Maternal Sepsis Linda Bartlett MD, MHSc. May 6, 2012

Acknowledgements

ANISA Team:

PI: Samir K Saha

Co-PI: Shams El Arifeen

Site PIs: Abdullah Baqui,

Anita Zaidi, Zulfiqar

Bhutta

Shahidul and Nicholas

Connor

CDC

ICCDRB

Shimantik

MCHIP Quality of Care

Survey Team:

Barbara Rawlins

Heather Rosen

David Cantor

Jim Ricca

Patricia Gomez

Rebecca Levine

Eva Bazant

Outline

Epidemiology

Prevention at facility and community levels

Management

Research: ANISA PP Sepsis

WHO Definition of puerperal sepsis

(PP sepsis)

Infection of the genital tract occurring at any time

between the onset of the rupture of membranes or

labour and the 42nd day postpartum in which fever

and one or more of the following are present:

pelvic pain

abnormal vaginal discharge

abnormal odor of discharge

delay in the rate of reduction of size of the uterus.

Epidemiology

Incidence: 5 to 20% range

Variation by type of delivery (caesarean > vaginal), location of

birth (home > facility), and the use of antibiotic prophylaxis among

other factors.

WHO Global BoD = 5% non-facility births and 2.5% facility births

Complications:

septicemia, shock, peritonitis, or abscess formation

chronic pelvic inflammatory disease, tubal occlusion,

impaired fertility

infection may be transmitted to newborns

Mortality

CFR = 20% before the advent of

antibiotics and understanding of the

infectious nature of puerperal sepsis.

CFR = < 2% with appropriate antibiotic

treatment

3rd most frequent cause of maternal

mortality

75,000 maternal deaths

or about 12% of all maternal

deaths globally.

Indirect

14%

HIV

3%

Other direct causes

5%

unclassified

6%

Sepsis

11% Anemia

8%

Hypertensive

Disorder

10%

Hemorrhage

31%

Unsafe Abortion

5%

Obstructed Labor

7%

Country Distribution of Sepsis as Proportion

of Maternal Deaths

Khan KS, et al. Lancet. 2006;367:1066

PP Sepsis causes by polymicrobial pathogens.

(Source: Landscape Analysis of Serious and Life Threatening Maternal Infections)

Clinical Syndromes Commonly Associated Microorganisms

Puerperal Sepsis

(endometritis)

Aerobes:

Gram pos- Strep, Staph

Gram neg: E coli,

Gram Variable Gardnerella

Anaerobes: peptococcus

Others: Chlamydia

Ureaplasma parvum

Risk factors

Prolonged labour, PROM, caesarean section,

chorioamnionitis, > 5 vaginal exams

Particularly prevalent in developing countries:

Delivery by untrained birth attendants

Unhygienic conditions

Lack of access to adequate healthcare

Delays in reaching health facilities

Anemia

Malnutrition

HIV/AIDS

Timing of Maternal Deaths

24

16

45

23

14

8 6 4 0

5

10

15

20

25

30

35

40

45

50

Antepartum Intrapartum 0 - 1 PP 2 - 7 PP 8 - 14 PP 15 - 21 PP 22 - 30 PP 31 - 42 PP

10

Lee et al. The Post partum-period, the key to maternal mortality. Int Jrnl Ob Gyn 1994, 56

Hemorrhage

PE/E

PP sepsis

PREVENTION

AND

MANAGEMENT

Prevention at Facility Level

Reduce the length of labor

Partograph

Ambulation

Labor support

Appropriate controlled augmentation of labor

Reduce the time of rupture of membranes

Delay artificial rupture of membranes

Shorten labor

Reduce the number of vaginal exams

Treatment for PROM

Infection Prevention

Availability of infection prevention supplies

in the delivery room

Notes: Bars represent average of mean

scores for all countries and high-low error

bars show the by-country range.

(Results from MCHIP Quality of Care surveys in 7 African

countries)N= 643 facilities

71% 97% 90% 88% 0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Soap and pipedwater/bucket with tap

Sharps container Already mixeddecontaminating solution

Clean (or sterile) gloves

Quality of infection prevention

practices during labor & delivery

38%

37%

93%

57%

94%

86%

95%

30%

74%

67%

0% 20% 40% 60% 80% 100%

Initial assessment: Washes his/her hands before anyexamination

1st stage: Washes his/her hands before any examination

Wears high-level disinfected or sterile gloves for vaginalexamination

Puts on clean protective clothing in preparation for birth

Disposes of all sharps in puncture-proof container

Decontaminates all reusable instruments in 0.5% chlorinesolution

Disposes of all contaminated waste in leakproofcontainers

Wipes apron with 0.5% chlorine solution

After delivery: Washes his/her hands

Mean percent score

N= 2689 observations

Availability of Supplies to Manage Sepsis

Notes: Bars represent average of mean

scores for all countries and high-low error

bars show the by-country range.

N= 643 facilities

49% 58% 90% 88% 0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Amoxicillin or ampicillin Gentamicin Syringes and needles Ringer's lactate, D5NS orNS infusion

Management of Infection

Antibiotics

started early

WHO - Managing

Complications of Pregnancy

and Childbirth

Prevention at Community level: Issues

Reducing maternal mortality due to sepsis in South Asia

(SA) hampered by large proportion of births that occur

outside of formal health sector.

41% births attended by SBA in SA

• 14% Bangladesh – 11% in rural areas where 80% births occur

Even where deliveries take place in facilities, majority of

women are home within 24-48 hours of delivery BEFORE

the time when sepsis deaths occur.

Prevention at Community level 2

Training traditional birth attendants and/or arming them with

clean birth kits was associated with reduced infection and

maternal mortality in Pakistan, Egypt and Tanzania.

In Pakistan, odds of puerperal sepsis were greatly

reduced in the training intervention group (OR 0.17,

95%CI 0.13-0.23) compared to control and there was a

non-significant reduction in maternal mortality (OR 0.74,

95%CI 0.45-1.23). (Bhutta)

Women who used clean delivery kits were 3.2 times less

likely to develop puerperal sepsis than women who did not

in Tanzania (Winan et al, 2007).

Prevention at Community level 3

Cleansing of vaginal canal with Chlorhexidine has shown

to reduce PP infection.

Malawi: 0.25% chlorhexidine used

postpartum infection rates were 1.7 in the intervention and

5.1 in non-intervention per 1000 deliveries (OR: 0.37, 0.13

to 0.82). (Taha et al. 1997)

Evidence also suggests that supplementation with vitamin

A or other micronutrients can reduce sepsis mortality.

Identification and Management

Women’s groups in Nepal reported increased care seeking for

maternal illness, clean birth kit usage and hand washing by birth

attendants

Lower maternal mortality (OR 0.22, 95%CI 0.05-0.90), although

the cause-specific morbidity and mortality was not reported.

(Manandhar DS.)

Where do we go next?

Facility:

Research to better understand quality of care

Identify most important interventions

Find out what barriers are

Innovations: Biomarkers

Community:

Population based studies

ANISA: Aetiology of Neonatal Infection

in South Asia

Determine incidence of aetiology of

community acquired neonatal infections

and the antibiotic resistance patterns of

bacterial isolates.

Identified using both community-based

surveillance of pregnant women and their

newborns and confirming sepsis through

standard and new laboratory methods.

22

Supplement al study

ANISA Maternal Post-partum Sepsis

Development of a community-based

presumptive clinical diagnosis algorithm and

treatment regimen for maternal puerperal

sepsis

Goal: To prevent maternal deaths and long term health

consequences of PP sepsis among women in 2 low resource

South Asian countries: Pakistan and Bangladesh

1. Development and clinical validation of a suitable diagnostic

algorithm to identify PP sepsis in the community by front-line

workers.

2. Identify incidence and risk factors for PP sepsis measured and

analyzed to inform preventive strategies and further refinement of

the algorithm.

3. Collection of samples (urine blood, and endometrium) among all

women suspected to have PP sepsis and among matched controls.

4. Identify aetiology-specific incidence of community-acquired

bacterial infections.

24

Characteristics of the sample Characteristics

Bangladesh

Rural

Pakistan

Rural Pakistan Urban Total

Population ~340,000 ~340,000 ~ 270,000 950, 000

Birth cohort per year, all women

who consent will be assessed for PP

sepsis

10,200 8,500 7,500 26,200

Expected number of PP sepsis cases

using conservative estimate of 5% of

PP women

510 350 425 1325

Expected number of women with

suspected PP sepsis who will consent

to participate (Assume 70%

participation rate)

360 300 265 925

Expected number of women without

sepsis (controls) who will consent to

participate

360 300 265 925

Total specimens 720 600 530 1850

Timeline:

Formative: Now – October, 2012

Pregnancy Surveillance; Nov. 2012 – 2013

Analyses and Dissemination: Dec. 2013 –

July 2013.

Thank you!

Additional slides

Soft Tissue

3rd Trimester 1st Trimester 2nd Trimester PP L&D

Pyelonephritis/Urosepsis

Chorioamnionitis/Puerperal Sepsis

Septic Abortion

Skin & Soft Tissue Infection

STIs

Peak Occurrence of Priority Maternal Infections

Source: Landscape Analysis of Serious and Life Threatening Maternal Infections)

Disease

Occurrence High Low

Disease

Occurrence High Low Treatment

1st Trimester 2nd Trimester 3rd Trimester L&D PP

Prophylactic

antibiotics for women

with PROM

Cervical vaginal

screening at time of

PROM

Chorioamnionitis/Puerperal Sepsis

Disease Burden

• Wide incidence:

• Puerperal sepsis 2%-20%

• Chorioamnionitis 5%

• 10%-15% of all maternal deaths

• 75,000 deaths annually

• Risk factors: PPROM, prolonged labor,

Cesarean

Etiology

• Polymicrobial indigenous

flora

• Anaerobes

Estimated Contribution of Maternal

Infection to Maternal Mortality

Other, 18%

Hypertension, 11%

Haemorrhage, 25%

Puerperal Sepsis, 13

Septic Abortion, 12

Urosepsis, 5

Soft Tissue, 1 HIV/AIDS, 5

Malaria, 9

Infections 45%

Courtesy of M. Gravett, PATH

3rd Trimester 1st Trimester 2nd Trimester PP L&D

Urosepsis

Septic Abortion

STIs

Narrowing Priority Pathogens/Syndromes to

Actionable Targets

Opportunities for Bundled Interventions

Chorio/Puerperal Sepsis

Skin & Soft Tissue Infection

L&D

PROM

Prophylaxis

Perinate

STIs

Initiation of ANC

Bacteruria

STI

Likely to be cost effective Prata N, et al. Health Policy 2010;94:1-13

Courtesy of M. Gravett, PATH