Syphilis

Dr Sandip Click to edit Master subtitle style Dr Aashima Dr Rashmi Bagga

7/27/12

Overview

One of the most common STDs All women with genital ulcers should undergo a serological test for syphilis A painless & minimally tender ulcer, not accompanied by inguinal lymphadenopathy, is likely to be syphilis, especially if the ulcer is indurated
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Mode Of Transmission

Intimate contact with infected partner Incubation Period-3 to 90 days

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Classification Of Syphilis
Primary syphilis Secondary syphilis 6 weeks after primary Early latent Clinical features Chancre

Late latent Tertiary syphilis Gummas

3-12 weeks > 1 year after secondary

Predominan Lasting for tly 1 year dermatologi c and other systemic manifestati ons Infectivity ++++ (spirochetem ia) 7/27/12 ++++ Vertical +++ +++ + -

+++

++

Diagnosis
v

Non-treponemal serological testVDRL, RPR Confirmatory tests(Treponemal serological tests)-FTA-abs, TPHA The results of nontreponemal testscorrelate with disease activity & should be reported quantitatively Syphilis screening in pregnancy-VDRL

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Sensitivity% Specificity %Advantages Disadvantag es

Non treponema l tests

97-99

Can be Relatively quantified non specific and used to assess response to treatment

Primary Secondary Latent Tertiary

78-86 100 95-98 71-73 97-99 Highly specific Cannot be used for assessing response to treatment

Treponema l tests

Primary 7/27/12

76-84

Syphilis & Pregnancy

o

Timing of infection-usually after 18 weeks(due to fetal immunocompetence prior to 18weeks, fetus does not manifest immunological inflammatory response;Silverstein,1962) Mode of transmissionTransplacental transmission(commonest) Neonatal infection-contact with

1)

2)

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Syphilis & Pregnancy

o

Congenital infection depends on degree of spirochetemia & duration of disease Associated with-substance abuse(cocaine),HIV infection,lack of perinatal care,treatment failures & reinfection,minority race or ethnicity(Taylor & co-workers,2008)

Increased risk of- fetal 7/27/12 infection,preterm labour,fetal death

Syphilis & Pregnancy

o

Early congenital syphilis first 2 years of life rash, hepatosplenlmegaly, snuffles, periostitis. Late congenital syphilis - > 2 years Hutchinsons triad

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Diagnosis

If VDRL >1:8 then treat infection If VDRL < 1:8 then confirm with TPHA If TPHA > 1:80 then treat infection If TPHA < 1:80 then repeat test after 3-4 weeks

Similar protocol for the spouse, ideally contact tracing should be done.

All VDRL positive should be tested for HIV

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Treatment
Early syphilis: Benzathine penicillin G 2.4 million units IM single dose Latent syphilis: Benzathine penicillin G 2.4 million units IM weekly for 3 doses Neurosyphilis : Aq. Crys.penicillin G 3-4 million units IV every 4 hours for 10 to 14 days Or Procaine penicillin G 2.4 million units IM daily plus probenecid 500 mg orally 4 times daily, both for 10-14 days Efficacy depends on stage of disease 100% for primary ,latent, tertiary syphilis 95% for secondary and early latent syphilis If treated before 18-20 weeks 100% efficacy regardless 7/27/12 of stage

Penicillin Allergic Individuals

Penicillin desensitization- oral or parenteral Phenoxymethyl penicillin given over 3.75 hours Lasts for 3-4 weeks Azithromycin and ceftriaxone offer potential alternatives but data is insufficient

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Jarisch Herxheimer reaction

systemic reaction of probably due to rapid killing and release of spirochetal antigens. Occurs 2-4 hours after treatment with penicillin

s/s fever, chills, hypotension, myalgias, accentuation of cutaneous lesions. Will last for 12-48 hours and then abate

More common in HIV coinfected and early disease

Pregnant woman may develop PTL, decreased fetal movements, fetal distress (maximum risk within 48 hours of treatment)

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Follow Up
VDRL at 6 and 12 months . 24 month sample in case of latent disease. 4 fold decrease by 6-12 months primary & secondary 12-24 months early latent > 24 months late latent
v

Decrease is slower in case of later stage, HIV coinfection, multiple episodes, pregnancy
v

HIV coinfected every 3 months in the first year and then at 24 months
v

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Follow Up In Pregnancy
q q

Serologic responses similar to non pregnant women After treatment VDRL at 28-32 weeks, and at delivery suffices Monthly titers in patients with risk of re-infection and where prevalence of infection is high
q

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Failures
v

Treatment

Repeat treatment is required if symptoms persist, recur, or if titers increase or do not decrease appropriately Serofast status : persistently low titers in adequately treated patients
v

Re-treat all women with titers >or= 1:4 for more than a year, BPG 2.4 million units for 3 weeks
v

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HIV And Pregnancy

Click to edit Master subtitle style

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The shocking figures

29 years old epidemic(The first case was detected in July 1981 in Los Angeles, US) The first case in India-in 1986 in Chennai Already killed > 25 million people > 17.7 million women living with HIV

> 2.3 million children infected(>2 lakh in India) 7/27/12

The shocking facts

In India-1/3rd of the total affected population are rural

Classification of Indian Prevalence of HIV states infection High States >1% among antenatal Maharashtra,TN,Manip women urKarnataka,AP,Nagal and < 1% among Gujarat,Goa & antenatal women & Pandicherry >5% among high risk group < 1% among Other states antenatal women & <5% among high risk group

Intermediate

Low

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The shocking figures

The average prevalence rate-0.3% amongst pregnant women Nearly 1lakh infected mothers are delivering about 30,000 infected infants with an average rate of 30% perinatal transmission

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The shocking figures

Rates of MTCT(mother to child transmission)
o

Transmission rates in the USA & Western Europe-15 to 20% In developing countries-40% In India-24% in Mumbai,48% amongst tribal women

o o

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Ignorance prevails

In 2006, globally < 8% pregnant women offered HIV diagnosis & prevention services. 9 % HIV infected women received ART for prevention of mother to child transmission. Vertical transmission rate

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Routes of Transmission
Route of transmission Sexual Blood transfusion Percentage 84.6 3.2

Injection with contaminated needles 3.2 Perinatal trannmission 6.6

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Risk Factors For Transmission In Pregnancy

Type of HIV strain(HIV1 or HIV2) Timing of infection(early,late pregnancy or labour) Type of disease(symptomatic/asymptomatic) Viral load,CD4 counts & immune status(3.6% transmission rate when viral load-<1000 copies/ml) Vitamin A deficiency, absence of

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Obstetrical factors

Risk Factors For Transmission In Pregnancy

prematurity, pprom,chorioamnionitis,prolonged labour,operative interventions & blood transfusion tuberculosis,hepatitis,coagulopathy,HTN

Medical complications

Drugs likeMgSO4,anticoagulants,BDZ,anticonv ulsants(reduces the efficacy of 7/27/12

Effect Of Pregnancy On HIV Virus

HIV infection-slightly accelerated;hastens development of AIDS Plasma HIV1RNA-unaffected in pregnancy but increases in postpartum period CD4 count-reaches a nadir at 32weeks followed by rebound in postpartum period
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Unprotected sexual intercourse

The Effect Of HIV Infection On Pregnancy

Increased risk of abortion(3-6 times) IUGR(>2times) Preterm labour(>2times) Still birth Increased risk of maternal anemia & low birth weight babies

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Counseling
q

Types-

a)Opt out-provider initiated counseling & testing b)client initiated counseling & testing or direct walk-in
q

Former-prime strategy to include 7/27/12 maximum number of antenatal

Counseling
v

Preconception counselingimportant intervention in reducing unplanned pregnancy Pretest counseling-informed consent for testing is obtained; in case of refusal, client is recounseled;test report is kept confidential

Post test counseling-provides 7/27/12 information regarding disease status,

Disease classification

CDC classification - based on immunological

marker

WHO classification - based on clinical stage

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CDC Classification (1993)

Assesses disease severity by CD4 counts & presence of specific AIDS related conditions A B C

CD4 count > 500 cells / micro L

Asymp, acute Symtomatic AIDS indicator or PGL cond. Not A / C cond

A1

B1

C1

200-499 cells/ micro L

A2

B2

C2

<200 cells / micro L 7/27/12

A3

B3

C3

Recommendation for initiating ART

WHO clinical stage 1 (asymptomatic,PGL) 2 (unexpl mod wt loss, rec URTI, rec oral ulceration) 3 (unexpl severe wt loss,pul TB, chr diarrhoea, persistent fever) 4 (pneumocystis, CMV, kaposi, extrapul TB, invasive Ca Cx ) 7/27/12 CD4 test not available DO NOT TREAT CD4 test available

TREAT IF CD4<200

DO NOT TREAT

TREAT IF CD4<200

TREAT

TREAT IF CD4<350

TREAT

TREAT IRR OF CD4

Preconceptional Counseling

Select effective & appropriate contraceptive method-reduces unwanted pregnancies Safe sexual practices,eliminating alcohol & smoking Choice of appropriate ART-for disease control & prevent teratogenicity Attainment of-stable, maximally suppressed viral load prior to 7/27/12 conception

ARV To Treat Maternal Disease

Based on CD4 count & symptoms

Criteria
Symptomatic CD4- count <350 CD4- count >350

WHO Dec 2009 Guidelines

HAART HAART No need of ART

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Anti-Retroviral Drugs
Group of ARV NRTI Name of drugs Common adverse effects Zidovudine(ZDV),Lamiv Nausia,vomiting,anemia udine(3TC),Stavudine(D ,elevated liver 4t),Didanosine(ddL),Emtenzymes,lactic ricitabine,Tenofovir,Aba acidosis,hyperglycemia cavir Nevirapine(NVP),Delavir Liver dysfunction, idine(DLV),Efavirenz(EF hypersensitivity V),Atazanavir(ATV) reaction Indinavir(IND), Saquinavir(SQV), Ritonavir(RTV), Nelfinavir(NFV) Hyperglycemia,diabetic exacerbationketoacidosis,viral diarrhoea,deranged liver function

NNRTI

Protease Inhibitors

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Anti-Retroviral Drugs

Newer ARV drugsFusion Inhibitors-Enfuvirtide CCR5 Inhibitors-Maraviroc(MVC) Integrage Inhibitors-Raltegravir(RAL)

1) 2) 3)

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ARV In Resource Limited Settings

1)

ZDV-300mg BD,28 weeks onwards till 1 week postpartum; 4 weeks for neonate Single dose Nevirapine,200mg at the onset of labour; 2mg/kg wt. to neonate between 24 to 72 hours (NACO, India) 1 + 3 ( Thailand) ZDV + Lamivudine(3TC)-36 weeks 7/27/12 onwards to mother & 1 week

2)

3) 4)

International Recommendation To Prevent MTCT In Resource Limited Settings-2006 5) ZDV + 3TC + Single dose
Nevirapine at the onset of labour

ZDV + 3TC tail for 7 days postpartum(to reduce Nevirapine resistance) For newborn-single dose Nevirapine & 1 to 4 weeks of ZDV
WHO,

Dao etal, 2007 7/27/12

ARV Prophylaxis Options For Women Not Requiring Treatment For Their Own Health
v v

For mother Antepartum AZT from 14wks onward NEV at the onset of labour

1)

For mother OptionOption AB:Maternal triple Maternal AZT Triple ARV from ARV prophylaxis 14wks until 1wk after all exposure to breast milk has ended Breast feeding infant-Daily

2)

3)

AZT+3TC during labour, delivery 7/27/12

WHO Guidelines For Resource Limited Countries2009

Lifelong ART if CD4 count< 350,regardless of symptomatology Start ARV at 14 weeks & infant prophylaxis till 6 weeks Breast feeding till 12 months with ARV to mother or infant during breast feeding period

EBF for 1st 6 months; introduce complimentary food thereafter & 7/27/12 continue breastfeed for 12 months

WHO Guidelines For Resource Limited Countries2009

Breastfeed should be stopped once a nutritionally adequate & safe diet without breast milk can be provided Infant prophylaxis during breastfeeding (Nevirapine daily till 1 week after breastfeeding is completed)

HAART for mother in pregnancy & 1 week after breastfeeding is over & 7/27/12 infant prophylaxis till 6 weeks(AZT or

NACO Guidelines

AZT should be included as one of the components of the regimen unless there are absolute contraindications for using it. EFV should be avoided in the first trimester of pregnancy (because of the risk of teratogenicity). When NVP is used and the mothers CD4 count is >250/mm3, close monitoring of liver function is required. 7/27/12

NACO Guidelines

All HIV-positive women should be referred to the ART centre for registration into care and screened for medical eligibility for ART once they have been diagnosed in the PPTCT programme Co-trimoxazole prophylaxis is indicated in HIV-positive pregnant women as per the guidelines for adults The criteria for initiating ART in pregnant women are the same as for other adults: WHO clinical stage 3 or 4 disease WHO clinical stage 1 or 2 disease and CD4
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NACO Guidelines
The following are the first-line ART regimens for pregnant women requiring treatment for her own health:

AZT + 3TC + NVP EFV can be used as a substitute for NVP if there are contraindications to NVP, such as hepatotoxicity and rash EFV should be used with caution as it

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NACO Guidelines

If the liver enzymes increase to grade 3 or higher (ALT and/or AST >5.1 times the upper normal limit) without an alternative explanation, NVP should be permanently discontinued If symptoms suggesting hepatic toxicity, including rash, develop in pregnant women, NVP should be discontinued immediately
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NACO Guidelines

The combination of ddL and d4T should not be used because of associated increased toxicities in pregnant women In pregnant women who are on a first-line EFV-based regimen, EFV should be substituted with NVP in the first trimester. Women with higher CD4 cell counts should be monitored closely ART is recommended for postpartum breastfeeding women who meet the medical criteria for the initiation of ART for their own health. The preferred regimen is 7/27/12 AZT + 3TC + NVP

Issues Related To Antenatal Care

RNA level & CD4 count in each trimester Prophylaxis for opportunistic infection( if CD4 count<200) Complete hemogram, LFT, urine c/s, VDRL, HBsAg,chest X-Ray(if symptomatic) Sreening for STI(endocervical swab,urine for PCR),PAP smear(BV)

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Issues Related To Antenatal Care

Avoid invasive tests(CVS,Amniocentesis) Iron,calcium,vitamine suplementation High protein diet Discuss with the mother & husband regardingART Mode of delivery

a) b)

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Mode Of Delivery
v

Elective Caesarean deliveryLower transmission rate<2%(except ? If RNA<1000 copies/ml) Timing-38 weeks(before labour onset or membrane rupture) Transmission rate increases 2%/hour after membrane rupture

1)

2)

3)

4)

If duration of membrane rupture>4 hours,the benefit of Caesarean 7/27/12

Adverse Effects Of ARV Drugs

ZDV-Bone marrow depression & cause maternal anemia. Stavudine can replace ZDV till a blood transfusion is given to correct anemia Stavudine along with Didanosine may cause lactic acidosis

EFV(Category D)teratogenic,increases the risk of CNS 7/27/12 deffects & should not be used in the

Adverse Effects Of ARV Drugs

Nevirapine causes 10 fold increased risk of hepatic dysfunction & failure within first 18weeks of its use Indinavir & Atazanavir-risk of neonatal hyperbilirubinemia Tenofovir,Abacavir & Emtricitabinlacks sufficient data

All cases of ARV exposure during pregnancy should be reported to 7/27/12 Antiretroviral Pregnancy Registry

Care of HIV exposed newborn

Wipe mouth & nostrils at delivery of head. Clamp cord as early as possible. Avoid milking of cord. Initiate feeding within 1st hour according to mothers informed choice.
NACO 2007

guidelines

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Guidelines on infant feeding

HIV infected female should use replacement feeding only when it is A acceptable F feasible A affordable S sustainable S safe Otherwise practice exclusive breast feeding for 1st 6 months or until 7/27/12

Diagnosis in infant

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PCP prophylaxis in infants

All HIV exposed infants should get cotrimoxazole prophylaxis from 4-6 weeks of age or at 1st encounter until HIV infection is excluded.

Also recommended in

All HIV infected infants < 1 year of age irrespective of symptoms & CD4 count. All HIV infected children 1-5 years of age 7/27/12

HIV in preg with active TB

Commonest opportunistic infection recommend EFV containing regimen CD4 < 200 start ATT first start ART as soon as ATT is tolerated (b/w 2wks - 2months)

CD4 200-350

start ATT first (i.e. after completion of intensive phase)

start ART 8wks after starting ATT CD4 > 350 start ATT first re evaluate pt for ART at 8wks & at end of ATT
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Criteria for cotrimoxazole prophylaxis

CD4<200 (any clinical stage) WHO stage 3 or 4 (irresp of CD4 count)

PROPHYLAXIS 1 DS tablets once daily (i.e. 800mg SMZ + 160mg TMP)

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ART in Hep B co-infection

Include lamivudine in anti retroviral regimen Prefer EFV over NVP if liver dysfunction present Must do HbsAg at first antenatal visit For HbsAg negative

patients
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Contraception in HIV +ve

NVP & protease inhibitors reduce ethinyl estradiol levels Avoid hormonal contraception/use with caution & appropriate dose adjustment No interaction of depo provera inj. with anti retroviral drugs IUCDs to be used with caution because of risk of infection & increased menstrual NACO 2007 flow guidelines 7/27/12 Consistent use of condoms recommended