 31:4-13
We appraise the relationship between influenza and coronary
heart disease, on the basis of Bradford Hill’s criteria of
causality. We show that our proposed relationship meets the
following criteria: strength of association, consistency,
temporal sequence, coherence, biologic plausibility,
experimental evidence, and analogy.
INFECTIOUS AGENTS IMPLICATED IN ATHEROSCLEROSIS
Chlamydia pneumoniae
Cytomegalovirus
Herpes simplex viruses 1 and 2 (HSV-1, HSV-2)
Helicobacter pylori
Mycoplasma pneumoniae
Porphyromonas gingivalis
Enterovirus species
Salmonella typhi
Streptococcus sanguis
Coxsackie B virus
Adenovirus species
Mycoplasma gallisepticum
Marek’s disease virus
Measles virus
Epstein-Barr virus
Human immunodeficiency virus
Mycoplasma fermentans
Coxiella burnetti
Actinobacillus actinomycetemcomitans
Bacteroides forsythus
Hepatitis A virus
Prevotella intermedia
Influenza virus
EFFECTS OF INFLUENZA ON THE COAGULATION SYSTEM
Target
Effect
Study
Platelet aggregation50-53
Increased
In vivo human and animal
Platelet count50,54,55
Diminished
In vivo and in vitro human
AT III56
Diminished
In vivo human
Clotting time57
Increased
In vivo human
DIC prevalence58
Increased
In vivo human
PT61
Prolonged
In vivo human
PTT61
Prolonged
In vivo human
Fibrinogen62
Decreased
In vitro human
Factor V61
Diminished
In vivo human
Factor VIII61
Diminished
In vivo human
FDPs56,61,63
Markedly Increased
In vivo and in vitro human
Fibrin monomers63
Positive
In vitro human
Soluble fibrin61
Increased
In vivo human
Staphylococcal clumping
test61
Abnormal
In vivo human
Plasminogen
Decreased
In vivo human
1-Antitrypsin
Reduced
In vivo human
2-Macroglobulin5
Reduced
In vivo human
Plasmin inhibitor
complexes
Produced, then
consumed
In vivo human
Secondary fibrinolysis56
Initiation
In vivo human
Tissue factor64,65
Increased
In vivo human
Factor VII64
Activation
In vivo human
Factor X64
Activation
In vivo human
TFPI66
Exhausts the inhibitory
effect
In vivo human
Monocytes
Activate the procoagulant In vivo human
Endothelial cell damage57
A. Release of phosphatidyl serine
B. Lysis
a. Exposure of the prothrombotic extracellular matrix to the vascular lumen
b. Alteration of the procoagulant-anticoagulant balance
HILL’S CRITERIA FOR CAUSALITY
Strength of association
Consistency
Temporal sequence
Coherence
Biologic plausibility
Biologic gradient (dose-response
relationship)
Specificity
Experimental evidence
Analogy
RECOMMENDATIONS FOR IMPROVING INFLUENZA CONTROL IN
CARDIOVASCULAR PATIENTS
• Motivate doctors and patients by increasing recognition of
the heart-protective effect of flu shots
• Update cardiology practice guidelines to include flu shots
• Examine the feasibility of financial incentives to doctors and
patients to improve adherence to existing guidelines
• Determine which virus strains trigger cardiovascular events
• Strengthen educational efforts to persuade pediatricians,
internists, gynecologists, and family practitioners to improve
vaccination rate of household contacts of patients with heart
disease
• Intensify research on the mechanism of the effect of the
virus on the vascular system
• Design new clinical trials to determine high-risk groups that
may benefit from influenza prevention in terms of cardiovascular
prevention
PRION DISEASES
E
Nanobacteria
cause kidney
stones and
arterial
classifications
Kajander E (2006). "Nanobacteria--propagating calcifying nanoparticles". Lett
Appl Microbiol 42 (6): 549-52. www.nanobac.org
F AUTOIMMUNE DISEASES AND ALLERGIES
STRACHAN DV BMJ, 1989 – HYGIENE HYPOTHESIS
HYGIENE HYPOTHESIS
I.
Worm Therapy.
Worm therapy has been or is being studied in humans as a treatment for several
immunological diseases including Crohn's disease, Ulcerative Colitis, Multiple Sclerosis,
Eczema or atopic dermatitis and allergies. Autoimmune liver disease has also been
demonstrated to be modulated by active helminth infections.
II. The Hygiene Hypothesis & Worm therapy.
a. Extra-cellular antigens primarily trigger the TH2 response, as observed with allergies,
while intracellular antigens trigger a TH1 response. The Hygiene Hypothesis states that
there is a regulatory action between the two types of response.
b. The Old Friends Hypothesis modifies the Hygiene Hypothesis, proposing that T regulator
cells (T regs) only become mature and completely effective if they are stimulated by
repeated exposure to microorganisms and parasites that are relatively benign and which
have coexisted with humans throughout our evolutionary history.
III. Which worms are used in therapy?
Only Necator Americanus meet all these requirements, although Trichuris Suis Ova only , so
it is more expensive at therapeutic doses. The main difference between N. americanus and
T. suis is residency time, because T. suis has a lifespan of only 2-3 weeks in humans, while N.
americanus has an average life span of 5 years.
DC= DENDRITIC CELLS; APC=ANTIGEN PRESENTING CELLS;
DENDRITIC CELLS PRESENTATION OF ANTIGENS LEAD TO FORMATION OF Treg and TISSUE
GROWTH FACTOR (TGF-b)
CHILDREN IN WESTERN COUNTRIES VERSUS CHILDREN IN AFRICAN COUNTRIES
IL-25 elicits a multi-potent progenitor cell population that
promotes Th2 cytokine responses
Steven A. Saenz1, Mark C. Siracusa1, Jacqueline G. Perrigoue1, Sean P. Spencer1, Joseph
F. Urban Jr.2, Joel E. Tocker3, Alison L. Budelsky3, Melanie A. Kleinschek4, Robert A.
Kastelein4, Taku Kambayashi5, Avinash Bhandoola5, and David Artis.
Nature. 2010 April 29; 464(7293): 1362–1366. doi:10.1038/nature08901.
PARASITES AND ALLERGIC DISEASES
VACCINATION with Human Hookworm Vaccine "Necator
americanus Aspartic Protease-1 M74“ Generates
Neutralizing Antibodies and a Potent Immune Response in
BALB/c Mice.
Amar R. Jariwala, George Washington University; Xi Chen,
George Washington University; Mark S. Pearson, James
Cook University; Brian Keegan, Baylor College of Medicine;
Jill B. Brelsford, George Washington University; Medical
Immunology Commons; 4-22-2013
INFANT GUT MICROBIOTA AND THE HYGIENE
HYPOTHESIS OF ALLERGIC DISEASE: IMPACT OF
HOUSEHOLD PETS AND SIBLINGS ON MICROBIOTA
COMPOSITION AND DIVERSITY
Meghan B Azad1, Theodore Konya2, Heather Maughan3,
David S Guttman3, Catherine J Field4, Malcolm R Sears5,
Allan B Becker67, James A Scott2, Anita L Kozyrskyj17* and
CHILD Study Investigators7 . Allergy, Asthma & Clinical
Immunology 2013, 9:15 doi:10.1186/1710-1492-9-15
Model for the possible influence of pets and siblings on infant gut microbiota and subsequent development of atopic
disease. Household pets (D, dogs; C, cats) and siblings increase infant exposure to environmental microbes, promoting
enrichment for distinct combinations of organisms within the gut microbiota; overall richness and diversity are also
impacted. Despite favoring different microbiota profiles, the net effect of both pets and siblings is to promote healthy
immune system development and protect against atopic disease. Further research is required to characterize the
underlying biological mechanisms. Azad et al. Allergy, Asthma & Clinical Immunology 2013 9:15 doi:10.1186/17101492-9-15
G. MENTAL DISEASESDEPRESSION AND VIRAL INFECTIONS
Shalini, Malhotra; Nirmaljit, Kaur; P. Kumar; M.S. Bhatia; Charu, Hans. Delhi psychiatry
journal vol. 15 no.1
1.
2.
3.
4.
5.
6.
7.
8.
9.
Human immunodeficiency virus
Hepatitis C virus
Epstein-Barr Virus
Herpes simplex virus
Influenza virus
Hepatitis B virus
Hepatitis A virus
BORNA DISEASE VIRUS
Human T-cell Lymphotropic virus (HTLV)
. markers of inflammation (C-reactive protein, interleukin 1 and 6) were positively
correlated with depression.43
. Cytokines seem to trigger a quick onset of what is called ‘sickness behavior’-meaning
malaise and fatigue, as well as a delayed onset of depressed
. etanercept (a TNFtumor necrosis factor-blocker) reduced depressive symptoms in people
with psoriasis.
MECHANISM OF ACTION OF MICROBIAL PATHOGENS IN DEPRESSION
A. Chronic infection with any of these viruses can lead to raised
interferon-alpha levels (interferon-alpha is secreted by cells of the
immune system as it tries to control the virus), and it is now known
that interferon-alpha can significantly affect the serotonin system.
B Coxsackie virus B, which have a particular affinity for, and disruptive
action on, the hypothalamus.
C. Raising glutamate and quinolinic acid levels in the brain (high
glutamate levels are linked to depression). The excess
glutamate/quinolinic acid in this case comes from the activated
microglia cells (microglia are specialized macrophages permanently
resident in the brain).
D. Depression can sometimes be caused by low levels of the adrenal
hormone cortisol. Viruses like enterovirus often chronically infect
the adrenal glands.
E. Chronic fatigue syndrome, the working memory and long-term recall
is often severely disrupted.
H
LIST OF NON COMMUNICABLE DISEASES (NCDs) AND THEIR
KNOWN OR PROBABLE INECTIOUS RISK FACTORS
CARDIOVASCULAR
RESEARCHES IN CARDIOVASCULAR DISEASES
1. RHEUMATIC FEVER/ RHEUMATIC HEART
DISEASE- Grp A, B, C streptococcal
pharynigitis and skin infections –
Ogunbi et al (lagos) J. Epid. Comm. Health 1978 march 3(1) 68-71
2. Endomyocardial fibrosis(EMF) and loa loa
induced eosinophilia. Others trichinella
spiralis,ascaris, hookworm, toxoplasmosis
Andy JJ et al (Calabar, Ife) Acta tropica 1998; 69 127-140
Urhogide A, Falase A (Ibadan) Afri J Med Med Sci 1987, 16 133
3. PERIPARTUM CARDIAC FAILURE (PPCF)
Zaria syndrome- salt lake, Hot bath, volume overload ,pre HT, ? Viral
myocarditis
Davidson N, Parry E Q J Med N S 1976, 47 431-461,
Adesanya c et al Trop. Geog Med 1989, 41 (3) 190-196,
Ford l, Abdullahi et al Q J Med 1998 91 93-103
Danbauchi SS Trop Doc 2002,32 24-27
4. OTHERS DUE TO MYOCARDITIS from toxoplasmosis, coxsackie B virus and
chlamydia.
Falase A (Ibadan) Heart vessels Supp 1985 1, 232-35,
Cenac A et al(Niger) Med Trop(Mars) 2000,60,2, 137-40
5.
ECLAMPSIA AND INFECTION
Ekwempu CC(Zaria) Tropical doctor 1980 174-78
Ekwempu CC Int J Gynae Obstect 1980, 18 4, 300-2
NEUROLOGY/ PSYCHIATRY
RESEARCHES IN NEUROLOGICAL IN AFRICA
1. Tropical spastic paraparesis and HTLV1
Roman GC et al Neurology 1985,35, 1158
2. Epidemic seasonal ataxia and viral (arbovirus)
encephalitis
Adamolekun B et al Met Brain Dis 1997, 12, 251
3. Post malaria cerebellar ataxia
Osuntokun BO Afr J Med Med Sci 1983, sept 3-4 ,
165-172
4. Typhoid and Fregoli syndrome(rare persecutory
delusion)
Stanley et al (Jos), Nig J Med 2002,4, no 1,jan-march
33-34
5. Typhoid and neuropsychiatric manifestation
Osuntokun et al Arch 1972 Neurol 27 July 7-13
AUTOIMMUNE/ ENDOCRINE
NOTE: EFFECT OF MALARIA PLASMODIUM BERGHEI IN REDUCED INCIDENCE OF
AUTOIMMUNE DISEASES. B. M. GREENWOOD; VOLLER. A. SUPPRESSION OF
AUTOIMMUNE DISEASE IN NEW ZEALAND MICE ASSOCIATED WITH INFECTION IN
MALARIA II. NZB MICE. CLIN.EXP. 1970; IMMUNOL. 71(6) 805-815
GASTROINTESTINAL DISEASES
RESEARCHES IN GIT DISEASES
1. LIVER CIRRHOSIS , HBV AND SCHISTOSOMIASIS
FAKUNLE Y, ET AL (ZARIA)
2. HBV, HCV,HDV(DELTA VIRUS)
OJO S ET AL EAST AFRI MED J,1995 ,72 ,II,719-21
3. HELICOBACTER PYLORI AND PEPTIC ULCER
HOLCOMBE C ET AL (MAIDUGURI) TRANS R SOC TROP
MED HYG 1994 88,569
4. MALARIA AND TROPICAL SPLENOMEGALY SYNDROME
Fakunle Y, Greenwood B, 1976 Trans R Soc Trop Med Hyg
70 346-51
 Fakunle Y, Greenwood B,1977 Clin exp Immunol 28, 1536
RENAL DISEASES
SOME RESEARCHES ON RENAL DISEASES
1. QUARTAN MALARIAL NEPHROPATHY
Hendricks RG , Adeniyi A (Ibadan) Kidney Int 1979, 16,64
2. SCABIES AND NEPHRITIS INCLUDING NEPHROTIC SYNDROME
Whittle HC et al Trans R Soc Trop Med Hyg 1973 67, 349-363
Abdulrahman m,b 1984 J Inf Mar 8, 100-9
Aikionbare H et al 1984 Nig J Paed 11,2,59-62
3. VIRAL HEPATITIS AND IMMUNE COMPLEX
GLOMERULONEPHRITIS, LEPROSY, YERSINIA
ENTEROCOLITICA(BY RENNER .A) ETC.
RESPIRATORY DISEASES
RESEARCHES IN RESPIRATORY DISEASES
1. Asthma and air borne fungi (Aspergillus fumigatus), house dust
mite (dermatophagoides farinae/pterysinnus)
Lawande R, Onyemelukwe GC (Zaria) Ann allergy 1984 52(1) 47
Onyemelukwe GC (Zaria) et al Ann Allergy 1986 Feb 56(2), 167-70
2. Asthma and hookworm
Salako LA N.Eng J Med 1970,283,264
3. Asthma and strongyloides
Nwokolo CU, BMJ,1973, 1, 153
VICIOUS CYCLE HYPOTHESIS IN COPD
CANCERS AND OTHER DISEASES
RESEARCHES IN CANCER
1. Mutation of tumor suppressor gene in codon 249 by
aflatoxin in PLCC.
Ndububa et al Afri J Med Sci 2001 30, 125- 127
2. Schistosomiasis and bladder cancers
Bedwani R et al(Egypt) Bri J Cancer 1998, 77,1186-9
3. Aflatoxin B1B2 G1 G2(Aspergillus flavus) and PLCC
Ndububa et al Afri J.Med Sci 2001 30, 125- 127
Onyemelukwe et al Toxicol Letters,1982 ,56,2, 167-70