Technical updates on Voluntary Medical Male Circumcision:device methods, tetanus-toxoid containing vaccination

Julia Samuelson, WHO Department of HIV/AIDS26 February 2017

WHO Prequalification status on devices for adolescent and adult male circumcision for HIV prevention

ShangRing: prequalified to 13 years and older METHOD CHANGES pending data review: age to 10 years, topical

anaesthetic cream, no flip technique, fewer device sizes. Anticipated Q2 2017

PrePex: prequalified to 13 years and older NEW RISK and MANAGEMENT

use only with evidence of sufficient protection through vaccination or provision of doses(s) as needed.

tetanus --30 fold increased risk compared to conventional surgical CHANGES REQUESTED: pending review, age to 10 under review NEW METHOD : foreskin removal at Day 0

Requires series of studies and data per Framework for Clinical Evaluation

UniCirc: no full submission on PQ

Tetanus and Clostridium tetani

Causes spastic paralysis suffering requiring intensive care Often fatal in low resource setting (40-70%)

Caused by neurotoxin produced by Clostridium tetani Spores widespread in nature: dust, soil, faeces

Spores can survive extreme conditions such as Boiling for 10-15 minutes Disinfectants such as alcohol, phenol or formalin

Spores killed by iodine, bleach, H2O2, extreme heat Vegetative bacteria thrive in anaerobic conditions Any break in the skin can serve as entry point Effective cheap vaccine. Not communicable so no herd immunity. Incubation period average ~7 days

Annual VMMCs in East and Southern Africa by method and reported tetanus cases by year (n = 16)

(cases identified through VMMC programmes)

= 1 tetanus case after conventional surgery

= 1 tetanus case after elastic collar compression

Year

Over 12 million men reached in 14 countriesBy MMC method: 96% -- with conventional surgical

methods < 200 000 with PrePex

Chart1201020102011201120122012201320132014201420152015mid year 2016 (estim)mid year 2016 (estim)Total casesprepex42292488428317108455200265856611550324097761500262369852000130000069000Sheet1Total casesprepex20104229242011884283201217108455200201326585661155020143240977615002015262369852000mid year 2016 (estim)130000069000To resize chart data range, drag lower right corner of range.

Epidemiology: Tetanus incidence and incidence rate ratio by circumcision method, 2014 June 2016

Countries

Elastic collar

compression devicecases/circ

s

Incidence per 100,000 (95% CI)

Surgerycases/circs

Incidence per 100,000 (95% CI)

Incidence rate ratio (95% CI)

Kenya, Rwanda, Uganda and the United Republic of Tanzania

6 / 113,662 5.28 (1.94, 11.5) 6 / 3,717,338

0.161 (0.059, 0.351) 32.7 (8.74, 122)

Rwanda and Uganda only

6 / 110,800

5.45 (1.99, 11.8) 3 / 1,986,443 0.151 (0.031, 0.441)

35.9 (7.66, 222)

Countries included based on reports of Tetanus case by June 2016; Zimbabwe case not included but IRR remains similar

Biological plausibility on greater risk of tetanus with elastic collar compression method

All cases were generalized and fit association criteria A or B Potential contamination before and while wearing

Spores widespread in environment Germination of spores and multiplication

Anaerobic environment, necrotic tissue with PrePex Inherent method difference

Incubation 1 -112 days all cases 9-12 days post placement Presence of flagella

migration possible Toxin entry possible:

microabrasions, bleeding at removal, granulation tissue friable

Tetanus toxoid-containing vaccination and sero protection

Global and regional diphtheria-tetanus-pertussis 3 (DTP) immunization coverage,

19802013, and VMMC age cohort examples

In 2015 age 30 year:

30%

In 2015 age

10 years: 60%

coverage

In 2015, age 20

year: 55%

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Summary of hospital studies of non-neonatal tetanus in sub-Saharan Africa published 2003-2014 71% males, 32.7 years

Gender differential in sero protectionTetanus cases by age and sex in Viet Nam

Tetanus sero protection Africa

2006

1914

First Tetanus toxoid vaccine

V B.C.

Aristotle described tetanus

1924

Passive massive immunization in humans

2007

WHO: Tetanus toxoid containing vaccination for general population in addition to maternal and infant schedules

1-2 countries with post-infant booster dose policy

VMMC for men in high HIV prevalence settings. ~ 12 million MCs in 14 countries

2 paces of implementing WHO recommendations

on prevention of HIV and tetanus in ESA

2016

Some key points Exponential expansion of medical male circumcision

services to men in 5 years

Gender differential on tetanus protection men not reached systematically with TTCV vaccination

policy and practice of boosters limited or lacking

VMMC is safe with low numbers of adverse events despite large numbers of circumcisions performed in resource limited settings tetanus rare after VMMC, but risk exists with wound and is

preventable

Risk differs by method so risk mitigation will differ

WHO Advice - July and September 2016 For conventional surgical methods in which the foreskin was removed at

the time of the surgery, no modification to the 2015 consultation advice on vaccination:

Ministries of health were advised to develop and phase-in effective and practical delivery strategies for providing tetanus vaccination in the context of their programmes (VMMC and vaccination).

strategies depend on the countrys TTCV schedule and practices, and its tetanus burden.

unless an individual has documented evidence of received of a full five-dose TTCV series, it is advised that a single TTCV dose be administered before or at the time of circumcision.

WHO Advice: July and September 2016 TTCV Differential Mitigation

Circumcision with a device method where the foreskin is left in situ and removed several days after application should be undertaken only if the client is adequately protected against tetanus by immunization with tetanus-toxoid-containing vaccine (TTCV):

two TTCV doses at least 4 weeks apart, with the second dose at least 2 weeks before device placement; or

if received three infant doses, or one dose during adolescence or adulthood, a TTCV booster at least 2 weeks before device placement (a booster at the time of placement provides only limited protection as it takes 714 days for antibodies to rise to protective levels); or

a series of five doses of TTCV.

July and September 2016 reports A clean care approach for all circumcision methods:

Encourage personal cleanliness, asking the client to wash his genital area, including under the foreskin, before circumcision and encouraging him to wear clean undergarments.

Follow standard surgical protocols on skin preparation Enhance individual and community education on clean wound care

clear and understandable instructions on wound care and genital hygiene

clean or sterile dressings to use at home when to return to the health-care facility for post-procedure

care educate on benefits of vaccination against tetanus and educate

on dangers of applying substances that may contain Clostridium tetani (e.g. animal dung poultices or herbal remedies).

Tetanus toxoid-containing vaccination recommendationWER NO 6., Feb 2017, WHO SAGE recommendations and advocacy for TTCV for adolescent boys

Inputs from VMMC and gender difference 6 doses 3 primary doses plus 3 booster doses (12-23 mo, 4-7 y, 9-15 y) 5 doses if start any time after infancy

Adolescents. 9 15 years. Aligned with HPV. Pre-adolescent and adolescent boosters are also programmatically feasible and

align with the human papillomavirus immunization schedule (girls 9 14 years)

Catch up boosters: military, synergies with adolescent VMMC, method specific

Provide vaccination cards Preferably Td Cost 0.10 USD per dose Other prevention efforts needed:

community education on clean wound care

Collaborate with MoEd

Potential issues on implementation

Resources - Stock of vaccine available? Funding?

Safety monitoring strengthening within national programmes -- reporting tetanus and other adverse events. Only Uganda reports non-neonatal tetanus

Immediate and longer term method perspectives: Maintain high quality essential surgical skills for other interventions Will method choice make difference to accelerate for 15 29 yo through 2020 Adolescents - younger adolescents need another method as not eligible for ECC

method ShangRing of interest?

Thank You

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Technical updates on Voluntary Medical Male Circumcision:device methods, tetanus-toxoid containing vaccination WHO Prequalification status on devices for adolescent and adult male circumcision for HIV preventionSlide Number 3Annual VMMCs in East and Southern Africa by method and reported tetanus cases by year (n = 16) (cases identified through VMMC programmes)Slide Number 6Biological plausibility on greater risk of tetanus with elastic collar compression methodTetanus toxoid-containing vaccination and sero protectionGlobal and regional diphtheria-tetanus-pertussis 3 (DTP) immunization coverage, 19802013, and VMMC age cohort examplesGender differential in sero protectionSlide Number 11Slide Number 12WHO Advice - July and September 2016WHO Advice: July and September 2016 TTCV Differential MitigationJuly and September 2016 reportsTetanus toxoid-containing vaccination recommendationPotential issues on implementationThank You