Finding the best questions for measuring AIDS mortality

using verbal autopsy:A validation study in

Kisesa, Tanzania and

Manicaland, Zimbabwe

Ben Lopman

Co-authorsManicaland Cohort• Jennifer Smith• Godwin Chawira • Simon Gregson

Kisesa Cohort• Adrian Cook• Yusufu Kumogola• Milalu Ndege• Basia Zaba • Mark Urassa• Raphael Isingo

WHO• Ties Boerma

Objective•To develop a classification

system of AIDS/ non-AIDS deaths using VA data validated against HIV testing that performs consistent in–Place–Time

VA for AIDS mortality

• HIV/AIDS is the leading cause of death among young adults

• Hospital records and vital registration of deaths are inadequate for AIDS – bias, underreporting and stigma.

• Improving measurement of AIDS mortality is urgent

• Monitoring the success of programmes relies on accurate measurement of AIDS deaths

KisesaWard (Magu DSS)

HIV Prev1994/1995: 6.0%2000/2001: 8.3%

Manicaland HIV/STD Prevention Study

HIV Prev1998/2000: 23.0%2001/2003: 20.5%

Mortality surveillance and VA tool

• The study teams identified deaths through the use of checklists of all individuals interviewed at baseline

• Nurse conducted interview with primary caregiver• VA developed in Kisesa, used in that site until

2002. After which, a verbal autopsy questionnaire based on the INDEPTH standard was used – This questionnaire lacked a number of questions related

to opportunistic infections often seen in AIDS patients

• A nearly identical version was used in Manicaland in both Round 1 and Round 2.

Gold Standard

• Gold standard of AIDS deaths. An individual who was – a) HIV positive at previous test – b) not accident/injury– c) not direct obstetric deaths

3945 to 59Test

15815 to 44TestK isesa

3845 to 59TestRound 2

18115 to 44TestRound 2

5145 to 59TestRound 1

8815 to 44TestRound 1

23715 to 44TrainRound 1Manicaland

Total with HIV test and VA (n)Age range

3945 to 59Test

15815 to 44TestK isesa

3845 to 59TestRound 2

18115 to 44TestRound 2

5145 to 59TestRound 1

8815 to 44TestRound 1

23715 to 44TrainRound 1Manicaland

Total with HIV test and VA (n)Age range

Training and testing datasets

AIDS deaths (gold standard)

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

15 to 44 15 to 44 45 to 59 15 to 44 45 to 59 15 to 44 45 to 59

Train Test Test Test Test Test Test

Round 1 Round 1 Round 1 Round 2 Round 2

Manicaland Kisesa

Rule-based algorithm• On TRAIN data• Calculate LR for all signs &

symptoms • Based on SPECIFICITY

1. Weight loss

2. …

.

WeightlossVaginal tumours

Wasting

Zoster

Abscesses

ARTIJaundice

Oral candidiasis

Diarrhoea

Recent TB

0.00

0.25

0.50

0.75

1.00

Sen

sitiv

ity

0.00 0.25 0.50 0.75 1.001 - Specificity

Area under ROC curve = 0.7697

.

WeightlossVaginal tumours

Wasting

Zoster

Abscesses

ARTIJaundice

Oral candidiasis

Diarrhoea

Recent TB

0.00

0.25

0.50

0.75

1.00

Sen

sitiv

ity

0.00 0.25 0.50 0.75 1.001 - Specificity

Area under ROC curve = 0.7697

Specificity: 15 to 44 year

80

85

90

95

100W

eigh

t los

s

Her

pes

zost

er

Jaun

dice

Vag

inal

tum

ours

Was

ting

AR

TI

Abs

cess

es o

r so

res

Ora

l can

didi

asis

Dia

rrho

ea

Rec

ent T

B

Manicaland

Kisesa

Sensitivity: 15 – 44 year

0

10

20

30

40

50W

eigh

t los

s

Her

pes

zost

er

Jaun

dice

Vag

inal

tum

ours

Was

ting

AR

TI

Abs

cess

es o

r so

res

Ora

l can

didi

asis

Dia

rrho

ea

Rec

ent T

B

Manicaland

Kisesa

15 to 44 years (9 Signs/Symptoms)

0%

25%

50%

75%

100%

Round OneTest

Round Tw o 1994 – 2002

Manicaland Kisesa

0%

25%

50%

75%

100%

Round OneTest

Round Tw o 1994 – 2002

Manicaland Kisesa

Sensitivity Specificity

Manicaland Kisesa Manicaland Kisesa

0%

25%

50%

75%

100%

Round OneTest

Round Tw o 1994 – 2002

Manicaland Kisesa

0%

25%

50%

75%

100%

Round OneTest

Round Tw o 1994 – 2002

Manicaland Kisesa

45 to 59 years (9 Signs/Symptoms)

Sensitivity Specificity

Manicaland Kisesa Manicaland Kisesa

0%

25%

50%

75%

100%

Round Tw o 1994 – 2002

Manicaland Kisesa

0%

25%

50%

75%

100%

Round Tw o 1994 – 2002

Manicaland Kisesa

15 to 44 years, INDEPTH variables

(5 Signs/Symptoms)Sensitivity Specificity

Manicaland Kisesa Manicaland Kisesa

Using INDEPTH questionsKisesa 1994-2002

40

45

50

55

60

65

70

75

80

85

5 av

ailab

le sy

mtp

oms

Dys

ente

ry

Fev

er w

conv

ulsion

s

Fev

er w

unc

onsc

iousn

ess

TB re

porte

d

TB sy

mpt

oms

HIV

/AID

S repo

rted

Weig

ht lo

ss w

ith d

ry/cr

acke

d sk

in

Weig

ht lo

ss w

ith o

edem

a

Fev

er w

pale

ness

and

shive

rs

Chr

onic

diarrh

oea

Fev

er w

coug

h an

d pa

in br

eath

ing

SenSpec

Using INDEPTH questionsManicaland R2

40

45

50

55

60

65

70

75

80

85

5 av

ailab

le sy

mtp

oms

Dys

ente

ry

Weig

ht lo

ss w

ith o

edem

a

TB re

porte

d

Fev

er w

conv

ulsion

s

Fev

er w

pale

ness

and

shive

rs

HIV

/AID

S repo

rted

Fev

er w

unc

onsc

iousn

ess

Fev

er w

coug

h an

d pa

in br

eath

ing

Chr

onic

diarrh

oea

Weig

ht lo

ss w

ith d

ry/cr

acke

d sk

in

TB sy

mpt

oms

SenSpec

AIDS CSMF, Correcting for misclassification

Estimate True

Manica R1 76% 74%

Manica R2 88% 76%

Kisesa 51% 53%

Estimating HIV prevalence

Estimate (95% CI)

True

Manica R1 24% (18-31)

23%

Conclusions

• Developed a set of criteria using VA that consistently measures AIDS mortality

• Algorithm performs consistently in these settings of variable HIV prevalence

• Only reliable for adults under age 45– OK in Manicaland, fewer female AIDS deaths

in older adults in Kisesa• Not subject to clinical biases• Can estimate HIV mortality in

populations lacking serosurveillance

INDEPTH and WHO VA

• Either of these widely used VA tools would face some limitations surveying AIDS mortality with the proposed criteria– Highly predictive and common

• Herpes zoster, oral candidiasis, abscesses/sores

– Highly predictive and rare• Vaginal tumors

Acknowledgements

• Funding– Health Metrics Network– Wellcome Trust– Netherlands Government

• People of Kisesa Ward, Tanzania and Manicaland Province, Zimbabwe– Especially Kin and Caregivers