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Hidden Epidemics
Stigma
1
 Common bacterial infections
 Neisseria gonorrhoeae (causes
gonorrhoea or gonococcal
infection)
 Chlamydia trachomatis (causes
chlamydial infections)
 Treponema pallidum (causes
syphilis)
 Haemophilus ducreyi (causes
chancroid)
 Klebsiella granulomatis (causes
granuloma inguinale or
donovanosis).
 Common Fungal infections
 Candida albicans Vulvovaginitis,
penile candidiasis
http://www.who.int/mediacentre/factsheets/fs110/en/
 Common viral infections
 HIV (causes AIDS)
 HSV 1-2
 HPV (causes genital warts and certain
subtypes lead to cervical cancer in
women)
 HBV (causes hepatitis and chronic
cases may lead to cancer of the liver)
 Commom Parasitic infection
 Crab louse, colloquially known as
"crabs" or "pubic lice" (Pthirus pubis)
 Scabies (Sarcoptes scabiei)
 Trichomoniasis (Trichomonas
vaginalis), colloquially known as
"trich"
1
Unintended pregnancy, Potentiated HIV risk (three to six times the risk)
STDs Background
2
(PID)
6 Ways STDs Impact Women Differently from Men
 A woman’s anatomy can place her at a unique risk for STD infection,
compared to a man.
 Women are less likely to have symptoms of common STDs — such as
chlamydia and gonorrhea — compared to men.
 Women are more likely to confuse symptoms of an STD for
something else.
 STDs can lead to serious health complications and affect a woman’s
future reproductive plans.
3
6 Ways STDs Impact Women Differently from Men
 Women who are pregnant can pass STDs to their babies.
 Human papillomavirus (HPV) is the most common sexually
transmitted infection in women, and is the main cause of cervical
cancer.
 Women typically see their doctor more often than men.
 There is a vaccine to prevent HPV; and available treatments for
other STDs can prevent serious health consequences, such as
infertility, if diagnosed and treated early.
3
2
In World
ESTIMATED
NEW CASES
OF
CURABLE
STI
AMONG
ADULTS,
1999
4
4
GLOBAL PREVALENCE AND INCIDENCE OF SELECTED CURABLE
SEXUALLY TRANSMITTED INFECTIONS OVERVIEW AND ESTIMATES 1999-2001
NORTHAMERICA
LATINAMERICA
&THECARIBBEAN
NORTHAFRICA
&THEMIDDLE
EAST
SUB-SAHARAN
AFRICA
WESTERN
EUROPE
EASTERNEUROPE
&CENTRALASIA
EASTASIA&
PACIFIC
SOUTH&
SOUTHEASTASIA
AUSTRALIA&
NEWZEALAND
GLOBAL
TOTAL
CHLAMYDIAL
INFECTIONS 4 9.5 3 16 5 6 5 43 0.5 92
GONORRHOEA 1.5 7.5 1.5 17 1 3.5 3 27 0.1 62
SYPHILIS 0.1 3 0.3 4 0.1 0.1 0.2 4 0.01 12
NEW CASES OF
CURABLE STI
AMONG
ADULTS
14 38 10 69 17 22 18 151 1 340
Digits are in MILLION 4
Incidence conveys
information about the
risk of contracting the
disease, whereas
prevalence indicates how
widespread the disease
is.
3
http://globalgrind.com/2013/02/14/cdc-says-us-highest-rates-stds-stats-in-world-details/ 5
Most shockingly,
HPV,
compromising 71
percent of all the
current
infections, and 72
percent of new
infections.
3
3
Chlamydia
3
Gonorrhea
Sexually Transmitted Disease Surveillance 2011, Division of STD Prevention December 2012 3
Gonorrhea
Sexually Transmitted Disease Surveillance 2011, Division of STD Prevention December 2012 3
Syphilis
Sexually Transmitted Disease Surveillance 2011, Division of STD Prevention December 2012 3
In Iran
Prisons
tested for
HIV
6
injecting drug 62%
sexual contact 26%
Result
507
patients
Candida Trichomona
Neisseria
gonorrhoeae
Chlamydia
Men %47 %8 %9 %34
Women %53 %18 %4 %22
7
between May 2005 and May 2007
9
• 100 women during
2009-2010
• HIV-Ab, Chlamydia
trachomatis-IgG and
syphilis infection
Result:
• The overall prevalence of C.trachomatis was 19%.
• No case with syphilis or HIV infection.
 358 parent were assessed for knowledge about HPV
 73% of parents had no information about HPV
 26% had obtained their information via internet
 Others from studying medical resources
 Average score of mothers information about HPV
infection was higher than that of fathers
 Parent knowledge about the hazards of HPV was higher
than their knowledge about modes of transmission
10
Most common sexually
transmitted diseases (STD)
Cervical cancer in women
resulting in 233,000 deaths
per year
HPV infection often clears
over without treatment
HPV types 16 and 18 can be
a hazard to change
precancerous lesions
Gonorrhea
The ticking time bomb
SEM TEM Methylene Blue Gram Stain
Clinical manifestations
23
Gonococcal pharyngitis Neonatal ophthalmia
Virulence FactorsCellsurfacecomponents
Capsule – antiphagocytic
Pili
• Composed of repeating peptide subunits of pilin.
• Mediate initial attachment of gonococci to epithelial cells.
• Specific cell receptor unidentified; high specificity of binding for genito-epithelial cells.
OuterMembrane
Proteins
Por (protein I)
• Most abundant outer membrane protein;
• Forms trimers through which some nutrients enter the cell.
• Role in virulence
Opa (protein II)
• When expressed, is a major component of the cell surface.
• Function in virulence
Rmp (protein III) - Reduction–modifiable protein
Tbp1, Tbp2 – two transferrin-binding proteins
Lpb – Lactoferrin-binding protein
LOS (Lipooligosaccharide)
xtracell
lar
roducts
Secretory IgA 1 protease
24
Common diagnostic tests (as of June 2012) for detection
of N. gonorrhoeae
23
• Azithromycin is safe and effective in pregnant women, but
doxycycline is contraindicated.
Treatment
• CDC: patients with uncomplicated genital or rectal infections be
treated with ceftriaxone (250 mg) given intramuscularly as a single
dose or 400 mg of oral cefixime as a single dose.
3
• azithromycin as a single 1-g oral dose or doxycycline 100 mg
orally twice daily for 7 days) is recommended for
administration with ceftriaxone.
Pic: Unemo M, Shafer WM. Antibiotic resistance in Neisseria gonorrhoeae: origin, evolution, and lessons learned for the future. Ann N Y Acad Sci. 2011;1230:E19-28
Merbromin
(Mercurochrome)
Gonococcal infections are usually treated with
single-dose therapy with an agent found to cure
>95 per cent of cases.
11
Antimicrobial susceptibility
and genetic characteristics Articles
Number of
Articles
Years Number of
Isolates
In Countries Techniques AMR
5 1990-2012 2047 ،‫بوتان‬،‫هند‬
‫و‬ ‫پاکستان‬
‫کشورهای‬
‫اروپایی‬
MIC
E Test
Nitrocefin
ST (ESC)
NG-MAST
Ciprofloxacin
Tetracycline
Penicillin G
Azithromycin
Ceftriaxone
Cefixime
Spectinomycin
Gentamicin
Ertapenem
12-165 Articles
Enzyme
base
Iodometric
Chromomeric
AcidometricGrowth
base
Dilution
Disk
Diffusion
Etest
Clover leaf
17
Detection of beta-lactamases
Clover leaf
17
Acidometric Method
17
Iodometric method
• Penicillin
solution
• several
colonies
• Starch
solution
• iodine
• Penicillin
phenol red
• Several
colonies
Nitrocefin
 Slide Surface Assay
 Direct Contact Assay
 Broth Suspension Assay
 Lysed Cell Assay
 Filter Paper Assay
(10.0 mg/mL)
in DMSO
(1.0 mg/mL)
diluted with PBS
25 units of beta-
lactamase
Vortexed mixture
Red color within 20-30 min 17
Detection of all known beta-lactamases Neisseria gonorrhoeae, Moraxella,
Staphylococcus, Haemophilus, Enterococcus spp., and some anaerobic bacteria
for the production of beta-lactamase.
Average Susceptibility
Antibiotic Average (%)
Ciprofloxacin 79
Tetracycline 68
Penicillin G 46
Azithromycin 12
Ceftriaxone 5
Cefixime 5
12-16
ESC resistance determinants
penA (encodes altered forms of PBP2)
ponA (encoding an altered form of PBP1)
penB (encodes mutations in the major outer membrane
porin (PorB1b))
mtrR (MtrR represses expression of the mtrCDE,
The mtrCDE-encoded efflux pump)
12-16
http://www.medscape.com/viewarticl
e/777317_6
ESC resistance
determinantsmtrR
penB
penA
ponA
Mtr120: C-to-T transition
mutation 120 bp
upstream of the mtrC
start codon: to be
stronger than the wild-
type promoter
12-16
18
NG-MAST
Porin PorB (porB) gene (908 bp)
Subunit B of the transferrin binding protein (tbpB) gene
(110 bp)
(ST 1407, ST 1901, ST 7363) in Europe and Japan is dominant and
relative with the recent reports of recommended third generation
cephalosporins resistance
(ST 225) associated with ciprofloxacin resistance
12-16
 Therapeutic dose 64 µg/ml (2grX1)
 High-level spectinomycin-resistant MIC >1,024 4g/ml
 Amino acids 19 to 33 in the N terminus of the ribosomal protein 5S
that form a loop structure (loop 2) which nonspecifically binds to
helix 34 of 16S rRNA and is within 50 nm of the spectinomycin-
binding site. Amino acid alterations at this loop can disrupt the
binding of spectinomycin to the ribosome, which results in
spectinomycin resistance. 19
 21 different nanomaterials
 1-120 nm in diameter
20
SEM
hollow and shrank 20
TEM
20
Cell wall depth of the control group: 152635 nm cell wall depth in bacteria exposed to Ag NPs
was reduced to 71625 nm
TEM
20
TEM
20
20
 This study highlighted that the CDS disc diffusion technique yielded excellent
category agreement with their analogous Etest minimal inhibitory
concentrations in comparison to CLSI technique.
 Applicable microbiological method to detect antimicrobial susceptibilities of
N. gonorrhoeae in resource-poor countries.
 This technique will facilitate enhanced antimicrobial resistance surveillance
and direct and meaningful comparison of resistance data generated within
different national and international laboratories.
26
• CFU: 1 x 107
• Annular diameter oc 18mm was selected as the uniform cut-off point.
Calibrated Dichotomous
Sensitivity Test
Thank You

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STD Prevalence in World, USA and Iran, and Neisseria gonorrhoeae

  • 2.  Common bacterial infections  Neisseria gonorrhoeae (causes gonorrhoea or gonococcal infection)  Chlamydia trachomatis (causes chlamydial infections)  Treponema pallidum (causes syphilis)  Haemophilus ducreyi (causes chancroid)  Klebsiella granulomatis (causes granuloma inguinale or donovanosis).  Common Fungal infections  Candida albicans Vulvovaginitis, penile candidiasis http://www.who.int/mediacentre/factsheets/fs110/en/  Common viral infections  HIV (causes AIDS)  HSV 1-2  HPV (causes genital warts and certain subtypes lead to cervical cancer in women)  HBV (causes hepatitis and chronic cases may lead to cancer of the liver)  Commom Parasitic infection  Crab louse, colloquially known as "crabs" or "pubic lice" (Pthirus pubis)  Scabies (Sarcoptes scabiei)  Trichomoniasis (Trichomonas vaginalis), colloquially known as "trich" 1
  • 3. Unintended pregnancy, Potentiated HIV risk (three to six times the risk) STDs Background 2 (PID)
  • 4. 6 Ways STDs Impact Women Differently from Men  A woman’s anatomy can place her at a unique risk for STD infection, compared to a man.  Women are less likely to have symptoms of common STDs — such as chlamydia and gonorrhea — compared to men.  Women are more likely to confuse symptoms of an STD for something else.  STDs can lead to serious health complications and affect a woman’s future reproductive plans. 3
  • 5. 6 Ways STDs Impact Women Differently from Men  Women who are pregnant can pass STDs to their babies.  Human papillomavirus (HPV) is the most common sexually transmitted infection in women, and is the main cause of cervical cancer.  Women typically see their doctor more often than men.  There is a vaccine to prevent HPV; and available treatments for other STDs can prevent serious health consequences, such as infertility, if diagnosed and treated early. 3
  • 6. 2
  • 9. 4
  • 10.
  • 11.
  • 12.
  • 13.
  • 14. GLOBAL PREVALENCE AND INCIDENCE OF SELECTED CURABLE SEXUALLY TRANSMITTED INFECTIONS OVERVIEW AND ESTIMATES 1999-2001 NORTHAMERICA LATINAMERICA &THECARIBBEAN NORTHAFRICA &THEMIDDLE EAST SUB-SAHARAN AFRICA WESTERN EUROPE EASTERNEUROPE &CENTRALASIA EASTASIA& PACIFIC SOUTH& SOUTHEASTASIA AUSTRALIA& NEWZEALAND GLOBAL TOTAL CHLAMYDIAL INFECTIONS 4 9.5 3 16 5 6 5 43 0.5 92 GONORRHOEA 1.5 7.5 1.5 17 1 3.5 3 27 0.1 62 SYPHILIS 0.1 3 0.3 4 0.1 0.1 0.2 4 0.01 12 NEW CASES OF CURABLE STI AMONG ADULTS 14 38 10 69 17 22 18 151 1 340 Digits are in MILLION 4
  • 15. Incidence conveys information about the risk of contracting the disease, whereas prevalence indicates how widespread the disease is. 3
  • 17. 3
  • 18. 3
  • 20. Gonorrhea Sexually Transmitted Disease Surveillance 2011, Division of STD Prevention December 2012 3
  • 21. Gonorrhea Sexually Transmitted Disease Surveillance 2011, Division of STD Prevention December 2012 3
  • 22. Syphilis Sexually Transmitted Disease Surveillance 2011, Division of STD Prevention December 2012 3
  • 24. Prisons tested for HIV 6 injecting drug 62% sexual contact 26%
  • 25. Result 507 patients Candida Trichomona Neisseria gonorrhoeae Chlamydia Men %47 %8 %9 %34 Women %53 %18 %4 %22 7 between May 2005 and May 2007
  • 26. 9 • 100 women during 2009-2010 • HIV-Ab, Chlamydia trachomatis-IgG and syphilis infection Result: • The overall prevalence of C.trachomatis was 19%. • No case with syphilis or HIV infection.
  • 27.  358 parent were assessed for knowledge about HPV  73% of parents had no information about HPV  26% had obtained their information via internet  Others from studying medical resources  Average score of mothers information about HPV infection was higher than that of fathers  Parent knowledge about the hazards of HPV was higher than their knowledge about modes of transmission 10 Most common sexually transmitted diseases (STD) Cervical cancer in women resulting in 233,000 deaths per year HPV infection often clears over without treatment HPV types 16 and 18 can be a hazard to change precancerous lesions
  • 28. Gonorrhea The ticking time bomb SEM TEM Methylene Blue Gram Stain
  • 30. Virulence FactorsCellsurfacecomponents Capsule – antiphagocytic Pili • Composed of repeating peptide subunits of pilin. • Mediate initial attachment of gonococci to epithelial cells. • Specific cell receptor unidentified; high specificity of binding for genito-epithelial cells. OuterMembrane Proteins Por (protein I) • Most abundant outer membrane protein; • Forms trimers through which some nutrients enter the cell. • Role in virulence Opa (protein II) • When expressed, is a major component of the cell surface. • Function in virulence Rmp (protein III) - Reduction–modifiable protein Tbp1, Tbp2 – two transferrin-binding proteins Lpb – Lactoferrin-binding protein LOS (Lipooligosaccharide) xtracell lar roducts Secretory IgA 1 protease 24
  • 31. Common diagnostic tests (as of June 2012) for detection of N. gonorrhoeae 23
  • 32. • Azithromycin is safe and effective in pregnant women, but doxycycline is contraindicated. Treatment • CDC: patients with uncomplicated genital or rectal infections be treated with ceftriaxone (250 mg) given intramuscularly as a single dose or 400 mg of oral cefixime as a single dose. 3 • azithromycin as a single 1-g oral dose or doxycycline 100 mg orally twice daily for 7 days) is recommended for administration with ceftriaxone.
  • 33.
  • 34. Pic: Unemo M, Shafer WM. Antibiotic resistance in Neisseria gonorrhoeae: origin, evolution, and lessons learned for the future. Ann N Y Acad Sci. 2011;1230:E19-28 Merbromin (Mercurochrome) Gonococcal infections are usually treated with single-dose therapy with an agent found to cure >95 per cent of cases. 11
  • 35. Antimicrobial susceptibility and genetic characteristics Articles Number of Articles Years Number of Isolates In Countries Techniques AMR 5 1990-2012 2047 ،‫بوتان‬،‫هند‬ ‫و‬ ‫پاکستان‬ ‫کشورهای‬ ‫اروپایی‬ MIC E Test Nitrocefin ST (ESC) NG-MAST Ciprofloxacin Tetracycline Penicillin G Azithromycin Ceftriaxone Cefixime Spectinomycin Gentamicin Ertapenem 12-165 Articles
  • 38. Acidometric Method 17 Iodometric method • Penicillin solution • several colonies • Starch solution • iodine • Penicillin phenol red • Several colonies
  • 39. Nitrocefin  Slide Surface Assay  Direct Contact Assay  Broth Suspension Assay  Lysed Cell Assay  Filter Paper Assay (10.0 mg/mL) in DMSO (1.0 mg/mL) diluted with PBS 25 units of beta- lactamase Vortexed mixture Red color within 20-30 min 17 Detection of all known beta-lactamases Neisseria gonorrhoeae, Moraxella, Staphylococcus, Haemophilus, Enterococcus spp., and some anaerobic bacteria for the production of beta-lactamase.
  • 40. Average Susceptibility Antibiotic Average (%) Ciprofloxacin 79 Tetracycline 68 Penicillin G 46 Azithromycin 12 Ceftriaxone 5 Cefixime 5 12-16
  • 41. ESC resistance determinants penA (encodes altered forms of PBP2) ponA (encoding an altered form of PBP1) penB (encodes mutations in the major outer membrane porin (PorB1b)) mtrR (MtrR represses expression of the mtrCDE, The mtrCDE-encoded efflux pump) 12-16
  • 42. http://www.medscape.com/viewarticl e/777317_6 ESC resistance determinantsmtrR penB penA ponA Mtr120: C-to-T transition mutation 120 bp upstream of the mtrC start codon: to be stronger than the wild- type promoter 12-16 18
  • 43. NG-MAST Porin PorB (porB) gene (908 bp) Subunit B of the transferrin binding protein (tbpB) gene (110 bp) (ST 1407, ST 1901, ST 7363) in Europe and Japan is dominant and relative with the recent reports of recommended third generation cephalosporins resistance (ST 225) associated with ciprofloxacin resistance 12-16
  • 44.  Therapeutic dose 64 µg/ml (2grX1)  High-level spectinomycin-resistant MIC >1,024 4g/ml  Amino acids 19 to 33 in the N terminus of the ribosomal protein 5S that form a loop structure (loop 2) which nonspecifically binds to helix 34 of 16S rRNA and is within 50 nm of the spectinomycin- binding site. Amino acid alterations at this loop can disrupt the binding of spectinomycin to the ribosome, which results in spectinomycin resistance. 19
  • 45.  21 different nanomaterials  1-120 nm in diameter 20
  • 48. Cell wall depth of the control group: 152635 nm cell wall depth in bacteria exposed to Ag NPs was reduced to 71625 nm TEM 20
  • 50. 20
  • 51.  This study highlighted that the CDS disc diffusion technique yielded excellent category agreement with their analogous Etest minimal inhibitory concentrations in comparison to CLSI technique.  Applicable microbiological method to detect antimicrobial susceptibilities of N. gonorrhoeae in resource-poor countries.  This technique will facilitate enhanced antimicrobial resistance surveillance and direct and meaningful comparison of resistance data generated within different national and international laboratories. 26 • CFU: 1 x 107 • Annular diameter oc 18mm was selected as the uniform cut-off point. Calibrated Dichotomous Sensitivity Test